Personality

Topical treatments are the foundation for patients with psoriasis; however, adherence can be limited by patient preferences and treatment burden.

Endometriosis is one of the leading causes of infertility, due to negative impact on ovarian folliculogenesis and endometrial receptivity. Literature show that endometriosis could be associated with perinatal complications such as preterm birth (PTB) and preeclampsia (PE). Authors hypothesized that women with endometriosis-related infertility conceived by assisted reproductive technology (ART) treatment have higher frequency of placental disorders. Main outcome is the occurrence of histopathologic alterations of term placentas in singleton pregnancies of women with endometriosis conceived by ART treatment, compared to healthy women with infertility due to male factor (MF) conceived by ART and to healthy women with spontaneous pregnancies. Secondary outcome include the occurrence of perinatal complications and the relationship of endometriosis and placental histopathologic characteristics.

To determine cardiotocographic patterns in newborns with metabolic acidosis, based on clinical signs of neurological alteration (NA) and the need for hypothermic treatment.

The occurrence of periodontal diseases is still to be determined in large samples of major Brazilian cities. This study aimed to assess the periodontal status of adults from Curitiba, Paraná, Brazil, using periodontitis definitions by the Centers for Disease Control and Prevention and the American Academy of Periodontology (CDC/AAP) and the recently published ACES 2018 Classification Framework.

To study the use of a quasi-experimental design to assess the effects of scaling reimbursement policies on the incidence of chronic-periodontitis procedures.

Implementing evidence-based practice (EBP) in clinical practice is an ongoing challenge for nurses. EQUIP-Evidence-based QUality Improvement Project- is a multiphase project aimed at equipping nurses with the essential skills to implement EBP and advanced nursing practice. EQUIP embraces the assumption that implementation science models and partnership models can facilitate the implementation process of EBP, leading to successful and sustainable change. The current study is one of the EQUIP feasibility investigations in which the perspective of 12 implementation lead nurses (IL nurses) who attended a 1-day PEACE-based workshop was explored. Thematic analysis identified 2 overarching themes, 6 themes, and 18 subthemes. The first overarching theme showed that the PEACE-based workshop has successfully achieved its intended training implications, and the second overarching theme gave insight into factors that may influence the role of IL nurses. IL nurses reported general satisfaction and willingness to use the PEACE model at work; however, some IL nurses found Step 3 difficult to apply. The study's findings provide evidence of the perceived usefulness of adopting the PEACE model as an augmented approach in the EQUIP and the interest and enthusiasm of IL nurses in receiving more training on the implementation process of EBP.

Adversity within low- and middle-income countries (LMICs) poses severe threats to neurocognitive development, which can be partially mitigated by high-quality early family experiences. Specifically, maternal scaffolding and home stimulation can buffer cognitive development in LMIC, possibly by protecting underlying neural functioning. However, the association between family experiences and neural activity remains largely unexplored in LMIC contexts. This study explored the relation of early family experiences to later cognitive skills and absolute gamma power (21-45 Hz), a neural marker linked to higher-order cognitive skills. Drawing data from the PEDS trial, a longitudinal study in rural Pakistan, we examined maternal scaffolding at 24 months and home stimulation quality at 18 months as predictors of verbal IQ, executive functions, and absolute gamma at 48 months for 105 mother-child dyads (52 girls). Maternal scaffolding interacted with gender to predict absolute gamma power, such that higher maternal scaffolding was related to higher gamma more strongly for girls. Maternal scaffolding also interacted with absolute gamma to predict executive functions, such that higher gamma was related to better executive functions only when maternal scaffolding was average to high. Individual differences in early family experiences may partially buffer the neural underpinnings of cognitive skills from adversity in LMIC.

Duplication of the optic disc is a rare phenomenon. Differentiating between true duplication and pseudo-duplication requires a comprehensive set of diagnostic procedures. Advancements in imaging provide new insights into this condition.

Lymphoplasmacytic lymphoma (LPL) is an incurable low-grade lymphoma with no standard therapy. Nine asymptomatic patients treated with a first-in-human, neoantigen DNA vaccine experienced no dose limiting toxicities (primary endpoint, NCT01209871). All patients achieve stable disease or better, with one minor response, and median time to progression of 72+ months. Post-vaccine single-cell transcriptomics reveal dichotomous antitumor responses, with reduced tumor B-cells (tracked by unique B cell receptor) and their survival pathways, but no change in clonal plasma cells. Downregulation of human leukocyte antigen (HLA) class II molecules and paradoxical upregulation of insulin-like growth factor (IGF) by the latter suggest resistance mechanisms. Vaccine therapy activates and expands bone marrow T-cell clonotypes, and functional neoantigen-specific responses (secondary endpoint), but not co-inhibitory pathways or Treg, and reduces protumoral signaling by myeloid cells, suggesting favorable perturbation of the tumor immune microenvironment. Future strategies may require combinations of vaccines with agents targeting plasma cell subpopulations, or blockade of IGF-1 signaling or myeloid cell checkpoints.

AKL-T01 is a digital therapeutic (DTx) that targets attention by generating conflict at dynamically updated difficulty levels during a multitasking game. Clinical trials support AKL-T01's efficacy in attention-deficit/hyperactivity disorder (ADHD), but there is a need to understand how in-game data can be used to monitor patient changes in cognition. We aimed to derive a real-time measure of attention from AKL-T01 gameplay data and validate it against clinical outcomes. Trials of AKL-T01 included: STARS-ADHD-Adult (NCT05183919), a 6-week trial in adults 18 and older (n = 221; M age = 39.9; 70% female); STARS-ADHD-Adolescent (NCT04897074), a 4-week trial in adolescents ages 13-17 (n = 162; M age = 14.4; 41% female); and STARS-ADHD (NCT02674633), a 4-week trial in children ages 8-12 (n = 180; M age = 9.7; 31% female). A cognitive metric was derived from targeting response speed, targeting sensitivity (d-prime), and navigation skill level. Using multiple linear regression models, we analyzed relationships between cognitive metric change and changes in the Test of Variables of Attention (TOVA)-Attention Comparison Score (ACS), controlling for TOVA-ACS baseline, cognitive metric baseline, age, and sex. We explored associations with ADHD symptoms and quality of life. Increases in the cognitive metric significantly predicted increases in TOVA-ACS in the adult (β = 0.16, p < 0.001), adolescent (β = .09, p = 0.007), and pediatric (β = 0.06, p = 0.014) trials. Cognitive metric changes additionally related to self-reported quality of life in adults and clinician-rated ADHD symptoms in adolescents. Findings support the clinical validity of a real-time measure of attention derived from AKL-T01 patient-device interactions.

When multiple visual stimuli are presented simultaneously in the receptive field, the neural response is suppressed compared to presenting the same stimuli sequentially. The prevailing hypothesis suggests that this suppression is due to competition among multiple stimuli for limited resources within receptive fields, governed by task demands. However, it is unknown how stimulus-driven computations may give rise to simultaneous suppression. Using fMRI, we find simultaneous suppression in single voxels, which varies with both stimulus size and timing, and progressively increases up the visual hierarchy. Using population receptive field (pRF) models, we find that compressive spatiotemporal summation rather than compressive spatial summation predicts simultaneous suppression, and that increased simultaneous suppression is linked to larger pRF sizes and stronger compressive nonlinearities. These results necessitate a rethinking of simultaneous suppression as the outcome of stimulus-driven compressive spatiotemporal computations within pRFs, and open new opportunities to study visual processing capacity across space and time.

The anterior cingulate cortex (ACC) has been implicated across multiple highly specialized cognitive functions-including task engagement, motivation, error detection, attention allocation, value processing, and action selection. Here, we ask if ACC lesions disrupt task performance and firing in dorsomedial striatum (DMS) during the performance of a reward-guided decision-making task that engages many of these cognitive functions. We found that ACC lesions impacted several facets of task performance-including decreasing the initiation and completion of trials, slowing reaction times, and resulting in suboptimal and inaccurate action selection. Reductions in movement times towards the end of behavioral sessions further suggested attenuations in motivation, which paralleled reductions in directional action selection signals in the DMS that were observed later in recording sessions. Surprisingly, however, beyond altered action signals late in sessions-neural correlates in the DMS were largely unaffected, even though behavior was disrupted at multiple levels. We conclude that ACC lesions result in overall deficits in task engagement that impact multiple facets of task performance during our reward-guided decision-making task, which-beyond impacting motivated action signals-arise from dysregulated attentional signals in the ACC and are mediated via downstream targets other than DMS.

Assessing the risk of cancer among people living with HIV (PLHIV) in the current era of antiretroviral therapy (ART) is crucial, given their increased susceptibility to many types of cancer and prolonged survival due to ART exposure. Our study aims to compare the association between HIV infection and specific cancer sites in Rwanda. Population-based cancer registry data were used to identify cancer cases in both PLHIV and HIV-negative persons. A probabilistic record linkage approach between the HIV and cancer registries was used to supplement HIV status ascertainment in the cancer registry. Associations between HIV infection and different cancer types were evaluated using unconditional logistic regression models. We performed several sensitivity analyses to assess the robustness of our findings and to evaluate the potential impact of different assumptions on our results. From 2007 to 2018, the cancer registry recorded 17,679 cases, of which 7% were diagnosed among PLHIV. We found significant associations between HIV infection and Kaposi's Sarcoma (KS) (adjusted odds ratio [OR]: 29.1, 95% CI: 23.2-36.6), non-Hodgkin lymphoma (NHL) (1.6, 1.3-2.0), Hodgkin lymphoma (HL) (1.6, 1.1-2.4), cervical (2.3, 2.0-2.7), vulvar (4.0, 2.5-6.5), penile (3.0, 2.0-4.5), and eye cancers (2.2, 1.6-3.0). Men living with HIV had a higher risk of anal cancer (3.1, 1.0-9.5) than men without HIV, but women living with HIV did not have higher risk than women without HIV (1.0, 0.2-4.3). Our study found that in an era of expanded ART coverage in Rwanda, HIV is associated with a broad range of cancers, particularly those linked to viral infections.

In recent years, obstructive sleep apnea (OSA) has been increasingly recognized as a significant health concern. No previous studies assessed the effect of recommended treatment modalities of patients with OSA on the temporomandibular joint (TMJ). The current study aimed to evaluate the effect of different treatment modalities of OSA, such as continuous positive airway pressure (CPAP), mandibular advancement device (MAD), and oral myofunctional therapy (OMT) on subjective symptoms, clinical, and radiographic signs of temporomandibular disorders.

Infertility increases women's risk of intimate partner violence (IPV). Cognitive behavioral therapy (CBT) is commonly used to treat mental health problems among fertility treatment seeking patients. CBT has not been tested for its potential to reduce IPV in this population. We pilot test the use of CBT to prevent IPV and improve patients' mental health in a fertility clinic in Jordan.

Invasive micropapillary carcinoma (IMPC) was first proposed as an entity by Fisher et al. In the 2003 World Health Organization (WHO) guidelines for histologic classification of the breast tumors. IMPC was recognized as a distinct, rare histological subtype of breast cancer. IMPC is emerging as a surgical and oncological challenge due to its tendency to manifest as a palpable mass, larger in size and higher in grade than IDC with more rate of lymphovascular invasion (LVI) and lymph node (LN) involvement, which changes the surgical and adjuvant management plans to more aggressive, with comparative prognosis still being a point of ongoing debate.

