Synthesis of 2,4-dihydroxyacetophenone derivatives as potent PDE-1 and -3 inhibitors: in vitro and in silico insights.

Aim: Synthesis of novel bis-Schiff bases having potent inhibitory activity against phosphodiesterase (PDE-1 and -3) enzymes, potentially offering therapeutic implications for various conditions. Methods: Bis-Schiff bases were synthesized by refluxing 2,4-dihydroxyacetophenone with hydrazine hydrate, followed by treatment of substituted aldehydes with the resulting hydrazone to obtain the product compounds. After structural confirmation, the compounds were screened for their in vitro PDE-1 and -3 inhibitory activities. Results: The prepared compounds exhibited noteworthy inhibitory efficacy against PDE-1 and -3 enzymes by comparing with suramin standard. To clarify the binding interactions between the drugs, PDE-1 and -3 active sites, molecular docking studies were carried out. Conclusion: The potent compounds discovered in this study may be good candidates for drug development.

[Box: see text].

Halogen Bond Unlocks Ultra-High Birefringence.

Anisotropy is crucial for birefringence (Δn) in optical materials, but optimizing it remains a formidable challenge (Δn > 0.3). Supramolecular frameworks incorporating π-conjugated components are promising for achieving enhanced birefringence since their structural diversity and inherent anisotropy. Herein, we first synthesized (C6H6NO2)+Cl- (NAC). And then constructed a halogen bonded supramolecular framework I+(C6H4NO2)- (INA) by halogen aliovalent substitution of Cl- with I+. The organic moieties are protonated and deprotonated nicotinic acid (NA), respectively. The antiparallel arrangement of birefringent-active units in NAC and INA leads to significant differences in bonding characteristics between interlayer and intralayer domains. Moreover, [O···I+···N] halogen bond in 1D [I+(C6H4NO2)-] chain exhibits stronger interactions and stricter directionality, resulting in a more pronounced in-plane anisotropy between the intrachain and interchain directions. Consequently, INA exhibits exceptional birefringent performance, with a value of 0.778 at 550 nm, twice that of NAC (0.363 at 550 nm). This value significantly exceeds those of commercial birefringent crystals, such as CaCO3 (0.172 at 546 nm), and is the highest reported value among ultraviolet birefringent crystals. This work presents a novel design strategy that employs halogen bonds as connection sites and modes for birefringent-active units, opening new avenues for developing high-performance birefringent crystals.

Association between bedtime and female infertility: a secondary analysis from a cross-sectional study.

Objective: To evaluate the association between bedtime and infertility and to identify the optimal bedtime for women of reproductive age. Methods: We conducted a cross-sectional study using data from 3,903 female participants in the National Health and Nutrition Examination Survey (NHANES) from 2015 to 2020. The effect of bedtime on female infertility was assessed using the binary logistic regression in different models, including crude model and adjusted models. To identify the non-linear correlation between bedtime and infertility, generalized additive models (GAM) were utilized. Subgroup analyses were conducted by age, body mass index (BMI), waist circumference, physical activity total time, marital status, smoking status, drinking status and sleep duration. Results: After adjusting for potential confounders (age, race, sleep duration, waist circumference, marital status, education, BMI, smoking status, drinking status and physical activity total time), a non-linear relationship was observed between bedtime and infertility, with the inflection point at 22:45. To the left side of the inflection point, no significant association was detected. However, to the right of it, bedtime was positively related to the infertility (OR: 1.22; 95% CI: 1.06 to 1.39; P = 0.0049). Subgroup analyses showed that late sleepers with higher BMI were more prone to infertility than those with a lower BMI (BMI: 25-30 kg/m2: OR: 1.26; 95% CI: 1.06 to 1.51; P = 0.0136; BMI ≥ 30 kg/m²: OR: 1.21, 95% CI: 1.09 to 1.34; P = 0.0014). Conclusion: Bedtime was non-linearly associated with infertility, which may provide guidance for sleep behavior in women of childbearing age.

Effect of teacher-student relationship on academic engagement: the mediating roles of perceived social support and academic pressure.

