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Treatment of patients with evidence of mast cell-mediated itch in the absence of hives with omalizumab
Auyeung KL and Kim BS
The presence of wheals or hives has been viewed as a hallmark symptom of urticaria, a highly debilitating disease. This study explores our experience with omalizumab in patients with apparent mast-cell mediated pruritus in the absence of hives.
Interpretation of Data from Translational Rodent Nerve Injury and Repair Models
Marsh EB, Snyder-Warwick AK, Mackinnon SE and Wood MD
This article highlights the use of rodents as preclinical models to evaluate the management of nerve injuries, describing the pitfalls and value from rodent nerve injury and regeneration outcomes, as well as treatments derived from these rodent models. The anatomic structure, size, and cellular and molecular differences and similarities between rodent and human nerves are summarized. Specific examples of success and failure when assessing outcome metrics are presented for context. Evidence for translation to clinical practice includes the topics of electrical stimulation, Tacrolimus (FK506), and acellular nerve allografts.
Traumatic brain injury in elderly population: a global systematic review and meta-analysis of in-hospital mortality and risk factors among 2.22 million individuals
Ma Z, He Z, Li Z, Gong R, Hui J, Weng W, Wu X, Yang C, Jiang J, Xie L and Feng J
Traumatic brain injury (TBI) among elderly individuals poses a significant global health concern due to the increasing ageing population.
Visible light-induced photocatalytic degradation of tetrabromobisphenol A on platinized tungsten oxide
Tarif A, Tran KD, Ahn YY, Kim K, Kim J and Park H
In this study, we investigated the degradation of the flame retardant tetrabromobisphenol A (TBBPA) using platinized tungsten oxide (Pt/WO), synthesized via a simple photodeposition method, under visible light. The results of degradation experiments show a significant enhancement in TBBPA degradation upon surface platinization of WO, with the degradation rate increasing by 13.4 times compared to bare WO. The presence of Pt on the WO surface stores conduction band electrons, which facilitates the two-electron reduction of oxygen and enhances the production of valence band holes (h) and hydroxyl radicals (OH). Both h and OH are significantly involved in the degradation of TBBPA in the visible light-irradiated Pt/WO system. This was verified through fluorescence spectroscopy employing coumarin as a chemical probe and oxidizing species-quenching experiments. The analysis of degradation products and their toxicity assessment demonstrate that the toxicity of TBBPA-contaminated water is significantly reduced after Pt/WO photocatalysis. The degradation rate of TBBPA increased with increasing Pt/WO dosage, reached an optimum at a Pt content of 0.5 wt%, but decreased with increasing TBBPA concentration. The decrease in degradation efficiency of Pt/WO was minor, both in the presence of various anions and after repeated use. This study proposes that Pt/WO is a viable photocatalyst for the degradation of TBBPA in water under visible light.
The impact of diabetes mellitus on foot perfusion measured by ICG NIR fluorescence imaging
Koning S, van Kersen J, Tange FP, Kruiswijk MW, Peul RC, van Schaik J, Schepers A, Vahrmeijer AL, Hamming JF, van den Hoven P and van der Vorst JR
Diabetes Mellitus (DM) is a common chronic disease, affecting 435 million people globally. Impaired vasculature in DM patients leads to complications like lower extremity arterial disease (LEAD) and foot ulcers, often resulting in amputations. DM causes additional peripheral neuropathy leading to multifactorial wound problems. Current diagnostics often deem unreliable, but Near-Infrared Fluorescence with Indocyanine Green (ICG NIR) can be used to assess the foot perfusion. Therefore, this study explores DM's impact on foot perfusion using ICG NIR.
A Closer Look into Gastrointestinal Bleeding in Heart Failure Patients
Zaher A, ElSaygh J, Midani A, Treihaft A, Banerji B, Bouso MF, Mushannen M, Hussein R and Crawford CV
The frequency and risk factors for gastrointestinal bleed (GIB) in patients with heart failure with reduced ejection fraction (HFrEF) have not been extensively researched.
Biodistribution of the cationic host defense peptide LL-37 using SPECT/CT
Esposito TVF, Rodríguez-Rodríguez C, Blackadar C, Kłodzińska S, Mørck Nielsen H, Saatchi K and Häfeli UO
Human cathelicidin LL-37, a cationic host defense peptide (CHDP), has several important physiological roles, including antimicrobial activity, immune modulation, and wound healing, and is a being investigated as a therapeutic candidate for several indications. While the effects of endogenously produced LL-37 are well studied, the biodistribution of exogenously administered LL-37 are less known. Here we assess the biodistribution of a gallium-67 labeled variant of LL-37 using nuclear imaging techniques over a 48 h period in healthy mice. When administered as an intravenous bolus just over 20 µg, the LL-37-based radiotracer was rapidly cleared from the blood, largely by the liver, while an appreciable fraction of the dose temporarily distributed to the lungs. When administered subcutaneously at the same dose level, the radiotracer was absorbed systemically following a two-phase kinetic model and was predominately cleared renally. Uptake into sites rich in immune cells, such as the lymph nodes and the spleen, was observed for both routes of administration. Scans of free gallium-67 were also performed as controls. Important preclinical insights into the biodistribution of exogenously administered LL-37 were gained from this study, which can aid in the understanding of this and related cationic host-defense peptides.
RIFM fragrance ingredient safety assessment, 3,7-dimethyl-7-methoxyoctan-2-ol, CAS Registry Number 41890-92-0
Api AM, Bartlett A, Belsito D, Botelho D, Bruze M, Bryant-Freidrich A, Burton GA, Cancellieri MA, Chon H, Dagli ML, Dekant W, Deodhar C, Farrell K, Fryer AD, Jones L, Joshi K, Lapczynski A, Lavelle M, Lee I, Moustakas H, Muldoon J, Penning TM, Ritacco G, Sadekar N, Schember I, Schultz TW, Siddiqi F, Sipes IG, Sullivan G, Thakkar Y and Tokura Y
Quiescent frame, contrast-enhanced coronary magnetic resonance angiography reconstructed using limited number of physiologic frames from 5D free-running acquisitions
Yang Y, Hair J, Yerly J, Piccini D, Di Sopra L, Bustin A, Prsa M, Si-Mohamed S, Stuber M and Oshinski JN
5D, free-running imaging resolves sets of 3D whole-heart images in both cardiac and respiratory dimensions. In an application such as coronary imaging when a single, static image is of interest, computationally expensive offline iterative reconstruction is still needed to compute the multiple 3D datasets.
Cajaninstilbene acid ameliorates depression-like behaviors in mice by suppressing TLR4/NF-κB mediated neuroinflammation and promoting autophagy
Tao X, Zhou Y, Wang Z, Wang L, Xia T, Yan M and Chang Q
Depression is a life-threatening neurodegenerative disease lacking a complete cure. Cajaninstilbene acid (CSA), a potent stilbene compound, has demonstrated neuroprotective effects, however, studies on its antidepressant mechanisms are still scarce. This study examined the effects of CSA on lipopolysaccharide (LPS)-induced and chronic unpredictable mild stress (CUMS)-induced depression in mice, investigating its mechanisms related to inflammation and autophagy. Mice were treated with CSA (7.5, 15, and 30mg/kg) daily for 3 weeks before intraperitoneal LPS injection (0.8mg/kg). Another cohort underwent the same doses of CSA (7.5-30mg/kg) daily for 6 weeks in accompany with CUMS stimulation. Behavioral assessments were conducted, and cortical samples were collected for molecular analysis. Findings indicate that CSA ameliorated depressive behaviors induced by both LPS and CUMS. Notably, CSA (15mg/kg) reversed despair behavior in mice more persistently than amitriptyline, indicating that optimal doses of CSA may effectively decelerate the procession of mood despair and yield a good compliance. CSA countered CUMS-induced activation of TLR4/NF-κB pathway and the reduction in autophagy levels. Furthermore, CSA attenuated the CUMS-induced decline in neuroplasticity. Collectively, these findings suggest that CSA mitigates depression-like behaviors in mice by inhibiting TLR4/NF-κB-mediated neuroinflammation and enhancing autophagy. This research provides further insights into CSA's mechanisms of action in ameliorating depressive behaviors, offering a scientific foundation for developing CSA-based antidepressants.
Inadequate Rhinitis Control in Real Life-What to Do?
Scadding GK
The importance of long-term follow-up of oral immunotherapy in food allergy
Loke P, Lloyd M and Tang MLK
Traversing the Diagnostic Dilemma: Leaving the Bronchodilator Response Behind
Watson J and Kaminsky DA
Some Thoughts on Lung Cancer Risk Prediction Models for Long-Term Smokers in Asia
Shen LT and Chen HL
Small airway dysfunction is common even in mild asthma and suggests increased exacerbation risk
Galant SP
"Some Thoughts on Lung Cancer Risk Prediction Models for Long-Term Smokers in Asia"
Yang JJ, Wen W, Zheng W and Shu XO
Effects of background music on numerical and spatial location working memory: differences between extraverts and introverts
Deng M, Gu X and Wu F
This experimental research explored background music's influence on the performance of numerical and spatial location working memory of extraverts and introverts. Sixty participants (30 extraverts and 30 introverts) were asked to complete numerical and spatial location working memory tests, under the conditions of background music and silence. Results showed a main negative effect of background music on the participants' performance of spatial location working memory. A significant interaction effect between music and personality (extroversion and introversion) on this performance was also observed. It revealed that a more negative effect of music in introverts as compared with extroverts. In contrast, no main or interaction effect was observed for the performance of numerical working memory. According to the influence of music on working memory, introversion-extraversion personality factors of workers such as cashiers or drivers require consideration.
Evaluation of self-contained breathing apparatus (SCBA) weight on firefighter stamina, comfort, and postural stability
Kesler RM, Powell J, Nguyen D, Massey KA, Joshi S, Xu S, Zhuang Z, Horn GP, Burd NA and Masoud F
Firefighters wear personal protective equipment to protect them from the thermal and chemical environment in which they operate. The self-contained breathing apparatus (SCBA) provides isolation of the airway from the hazardous fireground. National standards limit SCBA weight, however, integration of additional features could result in an SCBA exceeding the current limit. The purpose of this study was to examine the effects of increased SCBA weight on firefighters' physiological responses, work output, dynamic stability, and comfort. Completion of simulated firefighting activities induced a strong physiological response. Peak oxygen consumption was higher with the lightest SCBA than the heaviest SCBA. Few other physiological differences were noted as SCBA weight increased. Importantly, increased SCBA weight resulted in significantly more negative perceptions by the firefighters and a trend towards significance for the duration of work time prior to reaching volitional fatigue. These results should be considered when assessing changes to existing SCBA weight limits.
Drug-Induced Anaphylaxis in Mastocytosis: A Cause for Concern?
Jayasundera J and Watts TJ
French Validation of the oMtFSFI Questionnaire for Assessing the Sexual Function of Transgender Women After Vulvo-vaginoplasty
Richard C, Sabbagh P, Bourillon A, Vedovo F, Morel-Journel N, Neuville P, Dessaux N, Manunta A, Vidart A, Madec FX, Peyronnet B and Freton L
The Operated Male-to-Female Sexual Function Index (oMtFSFI) questionnaire is the first scoring system developed to assess sexual function after gender-affirming vulvo-vaginoplasty, and was initially developed and validated in Italian. The aim of this study was to provide linguistic validation of the questionnaire in French through several steps including use of the questionnaires across a series of patients who had undergone gender-affirming vulvo-vaginoplasty between 2020 and 2022 at two French academic centers.
Phylogenomics and biogeography of sawflies and woodwasps (hymenoptera, symphyta)
Wutke S, Blank SM, Boevé JL, Faircloth BC, Koch F, Linnen CR, Malm T, Niu G, Prous M, Schiff NM, Schmidt S, Taeger A, Vilhelmsen L, Wahlberg N, Wei M and Nyman T
Phylogenomic approaches have recently helped elucidate various insect relationships, but large-scale comprehensive analyses on relationships within sawflies and woodwasps are still lacking. Here, we infer the relationships and long-term biogeographic history of these hymenopteran groups using a large dataset of 354 UCE loci collected from 385 species that represent all major lineages. Early Hymenoptera started diversifying during the Early Triassic ∼249 Ma and spread all over the ancient supercontinent Pangaea. We recovered Xyeloidea as a monophyletic sister group to other Hymenoptera and Pamphilioidea as sister to Unicalcarida. Within the diverse family Tenthredinidae, our taxonomically and geographically expanded taxon sampling highlights the non-monophyly of several traditionally defined subfamilies. In addition, the recent removal of Athalia and related genera from the Tenthredinidae into the separate family Athaliidae is supported. The deep historical biogeography of the group is characterised by independent dispersals and re-colonisations between the northern (Laurasia) and southern (Gondwana) palaeocontinents. The breakup of these landmasses led to ancient vicariance in several Gondwanan lineages, while interchange across the Northern Hemisphere has continued until the Recent. The little-studied African sawfly fauna is likewise a diverse mixture of groups with varying routes of colonization. Our results reveal interesting parallels in the evolution and biogeography of early hymenopterans and other ancient insect groups.