The risk assessment of dental erosion among children and adolescents is an important aspect of dental care, as dental erosion constitutes a rapidly growing, global problem. Dental professionals rely solely on their own perception, as the current risk assessment process is not completely automatized, which affects the risk assessment reliability.

Early childhood caries (ECC) is one of the most common childhood diseases affecting the primary teeth of children younger than 6 years of age. ECC progression can be reversed in the early stages although these lesions often go undetected. New approaches are needed to detect oral diseases at an early stage when they can be better controlled. The aim of the study is to assess the effectiveness of ECC tele-detection methods combined with referral pathways with and without user fee removal in controlling ECC.

Community acceptance is an important criterion to assess in community trials, particularly for new tools that require high coverage and use by a target population. Installed on exterior walls of household structures, the attractive targeted sugar bait (ATSB) is a new vector control tool designed to attract and kill mosquitoes. ATSBs were evaluated in Western Zambia during a two-year cluster randomized controlled trial to assess the efficacy of ATSBs in reducing malaria transmission. Community acceptance of ATSBs was critical for successful trial implementation.

Health professionals and health professions educators (HPEs) worldwide were confronted by the COVID-19 pandemic, which disrupted standard practice and forced HPEs to develop creative, alternative modes of training and education. The ability of people to work successfully and efficiently in non-standard situations can be called adaptive expertise in which people quickly overcome changes in work requirements using their expert knowledge in novel ways. The objectives of the current study were to investigate how the adaptive expertise of a group of HPEs influenced perceived work performance in a non-standard situation and to see whether there were relationships between the level of adaptive expertise and academic ranking and work experience of HPEs.

AGTPBP1 is a cytosolic carboxypeptidase that cleaves poly-glutamic acids from the C terminus or side chains of α/β tubulins. Although its dysregulated expression has been linked to the development of non-small cell lung cancer, the specific roles and mechanisms of AGTPBP1 in pancreatic cancer (PC) have yet to be fully understood. In this study, we examined the role of AGTPBP1 on PC in vitro and in vivo.

Fatigue, depression, anxiety and cognitive difficulties are reported by 1/3 of patients following transient ischemic attack (TIA).

Mycoplasma pneumoniae (M. pneumoniae) is a common pathogen causing respiratory diseases in children. This study aimed to characterize epidemiological and disease severity shifts of M. pneumoniae: infections in Guangzhou, China during and after the coronavirus disease 2019 (COVID-19) pandemic.

The present study aimed to explore the association between serum cystatin C (Cys-C) levels and visceral fat area (VFA) in patients with type 2 diabetes mellitus (T2DM). A total of 208 previously diagnosed T2DM patients who visited our hospital from September 2019 to December 2021 were included and divided into three groups based on tertiles of Cys-C levels, namely, Groups C1, C2, and C3. The clinical data of the subjects were collected, biochemical parameters such as Cys-C levels were determined, and bioelectrical impedance analysis was applied to determine the VFA and subcutaneous fat area (SFA). The VFA in Group C1 was lower than that in Groups C2 and C3 (all P < 0.05), with no significant difference in VFA between Groups C2 and C3 (P > 0.05). Spearman's correlation analysis revealed that the serum Cys-C level was positively correlated with age, VFA, SFA, insulin resistance index, waist circumference, body mass index, systolic blood pressure, serum creatinine level, and blood uric acid level (r = 0.543, 0.353, 0.168, 0.148, 0.365, 0.264, 0.25, 0.497, and 0.155, respectively; P < 0.05) and negatively correlated with glycated haemoglobin levels (r = -0.175, P < 0.05). Univariate linear regression analysis revealed that VFA was positively correlated with the Cys-C level (β = 0.002, 95% CI = 0.001-0.003, P < 0.05), with an increase of 0.002 mg/L in the Cys-C level for each 1 cm increase in VFA. Further multivariate linear regression analysis was performed with the serum Cys-C level as the dependent variable and age, VFA, SFA, insulin resistance (HOMA-IR), WC, BMI, SBP, Cr, UA, and HbA1c as the independent variables. The results suggested that VFA was positively correlated with serum Cys-C level (β = 0.001, 95% CI = 0.000-0.002, P < 0.05), with serum Cys-C levels increasing by 0.001 mg/L for every 1 cm increase in VFA. Using a VFA ≥ 100 cm as the criterion for visceral obesity, ROC analysis revealed that the Cys-C level was a better predictor of visceral obesity, with an area under the ROC curve (AUC) of 0.701 (95% CI = 0.631-0.771, P < 0.05), an optimal cut-off of 0.905 mg/L, and a sensitivity and specificity of 58.3% and 75.2%, respectively. The results suggested that the serum Cys-C level was correlated with the VFA in patients with T2DM and that Cys-C may play a vital role in T2DM patients with visceral obesity.

China has the largest population of diabetic patients worldwide. A diverse population and regional discrepancy in access to health care and diabetes management may lead to unique risk factors for diabetic retinopathy (DR) in different regions of China. This study aimed to evaluate the prevalence and risk factors of DR in rural patients with type 2 diabetes.

There is insufficient data on systemic embolic events (SSEs) in patients with ischemic left ventricular aneurysm (LVA) concerning the impact of anticoagulation therapy. In this retrospective cohort study with 1043 patients with ischemic LVA, SSEs occurred in 7.2% over 2.4 years. After adjusting for relevant factors, the use of anticoagulants was independently associated with a lower incidence of SSE (3.1% vs. 9.0%, P < 0.001; subdistribution hazard ratios (SHR) 0.21, 95% confidence intervals (CI) 0.10-0.44, P < 0.001), with no significant difference in net adverse clinical events (NACEs) (10.6% vs. 13.3%, P = 0.225). Specifically, anticoagulation in patients with apical segment akinesis significantly reduced SSEs (3.9% vs. 13.6%, P = 0.002) and NACE rates (7.8% vs. 19.4%, P = 0.002). Major bleeding rates did not significantly differ between groups (5.6% vs. 3.5%, P = 0.111). These findings highlight the SSE risk in ischemic LVA and suggest potential benefits of anticoagulation, particularly in those with apical segment akinesis. These findings need to be validated in independent datasets.

Children represent a particularly vulnerable demographic in the context of drug-resistant (DR) tuberculosis (TB) due to their increased likelihood of close contact with adults diagnosed with the disease. Approximately 25 000-30 000 children develop DR-TB annually. While treatment success rates for DR-TB in children surpass those in adults, children and adolescents encounter distinct challenges throughout the diagnosis and treatment of DR-TB (including MDR-TB, Pre-XDR TB, and XDR-TB).

It is elusive why some heavy drinkers progress to severe alcohol-related liver disease (ALD) while others do not. This study aimed to investigate if the association between alcohol consumption and severe ALD is modified by diet. This prospective study included 303,269 UK Biobank participants. Alcohol consumption and diet were self-reported. The diet score was created from 4 items selected using LASSO. Cox proportional hazard model showed that the diet score was monotonically associated with severe ALD risk, adjusted for sociodemographics, lifestyle factors, and alcohol consumption. Relative excess risk due to interaction analysis indicated that having a higher ALD diet score and a higher alcohol consumption simultaneously confers to 2.44 times (95% CI: 1.06-3.83) higher risk than the sum of excess risk of each factor. In this work, we show that people who have a poor diet might be more susceptible to severe ALD due to alcohol consumption.

Patients perceive effective patient-doctor communication as an important metric when evaluating their satisfaction with health systems. Hence, optimal patient-physician communication is fundamental for quality healthcare. High-income countries (HICs) have extensively studied patient-resident communication. However, there is a dearth of similar studies in low- and middle-income countries (LMICs). Therefore, we aimed to explore the current state of and barriers to practicing good patient-resident communication and explore possible solutions to mitigate these challenges at one of the largest Academic Medical Centers in an LMIC.

Cancer affects patients as well as their spouses. Patients and their spouses use different strategies to cope with cancer and the associated burden. This study aimed to gain a deeper and more differentiated understanding of support systems for patients and their spouses. This was an exploratory qualitative study conducted in China. The study was based on 20 semistructured face-to-face interviews. Ten pancreatic cancer patients and their spouses were interviewed. The interviews took place at a tertiary hospital from June 2023 to December 2023. The data were analysed using thematic analysis according to Braun and Clarke's methodology. This study was guided by the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist. Twenty participants of different ages (patients: range = 49-75 years; spouses: range = 47-73 years) participated. Patients with different cancer stages (e.g., potentially resectable, borderline resectable, locally advanced) and cancer types (initial diagnosis or relapse) participated in the study. Five themes emerged from the data, namely, denial and silence, fear and worry, struggle, coping strategies and cherishing the present. Active dyadic coping is conducive to promoting disease adaptation, and spouses seem to need more psychological support to improve their own well-being. Health care providers should pay attention to pancreatic cancer patients and their spouses in terms of five themes: denial and silence, fear and worry, struggle, coping strategies and cherishing the present. Future studies should use a combination of qualitative and quantitative methods to explore dyadic coping in greater depth.

The HUNT Lung Cancer Model (HUNT LCM) predicts individualized 6-year lung cancer (LC) risk among individuals who ever smoked cigarettes with high precision based on eight clinical variables. Can the performance be improved by adding genetic information?

To accurately measure the vaginal mucosa thickness across different age groups using histopathologic techniques and investigate the factors that may influence the thickness changes. This study aims to provide clinicians with objective evidence of variations in vaginal mucosal thickness, facilitating personalized medical decisions for patients. A retrospective analysis was conducted on clinical data from 348 patients who underwent local vaginal wall resection at the West China Second University Hospital, Sichuan University, from January 2021 and May 2022. The thickness of vaginal mucosa, epithelium and lamina propria was measured precisely under the microscope. And the 10th, 25th, 50th, 75th, and 90th percentile values of vaginal mucosa thickness across different age groups were counted and charted a dot-line plot. The percentile values for vaginal mucosa thickness exhibited a decreasing trend with increasing age; vaginal mucosa thickness showed significant correlations with times of delivery (P = 0.031) and age (P < 0.001), both of which were negatively associated. And vaginal mucosa thickness demonstrated no significant correlation with body mass index (BMI) (P = 0.325), times of abortions (P = 0.511), times of gestation (P = 0.101), menstrual cycle (P = 0.533), or types of delivery (P = 0.056); epithelial thickness showed significant associations with age (P < 0.001) and types of delivery (P = 0.017), both of which were negative correlations. Moreover, BMI (P = 0.429), times of abortions (P = 0.764), delivery (P = 0.079), gestation (P = 0.475), and menstrual cycle (P = 0.950) were nonassociated with epithelial thickness; lamina propria thickness displayed a significant correlation only with age (P = 0.002), and there were no obvious correlations observed between lamina propria thickness and BMI (P = 0.374), times of abortion (P = 0.417), delivery (P = 0.053), gestation (P = 0.101), types of delivery (P = 0.132) and menstrual cycle (P = 0.495). Moreover, when the age segmentation was thresholded at 35 and 50 years, both epithelial thickness and vaginal mucosa thickness were significantly correlated with age (P < 0.05). Lamina propria thickness was associated with age when the age threshold was set at 35 years (P = 0.007), whereas it showed no strong link with age when the age threshold was 50 years (P = 0.072). This study has innovatively established percentile reference values for vaginal mucosa thickness based on histopathology, furnishing clinicians with objective evidence of variations in vaginal mucosal thickness to facilitate personalized medical decisions for patients. The findings demonstrated a strong link between vaginal mucosa thickness and age, with epithelium likely playing a predominant role, while the association with lamina propria appeared to be less significant. Further research involving a larger sample size is warranted to elucidate the potential relationship with the lamina propria.