Although previous research has established that a strong teacher-student relationship can enhance students' academic engagement, the mechanisms underlying this effect remain less explored. Therefore, this study examined the mediating roles of perceived social support and academic pressure in the association between teacher-student relationship and academic engagement. A survey involving 1,058 Chinese university students was conducted, with teacher-student relationship, perceived social support, academic pressure, and academic engagement being the evaluated factors. The results of structural equation modeling revealed that (a) teacher-student relationship directly and positively associated academic engagement, (b) teacher-student relationship indirectly and positively associated academic engagement through perceived social support, and (c) teacher-student relationship indirectly and positively associated academic engagement through both perceived social support and academic pressure. These results indicate that perceived social support and academic pressure are the primary factors mediating the effect of teacher-student relationship on academic engagement among university students.

A hybrid evaluation of the intestinal absorption performance of compounds from molecular structure.

Intestinal absorption of compounds is significant in drug research and development. To evaluate this efficiently, a method combining mathematical modeling and molecular simulation was proposed, from the perspective of molecular structure. Based on the quantitative structure-property relationship study, the model between molecular structure and their apparent permeability coefficients was successfully constructed and verified, predicting intestinal absorption of drugs and interpreting decisive structural factors, such as AlogP98, Hydrogen bond donor and Ellipsoidal volume. The molecules with strong lipophilicity, less hydrogen bond donors and receptors, and small molecular volume are more easily absorbed. Then, the molecular dynamics simulation and molecular docking were utilized to study the mechanism of differences in intestinal absorption of drugs and investigate the role of molecular structure. Results indicated that molecules with strong lipophilicity and small volume interacted with the membrane at a lower energy and were easier to penetrate the membrane. Likewise, they had weaker interaction with P-glycoprotein and were easier to escape from it and harder to export from the body. More in, less out, is the main reason these molecules absorb well.

A proposed novel digital condylar position adjustment technique to help restore a normal disc-condyle relationship.

Objectives: To demonstrate a novel digital technique that enables real-time visualisation of occlusal transfer and adjustment of condyle position, to (1) improve the repeatability of occlusal transfer and the accuracy of condyle position adjustment and (2) be clinically effective in helping to restore the disc-condyle relationship. Materials and methods: Three participants were included in the study and underwent facebow transfers using two different methods. The digital method used patient-related three-dimensional imaging data matched with digital dental casts for occlusal transfer. The conventional method used anatomical facebows. The condylar position was adjusted based on occlusal transfer results. The results were evaluated and compared in three dimensions. In addition, clinical application data from 36 patients were analysed before and after condylar position adjustment. Statistical significance was set at p < 0.05. Results: Differences in the spatial positions of the three anatomical structures reproduced by both methods were statistically significant (p = 0.000). After adjusting the rotation of the condylar position, the positional deviation of the condylar point along the X- and Z-axes was significantly lower in the digital group (p < 0.05). After adjustment for translation (X and Z), the positional deviation showed no difference along the X- and Z-axes (p > 0.05) but a significant difference along the Y-axis (p < 0.001). Conclusion: A novel digital technique for occlusal transfer and condylar position adjustment was presented. This technique simplifies clinical practice, improves the accuracy of results, and can help restore a normal disc-condyle relationship.

Causal association between immune cells and lung cancer risk: a two-sample bidirectional Mendelian randomization analysis.

Background: Previous studies have highlighted the crucial role of immune cells in lung cancer development; however, the direct link between immunophenotypes and lung cancer remains underexplored. Methods: We applied two-sample Mendelian randomization (MR) analysis, using genetic variants as instruments to determine the causal influence of exposures on outcomes. This method, unlike traditional randomized controlled trials (RCTs), leverages genetic variants inherited randomly at conception, thus reducing confounding and preventing reverse causation. Our analysis involved three genome-wide association studies to assess the causal impact of 731 immune cell signatures on lung cancer using genetic instrumental variables (IVs). We initially used the standard inverse variance weighted (IVW) method and further validated our findings with three supplementary MR techniques (MR-Egger, weighted median, and MR-PRESSO) to ensure robustness. We also conducted MR-Egger intercept and Cochran's Q tests to assess heterogeneity and pleiotropy. Additionally, reverse MR analysis was performed to explore potential causality between lung cancer subtypes and identified immunophenotypes, using R software for all statistical calculations. Results: Our MR analysis identified 106 immune signatures significantly associated with lung cancer. Notably, we found five suggestive associations across all sensitivity tests (P<0.05): CD25 on IgD- CD24- cells in small cell lung carcinoma (ORIVW =0.885; 95% CI: 0.798-0.983; P IVW =0.022); CD27 on IgD+ CD24+ cells in lung squamous cell carcinoma (ORIVW =1.054; 95% CI: 1.010-1.100; P IVW =0.015); CCR2 on monocyte cells in lung squamous cell carcinoma (ORIVW =0.941; 95% CI: 0.898-0.987; P IVW =0.012); CD123 on CD62L+ plasmacytoid dendritic cells (ORIVW =0.958; 95% CI: 0.924-0.992; P IVW =0.017) as well as on plasmacytoid dendritic cells (ORIVW =0.958; 95% CI: 0.924-0.992; P IVW =0.017) in lung squamous cell carcinoma. Conclusion: This study establishes a significant genomic link between immune cells and lung cancer, providing a robust basis for future clinical research aimed at lung cancer management.