Incidence, risk factors, and impact of post-return of spontaneous circulation events in patients with out-of-hospital cardiac arrest: a population-based study in Tokyo, Japan
Shibahashi K, Nonoguchi N, Inoue K, Kato T and Sugiyama K
Patients with the return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest (OHCA) are unstable and often experience rearrest, after which ROSC may be reattained. This study investigated the incidence and risk factors of post-ROSC events (rearrest and subsequent reattainment of ROSC) and their impact on outcomes in patients with prehospital ROSC following OHCA.
Direct-acting antivirals for RSV treatment, a review
Bonneux B, Jacoby E, Ceconi M, Stobbelaar K, Delputte P and Herschke F
Respiratory syncytial virus (RSV) causes respiratory disease and complications in infants, the elderly and the immunocompromised. While three vaccines and two prophylactic monoclonal antibodies are now available, only one antiviral, ribavirin, is currently approved for treatment. This review aims to summarize the current state of treatments directly targeting RSV. Two major viral processes are attractive for RSV-specific antiviral drug discovery and development as they play essential roles in the viral cycle: the entry/fusion process carried out by the fusion protein and the replication/transcription process carried out by the polymerase complex constituted of the L, P, N and M2-1 proteins. For each viral target resistance mutations to small molecules of different chemotypes seem to delineate definite binding pockets in the fusion proteins and in the large proteins. Elucidating the mechanism of action of these inhibitors thus helps to understand how the fusion and polymerase complexes execute their functions. While many inhibitors have been studied, few are currently in clinical development for RSV treatment: one is in phase III, three in phase II and two in phase I. Progression was halted for many others because of strategic decisions, low enrollment, safety, but also lack of efficacy. Lessons can be learnt from the halted programs to increase the success rate of the treatments currently in development.
Artificial Intelligence in Parkinson's Disease: Early Detection and Diagnostic Advancements
Reddy A, Reddy RP, Roghani AK, Garcia RI, Khemka S, Pattoor V, Jacobs M, Reddy PH and Sehar U
Parkinson's disease (PD) is the second most common neurodegenerative disorder, globally affecting men and women at an exponentially growing rate, with currently no cure. Disease progression starts when dopaminergic neurons begin to die. In PD, the loss of neurotransmitter, dopamine is responsible for the overall communication of neural cells throughout the body. Clinical symptoms of PD are slowness of movement, involuntary muscular contractions, speech & writing changes, lessened automatic movement, and chronic tremors in the body. PD occurs in both familial and sporadic forms and modifiable and non-modifiable risk factors and socioeconomic conditions cause PD. Early detectable diagnostics and treatments have been developed in the last several decades. However, we still do not have precise early detectable biomarkers and therapeutic agents/drugs that prevent and/or delay the disease process. Recently, artificial intelligence (AI) science and machine learning tools have been promising in identifying early detectable markers with a greater rate of accuracy compared to past forms of treatment and diagnostic processes. Artificial intelligence refers to the intelligence exhibited by machines or software, distinct from the intelligence observed in humans that is based on neural networks in a form and can be used to diagnose the longevity and disease severity of disease. The term Machine Learning or Neural Networks is a blanket term used to identify an emerging technology that is created to work in the way of a "human brain" using many intertwined neurons to achieve the same level of raw intelligence as that of a brain. These processes have been used for neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease, to assess the severity of the patient's condition. In the current article, we discuss the prevalence and incidence of PD, and currently available diagnostic biomarkers and therapeutic strategies. We also highlighted currently available artificial intelligence science and machine learning tools and their applications to detect disease and develop therapeutic interventions.
IGF-1 inhibits inflammation and accelerates angiogenesis via Ras/PI3K/IKK/NF-κB signaling pathways to promote wound healing
Zhang X, Hu F, Li J, Chen L, Mao YF, Li QB, Nie CY, Lin C and Xiao J
Exogenous insulin-like growth factor-1 (IGF-1) has been reported to promote wound healing through regulation of vascular endothelial cells (VECs). Despite the existing studies of IGF-1 on VEC and its role in angiogenesis, the mechanisms regarding anti-inflammatory and angiogenetic effects of IGF-1 remain unclear. In this study, we investigated the wound-healing process and the related signaling pathway of IGF-1 using an inflammation model induced by IFN-γ. The results demonstrated that IGF-1 can increase cell proliferation, suppress inflammation in VECs, and promote angiogenesis. In vivo studies further confirmed that IGF-1 can reduce inflammation, enhance vascular regeneration, and improve re-epithelialization and collagen deposition in acute wounds. Importantly, the Ras/PI3K/IKK/NF-κB signaling pathways was identified as the mechanisms through which IGF-1 exerts its anti-inflammatory and pro-angiogenic effects. These findings contribute to the understanding of IGF-1's role in wound healing and may have implications for the development of new wound treatment approaches.
Prognostic impact of cytokines and chemokines in bronchoalveolar lavage fluid on acute exacerbation of fibrosing interstitial lung disease
Furuta K, Fujimoto D, Matsunashi A, Shibaki R, Taniya S, Tanaka M, Shimada Y, Nagata K, Tomii K and Yamamoto N
Acute exacerbation of fibrosing interstitial lung disease (AE-FILD) is a serious condition with a high mortality rate. We aimed to comprehensively analyze cytokines in bronchoalveolar lavage fluid and their association with the clinical course of AE-FILD.
An Elastomer with In Situ Generated Pure Zwitterionic Surfaces for Fibrosis-resistant Implants
Zhou X, Cao W, Chen Y, Zhu Z, Lai Y, Liu Z, Jia F, Lu Z, Han H, Yao K, Wang Y, Ji J and Zhang P
Polymeric elastomers are widely utilized in implantable biomedical devices. Nevertheless, the implantation of these elastomers can provoke a robust foreign body response (FBR), leading to the rejection of foreign implants and consequently reducing their effectiveness in vivo. Building effective anti-FBR coatings on those implants remains challenging. Herein, we introduce a coating-free elastomer with superior immunocompatibility. A super-hydrophilic anti-fouling zwitterionic layer can be generated in situ on the surface of the elastomer through a simple chemical trigger. This elastomer can repel the adsorption of proteins, as well as the adhesion of cells, platelets, and diverse microbes. The elastomer elicited negligible inflammatory responses after subcutaneous implantation in rodents for 2 weeks. No apparent fibrotic capsule formation was observed surrounding the elastomer after 6 months in rodents. Continuous subcutaneous insulin infusion (CSII) catheters constructed from the elastomer demonstrated prolonged longevity and performance compared to commercial catheters, indicating its great potential for enhancing and extending the performance of various implantable biomedical devices by effectively attenuating local immune responses. STATEMENT OF SIGNIFICANCE: The foreign body response remains a significant challenge for implants. Complicated coating procedures are usually needed to construct anti-fibrotic coatings on implantable elastomers. Herein, a coating-free elastomer with superior immunocompatibility was achieved using a zwitterionic monomer derivative. A pure zwitterionic layer can be generated on the elastomer surface through a simple chemical trigger. This elastomer significantly reduces protein adsorption, cell and bacterial adhesion, and platelet activation, leading to minimal fibrotic capsule formation even after six months of subcutaneous implantation in rodents. CSII catheters constructed from the PQCBE-H elastomer demonstrated prolonged longevity and performance compared to commercial catheters, highlighting the significant potential of PQCBE-H elastomers for enhancing and extending the performance of various implantable biomedical devices.
Metabolomic and lipidomic fingerprints in inflammatory skin diseases - Systemic illumination of atopic dermatitis, hidradenitis suppurativa and plaque psoriasis
Rischke S, Schäfer SMG, König A, Ickelsheimer T, Köhm M, Hahnefeld L, Zaliani A, Scholich K, Pinter A, Geisslinger G, Behrens F and Gurke R
Auto-inflammatory skin diseases place considerable symptomatic and emotional burden on the affected and put pressure on healthcare expenditures. Although most apparent symptoms manifest on the skin, the systemic inflammation merits a deeper analysis beyond the surface. We set out to identify systemic commonalities, as well as differences in the metabolome and lipidome when comparing between diseases and healthy controls. Lipidomic and metabolomic LC-MS profiling was applied, using plasma samples collected from patients suffering from atopic dermatitis, plaque-type psoriasis or hidradenitis suppurativa or healthy controls. Plasma profiles revealed a notable shift in the non-enzymatic anti-oxidant defense in all three inflammatory disorders, placing cysteine metabolism at the center of potential dysregulation. Lipid network enrichment additionally indicated the disease-specific provision of lipid mediators associated with key roles in inflammation signaling. These findings will help to disentangle the systemic components of autoimmune dermatological diseases, paving the way to individualized therapy and improved prognosis.
Design and development of locust bean gum-endowed/Phyllanthus reticulatus anthocyanin- functionalized biogenic gold nanosystem for enhanced antioxidative and anticancer chemotherapy
Eze FN, Eze RC, Okpara KE, Adekoya AE and Kalu HN
Herein, the design and fabrication of an anticancer nanoplatform (LBG/PRA-NG) based on locust bean gum-stabilized nanogold and functionalized with Phyllanthus reticulatus anthocyanins was described. LBG/PRA-NG was prepared in an eco-friendly, one-pot approach at room temperature, mediated by the anthocyanins and gum as bio-reductant and stabilizer, respectively. The nanostructure was elaborately characterized by FESEM, TEM, UV-visible, DLS, Zeta potential, FTIR, XRD, TGA/DTG, and XPS analysis. Its anticancer attributes were examined based on cytotoxicity on MCF-7 and MDA-MB-231 breast cancer cell lines, as well as the generation of intracellular reactive oxygen species. The results revealed the successful formation of a homogenous and highly stable nanocomposite (LBG/PRA-NG), with quasi-spherical shape, small size (14.73 nm), Zeta potential and PDI values of -58.30 mV and 0.237, respectively. The presence of a plasmonic peak at 525 nm was indicative of AuNPs. Compared to the galactomannan and anthocyanin, LBG/PRA-NG exhibited superior antioxidative properties with IC values of 35.44 μg/mL against DPPH and 24.55 μg/mL against ABTS. Notably, LBG/PRA-NG also demonstrated enhanced anticancer properties relative to LBG and anthocyanins, with IC values of 16.17 μg/mL and 25.06 μg/mL against MCF-7 and MDA-MB-231 cells. Meanwhile, the normal cells (HEK-293 and L929) resisted the innocuous effects of LBG/PRA-NG. Furthermore, treatment of breast cancer cells with LBG/PRA-NG drastically elevated the intracellular ROS levels. This suggested that the anticancer activity of LBG/PRA-NG may be mediated via amplification of ROS/oxidative stress-induced apoptosis. Altogether, these findings indicate the remarkable potential of LBG/PRA-NC in the development of anticancer therapy.
Preparation of a high-performance conductive lignocellulose hydrogel by directly using non-detoxified bisulfite-pretreated corncob
Wang P, Zheng T, Gan S and Yao J
Biomass-based hydrogels have become a research hotspot because of their better biocompatibility. However, the preparation of biomass hydrogels is complicated, and they often need to be modified by introducing other substances. In this study, corncob pretreated with bisulfite (125-185 °C) was used as a raw material to prepare lignocellulose hydrogels. The results showed that directly using the pretreated sample without the washing step lowered the total hydrogel costs while preserving the lignosulfonate (LS) produced during pretreatment. The best tensile (54.1 kPa) and compressive (177.7 kPa) stresses were obtained for the hydrogel prepared from non-detoxified pretreated corncob at 165 °C (NCH-165). The sulfonic acid groups in LS could enhance the interaction between plant cellulose, thus improving its mechanical properties. The capacitor assembled from NCH-165 achieved an energy density of 236.1 Wh/kg at a power density of 499.7 W/kg and a high coulombic efficiency of more than 99 % after 2000 charge/discharge cycles. In conclusion, the present study simplifies the pathway for the preparation of flexible, conductive, and anti-freezing hydrogels by directly utilizing a non-detoxified bisulfite-pretreated corncob.