Healthy siblings of children with life-limiting conditions often experience emotional and behavioural struggles over the course of the ill child's condition(s). Resources to support these siblings are limited due to a lack of understanding about their needs. Therefore, this study was designed to characterize the emotional and behavioural trajectories among siblings of children with progressive, life-limiting genetic, metabolic, or neurological conditions over a 12-month observation period.

Patients with severe community-acquired pneumonia (sCAP) admitted to the intensive care unit (ICU) often exhibit muscle catabolism, muscle weakness, and/or atrophy, all related to an increased morbidity and mortality. However, the relationship between thoracic skeletal muscle mass and sCAP-related mortality has not been well-studied. Early recognition of sarcopenia in ICU patients with sCAP would benefit their prognosis.

Typically mobile and vulnerable, migrants face significant barriers to access to routine malaria prevention, diagnostics and treatment, which leads to unchecked malaria transmission, particularly in border regions with a high population displacement. This study aimed to investigate the demographic and socioeconomic obstacles to access to malaria services among Myanmar migrants residing in the Thailand-Myanmar border areas.

Myelolipoma is an uncommon benign tumor composed of mature adipose tissue and hematopoietic elements. These tumors generally affect the adrenal glands, with anomalous presentations being rare and with few cases described in the literature. Most myelolipomas are asymptomatic and discovered incidentally, either through imaging tests or at autopsies. However, depending on the location and size of the lesion, myelolipomas can cause symptoms of mass effect. This article aims to report a very rare presentation of a symptomatic primary myelolipoma affecting the ribs.

To investigate aqueous humor cytokine levels in neovascular age-related macular degeneration (nAMD) patients with subretinal fibrosis and to explore the relationship between cytokine levels and disease severity.

In the context of early disease detection, machine learning (ML) has emerged as a vital tool. Feature selection (FS) algorithms play a crucial role in ensuring the accuracy of predictive models by identifying the most influential variables. This study, focusing on a retrospective cohort of 4778 COVID-19 patients from Iran, explores the performance of various FS methods, including filter, embedded, and hybrid approaches, in predicting mortality outcomes. The researchers leveraged 115 routine clinical, laboratory, and demographic features and employed 13 ML models to assess the effectiveness of these FS methods based on classification accuracy, predictive accuracy, and statistical tests. The results indicate that a Hybrid Boruta-VI model combined with the Random Forest algorithm demonstrated superior performance, achieving an accuracy of 0.89, an F1 score of 0.76, and an AUC value of 0.95 on test data. Key variables identified as important predictors of adverse outcomes include age, oxygen saturation levels, albumin levels, neutrophil counts, platelet levels, and markers of kidney function. These findings highlight the potential of advanced FS techniques and ML models in enhancing early disease detection and informing clinical decision-making.

The hypothalamus is a key link in neuroendocrine regulations, which are provided by neuropeptides and dopamine. Until the late 1980 s, it was believed that, along with peptidergic neurons, hypothalamus contained dopaminergic neurons. Over time, it has been shown that besides dopaminergic neurons expressing the dopamine transporter and dopamine-synthesizing enzymes - tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) - the hypothalamus contains neurons expressing only TH, only AADC, both enzymes or only dopamine transporter. The end secretory product of TH neurons is L-3,4-dihydroxyphenylalanine, while that of AADC neurons and bienzymatic neurons lacking the dopamine transporter is dopamine. During ontogenesis, especially in the perinatal period, monoenzymatic neurons predominate in the hypothalamic neuroendocrine centers. It is assumed that L-3,4-dihydroxyphenylalanine and dopamine are released into the neuropil, cerebral ventricles, and blood vessels, participating in the regulation of target cell differentiation in the perinatal period and the functioning of target cells in adulthood.

Furanoids are a class of contaminants prevalent in both airborne and occupational environments, with potential health implications through inhalation, oral ingestion, and skin penetration. Given their diminutive molecular size, there is a presumption that furanoids can readily permeate the skin. To systematically explore this presumption, we investigated the skin absorption and toxicity of a series of furans (furfuryl alcohol, furfuryl acetate, furfural, methyl 2-furoate, and 5-methylfurfural) using in silico, in vitro, and in vivo models. The in vitro permeation test (IVPT) from neat and aqueous suspension (5 mM) of furans demonstrated a facile absorption through pig and nude mouse skins. The lipophilicity of furans significantly influenced skin deposition, with higher lipophilicity displaying greater deposition. However, an opposing trend emerged in the receptor compartment accumulation. In barrier-defective skin simulating atopic dermatitis (AD) and psoriasis, enhanced deposition occurred with more hydrophilic furans but not with the more lipophilic ones. In the cell-based study, furanoids induced the proliferation of keratinocytes and skin fibroblasts except for the compounds with the aldehyde group (furfural and 5-methylfurfural). Both furfuryl acetate and 5-methylfurfural activated keratinocytes via the overexpression of COX-2 and PGE by 1.5‒2-fold. This stimulation involved the mitogen-activated protein kinase (MAPK) signaling pathway. For the in vivo mouse skin treatment, we selected furfuryl acetate (hydrophilic) and 5-methylfurfural (lipophilic). Both furans showed different patterns of skin lesions, where repeated application of furfuryl acetate caused epidermal hyperplasia and scaling, while 5-methylfurfural predominantly evoked skin inflammation and barrier disintegration. Toxicokinetics analysis revealed a higher plasma concentration of topically applied furfuryl acetate than that of the 5-methylfurfural (5.04 versus 2.34 nmol/ml), resulting in the mild injury of furfuryl acetate-treated peripheral organs. Conversely, no notable adverse effects on organs were observed for the 5-methylfurfural. This study established the relationship between cutaneous absorption and the toxicity of furans following skin exposure.

Community pharmacy is currently experiencing significant changes that will likely transform practice in unpredictable ways. With student interest in pursuing community pharmacy practice post-graduation on the decline, the Academy needs to ensure a sufficient mass of students passionate in community practice enter the workforce to guide this transformation in a positive manner for both the profession and patients. This commentary reviews ways pharmacy faculty may promote community pharmacy during students' academic experiences. These include being mindful of the messages we send our students, promotion of community pharmacy post-graduate training, optimization of community focused adjunct faculty relationships, and reviewing curricula to ensure contemporary community aspects are included.

Oral disintegrating films (ODFs) offer a patient-friendly approach with enhanced convenience and rapid onset of action over various health benefits. ODFs are fabricated for geriatric, pediatric, and individuals facing swallowing challenges. The present work aims to fabricate and characterize ODFs mainly composed of okra mucilage (OM), hyaluronic acid (HA), vitamin-C-loaded bioactive glass nanoparticles (VBG NPs), and clove essential oil. A bio-inspired method was employed to synthesize VBG NPs using fructose template. The nutrient analysis of OM depicted that it is a rich source of protein, carbohydrates, magnesium, and flavonoids (quercetin), accounting for its antioxidant activity. The physicochemical characteristics of the ODFs studied using contact angle measurement, surface pH, opacity, and in vitro disintegration time revealed that ODFs disintegrated rapidly in simulated saliva. The neutral surface pH of ODFs indicates their non-irritant behaviour to the oral mucosa. VBG NPs and essential oil (EO) addition enhance the thermal and mechanical properties. Further, EO infusion in the film matrix resulted in the porous and antibacterial nature of the functional film as revealed by FE-SEM micrographs and antibacterial disk diffusion assay respectively. The obtained novel nutrient-rich ODF is hemocompatible with a hemolysis rate (HR%) <5 % and suitable for functional food applications.

Hydrogel dressings with multiple functions are ideal options for wound repair. This study developed hydrogel dressings by interpenetrating the physically crosslinked xanthan gum (XG)/carboxylated chitosan (CCS) network and the chemically crosslinked polyacrylamide (PAAm) network via a one-pot method. The XG-CCS/PAAm hydrogels were found to display tunable mechanical properties, due to the formation of strong network structure. The hydrogels exhibited the strongest tensile strength of 0.6 MPa at an XG/CCS ratio of 40/60, while the largest compressive strength of 4.5 MPa is achieved at an XG/CCS ratio of 60/40. Moreover, the hydrogel with an XG/CCS ratio of 60/40 exhibited desirable adhesion strength on porcine skin, which was 3.7 kPa. It also had a swelling ratio, as high as 1200 %. After loading with cephalexin, the XG-CCS/PAAm hydrogels can deliver the antibacterial drugs following a first-order kinetic. As a result, both E. coli and S. aureus can be completely inactivated by the cefalexin-loaded hydrogels after 12 h. Furthermore, the XG-CCS/PAAm hydrogels were found to exhibit excellent biocompatibility as well as effective wound healing ability, as proven by the in vitro and in vivo tests. In this regard, XG-CCS/PAAm hydrogels can act as promising multifunctional wound dressings.

Intelligent indicator films with colorimetric pH indicator properties were developed, incorporating black soybean seed coat anthocyanin (BA), cellulose nanocrystals (CNC), and sodium alginate (SA) to monitor meat freshness. The effect of different CNC additions on the microstructure, water barrier properties of the films, and BA release kinetics were comprehensively investigated. The results showed that with the increasement of CNC addition, the mechanical properties of SA/BA/CNC films were improved, the water contact angle significantly increased from 51.6° to 69°. Moreover, water solubility, vapor adsorption, and permeability significantly decreased, indicating enhanced water barrier properties. The release kinetic results showed that BA was released rapidly within 72 h and slowly thereafter, and its release process was described by Fick's model. Films with 7 % and 10 % CNC had lower BA diffusion coefficients. Their diffusions were formulated as linear regression equations (y = nx + a), where R was >0.80 and n was <0.50. Structural characterization showed that CNC immobilized BA mainly through hydrogen bonding, forming compact network microstructures with SA and BA. Meat freshness monitoring results showed that the film containing 7 % CNC showed visible color changes with increasing total volatile basic nitrogen and pH, along with low BA release, high water barrier and mechanical properties. Therefore, CNC has great potential for improving the physicochemical properties of indicator films, and the intelligent colorimetric indicator film could be applied to various food product.

The emergence of antimicrobial resistance within bacterial communities poses formidable challenges to existing therapeutic strategies aimed at mitigating biofilm-mediated infections. Recent advancements in this domain have spurred the development of targeted antimicrobial agents, designed to selectively eradicate the primary etiological agents while preserving the beneficial microbial diversity of the oral cavity. Targeting glucosyltransferases (GTFs), which play crucial roles in dental biofilm formation, offers a precise strategy to inhibit extracellular polysaccharide synthesis without compromising oral microbiota. This review article delves into the intricate mechanisms underlying dental caries, with a specific focus on the role of GTFs, enzymes produced by S. mutans. It further provides an overview of current research on GTF inhibitors, exploring their mechanisms of action, efficacy, and potential applications in clinical practice. Furthermore, it discusses the challenges and opportunities in the development of novel GTF inhibitors, emphasizing the need for innovative approaches to combat biofilm-mediated oral diseases effectively.