Bridging the gap: exploring the causal relationship between metformin and tumors.

Objective: Numerous studies have reported that metformin can reduce the risk of tumor development. However, some of the results of these studies are conflicting, necessitating a more reliable evaluation. Methods: We conducted a Mendelian randomization phenome-wide association study (MR-PheWAS) of tumors to explore the causal relationship between metformin and tumors. Two cohorts of patients taking metformin were obtained from the UK Biobank. Complete phenotype data of the tumors were obtained from FinnGen_R10. We elucidated the causal relationship using a two-sample Mendelian randomization (MR) analysis. More importantly, we conducted a meta-analysis to ensure relatively unbiased results. In the MR analysis, we used the inverse-variance weighted (IVW) method as the main outcome indicator. Subsequently, two cohorts were integrated for the meta-analysis. Finally, we investigated the mechanisms through mediational MR analysis. Results: MR analysis revealed that metformin might have a causal relationship with 13 tumor-associated phenotypes in the training cohort. Four phenotypes were validated in the testing cohort. In the training and testing cohorts, metformin exhibited a protective effect against brain meningiomas and malignant neoplasms of the breast (HER-positive), oral cavity, tonsils, and the base of the tongue. Intriguingly, after integrating the results of the two cohorts for the meta-analysis, 12 results were statistically significant. Mediational MR analysis suggested that the effects of metformin on brain meningiomas may be weakened by the presence of the family Oxalobacteraceae. Conclusion: Metformin exhibits potential preventive and therapeutic effects on four types of tumors: brain meningioma, malignant neoplasms of the breast (HER-positive), oral cavity and tonsils, and the base of the tongue. Large randomized controlled trials are required to confirm these findings.

Packing in multimodal crystals and particle assemblies as models for dynamic packing during spontaneous and enforced particle movement: Settling, viscosity and elasticity.

Colloid particles (CP, 10-8-10-6 m = 10-1000 nm) are used as models for atom scale processes, such as crystallization since the process is experimentally observable. Packing of atoms in crystals resemble mono-, bi-, and trimodal packing of noncharged hard spheres (particles). When the size of one particle exceeds the two others an excluded volume consisting of small particles is created around large particles. This is also the case when colloid particles are dispersed in water. The formation of an excluded volume does not require attraction forces, but it is enforced by the presence of dissolved primary (cations) and secondary (protons of surface hydroxyls) potential determining ions. The outcome is an interfacial solid-liquid charge. This excluded volume, denoted Stern layer is characterized by the surface potential and charge density. Charge neutrality is identified by point of zero charge (pHpzc and pcpzc). Outside Stern layer another excluded volume is formed of loosely bound counterions which interact with Stern layer. The extent of this diffuse layer is given by inverse Debye length and effective ζ-potential. The overall balance between attractive and repulsive energies is provided by Derjaguin-Landau-Veerwey-Overbeek (DLVO) model. Charge neutrality is identified at isoelectric point (pHiep and pciep). The dependence of viscosity and yield stress on shear rate may be modeled by von Smoluchowski's volumetric collision frequency multiplied by some total interaction energy given by DLVO model. Equilibrium and dynamic models for settling and enforced particle movement (viscosity) are presented. Both compressive yield stress (sedimentation) and cohesive energy (viscoelasticity) are characterized by power law exponents of volume fraction. The transition of disperse suspensions (sols) to spanning clusters (gels) is identified by oscillatory rheology. The slope of linear plots of logarithmic storage (G´) and loss (G") moduli against logarithm of frequency or logarithm of volume fraction provide power law exponents from the slopes. These exponents relate to percolation and fractal dimensions characterizing the particle network. Moreover, it identifies the structure formation process either as diffusion limited cluster-cluster (DLCCA) or as reaction limited cluster-cluster (RLCCA) aggregation.