PBAT/lignin-ZnO composite film for food packaging: Photo-stability, better barrier and antibacterial properties
Wang S, Tang K, Zhang Z, Liu H, Yao Y and Liao X
When PBAT used as film, stability deteriorates under sunlight exposure, and the poor barrier and antibacterial properties are also limiting its application. In this work, lignin-ZnO nanoparticles were prepared by hydrothermal method, as additives to fill the PBAT matrix, and PBAT-lignin-ZnO composite films were successfully prepared by melting and hot-pressing method. It is found that lignin could well dispersed the ZnO when its implantation into PBAT films, and lignin-ZnO not only maintaining tensile strength and thermal stability, and could prompt PBAT's crystallinity. Especially, P-L-ZnO-2 composite films have good photostability. After 60 h aging, it can still maintain good molecular weight, chemical structure and mechanical properties. Besides, these composite films have improved hydrophobicity, barrier and antibacterial properties, could prevent mildew and significantly reduce the weight loss rate, color difference and hardness changes of strawberries during storage. This work provides a potential film material for outdoor applications and food packaging.
SCD1 promotes the stemness of gastric cancer stem cells by inhibiting ferroptosis through the SQLE/cholesterol/mTOR signalling pathway
Mao X, Wang L, Chen Z, Huang H, Chen J, Su J, Li Z, Shen G, Ren Y, Li Z, Wang W, Ou J, Guo W and Hu Y
Cancer stem cells (CSCs) play a substantial role in cancer onset and recurrence. Anomalous iron and lipid metabolism have been documented in CSCs, suggesting that ferroptosis, a recently discovered form of regulated cell death characterised by lipid peroxidation, could potentially exert a significant influence on CSCs. However, the precise role of ferroptosis in gastric cancer stem cells (GCSCs) remains unknown. To address this gap, we screened ferroptosis-related genes in GCSCs using The Cancer Genome Atlas and corroborated our findings through quantitative polymerase chain reaction and western blotting. These results indicate that stearoyl-CoA desaturase (SCD1) is a key player in the regulation of ferroptosis in GCSCs. This study provides evidence that SCD1 positively regulates the transcription of squalene epoxidase (SQLE) by eliminating transcriptional inhibition of P53. This mechanism increases the cholesterol content and the elevated cholesterol regulated by SCD1 inhibits ferroptosis via the mTOR signalling pathway. Furthermore, our in vivo studies showed that SCD1 knockdown or regulation of cholesterol intake affects the stemness of GCSCs and their sensitivity to ferroptosis inducers. Thus, targeting the SCD1/squalene epoxidase/cholesterol signalling axis in conjunction with ferroptosis inducers may represent a promising therapeutic approach for the treatment of gastric cancer based on GCSCs.
Structural and functional analysis of aquaporins in Bombus terrestris
Ma X, Chang X, Liu G, Han Q, Ke H, Ren B and Wang Y
Bombus terrestris are efficient pollinators in forestry and agriculture, with higher cold tolerance than other bees. Yet, their cold tolerance mechanism remains unclear. Aquaporins (AQPs) function as cell membrane proteins facilitating rapid water flow, aiding in osmoregulation. Recent studies highlight the importance of insect AQPs in dehydration and cold stress. Comparative transcriptome analysis of B. terrestris under cold stress revealed up-regulation of four AQPs, indicating their potential role in cold tolerance. Seven AQPs-Eglp1, Eglp2, Eglp3, DRIP, PRIP, Bib, and AQP12L-have been identified in B. terrestris. These are widely expressed in various tissues, particularly in the alimentary canal and Malpighian tubules. Functional analysis of BterAQPs in the Xenopus laevis oocytes expressing system showed distinct water and glycerol selectivity, with BterDrip exhibiting the highest water permeability. Molecular modeling of BterDrip revealed six transmembrane domains, two NPA motifs, and an ar/R constriction region (Phe131, His256, Ser265, and Arg271), likely contributing to its water selectivity. Silencing BterDRIP accelerated mortality in B. terrestris under cold stress, highlighting the crucial role of BterDRIP in their cold tolerance and providing a molecular mechanism for their cold adaptation.
The identification, evolutionary analysis, and immune roles of Rab family members in red swamp crayfish, Procambarus clarkii
Zhu L, Du Z, Kong Y, Wang X, Li H, Hou L and Kong X
The Rab GTPase constitutes the largest family of small GTPases that regulate intracellular trafficking. Different eukaryotes possess varying numbers of Rab paralogs. However, limited knowledge exists regarding the evolutionary pattern of Rab family in most major eukaryotic supergroups. This study cloned 24 Rab genes from transcriptome data of Procambarus clarkii haemocytes. The multiple sequence alignment and phylogenetic tree analysis revealed a relatively high degree of conservation for PcRab. Furthermore, PcRab exhibited similarities in motif composition with all members showing presence of G, PM, RabF, and RabSF motifs. The tertiary structure indicated that PcRab proteins mainly consisted of α-helices and β-strands, and most PcRab proteins shared similar tertiary structures, and it was indicated that they have similar protein characteristics. Protein-protein interaction prediction identified a total of 20 interacting proteins involved in vesicle trafficking, phagocytosis, and signal transduction with 193 interactions. Expression analysis showed wide expression patterns for PcRab in P. clarkii organs. Upon infection by white spot syndrome virus and Aeromonas veronii, significant induction was observed for PcRab gene expression levels, indicating their involvement in pathogen response mechanisms. The present study represents the pioneering effort in comprehensively identifying and cloning the Rab family genes in crustacean, followed by a systematic investigation into their evolutionary patterns and immune response upon pathogen infection. The results provided valuable insights for further investigation into the molecular mechanism underlying the response of P. clarkii to pathogen infection.
Exploring the antimicrobial and antioxidant potential of bacterial cellulose-cerium oxide nanoparticles hydrogel: Design, characterization and biomedical properties
Butulija S, Šobot AV, Todorović B, Petrović SM, Radovanović Ž, Ilić B, Matović B, Mihailović R, Zarubica A, Zmejkoski D and Tričković JF
Bacterial cellulose (BC) is a promising natural polymer prized for its biocompatibility, microporosity, transparency, conformability, elasticity, and ability to maintain a moist wound environment while absorbing exudates. These attributes make BC an attractive material in biomedical applications, particularly in skin tissue repair. However, its lack of inherent antimicrobial activity limits its effectiveness. In this study, BC was enhanced by incorporating cerium (IV)-oxide (CeO) nanoparticles, resulting in a series of bacterial cellulose-CeO (BC-CeO) composite materials. Characterization via FESEM, XRD, and FTIR confirmed the successful synthesis of the composites. Notably, BC-CeO-1 exhibited no cytotoxic or genotoxic effects on peripheral blood lymphocytes, and it additionally protected cells from genotoxic and cytotoxic effects in HO-treated cultures. Redox parameters in blood plasma samples displayed concentration and time-dependent trends in PAB and LPP assays. The incorporation of CeO nanoparticles also bolstered antimicrobial activity, expanding the potential biomedical applications of these composites.
Artificial Intelligence-Based Evaluation of Carotid Artery Compressibility via Point-of-Care Ultrasound in Determining the Return of Spontaneous Circulation During Cardiopulmonary Resuscitation
Park S, Yoon H, Yeon Kang S, Joon Jo I, Heo S, Chang H, Eun Park J, Lee G, Kim T, Yeon Hwang S, Park S and Jin Chung M
This study introduces RealCAC-Net, an artificial intelligence (AI) system, to quantify carotid artery compressibility (CAC) and determine the return of spontaneous circulation (ROSC) during cardiopulmonary resuscitation .
In-vitro and in-vivo investigation of wound healing efficacy of Syzygium cumini leaf extracts loaded carboxymethylcellulose film
Ayyanar CB, Bal T, Fahaduddin , Sharma S, Gayathri B, Rinusuba V, Nalini HE, Deepa S, Dharshinii MD, Kharra P and Sinha A
The study focused on Syzygium cumini Leaf Extract (SCLE) loaded into Carboxymethylcellulose (CMC) film via Solution casting. Phytochemical screening revealed carbohydrates, and HPLC analysis identified quercetin, known for promoting wound healing. FT-IR spectroscopy confirmed various functional groups. X-Ray diffraction (XRD) determined the crystallite size to be 14.58 nm. Field Emission Scanning Electron Microscopy (FESEM) showed the dispersion of extracts, and Energy Dispersive X-ray (EDX) analysis detailed the weight percentages of components. Antibacterial activity tests revealed zones of inhibition for S. aureus (15 mm) and E. coli (11 mm). The film exhibited 63.11 % antioxidant activity at 517 nm with DPPH at a 750 μL sample concentration. Drug release kinetics were also studied. In-vitro wound healing using the L929 cell line showed 83 % healing at a 100 μL concentration. Over 14 days, the treatment group's wounds healed completely within 7 days, unlike the control groups which showed no recovery after 14 days. These findings indicate that the SCLE-CMC film is highly effective in promoting wound healing.
Evidence that robot-assisted gait training modulates neuroplasticity after stroke: An fMRI pilot study based on graph theory analysis
Tang Z, Zhao Y, Sun X, Liu Y, Su W, Liu T, Zhang X and Zhang H
To investigate alterations of whole-brain network after stroke and therapeutic mechanisms of robot-assisted gait training (RAGT).
The first report of a C-type lectin contains a CLIP domain involved in antibacterial defense in Macrobrachium nipponense
Ren Q and Huang X
We identified a novel C-type lectin (CTL) from Macrobrachium nipponense, designated as Mn-clip-Lec. It consists of 1315 bp with an open reading frame of 1098 bp, encoding a polypeptide of 365 amino acids. Mn-clip-Lec contains 6 exons and 5 introns. Mn-clip-Lec possessed a CLIP domain at the N-terminal and two carbohydrate recognition domains at the C-terminal. Interaction between Mn-clip-Lec and MnLec was found by Yeast two-hybrid analysis. The expressions of Mn-clip-Lec, MnLec, prophenoloxidase (proPO)-activating system-associated genes (MnPPAF, MnPPAE, and MnPO), and antimicrobial peptide (AMPs) (MnALF and MnCRU) were up-regulated after the challenge with Staphylococcus aureus. RNA interference (RNAi)-mediated suppression of the Mn-clip-Lec and MnLec genes in S. aureus-challenged prawns reduced the transcripts of MnPPAF, MnPPAE, MnPO, MnALF and MnCRU. Knockdown of Mn-clip-Lec and MnLec resulted in decrease in PO activity in M. nipponense infected with S. aureus. The recombinant Mn-clip-Lec (rMn-clip-Lec) protein bound all tested bacteria and agglutinated S. aureus. A sugar-binding assay revealed that rMn-clip-Lec could bind to LPS or PGN. rMn-clip-Lec accelerated the clearance of S. aureus in vivo. Our findings suggest that Mn-clip-Lec and its interacting MnLec play important roles in the induction of the proPO system and AMPs expression in M. nipponense during bacterial infection.
Promoting Biological Similarity by Collagen Microfibers in 3D Colorectal Cancer-Stromal Tissue: Replicating Mechanical Properties and Cancer Stem Cell Markers
Sasaki N, Asano Y, Sorayama Y, Kamimura C, Kitano S, Irie S, Katayama R, Shimoda H and Matsusaki M
The extracellular matrix (ECM) of cancer tissues is rich in dense collagen, contributing to the stiffening of these tissues. Increased stiffness has been reported to promote cancer cell proliferation, invasion, metastasis, and prevent drug delivery. Replicating the structure and mechanical properties of cancer tissue in vitro is essential for developing cancer treatment drugs that target these properties. In this study, we recreated specific characteristics of cancer tissue, such as collagen density and high elastic modulus, using a colorectal cancer cell line as a model. Using our original material, collagen microfibers (CMFs), and a constructed three-dimensional (3D) cancer-stromal tissue model, we successfully reproduced an ECM highly similar to in vivo conditions. Furthermore, our research demonstrated that cancer stem cell markers expressed in the 3D cancer-stromal tissue model more closely mimic in vivo conditions than traditional two-dimensional cell cultures. We also found that CMFs might affect an impact on how cancer cells express these markers. Our 3D CMF-based model holds promise for enhancing our understanding of colorectal cancer and advancing therapeutic approaches. STATEMENT OF SIGNIFICANCE: Reproducing the collagen content and stiffness of cancer tissue is crucial in comprehending the properties of cancer and advancing anticancer drug development. Nonetheless, the use of collagen as a scaffold material has posed challenges due to its poor solubility, hindering the replication of a cancer microenvironment. In this study, we have successfully recreated cancer tissue-specific characteristics such as collagen density, stiffness, and the expression of cancer stem cell markers in three-dimensional (3D) colorectal cancer stromal tissue, utilizing a proprietary material known as collagen microfiber (CMF). CMF proves to be an ideal scaffold material for replicating cancer stromal tissue, and these 3D tissues constructed with CMFs hold promise in contributing to our understanding of cancer and the development of therapeutic drugs.