Two microwave (MW) responsive heterojunction nanocomposite catalysts, i.e., α-BiO/CoFeO (BO/CFO) and ZnO/CoFeO (ZO/CFO), with weight% ratio of 70/30, 50/50, 30/70 were synthesized by sequential thermal decomposition and co-precipitation methods, and used for the degradation of tetracycline (TC) under MW irradiation. The formation of desired catalysts was confirmed through the characterization results of XRD, FT-IR, SEM, VSM, UV-DRS, XPS, BET, etc. Using batch MW experiments, the catalyst dose, pH, initial TC concentration, reaction temperature, and MW power were optimized for TC removal. Under the following reaction conditions: catalyst dose ∼1 g/L, initial TC concentration ∼1 mg/L, temperature ∼90ºC, MW ∼450 W, BO/CFO and ZO/CFO showed ∼97.55% and 88.23% TC degradation, respectively, after 5 min. The difference in the catalytic response against TC degradation indicated the difference in reflective loss (RL) between these two catalysts. The presence of other competitive anions has affected the removal efficiency of TC due to the scavenging effect. The radical trapping study revealed the significant contribution of TC degradation by hydroxyl radicals in the case of ZO/CFO, whereas for BO/CFO, superoxide (O) and hydroxyl radicals (OH) both played influential roles. The Z-scheme heterojunction of BO/CFO allowed the formation of O but the same was inhibited in type-II heterojunction of ZO/CFO due to the valance band position. The dielectric loss, magnetic loss, interfacial polarization, and high electrical conductivity, 'hotspots' were produced over the catalyst surface alongside electron-hole separation at heterojunctions, which were responsible for the generation of reactive oxygen species. In addition, Co/Co and Fe/Fe redox cycles have promoted O and sulfate radical production during persulfate application. Among the two MW responsive catalysts, BO/CFO could be a potential material for rapidly destroying emerging organic pollutants from wastewater without applying other oxidative chemicals under MW irradiation.

The Balearic Islands, a top tourist destination for sunny beaches, face physical and chemical pressures from human activities, impacting keystone species like the endemic seagrass Posidonia oceanica and its associated microbiome. This study evaluated the effects of ZnO and TiO nanoparticles and three commercial sunscreens with varying protection factors (50 or 90) and chemical complexities (1- SPF50_E "eco-friendly"; 2- SPF50 not "eco-friendly"; 3- SPF90 not "eco-friendly") on five heterotrophic bacteria (Pseudomonas azotifigens, Marinobacterium litorale, Thiothrix nivea, Sedimenticola thiotaurini and Cobetia sp) and two autotrophic cyanobacteria (Halothece sp. and Fischerella muscicola) associated to P. oceanica, as well as a natural leaf epiphytic community. Results indicated that TiO affected all heterotrophic bacteria, while ZnO was toxic to only two species, while autotrophs were unaffected. Commercial sunscreens impacted three heterotrophs and the natural epiphytic community, while autotrophs were only affected by SPF50. SPF50_E reduced phosphorus uptake, and both SPF50 and SPF90 decreased alkaline phosphatase activity. Reactive oxygen species production was mainly induced by SPF90, followed by SPF50_E and SPF50. Generally, the smallest bacteria were most sensitive to UV-filters (UVFs). This study indicates that UVFs exposure may alter the epiphytic community structure of P. oceanica.

Alzheimer's disease (AD), the most common cause of dementia, leads to neurodegeneration and cognitive decline. We investigated the therapeutic effects of L-carnitine on cognitive performance and anxiety-like behavior in a rat model of AD induced by unilateral intracerebroventricular injection of β-amyloid (Aβ). L-carnitine (100 mg/kg/day) was administered intraperitoneally for 28 consecutive days. Following this, the open-field test, novel object recognition test, elevated plus-maze test, Barnes maze test, and passive avoidance learning test were used to assess locomotor activity, recognition memory, anxiety-like behavior, spatial memory, and passive avoidance memory, respectively. Plasma and hippocampal oxidative stress markers, including total oxidant status (TOS) and total antioxidant capacity (TAC), were examined. In addition, histological investigations were performed in the dentate gyrus of the hippocampus using Congo red staining and hematoxylin and eosin staining. The injection of Aβ resulted in cognitive deficits and increased anxiety-like behavior. These changes were associated with an imbalance of oxidants and antioxidants in plasma and the hippocampus. Also, neuronal death and Aβ plaque accumulation were increased in the hippocampal dentate gyrus region. However, injection of L-carnitine improved recognition memory, spatial memory, and passive avoidance memory in AD rats. These findings provide evidence that L-carnitine may alleviate anxiety-like behavior and cognitive deficits induced by Aβ through modulating oxidative-antioxidant status and preventing Aβ plaque accumulation and neuronal death.

The principal objective of this study is to ascertain the connections between well-known risk factors of oral cancer, including smoking (cigarette and tobacco), alcohol consumption, betel quid chewing, irritations in the oral cavity, history of head and neck cancer, and history of working outdoor more than 4 days/week, and the presence of OPMDs within the Thai population.

Early-onset epilepsy following ischemic stroke is a severe neurological condition, the pathogenesis of which remains incompletely understood. Recent studies suggest that Neural stem/progenitor cells (NSPCs) play a crucial role in the disease process, yet the precise molecular mechanisms regulating NSPCs have not been thoroughly investigated. This study utilized single-cell transcriptome sequencing and bioinformatics analysis to identify disease-related genes, which were subsequently validated in both in vitro and in vivo experiments. The findings revealed that Hsp90aa1 (heat shock protein 90 kDa alpha, class A member 1), Jun proto-oncogene (JUN), and CC Motif Ligation 2 (Ccl2) constitute an important regulatory axis influencing the migration and differentiation of NSPCs, potentially impacting the onset and progression of early-onset epilepsy post-ischemic stroke. Additionally, the expression of Hsp90aa1 was found to influence the likelihood of seizure occurrence and the severity of brain ischemia.

Breast cancer (BC) is the most common and malignant tumor diagnosed in women, with 2.9 million cases in 2023 and the fifth highest cancer-causing mortality worldwide. Recent developments in targeted therapy options for BC have demonstrated the promising potential of small interfering RNA (siRNA)-based cancer therapeutic approaches. As BC continues to be a global burden, siRNA therapy emerges as a potential treatment strategy to regulate disease-related genes in other types of cancers, including BC. siRNAs are tiny RNA molecules that, by preventing their expression, can specifically silence genes linked to the development of cancer. In order to increase the stability and effectiveness of siRNA delivery to BC cells, minimize off-target effects, and improve treatment efficacy, advanced delivery technologies such as lipid nanoparticles and nanocarriers have been created. Additionally, combination therapies, such as siRNAs that target multiple pathways are used in conjunction with conventional chemotherapy agents, have shown synergistic effects in various preclinical studies, opening up new treatment options for breast cancer that are personalized and precision medicine-oriented. Targeting important genes linked to BC growth, metastasis, and chemo-resistance has been reported in BC research using siRNA-based therapies. This study reviews recent reports on therapeutic approaches to siRNA for advanced treatment of BC. Furthermore, this review evaluates the role and mechanisms of siRNA in BC and demonstrates the potential of exploiting siRNA as a novel target for BC therapy.

The dorsal raphe nucleus (DRN) receives dopaminergic inputs from the ventral tegmental area (VTA). Also, the DRN contains a small population of cells that express dopamine (DRN neurons). However, the physiological role of dopamine (DA) in the DRN and its interaction with serotonergic (5-HT) neurons is poorly understood. Several works have reported moderate levels of D1, D2, and D3 DA receptors in the DRN. Furthermore, it was found that the activation of D2 receptors increased the firing of putative 5-HT neurons. Other studies have reported that D1 and D2 dopamine receptors can interact with glutamate NMDA receptors, modulating the excitability of different cell types. In the present work, we used immunocytochemical techniques to determine the kind of DA receptors in the DRN. Additionally, we performed electrophysiological experiments in brainstem slices to study the effect of DA agonists on NMDA-elicited currents recorded from identified 5-HT DRN neurons. We found that D2 and D3 but not D1 receptors are present in this nucleus. Also, we demonstrated that the activation of D2-like receptors increases NMDA-elicited currents in 5-HT neurons through a mechanism involving phospholipase C (PLC) and protein kinase C (PKC) enzymes. Possible physiological implications related to the sleep-wake cycle are discussed.

Food deprivation is used in many experimental models and is becoming increasingly prevalent in human diets. The impact of food deprivation on specific brain regions, including the nucleus of the tractus solitarius (NTS), a region that is involved in hunger and satiety sensing, remains to be determined. The NTS is a heterogeneous nucleus that includes corticotropin releasing factor receptor 1 (CRF1) neurons. CRF1 is implicated in both stress and appetite regulation, but the effects of food deprivation on CRF1 NTS neurons are unclear. We used immunofluorescence to examine the effects of 24-hour food deprivation on NTS activity in male and female Sprague-Dawley (SD) rats and CRF1-cre rats using cFos, an immediate early gene and neuronal marker of activation. NTS activity was increased in food deprived male but not female SD rats. In food deprived CRF1-cre rats, males had an increased proportion of active CRF1 + neurons with no change in females. In CRF1-cre rats, increased global NTS activity was observed in food deprived and refed males. Activation of CRF1 + neurons was also increased after deprivation but was reduced by refeeding. In females, food deprivation decreased global NTS activity that was then increased by refeeding, while CRF1 activity was unchanged. Collectively, these data suggest the NTS is differentially activated after food deprivation in a sex-specific manner, whereby males are more sensitive than females. These results provide insight into the role of brainstem stress circuitry in changes associated with conditions including intermittent fasting and eating disorders like anorexia.

Behçet's Disease (BD) is an intricate medical puzzle, captivating researchers with its enigmatic pathogenesis. This complex ailment, distinguished by recurrent mouth and genital lesions, eye irritation, and skin injuries, presents a substantial obstacle to therapeutic research. This review explores the complex interaction of microRNAs (miRNAs) with BD, highlighting their crucial involvement in the disease's pathophysiology. miRNAs, recognized for regulatory influence in diverse biological processes, hold a pivotal position in the molecular mechanisms of autoimmune diseases, such as BD. The exploration begins with examining miRNA biogenic pathways and functions, establishing a foundational understanding of their regulatory mechanisms. Shifting to the molecular landscape governing BD, the review highlights miRNA-mediated impacts on critical signaling pathways like Notch, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and protein kinase B (AKT)/mammalian target of rapamycin (mTOR), offering insights into intricate pathophysiological mechanisms. Dissecting the immunological landscape reveals the profound influence of miRNAs on BD, shedding light on the intricate modulation of immune responses and offering novel perspectives on disease etiology and progression. Beyond molecular intricacies, the review explores the clinical relevance of miRNAs in BD, emphasizing their potential as diagnostic and prognostic indicators. The discussion extends to the promising realm of miRNA-based therapeutic interventions, highlighting their potential in alleviating symptoms and altering disease progression. This comprehensive review, serving as a valuable resource for researchers, clinicians, and stakeholders, aims to decipher the intricate molecular tapestry of BD and explore the therapeutic potential of miRNAs.

In this study, a novel strain Burkholderia stabilis TF-2 capable of assimilatory and co-metabolic degradation of chlorobenzenes was obtained. The interaction between chlorobenzene (CB) and target enzymes, as well as the metabolic pathways in TF-2, were elucidated using multi-omics and molecular docking techniques. Results of degradation experiments indicated that TF-2 assimilated CB at a rate of 0.22-0.66 mg·g·h in concentrations of 20-200 mg·L. Additionally, TF-2 also used sodium succinate and sodium citrate as substrates to co-metabolize CB, with degradation rates of 0.26-2.00 and 0.31-1.72 mol·g·h, respectively. Whole-genome sequencing revealed over 18 novel genes associated with aromatic hydrocarbon degradation in TF-2. Transcriptomic analysis showed that CB induced the high expression of 119 genes involved in CB metabolism and late mineralization. The significant up-regulation of the bedC1 (encoding a ring-hydroxylated dioxygenase), CatA (chlorocatechol 1,2-dioxygenase), pcaJ (3-oxoadipate CoA-transferase alpha subunit) and fadA (acetyl-CoA acyltransferase) genes facilitated CB metabolism. Based on these findings, a metabolic pathway for CB was constructed, with the key step involving ortho cleavage of the aromatic ring under the action of the catA gene. Furthermore, molecular docking revealed that CB bound to bedC1 with -4.5 kcal·mol through hydrophobic bonds, π-stacking, and a halogen bond. These results provide strong support for development of efficient strains to enhance the removal of chlorinated organic compounds.

Glioblastoma (GB) is the most aggressive and prevalent glioma within the central nervous system. Despite considerable efforts, GB continues to exhibit a dismal 5-year survival rate (∼6%). This is largely attributed to unfavorable prognosis and lack of viable treatment options. Therefore, novel therapies centered around plant-derived compounds emerge as a compelling avenue to enhance patient survival and well-being. The South African species, Plectranthus hadiensis Schweinf. (P. hadiensis), a member of the Lamiaceae family, has a history of use in traditional medicine for treating a range of diseases, including respiratory, digestive, and liver disorders. This species exhibits diverse biological activities, such as anti-inflammatory and antitumoral properties, likely attributed to its rich composition of naturally occurring diterpenes, like the abietane diterpene, 7α-acetoxy-6β-hydroxyroyleanone (Roy). Roy has demonstrated promising antitumor effects in various cancer cell lines, making it a compelling candidate for further investigation into its mechanisms against GB.

Per- and polyfluoroalkyl substances (PFAS) are artificial chemicals extensively utilized in everyday products, and numerous cross-sectional epidemiological studies consistently link PFAS exposure with lipid profiles across diverse populations and age groups. In longitudinal studies, the findings also indicate a positive correlation between PFAS and lipid profiles; however, this association remains unexplored in adolescents and young adults. Notably, previous research has predominantly focused on conventional lipid biomarkers, with limited exploration of the relationship between PFAS and diverse lipoprotein subfractions. Furthermore, there is a lack of comprehensive investigation into the temporal trends in PFAS concentrations in Taiwan. To address this research gap, we conducted a prospective study following 592 adolescents and young adults (12-30 years old at enrollment) from the YOung TAiwanese Cohort (YOTA) over a duration of 10 years. During the follow-up period, we measured 11 types of PFAS and various lipid profile biomarkers (low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C), low-density lipoprotein triglyceride (LDL-TG), high-density lipoprotein cholesterol (HDL-C), HDL3-C, lipoprotein(a), triglyceride). Our results revealed a general decline in PFAS concentrations in the study population. Regarding the correlation between the average levels (averaged across the initial and second tracking periods) of PFAS and lipid profiles (during the second tracking period), we observed positive correlations with total cholesterol and LDL-C for perfluorononanoic acid (PFNA), perfluoroundecanoic acid (PFUdA), perfluorododecanoic acid (PFDoA), N-methylperfluorooctane sulfonamide acetic acid (N-MeFOSAA), and the sum of PFAS (sum of the 11 kinds of PFAS). Additionally, average levels of PFUdA, N-MeFOSAA, and the sum of PFAS exhibited positive associations with sdLDL-C. This study unveiled an overall decrease in PFAS concentrations and underscores a potential link between PFAS exposure and adverse changes in lipid profiles among young populations, emphasizing the need for further exploration into the mechanisms of PFAS on lipid metabolism and atherosclerosis.

Depression is a prevalent stress disorder, yet the underlying physiological mechanisms linking stress to appetite and weight loss remain elusive. While most antidepressants are associated with excessive weight and appetite gain, sertraline (SER) exhibits a lower risk of these side effects. Metacinnabar (β-HgS), the primary component of Tibetan medicine Zuotai, has been shown to enhance mice's resilience against external stress without causing excessive increases in weight or appetite. However, the precise physiological pathway through which β-HgS restores appetite and weight in stressed mice remains unclear.

Emerging and persistent contaminants (EPC) pose a significant challenge to water quality monitoring efforts. Effect-based monitoring (EBM) techniques provide an efficient and systematic approach in water quality monitoring, but they tend to be resource intensive. In this study, we investigated the EPC distribution for various land uses using target analysis (TA) and non-target screening (NTS) and in vitro bioassays, both individually and integrated, in the upper Ping River Catchment, northern Thailand. Our findings of NTS showed that urban areas were the most contaminated of all land use types, although agriculture sites had high unexpected pollution levels. We evaluated the reliability of NTS data by comparing it to TA and observed varying inconsistencies likely due to matrix interferences and isobaric compound interferences. Integrating NTS with in vitro bioassays for a thorough analysis posed challenges, primary due to a scarcity of concentration data for key compounds, and potentially additive or non-additive effects of mixture samples that could not be accounted for. While EBM approaches place emphasis on toxic sites, this study demonstrated the importance of considering non-bioactive sites that contain toxic compounds with antagonistic effects that may go undetected by traditional monitoring approaches. The present work emphasizes the importance of improving NTS workflows and ensuring high-quality EBM analyses in future water quality monitoring programs.

Recent interest in tissue engineering (TE) has focused on electrically conductive biomaterials. This has been inspired by the characteristics of the cells' microenvironment where signalling is supported by electrical stimulation. Numerous studies have demonstrated the positive influence of electrical stimulation on cell excitation to proliferate, differentiate, and deposit extracellular matrix. Even without external electrical stimulation, research shows that electrically active scaffolds can improve tissue regeneration capacity. Tissues like bone, muscle, and neural contain electrically excitable cells that respond to electrical cues provided by implanted biomaterials. To introduce an electrical pathway, TE scaffolds can incorporate conductive polymers, metallic nanoparticles, and ceramic nanostructures. However, these materials often do not meet implantation criteria, such as maintaining mechanical durability and degradation characteristics, making them unsuitable as scaffold matrices. Instead, depositing conductive layers on TE scaffolds has shown promise as an efficient alternative to creating electrically conductive structures. A stratified scaffold with an electroactive surface synergistically excites the cells through active top-pathway, with/without electrical stimulation, providing an ideal matrix for cell growth, proliferation, and tissue deposition. Additionally, these conductive coatings can be enriched with bioactive or pharmaceutical components to enhance the scaffold's biomedical performance. This review covers recent developments in electrically active biomedical coatings for TE. The physicochemical and biological properties of conductive coating materials, including polymers (polypyrrole, polyaniline and PEDOT:PSS), metallic nanoparticles (gold, silver) and inorganic (ceramic) particles (carbon nanotubes, graphene-based materials and Mxenes) are examined. Each section explores the conductive coatings' deposition techniques, deposition parameters, conductivity ranges, deposit morphology, cell responses, and toxicity levels in detail. Furthermore, the applications of these conductive layers, primarily in bone, muscle, and neural TE are considered, and findings from in vitro and in vivo investigations are presented. STATEMENT OF SIGNIFICANCE: Tissue engineering (TE) scaffolds are crucial for human tissue replacement and acceleration of healing. Neural, muscle, bone, and skin tissues have electrically excitable cells, and their regeneration can be enhanced by electrically conductive scaffolds. However, standalone conductive materials often fall short for TE applications. An effective approach involves coating scaffolds with a conductive layer, finely tuning surface properties while leveraging the scaffold's innate biological and physical support. Further enhancement is achieved by modifying the conductive layer with pharmaceutical components. This review explores the under-reviewed topic of conductive coatings in tissue engineering, introducing conductive biomaterial coatings and analyzing their biological interactions. It provides insights into enhancing scaffold functionality for tissue regeneration, bridging a critical gap in current literature.

Zoonotic viruses are widely seen as the primary threat for future pandemics. Bats are the most diverse group of mammals, with more than 1400 species distributed across most habitats on Earth. So far, 31 known virus families were associated with bats, although the understanding of most viruses were insufficient. Continuous efforts to discover, understand and monitor these bats viruses, is thereby an area of public health interest. This systematic review was designed to catalogue publications reporting novel bat virus discoveries within PubMed, SCOPUS, and Web of Science databases, within a 5-year period from 2018-2022. Various experimental parameters, including sampling locations, methodology, bat species diversity, similarity to known viruses, species demarcation of new viruses, and genomic sequencing strategies, were extracted from 41 publications and analyzed. In total, 72 novel viruses from 19 virus families were identified between 2018 and 2022, particularly from Genomoviridae (DNA viruses) and Coronaviridae (RNA viruses). That said, only a limited number of bat families featured extensively despite noticeable shift towards next generation sequencing methods and metagenomics pipeline for virus identification across different sampling methods. This review aims to provide a comprehensive analysis of the global efforts made over the past five years to identify and characterize emerging viruses in bat species, and to provide a detailed overview of the current technologies and methodologies used in these studies.

Wnt signal is crucial to correctly regenerate tissues along the original axis in many animals. Lizards are able to regenerate their tails spontaneously, while the anterior-posterior axis information required for the successful regeneration is still elusive. In this study, we investigated the expression pattern of Wnt ligands and HOX genes during regeneration. The results of in situ hybridization revealed that Wnt6 level is higher in wound epithelium (WE) than that in blastema during regeneration. In addition, we showed that Wnt agonist positively regulated the expression of HOXA13 in cultured blastema cells, while did not show similar effect on that of HOXB13, HOXC13 and HOXD13. Finally, we found that HOXA13 showed a gradient level along the anterior-posterior axis of regenerated blastema, with higher level at the caudal end. These data proposed that Wnt6 and HOXA13 might play an important role in establishing distal position for regeneration.

The rich active hydroxyl groups on starch nanocrystals (SNC) surface limits its dispersion and stability in the aqueous phase. To address this issue, ozone modification for 0 (SNC), 0.5 (SNC-1), 1 (SNC-2), 1.5 (SNC-3), and 2 h (SNC-4) as compared to conventionally chemical methods was applied to functionally modify the SNC. The impact of ozone treatment on the structural and surface characteristics of waxy rice starch nanocrystals. The findings revealed that longer ozone treatment durations favored the formation of carbonyl groups in starch molecules. Initially, ozone oxidized the hydroxyl group of the macromolecule. Once the carbonyl groups formed, the cross-linking reaction occurred among starch nanocrystals through condensation reactions, leading to the increasing molecular orderliness. X-ray photoelectron spectroscopy, X-ray diffraction and Small-angle X-ray scattering analyses of SNC-2 supported this finding with a reduced O/C ratio, and implied that surface oxidation did not alter the crystal type but rather enhanced molecular hydration in an aqueous system, leading to increased interfacial thickness and fractal dimension. Additionally, ozone oxidation improved surface properties such as charge and hydrophobicity. Oxidized SNC also exhibited altered gelatinization properties due to surface degradation. This study offers a promising strategy for enhancing SNC surface properties, crucial for food science applications.

To describe the development of an innovative pre-pharmacy underrepresented mentorship program (PUMP) to provide guidance and support to pre-pharmacy students who are committed to serving underrepresented communities with health disparities.