Vigour as a marker of positive mental health among social media respondents
Dlagnekova A and Van Staden W
Quantitative research on vigour as a therapeutically responsive marker of positive mental health, has become possible by virtue of the validation of the Vigour Assessment Scale (VAS). Considering that its validation and therapeutic responsiveness were examined in an avolitional schizophrenia population, using the VAS outside these constraints requires that its psychometric properties be investigated in a more general non-clinical population.
Effects of increased nitrate intake from beetroot juice on blood markers of oxidative stress and inflammation in older adults with hypertension
Fejes R, Pilat N, Lutnik M, Weisshaar S, Weijler AM, Krüger K, Draxler A, Bragagna L, Peake JM, Woodman RJ, Croft KD, Bondonno CP, Hodgson JM, Wagner KH, Wolzt M and Neubauer O
Vascular oxidative stress and low-grade inflammation are important in the pathology of cardiovascular disorders, including hypertension. Cell culture and animal studies suggest that inorganic dietary nitrate may attenuate oxidative stress and inflammation through nitric oxide (NO), and there is a need to investigate whether this translates to humans.
Relationships between the gut microbiome and brain functional alterations in first-episode, drug-naïve patients with major depressive disorder
Wang D, Jiang X, Zhu H, Zhou Y, Jia L, Sun Q, Kong L and Tang Y
Increasing evidence has shown that the microbiota-gut-brain axis (MGB) is involved in the mechanism of major depressive disorder (MDD). However, the relationship between the gut microbiome and brain function in MDD patients has not been determined. Here, we intend to identify specific changes in the gut microbiome and brain function in first-episode, drug-naïve MDD patients and then explore the associations between the two omics to elucidate how the MGB axis plays a role in MDD development.
Dietary pectin and inulin: a promising adjuvant supplement for collagen-induced arthritis through gut microbiome restoration and CD4 T cell reconstitution
Lou Y, Wen X, Song S, Zeng Y, Huang L, Xie Z, Shao T and Wen C
Dietary strategies rich in fiber have been demonstrated to offer benefits to individuals afflicted with rheumatoid arthritis (RA). However, the specific mechanisms through which a high-fiber diet (HFD) mitigates RA's autoimmunity remain elusive. Herein, we investigate the influence of pectin- and inulin-rich HFD on collagen-induced arthritis (CIA). We establish that HFD significantly alleviates arthritis in CIA mice by regulating the Th17/Treg balance. The rectification of aberrant T cell differentiation by the HFD is linked to the modulation of gut microbiota, augmenting the abundance of butyrate in feces. Concurrently, adding butyrate to the drinking water mirrors the HFD's impact on ameliorating CIA, encompassing arthritis mitigation, regulating intestinal barrier integrity, and restoring the Th17/Treg equilibrium. Butyrate reshapes the metabolic profile of CD4 T cells in an AMPK-dependent manner. Our research underscores the importance of dietary interventions in rectifying gut microbiota for RA management and offers an explanation of how diet-derived microbial metabolites influence RA's immune-inflammatory-reaction.
Report of the 2023-2024 Strategic Engagement Standing Committee
Palombi LC, Silvia R, Dugan S, Khan MOF, Kawahara B, O'Neal KS, Robinson E, Tyler L, Unni E, Shrader S and Moore T
The American Association of Colleges of Pharmacy (AACP) has long emphasized the value of strategic engagement, recognizing that it is critical to the success of pharmacy education, contributing to the expansion of pharmacy and public health practice, the fulfillment of institutional missions, and the meeting of programmatic needs. The 2023-2024 Strategic Engagement Committee (SEC or the Committee) was charged with operationalizing Advocacy Champions, creating an Advocacy Resource Guide to support Advocacy Champions in their engagement with diverse public and private stakeholders, offering formal training to Advocacy Champions in the form of a new Connect Community and Webinar Series, and conducting focus groups at the 2024 Annual Meeting to determine strengths of the Advocacy Guide and opportunities to support Advocacy Champions further.
Traumatic brain injury and long-term associations with work, divorce and academic achievement
Rytter HM, Hjorthøj C, Graff HJ, Eplov LF, Nordentoft M, Benros ME, Erlangsen A and Madsen T
Traumatic brain injuries (TBI), irrespective of severity, may have long-term social implications. This study explores the relationships between TBI severity and outcomes related to work stability, divorce, and academic achievement.
Evolution and development of Drosophila melanogaster under different thermal conditions affected cell sizes and sensitivity to paralyzing hypoxia
Szabla N, Maria Labecka A, Antoł A, Sobczyk Ł, Angilletta MJ and Czarnoleski M
Environmental gradients cause evolutionary and developmental changes in the cellular composition of organisms, but the physiological consequences of these effects are not well understood. Here, we studied experimental populations of Drosophila melanogaster that had evolved in one of three selective regimes: constant 16 °C, constant 25 °C, or intergenerational shifts between 16 °C and 25 °C. Genotypes from each population were reared at three developmental temperatures (16 °C, 20.5 °C, and 25 °C). As adults, we measured thorax length and cell sizes in the Malpighian tubules and wing epithelia of flies from each combination of evolutionary and developmental temperatures. We also exposed flies from these treatments to a short period of nearly complete oxygen deprivation to measure hypoxia tolerance. For genotypes from any selective regime, development at a higher temperature resulted in smaller flies with smaller cells, regardless of the tissue. At every developmental temperature, genotypes from the warm selective regime had smaller bodies and smaller wing cells but had larger tubule cells than did genotypes from the cold selective regime. Genotypes from the fluctuating selective regime were similar in size to those from the cold selective regime, but their cells of either tissue were the smallest among the three regimes. Evolutionary and developmental treatments interactively affected a fly's sensitivity to short-term paralyzing hypoxia. Genotypes from the cold selective regime were less sensitive to hypoxia after developing at a higher temperature. Genotypes from the other selective regimes were more sensitive to hypoxia after developing at a higher temperature. Our results show that thermal conditions can trigger evolutionary and developmental shifts in cell size, coupled with changes in body size and hypoxia tolerance. These patterns suggest links between the cellular composition of the body, levels of hypoxia within cells, and the energetic cost of tissue maintenance. However, the patterns can be only partially explained by existing theories about the role of cell size in tissue oxygenation and metabolic performance.
Prevention of Post COVID-19 Condition by Early Treatment with Ensitrelvir in the Phase 3 SCORPIO-SR Trial
Yotsuyanagi H, Ohmagari N, Doi Y, Yamato M, Fukushi A, Imamura T, Sakaguchi H, Sonoyama T, Sanaki T, Ichihashi G, Tsuge Y, Uehara T and Mukae H
This exploratory analysis of the double-blind, phase 3, SCORPIO-SR trial assessed the effect of ensitrelvir in preventing post coronavirus disease 2019 (COVID-19) condition (PCC). Patients with mild-to-moderate COVID-19 were randomized (1:1:1) within 120 hours of symptom onset; received 5-day oral ensitrelvir 125 mg (375 mg on day 1), 250 mg (750 mg on day 1), or a matching placebo once daily; and were assessed for the severity of typical PCC symptoms using a self-administered questionnaire. In total, 341, 317, and 333 patients were assessed in the ensitrelvir 125-mg, ensitrelvir 250-mg, and placebo groups, respectively (mean age, 35.6-36.5 years; men, 53.3%-58.3%). On days 85, 169, and 337, ensitrelvir 125-mg treatment showed 32.7% (95% confidence interval [CI]: -30.6, 66.1), 21.5% (95% CI: -37.3, 55.6), and 24.6% (95% CI: -43.7, 60.9) reductions versus placebo, respectively, in the risk of any of the 14 acute-phase COVID-19 symptoms (at least one mild, moderate, or severe symptom with general health not returning to the usual level). Ensitrelvir 250-mg treatment showed 10.9% (95% CI: -67.0, 52.8), 9.5% (95% CI: -56.6, 48.0), and 30.6% (95% CI: -36.2, 65.5) risk reductions versus placebo on days 85, 169, and 337, respectively. Risk reductions were observed in any of the 4 neurological symptoms and were more pronounced among patients with high acute-phase symptom scores at baseline and among those with a baseline body mass index ≥25 kg/m. Ensitrelvir treatment in the acute phase of COVID-19 may reduce the risk of various symptoms associated with PCC. TRIAL REGISTRATION NUMBER: jRCT2031210350.
Development and Bayesian validation of a competitive inhibition ELISA for detection of antibodies against Brucella abortus in cattle
Novoa MB, Aguirre N, Valentini B, Signorini M, Aznar N, Vanzini V and Torioni-de-Echaide S
Bovine brucellosis is a zoonotic disease caused by Brucella abortus, responsible for abortions in cows. It is endemic in low- and middle-income countries, where the brucellosis control and eradication programs are based on compulsory vaccination, detection of infected cattle through serologic assays, and culling of infected animals at slaughterhouses. The development of high sensitivity and specificity, and low-cost serologic assays guarantee their implementation in countries where the disease is endemic. The aim of the present study was to develop and validate a competitive inhibition enzyme-linked immune assay (ciELISA) to detect anti-B. abortus antibodies in sera from cattle. The developed ciELISA was validated using 2833 serum samples from dairy and beef cattle. From these, 1515 sera were from uninfected cows that belonged to free of brucellosis herds and 1318 were from infected cows that belonged positive to brucellosis herds. Sera were analyzed with the developed ciELISA, the buffer plate antigen (BPA) test, and the complement fixation test (CFT). The brucellosis status of the herds was officially established according to the country legislation and consistent for at least 5 years and was defined for each cow using the CFT as gold standard. The cutoff for the ciELISA was calculated using a ROC curve and its sensitivity and specificity were analyzed using the Bayesian Latent Class Model (BLCM) approach. The agreement among tests was calculated using the kappa (κ) value. In addition, 15 calves were vaccinated with 3×10 viable cells of B. abortus Strain 19 vaccine, and the dynamics of antibodies were measured by CFT, buffered plate antigen (BPA) test, and the developed ciELISA. The obtained cutoff for ciELISA was ≥ 47 percentage of inhibition (% I), at the BLCM approach the sensitivity was 99.01% (95% CI: 97.55-100) and the specificity 98.74% (95% CI: 97.68-99.8). The κ between the ciELISA and BPA was κ = 0.88 and between the ciELISA and CFT κ = 0.95. Antibodies against B. abortus were detected in all the vaccinated calves 7 days after vaccination (AV) by the three assays, at day 135 AV all the calves were negative to CFT (15/15), 93.3% (14/15) to ciELISA and 73.3% (11/15) to BPA, and at day 190 AV all the calves were negative to the three assays. The developed ciELISA showed a very good performance, could detect the majority of vaccinated animals as negative after 135 days and could be used for the detection of anti-B. abortus antibodies in serum samples for the brucellosis control and eradication program.
Interobserver variability in the histopathological evaluation of melanoma: analysis of 60 case reports
Sanz-Motilva V, Martorell A, Manrique-Silva E, Terradez-Mas L, Requena C, Traves V, Sanmartín O, Rodríguez-Peralto JL and Nagore E
Since the field of dermatopathology is not an exact science, it is prone to personal subjectivity, which sometimes causes disagreements on the diagnosis and assessment of some histological features. In the case of melanoma, some variables such as regression are associated with low interobserver agreement. On the contrary, other variables such as the measurement of Breslow thickness show high reproducibility.
Integrated serum metabolomics, 16S rRNA sequencing and bile acid profiling to reveal the potential mechanism of gentiopicroside against nonalcoholic steatohepatitis in lean mice
Li Z, Zhu X, Li C, Tang R, Zou Y and Liu S
Lean nonalcoholic steatohepatitis (NASH) poses a serious threat to public health worldwide. Herbs of the genus Gentiana have been used for centuries to treat hepatic disease or have been consumed for hepatic protection efficiency. Gentiopicroside (GPS), the main bioactive component of Gentiana herbs, has been shown to be beneficial for protecting the liver, improving intestinal disorders, modulating bile acid profiles, ameliorating alcoholic hepatosteatosis, and so on. It is plausible to speculate that GPS may hold potential as a therapeutic strategy for lean NASH. However, no related studies have been conducted thus far.