Structural insight eludes on how full-length gelsolin depolymerizes and caps filamentous (F-)actin, while the same entity can nucleate polymerization of G-actins. Analyzing small angle X-ray scattering (SAXS) data, we deciphered assemblies which enable these contrasting processes. Mixing Ca-gelsolin with F-actin in high salt F-buffer resulted in depolymerization of ordered F-actin rods to smaller sized species which became monodispersed upon dialysis with low salt G-buffer. These entities were the ternary (GA) and binary (GA) complexes of gelsolin and actin with radius of gyration and maximum linear dimension of 4.55 and 4.68 nm, and 15 and 16 nm, respectively. Using size exclusion chromatography in-line with SAXS, we confirmed that initially GA and GA species are formed as seen upon depolymerization of F-actin followed by dialysis. Interestingly, while GA could seed formation of native-like F-actin in both G- and F-buffer, GA failed in G-buffer. Thus, GA and GA are the central species formed via depolymerization or towards nucleation. SAXS profile referenced modeling revealed that: 1) in GA, actin is bound to the C-terminal half of gelsolin, and 2) in GA, second actin binds to the open N-terminal half accompanied by dramatic rearrangements across g1-g2 and g3-g4 linkers.

All pharmacists are expected to accurately perform pharmaceutical calculations to ensure patient safety. In recent years, there have been trends in declining performance on the North American Pharmacist Licensure Examination related to calculations. Understanding the cause of this decline and determining methods to correct underlying issues could benefit pharmacy administration, faculty, students, and patients. The aims of this commentary are to present factors impacting students' pharmaceutical calculations abilities, discuss the consequences of declining math skills, and provide a call to action for scholarship of teaching and learning pertaining to calculations as well as increased administrative support to rectify this challenge.

Bacterial resistance to antibiotics is a significant challenge that is associated with increased morbidity and mortality. Gram-negative bacteria are particularly problematic due to an outer membrane (OM). Current alternatives to antibiotics include antimicrobial peptides or proteins and multifunctional systems such as dendrimers. Antimicrobial proteins such as lysins can degrade the bacterial cell wall, whereas dendrimers can permeabilize the OM, enhancing the activity of endolysins against gram-negative bacteria. In this study, we present a three-stage action of endolysin combined with two different carbosilane (CBS) silver metallodendrimers, in which the periphery is modified with N-heterocyclic carbene (NHC) ligands coordinating a silver atom. The different NHC ligands contained hydrophobic methyl or N-donor pyridyl moieties. The effects of these endolysin/dendrimer combinations are based on OM permeabilization, peptidoglycan degradation, and reactive oxygen species production. The results showed that CBS possess a permeabilization effect (first action), significantly reduced bacterial growth at higher concentrations alone and in the presence of endolysin, increased ROS production (second action), and led to bacterial cell damage (third action). The complex formed between the CHAP domain of endolysin and a CBS silver metallodendrimer, with a triple mechanism of action, may represent an excellent alternative to other antimicrobials with only one resistance mechanism.

A colloidal gold immunochromatographic assay (CGIA) based on single-chain variable fragments (scFvs) has been successfully developed for the detection of monensin (MON). Colloidal gold probes were conjugated to anti-MON scFvs through electrostatic interaction, with the conjugated objects serving as the visual signals. The detection lines were formed by capturing the antibody with MON-OVA. This assay offers a rapid detection time of 15 min, a wide linear range from 2.19 to 10.76 ng mL, and boasts high accuracy, precision, and an absence of cross-reactivity. By homology modeling and molecular docking, we predicted the interaction patterns between the scFv and monensin, and the amino acid residues involved in the recognition of MON by the antibody were analyzed. These key amino acid sites are presumed integral to ligand recognition per current interaction models. This hypothesis was confirmed by computer-aided alanine scanning mutation, MM/P(G)BSA molecular dynamics simulation, and in vitro binding experiments. In this study, we successfully developed the scFvs-based CGIA system for rapid and easy quantification of monensin, providing a simple, efficient routine detection of chicken muscle samples.

To develop and validate the Oral Lichen Planus-Disease Activity Scale (OLP-DAS) for assessing overall disease activity of OLP.

Policy synergies effectively contribute to the integrated management of air pollution and carbon emissions, which is crucial for safeguarding ecosystem stability and public health. This study uses the causal network model of Gaussian process regression to analyze the combined impacts of dynamic and static carbon emission reduction and air quality policies on carbon emissions and air quality. The causal effects of policy measures and their synergistic effects are also examined. The study results indicate: (1) There is significant geographical heterogeneity in the implementation of environmental policies and regional economic development, with the economically developed eastern coastal regions adopting more stringent carbon emission and air pollution control measures, while the western provinces adopt relatively lax environmental policies. (2) The synergistic effect of carbon emission reduction policies and air quality policies exists, and the two types of static policies are substitutable for managing carbon dioxide emissions and air pollution. (3) Policies' forced effect exists, where the exacerbation of environmental problems leads to the formation and implementation of policies. (4) The value added by the secondary industry is a key motivation for forming carbon emission reduction policies and air quality control policies. Additionally, the value added by the secondary industry directly impacts the incidence of respiratory diseases (e.g., tuberculosis). Finally, dynamic and synergistic policy recommendations are proposed based on the study's findings.

Recombinant high-density lipoprotein (rHDL) as anti-atherosclerosis (AS) vehicle has unique advantages including multiple anti-atherogenic functions and homing features to plaques. However, rHDL may be converted into dysfunctional forms due to complex treatment during preparation. Herein, oxidation-induced dysfunction of non-split HDL and rHDL was initially investigated. It was found that although both non-split HDL and rHDL showed oxidative dysfunction behavior, non-split HDL demonstrated superior oxidation defense compared to rHDL due to its intact composition and avoidance of overprocessing such as split and recombination. Unfortunately, in vivo oxidative stress could compromise the functionality of HDL. Therefore, surface engineering of non-split HDL and rHDL with cascade antioxidant enzyme analogues Ebselen and mitochondrial-targeted TPGS-Tempo was conducted to construct a dual-line defense HDL nano system (i.e., T@E-HDLs/rHDL), aiming to restore plaque redox balance and preserving the physiological function of HDL. Results indicated that both T@E-HDLs and rHDLs performed without distinction and exhibited greater resistance to oxidative stress damage as well as better functions than unmodified HDLs in macrophage foam cells. Overall, the modification of dual antioxidants strategy bridges the gap between non-split HDL and rHDL, and provides a promising resolution for the dilemmas of oxidative stress in plaques and HDL self dysfunction.

Conditioned taste aversion (CTA) is a robust associative learning; liquid deprivation during this conditioning allows researchers to obtain readable measures of associative learning. Recent research suggests that thirst could be a crucial motivator that modulates conditioning and memory extinction processes, highlighting the importance of the body's internal state during learning. Furthermore, the histaminergic system is one of the major modulatory systems controlling several behavioral and neurobiological functions, such as feeding, water intake, and nociception. Therefore, this research aimed to assess the effect of H3 histaminergic receptor activation in the insular cortex (IC) during CTA. For this, we conditioned adult male Wistar rats under two regimens: water deprivation and water ad libitum. A classical CTA protocol was used for water deprivation. Before CTA acquisition, 10 μM R-α-methylhistamine (RAMH), an H3 receptor agonist, was injected into the IC. Results showed that RAMH injections decreased CTA in water-deprived rats without affecting the significant aversion conditioning in rats that were given water ad libitum. Moreover, RAMH accelerated the process of aversive memory extinction under ad libitum water conditions. According to our findings, the degree of liquid satiety differentially affected taste-aversive memory formation, and H3 histamine receptors were more involved under water deprivation conditions during acquisition. However, these receptors modulated the strength of aversive conditioning by altering the rate of aversive memory extinction in the absence of deprivation. In conclusion, histaminergic activity in the IC may influence taste memory dynamics through different mechanisms depending on the degree of liquid satiety or deprivation during conditioning.

Cannabidiol (CBD) has gained widespread popularity; however, its pharmacological and toxicological profiles in the context of human genetic diversity remain largely unexplored. Here, we investigated the variability in metabolism and toxicity of CBD-rich cannabis extract (CRCE) in genetically diverse mouse models: C57BL/6J, B6C3F/J, and NZO/HlLtJ strains. Mice received a single dose of CRCE containing 57.9% CBD at dosages of 0, 246, 738, and 2,460 mg/kg of CBD. At 24 h after treatment, no appreciable histomorphological changes were detected in the liver. Plasma bilirubin levels increased markedly in all strains at the highest CBD dose. Mice in all treatment groups displayed significant but distinct increases in ALT and AST levels. While B6C3F/J and NZO/HlLtJ mice had negligible plasma CBD levels at 738 mg/kg, C57BL/6J mice exhibited levels exceeding 7,000 ng/mL. At 2,460 mg/kg, high CBD concentrations were found in B6C3F/J and C57BL/6J mice, but markedly lower levels were seen in NZO/HlLtJ mice. Gene expression profiling showed significant increases in Cyp2b10 across all strains but varying responses in Cyp1a1 expression, indicating strain-specific CYP dysregulation. Genetically diverse mice exhibited differential pharmacological and toxicological responses to CRCE, suggesting a high potential for inter-individual variability in the pharmacology and toxicology of CBD in humans.

Aortic dissection remains a life-threatening condition necessitating accurate diagnosis and timely intervention. This study aimed to unravel phenotypic heterogeneity in Stanford type B aortic dissection (TBAD) patients through machine learning clustering analysis of cardiovascular CT imaging.

The efficiency of zinc oxide (ZnO) nanoparticles for environmental decontamination is limited by their reliance on ultraviolet (UV) light and rapid charge carrier recombination. Carbon doping has been proposed to address these challenges by potentially enhancing visible light absorption and charge separation.

The molecular structures of starch and sugar/sugar alcohol are recognized as critical determinants of starch pasting and retrogradation properties. However, their combined effects on these properties remain elusive. This study for the first time examined the pasting and retrogradation properties of nine starches with diverse molecular structures, both with and without the addition of glucose, sucrose, isomaltose, isomalt, and sorbitol. The presence of sugar/sugar alcohol significantly enhanced starch pasting viscosity. In particular, the variations of the peak viscosity of wheat starch were more pronounced than other starches, possibly due to its distinct molecular structures. The changes in melting temperatures and enthalpy of retrograded starches were complex, varying depending on the type of starch and sugar/sugar alcohol used. For example, the melting peak temperature ranged from 56.45 °C (TS) to 61.9 °C (WMS), and the melting enthalpy ranged from 0.16 J/g (TS) to 5.6 J/g (PES). The micromorphology of retrograded starch revealed agglomeration and needle-like structures, instead of a network structure, after the addition of glucose and sorbitol, respectively. Correlations between starch molecular structure and pasting properties remained largely unchanged, while the relationship between starch molecular structure and retrogradation properties exhibited notable variations after the addition of sugars or sugar alcohols. These findings help a better understanding of the effects of starch molecular structure and the presence of sugar/sugar alcohol on starch pasting and retrogradation properties.