RevGraphVAMP: A protein molecular simulation analysis model combining graph convolutional neural networks and physical constraints
Huang Y, Zhang H, Lin Z, Wei Y and Xi W
Molecular simulation (MD) is a crucial research domain within the life sciences, focusing on comprehending the mechanisms of biomolecular interactions at atomic scales. Protein simulation, as a critical subfield, often utilizes MD for implementation, with trajectory data play a pivotal role in drug discovery. The advancement of high-performance computing and deep learning technology becomes popular and critical to predict protein properties from vast trajectory data, posing challenges regarding data features extraction from the complicated simulation data and dimensionality reduction. Simultaneously, it is essential to provide a meaningful explanation of the biological mechanism behind dimensionality. To tackle this challenge, we propose a new unsupervised model named RevGraphVAMP to intelligently analyze the simulation trajectory. This model is based on the variational approach for Markov processes (VAMP) and integrates graph convolutional neural networks and physical constraint optimization to enhance the learning performance. Additionally, we introduce attention mechanism to assess the importance of key interaction region, facilitating the interpretation of molecular mechanism. In comparison to other VAMPNets models, our model showcases competitive performance, improved accuracy in state transition prediction, as demonstrated through its application to two public datasets and the Shank3-Rap1 complex, which is associated with autism spectrum disorder. Moreover, it enhanced dimensionality reduction discrimination across different substates and provides interpretable results for protein structural characterization.
Unveiling microbial community structure and metabolic pathway over carbon cloth-titanium nitride-polyaniline biocathode for effective dichloromethane transformation
Wu M, Yang F, Hu J, Yu Z, Yu J and Chen J
Chlorinated volatile organic compounds (Cl-VOCs) have dramatically biotoxicity and environmental persistence due to the presence of chlorine atoms, seriously jeopardizing ecological security and human health. Dichloromethane (DCM) as a model pollutant, is widely applied in solvents, extractants and cleaning agents in the pharmaceutical, chemical and food industries. In this study, highly biocompatible and conductive carbon cloth- titanium nitride-polyaniline (CC-TiN-PANI) bioelectrodes were obtained for DCM degradation in microbial electrolysis cell (MEC). The good adhesion of TiN and PANI on the electrode surface was demonstrated. The degradation kinetics were fitted by the Haldane model, compared to the CC bioelectrode (0.8 h), the proportion of maximum degradation rates to half-saturation concentration (V/K) of CC-TiN (1.4 h) and CC-TiN-PANI (2.2 h) bioelectrodes were enhanced by 1.8 and 2.8 times, respectively. Microbial community structure analysis illuminated that the dominant genera on the biofilm were Alicycliphilus and Hyphomicrobium, and the abundance was enhanced significantly with the modification of TiN and PANI. The dechlorination of DCM to formaldehyde could be catalyzed by DCM dehalogenase (DcmA) or by haloalkane dehalogenase (DhlA). And further oxidized to formate: 1) direct catalyzed by formaldehyde dehydrogenase (FdhA); 2) conjugated with glutathione by S-(hydroxymethyl)-glutathione synthase (Gfa), S-(hydroxymethyl)-glutathione dehydrogenase (FrmA) and S-formyl-glutathione hydrolase (FrmB); 3) conjugation with tetrahydrofolate (HF) and/or tetrahydromethanopterin.
Characteristics and aging of microplastics in waste activated sludge under persulfate and hydrothermal co-treatment: Impact of solid content and temperature
Wang Y, Shi Y, Fang L, Wang Z, Wu P, Yang X, Shi X and Pi K
Activated persulfate and hydrothermal treatment (HTT) are often employed to treat waste activated sludge, which can improve the efficiency of subsequent sludge treatment and change the distribution of pollutants in the sludge. However, the impact of sludge solid content and temperature on the occurrence and aging of microplastics (MPs) during HTT remains poorly understood. This study investigated the effects of persulfate-HTT (SPS-HTT) co-treatment on the migration, occurrence, and aging of MPs in sludge with different solid contents (2% and 5% solid content). The results indicated that SPS-HTT co-treatment triggers both the disruption of sludge flocs and the melting deformation of MPs at high temperatures, leading to variations in the increasing trend of MP concentration in the solid-liquid phase at different solid contents. 5% solid content sludge showed a weak release of MPs from the solid phase. The proportion of fiber MPs first increased and then decreased with increasing temperature, while no significant changes were observed in the color and type of MPs. Higher temperature and solid content induced the melting deformation of MPs, exacerbated the aging of polypropylene MPs, and resulted in rough surfaces, higher carbonyl index, and variations in crystallinity. Moreover, the correlation between the carbonyl index and aging indicators increased with increasing solid content. The MP-derived dissolved organic matter under HTT primarily comprised soluble microbial by-products and humic acid-like substances. These findings underscore the significance of sludge solid content in affecting the migration and aging of MPs during HTT, and offer novel insights into the application of HTT to MP management in sludge treatment.
Modulation of microglia activation by the ascorbic acid transporter SVCT2
Marino AL, Rex TS and Harrison FE
Neuroinflammation is a major characteristic of pathology in several neurodegenerative diseases. Microglia, the brain's resident myeloid cells, shift between activation states under neuroinflammatory conditions, both responding to, but also driving damage in the brain. Vitamin C (ascorbate) is an essential antioxidant for central nervous system function that may have a specific role in the neuroinflammatory response. Uptake of ascorbate throughout the central nervous system is facilitated by the sodium-dependent vitamin C transporter 2 (SVCT2). SVCT2 transports the reduced form of ascorbate into neurons and microglia, however the contribution of altered SVCT2 expression to the neuroinflammatory response in microglia is not well understood. In this study we demonstrate that SVCT2 expression modifies microglial response, as shown through changes in cell morphology and mRNA expression, following a mild traumatic brain injury (mTBI) in mice with decreased or increased expression of SVCT2. Results were supported by in vitro studies in an immortalized microglial cell line and in primary microglial cultures derived from SVCT2-heterozygous and transgenic animals. Overall, this work demonstrates the importance of SVCT2 and ascorbate in modulating the microglial response to mTBI and suggests a potential role for both in response to neuroinflammatory challenges.
The effect of ethanol extracts of Loulu flower on LPS-induced acute lung injury in mice
Wurentuya , Han S, Mei S, Lai M, Sirigunqiqige , Luoricuo , Yang M, Feng Y, Zhong G, Zhu J and Li M
In Mongolian medicine, Loulu flower (LLF), the dried inflorescence of Rhaponticum uniflorum (L.) DC. from the Compositae family, has been used to clear heat and relieve toxicity for millennia, particularly in the treatment of pneumonia.
Should patients with a large local reaction be offered VIT? A Pro-Con debate
Bilò MB, Golden DBK, Braschi MC and Martini M
Insect stings can cause large local reactions (LLRs) that are IgE-mediated and associated with considerable morbidity. A risk for systemic reactions including anaphylaxis to subsequent stings has been reported and is often noted by patients and health care providers. Guidelines do not recommend venom immunotherapy (VIT) for LLR based on the relatively low risk of anaphylaxis, but this is debated in this review. On the Pro side: the risk of anaphylaxis may be higher than reported in the limited literature, especially in patients who had only 1 LLR; new species with more potent stings are spreading into new areas; the quality of life can be markedly impaired by LLR; VIT is generally safe and highly effective. On the Con side: LLR are benign; stings occur infrequently; VIT has significant cost; systemic reactions occur more often to VIT than to stings in patients with LLR; FDA approval and published guidelines do not recommend VIT for LLR. In practice, shared decision-making is appropriate to incorporate knowledge of the natural history and known high-risk factors in the context of the patient's personal values and preferences.
Targeted pH-responsive biomimetic nanoparticle-mediated starvation-enhanced chemodynamic therapy combined with chemotherapy for ovarian cancer treatment
Ye M, Ye R, Wang Y, Guo M, Zhu M, Yin F, Wang Y, Lai X, Wang Y, Qi Z, Wang J and Chen D
In recent years, the use of arsenic trioxide (ATO) in the context of ovarian cancer chemotherapy has attracted significant attention. However, ATO's limited biocompatibility and the occurrence of severe toxic side effects hinder its clinical application. A nanoparticle (NP) drug delivery system using ATO as a therapeutic agent is reported in this study. Achieving a synergistic effect by combining starvation therapy, chemodynamic therapy, and chemotherapy for the treatment of ovarian cancer was the ultimate goal of this system. This nanotechnology-based drug delivery system (NDDS) introduced arsenic-manganese complexes into cancer cells, leading to the subsequent release of lethal arsenic ions (As) and manganese ions (Mn). The acidic microenvironment of the tumor facilitated this process, and MR imaging offered real-time monitoring of the ATO dose distribution. Simultaneously, to produce reactive oxygen species that induced cell death through a Fenton-like reaction, Mn exploited the surplus of hydrogen peroxide (HO) within tumor cells. Glucose oxidase-based starvation therapy further supported this mechanism, which restored HO and lowered the cellular acidity. Consequently, this approach achieved self-enhanced chemodynamic therapy. Homologous targeting of the NPs was facilitated through the use of SKOV3 cell membranes that encapsulated the NPs. Hence, the use of a multimodal NDDS that integrated ATO delivery, therapy, and monitoring exhibited superior efficacy and biocompatibility compared with the nonspecific administration of ATO. This approach presents a novel concept for the diagnosis and treatment of ovarian cancer.
Evaluating the combined and individual cytotoxic effect of beauvericin, enniatin B and ochratoxin a on breast cancer cells, leukemia cells, and fresh peripheral blood mononuclear cells
Juan-García A, Ilie AM, Juan C and Martínez L
Beauvericin (BEA), Enniatin B (ENN B), and Ochratoxin A (OTA) are mycotoxins produced by fungi species. Their main effect on several organs and systems is associated with chronic exposure going from immunotoxicity, estrogenic disorders, and renal failure to cancer (in animals and humans). OTA belongs to Group 1 according to the International Agency for Research in Cancer (IARC) and it has legislated limited values; not happening for BEA nor ENN B. Exposure to mixtures of mycotoxins occurs through food intake in daily consumption. The aim of this study was to evaluate the implication of BEA, ENN B, and OTA individually and combined in producing cytotoxicity in cells for immunological studies and cancer cell lines (human leukemia cells (HL-60), fresh human peripheral blood mononuclear cells (PBMCs), and human breast cancer (MDA-MB-231) cells). Cells were treated for 4 h and 24 h at different concentrations of BEA, ENN B, and OTA, respectively. Viability assays were carried out by flow cytometry using DAPI (4',6-diamindino-2-phenylindole, dihydrochloride) as a viability dye and the potential effects of synergism, addition, and antagonism were assessed through the Chou and Talalay method. Individual OTA treatment exerted the greatest cytotoxicity for PBMC cells (IC 0.5 μM) while ENN B for HL-60 (IC 0.25 μM) and MDA-MB-231 (IC 0.15 μM). In binary combination [ENN B + OTA] resulted in exerting the greatest cytotoxicity for HL-60 and MDA-MB-231 cells; while [BEA + OTA] in PBMC cells. The triple combination resulted in being highly cytotoxic for PBMC cells compared to HL-60 and MDA-MB-231 cells. In summary, PBMC cells were the most sensible cells for all three mycotoxins and the presence of OTA in any of the combinations had the greatest toxicity causing synergism as the most common cytotoxic effect.
Hydroxytyrosol permeability comparisons and strategies to improve hydroxytyrosol stability in formulations
Feng M, Li Y, Jiang Y and Zhao C
There has been a growing interest in hydroxytyrosol (HT) due to its powerful antioxidant and free-radical scavenging properties when added to formulations such as pharmaceuticals and cosmetics. To study the stability and transdermal properties of hydrogels and creams (HT-based formulations), a high-performance liquid chromatography method was developed for determining HT. In the Franz diffusion cell system, both hydrogel and cream show a rapid and similar penetration profile through the Bama miniature pig skin. However, the Strat-M® membrane exhibits slightly lower permeability and is selective to different formulations; that is, the cream has a permeability value of 10.69%, while the hydrogel has a value of 5.27%. The dynamics parameters from the permeation assays indicate that the model using the Strat-M® membrane can be used as a screening tool to evaluate the skin uptake and permeation efficacy of different formulations. Adding 3-O-ethyl-L-ascorbic acid to HT-based formulations can effectively prevent discoloration under prolonged high-temperature storage, while combining multiple antioxidants delays degradation most effectively. This study provides novel ideas for functional formulation optimization to enhance the realism and reproducibility of cosmetic products containing HT and provides scientific evidence for the production, packaging, shelf life, storage, and transportation of products.
Smart laser Sintering: Deep Learning-Powered powder bed fusion 3D printing in precision medicine
Abdalla Y, Ferianc M, Awad A, Kim J, Elbadawi M, Basit AW, Orlu M and Rodrigues M
Medicines remain ineffective for over 50% of patients due to conventional mass production methods with fixed drug dosages. Three-dimensional (3D) printing, specifically selective laser sintering (SLS), offers a potential solution to this challenge, allowing the manufacturing of small, personalized batches of medication. Despite its simplicity and suitability for upscaling to large-scale production, SLS was not designed for pharmaceutical manufacturing and necessitates a time-consuming, trial-and-error adaptation process. In response, this study introduces a deep learning model trained on a variety of features to identify the best feature set to represent drugs and polymeric materials for the prediction of the printability of drug-loaded formulations using SLS. The proposed model demonstrates success by achieving 90% accuracy in predicting printability. Furthermore, explainability analysis unveils materials that facilitate SLS printability, offering invaluable insights for scientists to optimize SLS formulations, which can be expanded to other disciplines. This represents the first study in the field to develop an interpretable, uncertainty-optimized deep learning model for predicting the printability of drug-loaded formulations. This paves the way for accelerating formulation development, propelling us into a future of personalized medicine with unprecedented manufacturing precision.
Astragaloside IV promotes cerebral tissue restoration through activating AMPK- mediated microglia polarization in ischemic stroke rats
Li MC, Jia JT, Wang YX, Zhuang YM, Wang HY, Lin ZY, Lu Y, Li MZ, Wang ZJ and Zhao H
Astragaloside IV (AS), a key active ingredient obtained from Chinese herb Astragalus mongholicus Bunge, exerts potent neuroprotective and anti-inflammatory effects for treating neurodegenerative diseases. However, mechanisms of AS on improvement of ischemic brain tissue repair remain unclear.
Proteomic and lipidomic analysis of the mechanism underlying astragaloside IV in mitigating ferroptosis through hypoxia-inducible factor 1α/heme oxygenase 1 pathway in renal tubular epithelial cells in diabetic kidney disease
Liu J, Ren J, Zhou L, Tan K, Du D, Xu L, Cao W and Zhang Y
The limitations of modern medicine in mitigating the pathological process of diabetic kidney disease (DKD) necessitate novel, precise, and effective prevention and treatment methods. Huangqi, the root of Astragalus membranaceus Fisch. ex Bunge has been used in traditional Chinese medicine for various kidney ailments. Astragaloside IV (AS-IV), the primary pharmacologically active compound in A. membranaceus, is involved in lipid metabolism regulation; however, its potential in ameliorating renal damage in DKD remains unexplored.
Regulation of curcumin reductase curA (PA2197) through sodium hypochlorite and N-ethylmaleimide sensing by TetR family repressor CurR (PA2196) in Pseudomonas aeruginosa
Duang-Nkern J, Nontaleerak B, Thongphet A, Asano K, Chujan S, Satayavivad J, Sukchawalit R and Mongkolsuk S
Pseudomonas aeruginosa PA2196 is a TetR family transcriptional repressor. In this study, the deletion of the PA2196 gene caused increased expression of the downstream gene curA (PA2197), which encodes for a NADPH-dependent curcumin/dihydrocurcumin reductase. The PA2196 gene was then identified as curR, and a DNA footprinting assay showed that CurR directly bound to the curA promoter at an imperfect 15-bp inverted repeat, 5'-TAGTTGA-C-TGGTCTA-3'. A curA promoter-lacZ fusion assay and site-directed mutagenesis further demonstrated that the identified CurR binding site plays a crucial role in curA repression by CurR. curA transcription was inducible by sodium hypochlorite (NaOCl) and N-ethylmaleimide (NEM) but not by hydrogen peroxide, organic hydroperoxide, or curcumin. The oxidation and alkylation of CurR by NaOCl and NEM, respectively, resulted in the inactivation of its DNA-binding activity, which induced curA expression. Under the tested conditions, the deletion of either curR or curA did not affect the survival of P. aeruginosa under NaOCl stress in the absence or presence of curcumin.
RNA HELICASE 32 is essential for female gametophyte development in Arabidopsis
Yuan J, Jin H, Tian M, Li D, Meng Y, Zhou H, Liu M, Meng D, Wei Y, Feng L, Sang S, Chen C, Ji S and Li J
The normal progression of mitotic cycles and synchronized development within female reproductive organs are pivotal for sexual reproduction in plants. Nevertheless, our understanding of the genetic regulation governing mitotic cycles during the haploid phase of higher plants remains limited. In this study, we characterized RNA HELICASE 32 (RH32), which plays an essential role in female gametogenesis in Arabidopsis. The rh32 heterozygous mutant was semi-sterile, whereas the homozygous mutant was nonviable. The rh32 mutant allele could be transmitted through the male gametophyte, but not the female gametophyte. Phenotypic analysis revealed impaired mitotic progression, synchronization, and cell specification in rh32 female gametophytes, causing the arrest of embryo sacs. In the delayed pollination test, none of the retarded embryo sacs developed into functional female gametophytes, and the vast majority of rh32 female gametophytes were defective in the formation of the large central vacuole. RH32 is strongly expressed in the embryo sac. Knock-down of RH32 resulted in the accumulation of unprocessed 18S pre-rRNA, implying that RH32 is involved in ribosome synthesis. Based on these findings, we propose that RH32 plays a role in ribosome synthesis, which is critical for multiple processes in female gametophyte development.
The shell formation mechanism of Turbo argyrostomus based on ultrastructure and transcriptome analysis
Zhang Z, Zhang J, Chen H, Han C, Chen Y, Zhan X and Liu Y
The gold inner shell of Turbo argyrostomus is an important morphological classification characteristic in Gastropoda. However, the gene sets responsible for shell formation in gastropods remain poorly explored. In this study, we investigated the microstructure using scanning electron microscopy (SEM), hematoxylin-eosin (HE) and Alcian blue staining-periodic acid-Schiff (AB-PAS) staining. The SEM results illustrated that the T. argyrostomus shell exhibited a special "sandwich" microstructure. The results of histological observation demonstrated two major cell types: adipocytes and mucin cells. A total of 318 differentially expressed genes were identified between edge mantle and central mantle, among which whey acidic protein, N66, and nacre-like proteins, and Lam G and EGF domains may be related to shell microstructure. 22.39% - 25.20% of the mucin genes had biomineralization related domains, which supported for the relationship between mucins and shell formation. Moreover, this study revealed energy distribution differences between the edge mantle and central mantle. These results provide insights for further understanding of the biomineralization mechanism in Gastropoda.
Transgenic early japonica rice: Integration and expression characterization of stem borer resistance Bt gene
Hu Y, Tian C, Feng Y, Ma W, Zhang Y, Yang Q and Zhang X
Transgenic insect-resistant rice offers an environmentally friendly approach to mitigate yield losses caused by lepidopteran pests, such as stem borers. Bt (Bacillus thuringiensis) genes encode insecticidal proteins and are widely used to confer insect resistance to genetically modified crops. This study investigated the integration, inheritance, and expression characteristics of codon-optimised synthetic Bt genes, cry1C* and cry2A*, in transgenic early japonica rice lines.
The Effect of Experience on the Perception of Affordances for Aperture Crossing in Cycling
Vauclin P, Wheat J, Wagman JB and Seifert L
To ride successfully and safely, cyclists must perceive and act on the affordances that are available in a given situation. This study investigated whether experience in perceiving and acting with respect to a person-plus-object system would influence whether and how a person choses to cross an aperture of different widths, especially in relation to the maximal action capabilities. We also explore whether the distribution of action modes reflects this effect. We examined the performance (i.e., the probability of successfully crossing the aperture) and the decision (i.e., the probability of attempting to cross the aperture) of 8 experienced cyclists and 16 occasional cyclists in an aperture crossing task. In term of performance, experienced cyclists demonstrated greater ability to cross narrower apertures than occasional cyclists, but there were no such differences when aperture width was scaled to maximal action capabilities. In term of decision, both experienced and occasional cyclists tended to over-estimate their abilities, but the experienced cyclists did so to a greater extent. Our findings indicate that experience improves the ability to perform more complex tasks due to utilizing a wider repertoire of actions, but not necessarily the ability to perceive and actualize (action-scaled) affordances."
Mosquito (Diptera: Culicidae) diversity and arbovirus detection across an urban and agricultural landscape
Izquierdo-Suzán M, Zavala-Guerrero PB, Hugo M, Renato PS, Mauricio VP, José VTJ and Medellín RA
Fragmented landscapes in Mexico, characterized by a mix of agricultural, urban, and native vegetation cover, presents unique ecological characteristics that shape the mosquito community composition and mosquito-borne diseases. The extent to which landscape influences mosquito populations and mosquito-borne diseases is still poorly understood. This work assessed the effect of landscape metrics -agriculture, urban, and native vegetation cover- on mosquito diversity and arbovirus presence in fragmented tropical deciduous forests in Central Mexico during 2021. Among the 21 mosquito species across six genera we identified, Culex quinquefasciatus was the most prevalent species, followed by Aedes aegypti, Ae. albopictus, and Ae. epactius. Notably, areas with denser native vegetation cover displayed higher mosquito species richness, which could have an impact on phenomena such as the dilution effect. Zika and dengue virus were detected in 85% of captured species, with first reports of DENV in several Aedes species and ZIKV in multiple Aedes and Culex species. These findings underscore the necessity of expanding arbovirus surveillance beyond Ae. aegypti and advocate for a deeper understanding of vector ecology in fragmented landscapes to adequately address public health strategies.
Seasonal Variability and Stochastic Branching Process in Malaria Outbreak Probability
Akhi AA, Mohammad KM and Kamrujjaman M
Malaria is the world's most fatal and challenging parasitic disease, caused by the Plasmodium parasite, which is transmitted to humans by the bites of infected female mosquitoes. Bangladesh is the most vulnerable region to spread malaria because of its geographic position. In this paper, we have considered the dynamics of vector-host models and observed the stochastic behavior. This study elaborates on the seasonal variability and calculates the probability of disease outbreaks.
Rhabdomyosarcoma in a Rabbit
Kopp L, Garner M and Priest K
A geriatric Holland Lop rabbit presented for acute lameness. A pathologic fracture of the right distal femur associated with a pleomorphic rhabdomyosarcoma was diagnosed, and staging radiographs showed no overt metastasis upon initial presentation. The limb was amputated and submitted for microscopic examination. Immunohistochemical evaluation revealed the neoplastic cells were positive for desmin and MyoD1, and negative for cytokeratin AE1/AE3, CD204, IBA-1, and SMA. Gross, histologic, and immunohistochemical evaluation confirmed a diagnosis of pleomorphic rhabdomyosarcoma. The patient died 396 days after amputation, and a post-mortem examination showed metastatic sarcoma to multiple organs.
Quantification of Soluplus for Dissolution Tests: SEC Method Development and Validation
Horváth ZM, Lauberte L and Mohylyuk V
The quantification of both polymer and drug during the dissolution of an amorphous solid dispersion (ASD) in aqueous media arouses great interest and may aid in the formulation. However, the available quantification methods for polymer excipients are limited, expensive, and challenging compared to drugs. In this work, a size exclusion chromatography method (HPLC-SEC) was developed and validated to determine the concentration of a frequently used polymer excipient, Soluplus® (Sol). In order to develop a method for the quantification of dissolved Soluplus®, two methods (SEC-UV and SEC-RID) with two injection volumes were tested with standard solutions of three different batches of Soluplus. The developed HPLC-SEC-UV method showed acceptable linearity (R > 0.9990) for all batches of Soluplus, good accuracies above a concentration of 0.1 mg/mL (coefficient of variation < 2%), relatively good precision at a concentration of 0.1 mg/mL (coefficient of variation < 2.5%), and high recoveries at a concentration of 0.75 mg/mL (coefficient of variation < 0.5%). The presence of Felodipine (Fel) and Lumefantrine (Lum) in the liquid media did not interfere with Soluplus quantification. The use of various surfactants, such as Tween® 80, Tween® 20, Span® 80, Span® 20, Kolliphor® TPGS, and sodium lauryl sulphate at a low concentration (0.005 mg/mL) did not show any effect on Soluplus® and did not interfere with Soluplus® quantification with any of the Soluplus batches. The addition of lithium bromide (LiBr) to the mobile phase within a concentration range of 0.05 to 1.0 M did not improve Soluplus® quantification.