Isochorismate-derived metabolism enables biosynthesis of the plant defence hormone salicylic acid (SA) and its derivatives. In Arabidopsis thaliana, the stress-induced accumulation of SA depends on ISOCHORISMATE SYNTHASE1 (ICS1), and also requires the presumed isochorismate transporter ENHANCED DISEASE SUSCEPTIBILITY5 (EDS5) and the GH3 enzyme avrPphB SUSCEPTIBLE3 (PBS3). By comparative metabolite and structural analyses, we identified several hitherto unreported ICS1- and EDS5-dependent, biotic stress-inducible Arabidopsis metabolites. These involve meta-substituted SA derivatives (5-formyl-SA, 5-carboxy-SA, 5-carboxymethyl-SA), their benzoic acid (BA) analogues (3-formyl-BA, 3-carboxy-BA, 3-carboxymethyl-BA) and, besides the previously detected salicyloyl-aspartate (SA-Asp), the ester conjugate salicyloyl-malate (SA-Mal). SA functions as a biosynthetic precursor for SA-Mal and SA-Asp, but not for the meta-substituted SA- and BA-derivatives, which accumulate to moderate levels at later stages of bacterial infection. Interestingly, Arabidopsis leaves possess oxidising activity to effectively convert meta-formyl- into meta-carboxy-SA/BAs. In contrast to SA, exogenously applied meta-substituted SA/BA-derivatives and SA-Mal exert moderate impact on plant immunity and defence-related gene expression. While the isochorismate-derived metabolites are negatively regulated by the SA receptor NON-EXPRESSOR OF PR GENES1, SA conjugates (SA-Mal, SA-Asp, SA-glucose conjugates) and meta-substituted SA/BA-derivatives are oppositely affected by PBS3. Notably, our data indicate a PBS3-independent path to isochorismate-derived SA at later stages of bacterial infection, which does not considerably impact immune-related characteristics. Moreover, our results argue against a previously proposed role of EDS5 in the biosynthesis of the immune signal N-hydroxypipecolic acid and associated transport processes. We propose a significantly extended biochemical scheme of plant isochorismate metabolism that involves an alternative generation mode for benzoate- and salicylate-derivatives.

To mitigate environmental impacts in food preservation, the development of a multifunctional membrane for packaging is of importance. In this study, we have successfully fabricated a nanofibrous membrane using an eco-friendly electrospinning technique, comprising polyvinyl alcohol (PVA), chitosan (CS), and tannic acid (TA). The resulting nanofibrous membranes were crosslinked with glutaraldehyde (GA) and surface modified with ZnO. Our findings demonstrate that the crosslinking process enhances water resistance, reduces water vapor permeability, improves tensile strength (from 3 to 18 MPa), and enhances thermal stability (increasing decomposition temperature from 225 °C to 310 °C). Furthermore, the incorporation of TA and ZnO provides antioxidant properties to the membrane, effectively preventing food decomposition caused by UV-induced oxidation. Additionally, CS, TA, and ZnO synergistically exhibit a remarkable antibacterial effect with a bacteriostasis rate exceeding 99.9 %. The strawberry fresh-keeping experiment further confirms that our developed membrane significantly extends shelf life by up to 6 days. Moreover, cytotoxicity assays confirm the non-toxic nature of these membranes. The innovative significance of this study lies in proposing a robust GA-PVA/CS/TA@ZnO nanofibrous membrane with excellent mechanical properties, biocompatibility, and multiple functionalities including antibacterial, anti-ultraviolet, and anti-oxidation capabilities. It has tremendous potential for applications in active food packaging materials.

Protein and polysaccharides are the mostly used biopolymers for developing packaging film and their combination-based composite produced better quality film compared to their single counterpart. The combination of protein and polysaccharides are superior owing to the better physical properties like water resistance, mechanical and barrier properties of the film. The protein/polysaccharide-based composite film showed promising result in active and smart food packaging regime. This work discussed the recent advances on the different types of protein/polysaccharide combinations used for making bio-based sustainable packaging film formulation and further utilized in food packaging applications. The fabrication and properties of various protein/polysaccharide combination are comprehensively discussed. This review also presents the use of the multifunctional composite film in meat, fish, fruits, vegetables, milk products, and bakery products, etc. Developing composite is a promising approach to improve physical properties and practical applicability of packaging film. The low water resistance properties, mechanical performance, and barrier properties limit the real-time use of biopolymer-based packaging film. The combination of protein/polysaccharide can be one of the promising solutions to the biopolymer-based packaging and thus recently many works has been published which is suitable to preserve the shelf life of food as well trace the food spoilage during food storage.

Polylactic acid (PLA) is widely known for its biocompatibility, biodegradability, and high transparency. However, it still has varied limitations such as flammability, UV sensitivity, and poor oxygen barrier properties. To address these issues, a bio-based compound, hexasubstituted cyclotriphosphazene (HVP), was synthesized by using vanillin and hexachlorocyclotriphosphazene to enhance the overall performance of PLA. The resulting PLA/HVP composites demonstrated improved mechanical strength and UV resistance. Specifically, PLA/3HVP, with a 3 wt% HVP loading, achieved a UL-94 V-0 rating and a high limiting oxygen index of 26.5 %. Cone calorimeter tests revealed that PLA/3HVP possessed a significantly longer ignition time and a lower peak heat release rate compared to pure PLA. These burning testing results indicated the enhanced fire resistance. Additionally, the oxygen transmission rate of PLA/3HVP was reduced by 81.1 % compared to pure PLA. When used as food packaging, the weight loss of mangoes covered with PLA/3HVP film was 2.2 % after 7 days, compared to 2.5 % with pure PLA film, highlighting its potential for food preservation applications.

New nano/microcarriers of pesticides represent a highly promising novel field for sustainable pest management. However, despite extensive laboratory research, few studies on the design and evaluation of nanopesticides for field applications exist. In this study, we present a straightforward and green synthetic method of ultrasonic-assisted and hydrogen-bonded self-assembly at the oil-water interface for the synthesis of polylactic acid (PLA) microspheres encapsulating chlorantraniliprole (CAP), with precise control over the size of the microspheres. The resulting CAP-loaded PLA microspheres (CAP-PLA MS) exhibit both high pesticide encapsulation efficiency and stability in natural environments. It has been determined that non-Fickian diffusion mainly controls pesticide release, thus enabling dynamic control over molecular transport speeds. Importantly, our functional CAP-PLA MS demonstrates superior sustained pesticide release performance under both laboratory and field conditions while maintaining better exceptional insecticidal efficacy than normal CAP in controlling O. nubilalis at a concentration of 30 or 45 g/ha. Consequently, we propose that our functional PLA microspheres could serve as ideal pesticide carriers in the sustained treatment of O. nubilalis.

Organometallic catalyst is extensively applied for the non-enzymatic regeneration of nicotinamide adenine dinucleotide (phosphate) cofactors, but suffering from the mutual inactivation with the enzymes in one pot. The spatially separated immobilization of organometallic catalyst and enzymes on suitable carriers not only can reduce their mutual inhabitation but also can enhance their reusability. Here in this work, we present a hierarchical porous COFs (HP-TpBpy) that incorporated with [(Cp*RhCl] to generate the metalized COF, Rh-HP-TpBpy. The obtained Rh-HP-TpBpy exhibited superior performance in nicotinamide adenine dinucleotide (NADH) or nicotinamide adenine dinucleotide phosphate (NADPH) regeneration using formate as the hydride donor, significantly outperforming the natural formate dehydrogenases in cofactor preference toward NADP. Subsequently, the Lactobacillus fermentum short-chain dehydrogenase/reductase 1 (LfSDR1) was then cross-linked into enzyme aggregates (CLEA) and immobilized on hierarchical Rh-HP-TpBpy, achieving the integrated chemoenzymatic catalyst, LfSDR1@Rh-HP-TpBpy, which can catalyze the chemoenzymatic reduction of halogenated aryl ketones and give the corresponding optically active halohydrins with high conversion and enantiomeric excess (ee) value up to 99 %. The LfSDR1@Rh-HP-TpBpy also exhibits largely enhanced stability compared with the free LfSDR1 and the CLEAs-LfSDR1, enabling its excellent reusability.

The important role of Carbohydrate-binding module (CBM) in the cellulases catalytic activity has been widely studied. CBM3 showed highest affinity for cellulose substrate with 84.69 % adsorption rate among CBM1, CBM2, CBM3, and CBM4 in this study. How CBM affect the catalytic properties of GH5 endoglucanase III from Trichoderma viride (TvEG3) was systematically explored from two perspectives: the deletion of its own CBM(TvEG3dc) and the replacement of high substrate affinity CBM3 (TvEG3dcCBM3). Compared with TvEG3, TvEG3dc lost its binding ability on Avicel and filter paper, but its catalytic activity did not change significantly. The binding ability and catalytic activity of TvEG3dcCBM3 to Avicel increased 348.3 % and 372.51 % than that of TvEG3, respectively. The binding ability and catalytic activity of TvEG3dcCBM3 to filter paper decreased 51.7 % and 33.33 % than that of TvEG3, respectively. Further structural analysis of TvEG3, TvEG3dc, and TvEG3dcCBM3 revealed no changes in the positions and secondary structures of the key amino acids. These results demonstrated that its own CBM1 of TvEG3 did not affect its catalytic activity center, so it had no effect on its catalytic activity. But CBM3 changed the adsorption affinity for different substrates, which resulted in a change in the catalytic activity of the substrate.

The effect of whey protein isolate (WPI)- galacto-oligosaccharides (GOS)/fructo-oligosaccharides (FOS) conjugates on RAW264.7 cells, and further the effect of WPI-GOS conjugates on CTX-induced immunosuppressed mice were investigated. Compared to WPI-FOS conjugates, WPI-GOS conjugates exhibited deeper glycation extent, more pronounced structural unfolding and helix-destabilizing, and obviously improved functional indicators of RAW264.7 macrophages. In addition, WPI-GOS conjugates also repaired immune organ and intestinal barrier and increased IL-1β and IFN-γ levels in immunosuppressed mice. The alteration of gut microbiota induced by WPI-GOS conjugates changed the serum metabolites, causing the activation of NFκB pathway, which strengthens the immune system. The activation of NFκB pathway maybe associated with the mTOR signal pathway and ABC transporters. However, the precise mechanisms by which NFκB pathway interacts with mTOR signal pathway and ABC transporters to modulate the immune response need for further research.

Multidrug -resistant tuberculosis (MDRTB) is a serious threat to mankind. India has the highest number of MDRTB cases, although majority remain undiagnosed due to inadequate diagnostic infrastructure, leading to increased community transmission and mortality. This one-year observational retrospective study highlighted the effectiveness of the National Tuberculosis Elimination Program (NTEP) for prompt detection of drug- resistant TB by GeneXpert MTB/RIF assay and revealed its associated clinico- epidemiological factors. The overall detection rates of MTB and RRTB were 20.70% and 20.86% respectively. The pediatric population had 7.69% rifampicin resistance, and HIV was strongly associated with the development of TB and RRTB (P<0.01).

Skin wounds, prevalent and fraught with complications, significantly impact individuals and society. Wound healing encounters numerous obstacles, such as excessive reactive oxygen species (ROS) production and impaired angiogenesis, thus promoting the development of chronic wound. Traditional clinical interventions like hemostasis, debridement, and surgery face considerable challenges, including the risk of secondary infections. While therapies designed to scavenge excess ROS and enhance proangiogenic properties have shown effectiveness in wound healing, their clinical adoption is hindered by high costs, complex manufacturing processes, and the potential for allergic reactions. Lotus root, distinguished by its natural micro and macro porous architecture, exhibits significant promise as a tissue engineering scaffold. This study introduced a novel scaffold based on hybridization of lotus root-inspired and Gelatin Methacryloyl (GelMA), verified with satisfactory physicochemical properties, biocompatibility, antioxidative capabilities and proangiogenic abilities. In vivo tests employing a full-thickness wound model revealed that these scaffolds notably enhanced micro vessel formation and collagen remodeling within the wound bed, thus accelerating the healing process. Given the straightforward accessibility of lotus roots and the cost-effective production of the scaffolds, the novel scaffolds with ROS scavenging, pro-angiogenesis and re-epithelialization abilities are anticipated to have clinical applicability for various chronic wounds.