Zinc oxide nanoparticles loaded with linalool as a potential control agent of malaria infection
Alkhaibari AM, Albalawi AE, Shater AF, Almohammed HI, Alnomasy SF and Alanazi AD
This research aimed to produce and analyze zinc oxide nanoparticles (ZNPs) loaded with linalool (LZNPs), and to evaluate their in vitro and in vivo efficacy through targeting the inflammation and oxidative stress. LZNPs were synthesized using an ethanolic solution of polyvinyl alcohol. The Malstat technique was used to evaluate the effectiveness of LZNPs against both sensitive and resistant strains of Plasmosium falciparum. In vivo effects of ZNPs and LZNPs on parasite growth suppression, survival rate, oxidative stress markers, antioxidant genes, and gene and protein levels of inflammatory cytokines were evaluated by Real-time PCR and Western blot techniques. The results indicated that LZNPs demonstrated noteworthy (P<0.001) antiplasmodial activity against both susceptible and resistant strains of P. falciparum. P. berghei NK65 strain-infected mice treated with the ZNPs and LZNPs at doses of 5-15 mg/kg notably (p<0.001) increased the survival rates and parasite growth suppression. LZNPs at 5-15 mg/kg demonstrated a significant (p<0.001) decrease in oxidative stress markers, increased the expression level of antioxidant genes, and reduced the gene and protein expression level of inflammatory cytokines. The current experimental study demonstrated the potent in vitro antiplasmodial activity of LZNPs against chloroquine-resistant and sensitive strains of P. falciparum compared to ZNPs alone. Additionally, the study identified the potential benefits of this nanocomposite in suppressing the parasite and extending the survival rate in mice infected with P. berghei by targeting inflammation and oxidative stress. It also showed minimal toxicity in liver and kidney function in healthy mice. Nevertheless, further research is essential to elucidate the comprehensive mechanisms and practical effectiveness of LZNPs.
Validation of a Novel BCM Model for Recurrence Risk Prediction after Mucosectomy of Colorectal Lateral Spreading Tumors in a European Cohort
Bragança S, Garcia AC, Alexandrino G, Oliveira AM, Horta D, Lourenço LC and Costa MN
Piecemeal endoscopic mucosal resection (pEMR) is the best approach to resect large lateral spreading tumors (LST, > 20 mm width). However, it is associated with early recurrence (ER) and late recurrence (LR). This study aims to assess the risk factors associated with ER and LR and to validate different predictive scores (SMSA, SERT, and BCM) in identifying the risk of ER and LR after LST resected by pEMR in a European cohort.
Differential absorption and metabolic characteristics of organic acid components in Pudilan Xiaoyan Oral Liquid between young rats and adult rats
Yang Y, Qian Z, Wu C, Cheng Y, Yang B, Shao J, Zhao J, Zhu X, Jia X and Feng L
Pudilan Xiaoyan Oral Liquid (PDL) is a proprietary Chinese medicinal preparation approved by the State for treating acute pharyngitis in both adults and children (Approval No. Z20030095). It is worth noting that children exhibit unique physiopathological characteristics compared to adults. However, the in vivo regulatory characteristics of PDL in treating acute pharyngitis in children remain incompletely understood.
Targeting MAD2B as a strategy for ischemic stroke therapy
Zhang L, Cui H, Hu W, Meng X and Zhang C
Post-stroke cognitive impairment is one of the major causes of disability due to cerebral ischemia. MAD2B is an inhibitor of Cdh1/APC, and loss of Cdh1/APC function in mature neurons increases ROCK2 activity, leading to changes in synaptic plasticity and memory loss in mouse neurons. Whether MAD2B regulates learning memory capacity through ROCK2 in cerebral ischemia is not known.
Quaternized oxidized sodium alginate injectable hydrogel with high antimicrobial and hemostatic efficacy promotes diabetic wound healing
Ma S, Chen K, Ding Q, Zhang S, Lu Y, Yu T, Ding C, Liu W and Liu S
In this paper, a hydrogel material with efficient antibacterial, hemostatic, self-healing, and injectable properties was designed for the treatment of diabetic wounds. Firstly, quaternary ammonium salts were grafted with oxidized sodium alginate, and quaternized oxidized sodium alginate (QOSA) was synthesized. Due to the introduction of quaternary ammonium group it has antibacterial and hemostatic effects, at the same time, due to the presence of aldehyde group it can be reacted with carboxymethyl chitosan (CMCS) to form a hydrogel through the Schiff base reaction. Furthermore, deer antler blood polypeptide (DABP) was loaded into the hydrogel (QOSA&CMCS&DABP), showing good swelling ratio and bacteriostatic effect. In vitro and in vivo experiments demonstrated that the hydrogel not only quickly inhibited hepatic hemorrhage in mice and reduced coagulation index and clotting time in vitro, but also significantly enhanced collagen deposition at the wound site, accelerating wound healing. This demonstrates that the multifunctional hydrogel materials (QOSA&CMCS&DABP) have promising applications in the acceleration of skin wound healing and antibacterial promotion.
3-Year Left Ventricular Assist Device Outcomes and Strategy After Heart Transplant Allocation Score Change
Agronin J, Brown M, Calvelli H, Zhao H, Rakita V, Toyoda Y and Kashem MA
The United Network for Organ Sharing (UNOS) adopted new criteria for the heart allocation score on 10/18/2018 to reflect changing trends of candidates' mortality while awaiting transplant. We examined the impact of these policy changes on rates of left ventricular assist device (LVAD) implantation and outcomes posttransplant from a relatively newer UNOS database.
A multi-scale numerical study of monoclonal antibodies uptake by initial lymphatics after subcutaneous injection
Li C, Zhong X, Rahimi E and Ardekani AM
This paper studies the transport of monoclonal antibodies through skin tissue and initial lymphatics, which impacts the pharmacokinetics of monoclonal antibodies. Our model integrates a macroscale representation of the entire skin tissue with a mesoscale model that focuses on the papillary dermis layer. Our results indicate that it takes hours for the drugs to disperse from the injection site to the papillary dermis before entering the initial lymphatics. Additionally, we observe an inhomogeneous drug distribution in the interstitial space of the papillary dermis, with higher drug concentrations near initial lymphatics and lower concentrations near blood capillaries. To validate our model, we compared our numerical simulation results with experimental data, finding a good alignment. Our parametric studies on the drug molecule properties and injection parameters suggest that a higher diffusion coefficient increases the transport and uptake rate while binding slows down these processes. Furthermore, shallower injection depths lead to faster lymphatic uptake, whereas the size of the injection plume has a minor effect on the uptake rate. These findings advance our understanding of drug transport and lymphatic absorption after subcutaneous injection, offering valuable insights for optimizing drug delivery strategies and the design of biotherapeutics.
Post-PCI Anticoagulation with Unfractionated Heparin in Acute Coronary Syndrome: Insight from the STOPDAPT-3 Trial
Watanabe H, Natsuaki M, Morimoto T, Yamamoto K, Obayashi Y, Nishikawa R, Hamatani Y, Ando K, Domei T, Suwa S, Ogita M, Isawa T, Takenaka H, Yamamoto T, Ishikawa T, Hisauchi I, Wakabayashi K, Onishi Y, Hibi K, Kawai K, Yoshida R, Suzuki H, Nakazawa G, Kusuyama T, Morishima I, Ono K, Kimura T and
The current guidelines for acute coronary syndrome (ACS) have discouraged the use of anticoagulation after percutaneous coronary intervention (PCI) without specific indications, although the recommendation was not well supported by evidences. As a post-hoc analysis of the STOPDAPT-3 trial, the 30-day outcomes were compared between the two groups with and without post-PCI heparin administration among ACS patients without the use of mechanical support devices. The co-primary endpoints were the bleeding endpoint defined as the Bleeding Academic Research Consortium type 3 or 5 and the cardiovascular endpoint defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke. Among 4088 ACS patients, 2339 patients (57.2%) received post-PCI heparin. The proportion of patients receiving post-PCI heparin was higher in ST-elevation myocardial infarction than in the others (72.3% and 38.8%, P<0.001), and in patients with intraprocedural adverse angiographic findings than in those without (67.6% and 47.5%, P<0.001). Post-PCI heparin compared to no post-PCI heparin was associated with a significantly increased risk of bleeding endpoint (4.75% and 2.52%; adjusted HR 1.69 [95%CI 1.15-2.46], P=0.007) and a numerically increased risk of cardiovascular endpoint (3.16% and 1.72%; adjusted HR 1.56 [95%CI 0.98-2.46], P=0.06). Higher hourly dose or total doses of heparin were also associated with the higher incidence of both bleeding and cardiovascular events within 30 days. In conclusion, post-PCI anticoagulation with unfractionated heparin was frequently implemented in ACS patients. Post-PCI heparin use was associated with harm in terms of bleeding without a benefit in reducing cardiovascular events.
Anti-EGFR immunoliposomes for cabazitaxel delivery: From formulation development to in vivo evaluation in prostate cancer xenograft model
Carolina Cruz de Sousa A, da Silva Santos E, da Silva Moreira T, Gabriela Araújo Mendes M, Rodrigues Arruda B, de Jesus Guimarães C, de Brito Vieira Neto J, Santiago de Oliveira Y, Pedro Ayala A, Rodrigues da Costa MD, Lima Sampaio T, Paula Negreiros Nunes Alves A, Pessoa C, Petrilli R and Eloy JO
Liposomes functionalized with monoclonal antibodies offer targeted therapy for cancer, boasting advantages like sustained drug release, enhanced stability, passive accumulation in tumors, and interaction with overexpressed receptors on cancer cells. This study aimed to develop and characterize anti-EGFR immunoliposomes loaded with cabazitaxel and assess their properties against prostate cancer in vitro and in vivo. Using a Box-Behnken design, a formulation with soy phosphatidylcholine, 10% cholesterol, and a 1:20 drug-lipid ratio yielded nanometric particle size, low polydispersity and high drug encapsulation. Immunoliposomes were conjugated with cetuximab through DSPE-PEG-Maleimide lipid anchor. Characterization confirmed intact antibody structure and interaction with EGFR receptor following conjugation. Cabazitaxel was dispersed within the liposomes in the amorphous state, confirmed by solid-state analyses. In vitro release studies showed slower cabazitaxel release from immunoliposomes. Immunoliposomes had enhanced cabazitaxel cytotoxicity in EGFR-overexpressing DU145 cells without affecting non-tumor L929 cells. Cetuximab played an important role to improve cellular uptake in a time-dependent fashion in EGFR-overexpressing prostate cancer cells. In vivo, immunoliposomes led to significant tumor regression, improved survival, and reduced weight loss in xenograft mice. While cabazitaxel induced leukopenia, consistent with clinical findings, histological analysis revealed no evident toxicity. In conclusion, the immunoliposomes displayed suitable physicochemical properties for cabazitaxel delivery, exhibited cytotoxicity against EGFR-expressing prostate cancer cells, with high cell uptake, and induced significant tumor regression in vivo, with manageable systemic toxicity.
Advancing Cancer Therapy: The Role of MicroRNA in Clinical Applications
Li J, Zhang Y, Fu T, Xing G and Tong Y
Exploring the influence of hydrogen bond donor groups on the microstructure and intermolecular interactions of amorphous solid dispersions containing diflunisal structural analogues
Cools L, Derveaux E, Reniers F, Dehaen W, Adriaensens P and Van den Mooter G
Drug-polymer intermolecular interactions, and H-bonds specifically, play an important role in the stabilization process of a compound in an amorphous solid dispersion (ASD). However, it is still difficult to predict whether or not interactions will form and what the strength of those interactions would be, based on the structure of drug and polymer. Therefore, in this study, structural analogues of diflunisal (DIF) were synthesized and incorporated in ASDs with poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA) as a stabilizing polymer. The respective DIF derivatives contained different types and numbers of H-bond donor groups, which allowed to assess the influence of these structural differences on the phase behavior and the actual interactions formed in the ASDs. The highest possible drug loading of these derivatives in PVPVA were evaluated through film casting. Subsequently, a lower drug loading of each compound was spray dried. These spray dried ASDs were subjected to an in-depth solid-state nuclear magnetic resonance (ssNMR) study, including 1D spectroscopy and relaxometry, as well as 2D dipolar HETCOR experiments. The drug loading study revealed the highest possible loading of 50 wt% for the native DIF in PVPVA. The methoxy DIF derivative reached the second highest drug loading of 35 wt%, while methylation of the carboxyl group of DIF led to a sharp decrease in the maximum loading, to around 10 wt% only. Unexpectedly, the maximum loading increased again when both the COOH and OH groups of diflunisal were methylated in the dimethyl DIF derivative, to around 30 wt%. The ssNMR study on the spray dried ASD samples confirmed intermolecular H-bonding with PVPVA for native DIF and methoxy DIF. Studies of the proton relaxation decay times and 2D H-C dipolar HETCOR experiments indicated that the ASDs with native DIF and methoxy DIF were homogenously mixed, while the ASDs containing DIF methyl ester and dimethyl DIF were phase separated at the nm level. It was established that, for these systems, the availability of the carboxyl group was imperative in the formation of intermolecular H-bonds with PVPVA and in the generation of homogenously mixed ASDs.
Flock2: A model for orientation-based social flocking
Hoetzlein RC
The aerial flocking of birds, or murmurations, have fascinated observers while presenting many challenges to behavioral study and simulation. We examine how the periphery of murmurations remain well bounded and cohesive. We also investigate agitation waves, which occur when a flock is disturbed, developing a plausible model for how they might emerge spontaneously. To understand these behaviors a new model is presented for orientation-based social flocking. Previous methods model inter-bird dynamics by considering the neighborhood around each bird, and introducing forces for avoidance, alignment, and cohesion as three dimensional vectors that alter acceleration. Our method introduces orientation-based social flocking that treats social influences from neighbors more realistically as a desire to turn, indirectly controlling the heading in an aerodynamic model. While our model can be applied to any flocking social bird we simulate flocks of starlings, Sturnus vulgaris, and demonstrate the possibility of orientation waves in the absence of predators. Our model exhibits spherical and ovoidal flock shapes matching observation. Comparisons of our model to Reynolds' on energy consumption and frequency analysis demonstrates more realistic motions, significantly less energy use in turning, and a plausible mechanism for emergent orientation waves.
Toxicity of new psychoactive substance: Threo-4-methylmethylphenidate (4-Mmph) - Prediction of toxicity using in silico methods
Niżnik Ł, Jabłońska K, Orczyk M, Orzechowska M, Toporowska-Kaźmierak J, Sowińska M, Jasińska J and Jurowski K
This study represents the first application of in silico methods to evaluate the toxicity of 4-methylphenidate (4-Mmph), a new psychoactive substance (NPS). Using advanced in silico toxicology tools, it was feasible to anticipate key aspects of 4-Mmph's toxicological profile, including acute toxicity (LD), genotoxicity, cardiotoxicity, and possible endocrine disruption. The findings indicate significant acute toxicity with variability among species, a high potential for adverse effects in the gastrointestinal system and lungs, a low genotoxic potential, a significant likelihood of skin irritation, and a notable cardiotoxicity risk associated with hERG channel inhibition. Evaluation of endocrine disruption revealed a low likelihood that 4-Mmph interacts with the estrogen receptor alpha (ER-α), indicating minimal estrogenic activity. These insights, derived from in silico studies, play a crucial role in improving the comprehension of 4-Mmph in forensic and clinical toxicology. These initial toxicological inquiries establish the foundation for future investigations and help formulate risk assessment and management strategies regarding the use and abuse of NPS. This article is part of a larger project funded by the Polish Ministry of Education and Science, titled "Toxicovigilance, Poisoning Prevention, and First Aid in Poisoning with Xenobiotics of Current Clinical Importance in Poland" (Grant Number SKN/SP/570184/2023).
Phytocosmetic potential of Blumea balsamifera oil in mitigating UV-induced photoaging: Evidence from cellular and mouse models
Wang K, Hu X, Xie XL, Huang M, Wang D and Yu FL
Blumea balsamifera (L.) DC. (BB), the source of Blumea balsamifera oil (BBO), is an aromatic medicinal plant, renowned for its pharmacological properties and its traditional use in Southeast Asian countries such as China, Thailand, Vietnam, Malaysia, and the Philippines for centuries. Traditionally, BB has been used as a raw herbal medicine for treating various skin conditions like eczema, dermatitis, athlete's foot, and wound healing for skin injuries.
Mycoplasma spp. pneumonia and subsequent pulmonary hypertension in a domestic ferret (Mustela putorius furo)
Day AL, Katzenbach J, Manchester AC, Figueroa R, Karn M, Visser L, Sharpley J and Sadar MJ
Treatment of Mycoplasma spp. pneumonia has rarely been described in domestic ferrets (Mustela putorius furo). A 10-month-old, 0.53 kg, female spayed domestic ferret was presented for oxygen-dependent, chronic dyspnea of one-month's duration. Physical examination findings included dyspnea, tachypnea, increased bronchovesicular sounds bilaterally, and an intermittent non-productive cough. Bloodwork abnormalities included a mild leukocytosis (8.6×10/µL), mild neutrophilia (4.0×10/µL), mild hypoalbuminemia (2.7 g/dL), mild hyperglobulinemia (3.3 g/dL), mild hyponatremia (147 mEq/L), and mild hypochloremia (111.4 mEq/L). Radiographs revealed a marked diffuse bronchial pattern with peribronchial cuffing, a mild main pulmonary artery bulge, distended caudal lobar pulmonary arteries, and decreased serosal detail within the abdomen. An echocardiogram revealed indications of moderate pulmonary hypertension and systolic anterior motion of the mitral valve. Polymerase chain reaction testing for Mycoplasma spp. was positive, and treatment was initiated with doxycycline (10 mg/kg PO q 12 hours for 16 weeks), prednisolone (0.4 mg/kg PO q 12 hours for 13 weeks, tapered to 0.2 mg/kg PO q 12 hours for two weeks, then eventually increased to 0.7 mg/kg PO q 12 hours until further notice), sildenafil (0.3 mg/kg PO q 24 hours for 13 weeks), and oxygen supplementation via an oxygen cage for six weeks. On repeat echocardiogram eleven weeks after initiation of doxycycline therapy, the pulmonary hypertension had resolved. At follow up six months later, the ferret was stable on previously prescribed medications and did not require oxygen supplementation. Mycoplasma spp. and pulmonary hypertension should be considered in cases of respiratory distress in ferrets.
Neural Circuit Mechanisms of Sinisan formula for the Treatment of adolescent Depression: prefrontal cortex to dorsal raphe nucleus
Zhou L, Zhang C, Xie Z, Yu Q, Wang J, Gong Y, Zhao J, Bai S, Yang L, Deng D, Zhang R and Shi Y
Sinisan formula (SNSF), documented in the classic books Shanghan Lun, is known for its ability to regulate liver-qi and treat depression. However, its underlying mechanism, particularly its effects on dynamic real-time neuron activity and circuits remains to be fully elucidated.
Immunohistochemical Diagnosis of Amyloid Typing: Utility and Limitations as Determined by Liquid Chromatography-Tandem Mass Spectrometry
Shintani-Domoto Y, Ishino K, Fujii T, Kitamura T, Teduka K, Naiki H, Sakatani T and Ohashi R
Although immunohistochemical techniques and proteomic analysis are widely used for typing diagnosis of amyloidosis, the diagnostic utility of immunohistochemical evaluation is not well understood.
Importance of Early Diagnosis and Treatment of Perioperative Catatonia: A Case Report
Genda Y, Mase H and Sakamoto A
Symptoms of catatonia include silence, motionlessness, and postural retention. Although it is important to detect and treat catatonia early, before it becomes severe, postoperative cases have inherent risks that hinder diagnosis and treatment. A 60-year-old man with schizophrenia underwent endoscopic/thoracoscopic esophagectomy and was extubated in the operating room. In the intensive care unit (ICU), he had stiffness in the neck, ankles, and knees, catalepsy during passive knee flexion, mild disturbance of consciousness, mild creatine kinase elevation, and respiratory depression. Intravenous diazepam was administered for diagnosis, and the patient's rapid improvement indicated catatonia. He was intubated and started on lorazepam; tapering produced no recurrence of symptoms. The patient was extubated and transferred to the general ward on postoperative Day 2. Because this patient was extubated in the operating room and was managed postoperatively in the ICU with a full-time doctor, his symptoms were easily recognized and early diagnosis was possible. Thus, we were able to administer drug therapy quickly and adequately and perform forward management that accounted for postoperative risks, thereby achieving a favorable outcome.
A Case of Immune Aplastic Anemia during Combined Treatment with Atezolizumab and Chemotherapy for Non-Small Cell Lung Cancer
Matsuki S, Taniuchi N, Okada N, Sato J, Nishijima N, Kamio K, Motoda N, Okamoto M, Seike M and Azuma A
Immune check point inhibitors (ICIs) have durable antitumor effects. However, autoimmune toxicities, termed immune-related adverse events, occur in some patients. We report a case of severe immune aplastic anemia (AA) in a patient with non-small cell lung cancer who was receiving atezolizumab with bevacizumab/carboplatin/paclitaxel. Although the cancer has not recurred, his bone marrow is depleted and he did not respond to immunosuppressive therapy. He has survived for 1.5 years with blood transfusions and infection control. Immune AA associated with ICIs is rare, and a treatment has not yet been established. This case report provides information on the management and treatment response of patients with AA caused by ICIs. Further studies should investigate the mechanism and pathogenesis of immune AA caused by ICIs.
Prognosis of Lung Transplantation in Patients with Acute Exacerbations of Interstitial Lung Disease: A Meta-Analysis Based on Cohort Studies
Yang L, Xiang Z, Dai M, Zhang Q and Zhou Y
This meta-analysis aimed to examine the prognosis of patients with acute exacerbation of interstitial lung disease (AE-ILD) treated with lung transplantation compared to those with stable interstitial lung disease (ILD).
Evaluation of Coronary Circulation by N-Ammonia Myocardial Perfusion Positron Emission Tomography in Patients with Right Coronary Artery Occlusion Due to Kawasaki Disease
Suzuki N, Watanabe M, Kiriyama T, Imai S, Abe M, Fukazawa R and Itoh Y
Although occlusion of the right coronary artery (RCA) is common in the remote stages of Kawasaki disease, revascularization of the RCA is challenging in children and is usually managed by observation without intervention.
Effectiveness of the Abdominal Thrust Maneuver for Airway Obstruction Removal: Analysis of Data from the National Emergency Medical Services Information System
Suga R, Igarashi Y, Kitano S, Suzuki K, Yokobori S, Ogawa S and Yokota H
Foreign body airway obstruction (FBAO) is a life-threatening emergency. Abdominal thrusts are recommended as first aid, but the success rate for this technique is unclear. Using information from a large database of emergency medical services (EMS) data in the United States, we evaluated the success rate of abdominal thrusts and identified patient characteristics that were associated with the success of the technique.
Safety of Antithrombotic Therapy within 24 Hours after Recombinant Tissue-Plasminogen Activator Treatment for Large-Artery Atherosclerosis Stroke: Insights from Emergent PTA/CAS Cases
Sakamoto Y, Nito C, Nishiyama Y, Suda S, Matsumoto N, Aoki J, Saito T, Suzuki K, Okubo S, Mishina M and Kimura K
Antithrombotic therapy (AT) should generally be avoided within 24 hours after recombinant tissue-plasminogen activator (rt-PA) treatment but should be considered in patients with large-artery atherosclerosis (LAA) who undergo concomitant emergent endovascular treatment (EVT). The aim of the present study was to assess the safety of AT within 24 hours after rt-PA treatment in patients with hyperacute ischemic stroke due to LAA who received concomitant EVT.
Narrow Histopathological Margins are Acceptable in Surgical Resection of Basal Cell Carcinoma in Japanese: A Single-Center Retrospective Study
Miyazaki S, Hoashi T, Tone Y, Park A, Otani S, Kanda N and Saeki H
Basal cell carcinoma (BCC) is the most common cutaneous malignancy. BCCs occur mainly in exposed areas, such as the face and scalp. Therefore, surgical resection with narrow margins is highly desirable. However, narrow margins may increase the risk of positive histopathological margins. Outcomes for such treatment might be unfavorable, but evidence for such a conclusion is lacking.
Association between Mobility of Residual Left Atrial Thrombus and Stroke Severity in Patients with Nonvalvular Atrial Fibrillation
Kato Y, Hayashi T, Nakano S, Arai T, Fujiwara S, Watanabe K, Oryu K, Kimura R, Arai N, Nakagami T, Deguchi I, Takahashi S and Suda S
The differences in the characteristics of ischemic stroke associated with a mobile versus nonmobile residual left atrial thrombus (LAT) are unclear. We investigated whether the mobility of an LAT detected by transthoracic echocardiography is associated with the clinical features of stroke.
Association between Postoperative Adjuvant Vasodilator Therapy and In-Hospital Mortality for Non-Occlusive Mesenteric Ischemia: A Nationwide Observational Study
Takiguchi T, Nakajima M, Ohbe H, Sasabuchi Y, Tagami T, Kaszynski RH, Matsui H, Fushimi K, Kim S, Yokobori S and Yasunaga H
Although several clinical guidelines recommend vasodilator therapy for non-occlusive mesenteric ischemia (NOMI) and immediate surgery when bowel necrosis is suspected, these recommendations are based on limited evidence.
Remarkable features of removable partial dentures show great potential in increasingly super-aged societies
Wada J
Reliability of PainDETECT for Evaluating Low Back Pain Caused by Cluneal Nerve Entrapment
Takada C, Kim K, Kokubo R, Ideguchi M, Mihara R, Koketsu K and Murai Y
Superior/middle cluneal nerve entrapment (CN-E) is an elicitor of low back pain (LBP). The painDETECT questionnaire is used to characterize CN-E symptoms.
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