ABCA4 is an ATP-binding cassette (ABC) transporter that prevents the buildup of toxic retinoid compounds by facilitating the transport of N-retinylidene-phosphatidylethanolamine across membranes of rod and cone photoreceptor cells. Over 1500 missense mutations in ABCA4, many in the nucleotide binding domains (NBDs), have been genetically linked to Stargardt disease (STGD1). Here, we show by Cryo-electron microscopy that ABCA4 is converted from an open outward conformation to a closed conformation upon the binding of AMP-PNP. Structural information and biochemical studies were used to further define the role of the NBDs in the functional properties of ABCA4 and the mechanisms by which mutations lead to the loss in activity. We show that ATPase activity in both NBDs is required for the functional activity of ABCA4. Mutations in Walker A asparagine residues cause a severe reduction in substrate-activated ATPase activity due to the loss in polar interactions with residues within the D-loops of the opposing NBD. The structural basis for how disease mutations in other NBD residues including the R1108C, R2077W, R2107H and L2027F affect the structure and function of ABCA4 is described. Collectively, our studies provide insight into the structure and function of ABCA4 and mechanisms underlying STGD1.

Hypoxia and high concentration of glutathione (GSH) in tumor seriously hinder the role of reactive oxygen species (ROS) and oxygen-dependence strategy in tumor treatment. In this work, a self-generating oxygen and self-consuming GSH hyaluronic acid (HA)-coated porphyrin nanoplatform (TAPPP@CaO/Pt(IV)/HA) is established for enhancing photodynamic/ion/chemo targeting synergistic therapy of tumor. During the efforts of ROS production by nanosystems, a GSH consuming strategy is implemented for augmenting ROS-induced oxidative damage for synergetic cancer therapy. CaO in the nanosystems is decomposed into O and HO in an acidic environment, which alleviates hypoxia and enhances the photodynamic therapy (PDT) effect. Calcium overload causes mitochondria dysfunction and induces apoptosis. Pt (IV) reacts with GSH to produce Pt (II) for chemotherapy and reduce the concentration of GSH, protecting ROS from scavenging for augmenting ROS-induced oxidative damage. In vitro and in vivo results demonstrated the self-generating oxygen and self-consuming GSH strategy can enhance ROS-dependent PDT coupled with ion/chemo synergistic therapy. The proposed strategy not only solves the long-term problem that hypoxia limits therapeutic effect of PDT, but also ameliorates the highly reducing environment of tumors. Thus the preparation of TAPPP@CaO/Pt(IV)/HA provided a novel strategy for the effective combined therapy of cancers.

Cetuximab (CTX) is an effective targeted drug for the treatment of metastatic colorectal cancer, but it is effective only in patients with wild-type KRAS genes. Even in this subset of patients, the sensitivity of CTX in patients with right hemi-colon cancer is much lower than that in patients with left hemi-colon cancer. This significantly limits its clinical application. Therefore, further elucidation of the underlying molecular mechanisms is needed. N-myc downstream-regulated gene 1 (NDRG1) plays an important role in solid tumor invasion and metastasis, but whether it can influence CTX sensitivity has not been thoroughly investigated.

Multifunctional green food packaging films were developed by incorporating Koelreuteria paniculata Laxm. bract extract (KBE) and bio-waste-derived Ti-doped carbon dots (Ti-CDs) into a chitosan/locust bean gum (CG) matrix for the first time. Results from FTIR and XRD demonstrated the precise bonding of Ti-CDs to CG through a Schiff base reaction and hydrogen bonding, while KBE was effectively immobilized within the film matrix via hydrogen bonding. SEM and TGA analysis demonstrated enhanced thermal stability and density of the films. Addition of Ti-CDs synergistically improved the barrier properties and mechanical strength of the films through enhanced hydrogen bonding and Schiff base reactions. Specifically, the incorporation of 3 wt% Ti-CDs increased the oxygen barrier properties, tensile strength, water resistance, and vapor permeability of CG films by approximately 1.18, 0.75, and 1.51 times, respectively. Furthermore, the antimicrobial and antioxidant capabilities were significantly improved with the addition of KBE to films. The CG-3%CDs-KBE film coating effectively prolonged the shelf life of strawberries. Additionally, these films exhibited superior pH responsiveness and ammonia-sensitivity, enabling visual monitoring of shrimp freshness during storage. Importantly, CG-3%CDs-KBE films exhibited biodegradability in soil and displayed good biosafety. Overall, these findings underscore the promising potential of CG-3%CDs-KBE films as multifunctional green food packaging materials.

This study aims to investigate the effect of electroacupuncture (EA) treatment on depression, and the potential molecular mechanism of EA in depression-like behaviors rats.

The use of nitrogen fertilizers is a crucial agronomic practice to increase crop output and quality. This study investigated the impact of five nitrogen application levels (0, 60, 135, 210, and 285 kg N/hm) on the physicochemical properties of foxtail millet (FM) starch. Optimal nitrogen application (210 kg N/hm) significantly increased L*, a*, and b* values, water and oil absorption capacity, water solubility, and swelling power. The number of small starch granules increased as the nitrogen application rate increased, but the granule morphology and typical A-type pattern did not change among the treatments. Nitrogen application increased the relative crystallinity and ordered structure, resulting in a higher gelatinization enthalpy. Compared to the control group (7.02 J/g), the enthalpy increased by 21.94 %, 66.38 %, 73.50 %, and 103.28 % under the nitrogen application rates, respectively. Moreover, nitrogen application greatly increased the percentage of A and B3 chains while it lowered the apparent amylose content, peak viscosity, and final viscosity. The effects of 210 and 285 kg N/hm treatments on the water solubility and swelling power, water and oil absorption, and light transmission of starch were greater compared to the 60 and 135 kg N/hm treatments. These results indicate that nitrogen fertilization significantly affects the physicochemical properties of FM starch.

Indole-3-acetic acid (IAA), a protein-bound uremic toxin, has been linked to cardiovascular morbidity and mortality in chronic kidney disease (CKD) patients. This study explores the influence of IAA (125mg/kg) on cardiovascular changes in adenine sulfate-induced CKD rats. HPLC analysis revealed that IAA-exposed CKD rats had lower excretion and increased circulation of IAA compared to both CKD and IAA control groups. Moreover, echocardiography indicated that CKD rats exposed to IAA exhibited heart enlargement, thickening of the myocardium, and cardiac hypertrophy in contrast to CKD or IAA control group. Biochemical analyses supported the finding that IAA-induced CKD rats had elevated serum levels of c-Tn-I, CK-MB, and LDH; there was also evidence of oxidative stress in cardiac tissues, with a significant decrease in SOD and CAT levels, as well as an increase in MDA levels. The gene expression analysis found significant increases in ANP, BNP, β-MHC, TNF-α, IL-1β, and NF-κB levels in IAA-exposed CKD groups in contrast to the CKD or IAA control group. In addition, higher cardiac fibrosis markers, including Col-I and Col-III. The findings of this study indicate that IAA could trigger cardiovascular fibrosis in CKD conditions.

Chronic wounds (CWs) treatment still represents a demanding medical challenge. Several intrinsic physiological signals (i.e., pH) help to stimulate and support wound healing. CWs, in fact, are characterized by a predominantly alkaline pH of the exudate, which acidifies as the wound heals. Therefore, pH-responsive wound dressings hold great potential owing to their capability of tuning their functions according to the wound conditions. Herein, porous chitosan (CS)-based scaffolds loaded with cellulose nanocrystals (CNCs) and graphene oxide (GO) were successfully fabricated using a freeze-drying method. CNCs were extracted from bagasse pulps fibers through acid hydrolysis. GO was synthesised by Hummer's method. The scaffolds were then ionically cross-linked using the amino acid L-Arginine (Arg), as a bioactive agent, and tested as potential pH-responsive wound dressing. Notably, the effect of CNCs and GO singly and simultaneously loaded within the CS-Arg scaffolds was investigated. The modulation of CNCs and GO content within CS-Arg scaffolds facilitated the development of scaffolds with an optimal pH-dependent swelling ratio capability and extended degradation time. Furthermore, CS/CNC/GO-Arg scaffolds exhibited tuned biological features, in terms of antimicrobial activity, cellular proliferation/migration ability, and the expression of extracellular matrix specific markers (i.e., elastin and collagen I) related to wound healing in human dermal fibroblasts.

Immune dysregulation can play a role in depression pathophysiology, and immunological antagonists can improve depressive symptoms in treatment-resistant bipolar depression (TRD) patients according to studies.

Lead is a common environmental pollutant which can accumulate in the kidney and cause renal injury. However, regulatory effects and mechanisms of Sparassis latifolia polysaccharide (SLP) on lipid metabolism abnormality in kidney exposed to lead are not clarified. In this study, mice were used to construct an animal model to observe the histopathological changes in kidney, measure lead content, damage indicators, differentially expressed metabolites (DEMs) and genes (DEGs) in key signaling pathways that cause lipid metabolism abnormalities based on lipidomics and transcriptomics, which were later validated using qPCR and western blotting. Co-treatment of Pb and N-acetylcysteine (NAC) were used to verify the link between SLP and oxidative stress. Our results indicated that treatment with SLP identified 276 DEMs (including metabolism of glycerophospholipid, sphingolipid, glycerolipid and fatty acid) and 177 DEGs (including genes related to oxidative stress, inflammation, autophagy and lipid metabolism). Notably, regulatory effects of SLP on abnormal lipid metabolism in kidney were mainly associated with oxidative stress, inflammation and autophagy; SLP could regulate abnormal lipid metabolism in kidney by reducing oxidative stress and affecting its downstream-regulated autophagy and inflammatory to alleviate renal injury caused by lead exposure. This study provides a theoretical basis for SLP intervention in lead injury.

We piloted the delivery of a prototype couples-focused intervention, 'Diabetes Together' with 14 people living with diabetes (PLWD) and their partners, in Cape Town, South Africa in 2022. We aimed to: assess feasibility of recruiting couples in this setting; explore acceptability of intervention materials and changes needed; and investigate whether our prespecified logic model captured how the intervention may work. We used questionnaires, interviews and focus groups after each workshop and after couples completed counselling. We conducted a process evaluation to identify intervention modifications and used inductive thematic analysis to explore whether the data supported our logic model. Twelve of the 14 couples completed the second workshop and 2 couples completed two counselling sessions post-workshop. Feedback showed participants appreciated the intervention and limited improvements were made. Thematic analysis identified four main themes: (1) involving partners matters; (2) group work supports solidarity with other couples; (3) improving communication between partners is crucial; and (4) taking part helped couples to take control of diabetes. Data suggested the logic model should explicitly acknowledge the importance of group education and of equalising partners' knowledge. This pilot suggests that 'Diabetes Together' increased knowledge and skills within couples and could facilitate improved, collaborative self-management of diabetes.

Focused ultrasound ablation surgery (FUAS) has been widely employed to treat patients with uterine fibroid (UF). This study aimed to estimate myometrial stiffness changes in patients who received FUAS for UFs or myomectomy (ME) and compare the recovery of surrounding myometrium between FUAS and ME groups. Our results may provide more evidence for guiding the proper conception timing in patients with UF.