Extraction, purification, structural characterization, and bioactivities of the genus Rhodiola L. polysaccharides: A review.

The genus Rhodiola L., an integral part of traditional Chinese medicine and Tibetan medicine in China, exhibits a broad spectrum of applications. This genus contains key compounds such as ginsenosides, polysaccharides, and flavonoids, which possess anti-inflammatory, antioxidant, hypoglycaemic, immune-enhancing, and anti-hypoxic properties. As a vital raw material, Rhodiola L. contributes to twenty-four kinds of Chinese patent medicines and 481 health food products in China, finding extensive application in the health food sector. Recently, polysaccharides have emerged as a focal point in natural product research, with applications spanning the medicine, food, and materials sectors. Despite this, a comprehensive and systematic review of polysaccharides from the genus Rhodiola L. polysaccharides (TGRPs) is warranted. This study undertakes a systematic review of both domestic and international literature, assessing the research advancements and chemical functional values of polysaccharides derived from Rhodiola rosea. It involves the isolation, purification, and identification of a variety of homogeneous polysaccharides, followed by a detailed analysis of their chemical structures, pharmacological activities, and molecular mechanisms, structure-activity relationship (SAR) of TGRPs. The discussion includes the influence of molecular weight, monosaccharide composition, and glycosidic bonds on their biological activities, such as sulfation and carboxymethylation et al. Such analyses are crucial for deepening the understanding of Rhodiola rosea and for fostering the development and exploitation of TGRPs, offering a reference point for further investigations into TGRPs and their resource utilization.

PET/CT-Based Absorbed Dose Maps in 90Y Selective Internal Radiation Therapy Correlate with Spatial Changes in Liver Function Derived from Dynamic MRI.

Functional liver parenchyma can be damaged from treatment of liver malignancies with 90Y selective internal radiation therapy (SIRT). Evaluating functional parenchymal changes and developing an absorbed dose (AD)-toxicity model can assist the clinical management of patients receiving SIRT. We aimed to determine whether there is a correlation between 90Y PET AD voxel maps and spatial changes in the nontumoral liver (NTL) function derived from dynamic gadoxetic acid-enhanced MRI before and after SIRT. Methods: Dynamic gadoxetic acid-enhanced MRI scans were acquired before and after treatment for 11 patients undergoing 90Y SIRT. Gadoxetic acid uptake rate (k1) maps that directly quantify spatial liver parenchymal function were generated from MRI data. Voxel-based AD maps, derived from the 90Y PET/CT scans, were binned according to AD. Pre- and post-SIRT k1 maps were coregistered to the AD map. Absolute and percentage k1 loss in each bin was calculated as a measure of loss of liver function, and Spearman correlation coefficients between k1 loss and AD were evaluated for each patient. Average k1 loss over the patients was fit to a 3-parameter logistic function based on AD. Patients were further stratified into subgroups based on lesion type, baseline albumin-bilirubin scores and alanine transaminase levels, dose-volume effect, and number of SIRT treatments. Results: Significant positive correlations (ρ = 0.53-0.99, P < 0.001) between both absolute and percentage k1 loss and AD were observed in most patients (8/11). The average k1 loss over 9 patients also exhibited a significant strong correlation with AD (ρ ≥ 0.92, P < 0.001). The average percentage k1 loss of patients across AD bins was 28%, with a logistic function model demonstrating about a 25% k1 loss at about 100 Gy. Analysis between patient subgroups demonstrated that k1 loss was greater among patients with hepatocellular carcinoma, higher alanine transaminase levels, larger fractional volumes of NTL receiving an AD of 70 Gy or more, and sequential SIRT treatments. Conclusion: Novel application of multimodality imaging demonstrated a correlation between 90Y SIRT AD and spatial functional liver parenchymal degradation, indicating that a higher AD is associated with a larger loss of local hepatocyte function. With the developed response models, PET-derived AD maps can potentially be used prospectively to identify localized damage in liver and to enhance treatment strategies.

Synthesis, biological activities, and structure-activity relationships of Morita-Baylis-Hillman adducts: An update.

The Morita-Baylis-Hillman (MBH) reaction is a unique C-C bond-forming technique for the generation of multifunctional allylic alcohols (MBH adducts) in a single operation. In recent years, these MBH adducts have emerged as a novel class of compounds with significant biological potential, including anticancer, anti-leishmanial, antibacterial, antifungal, anti-herbicidal effects and activity against Chagas disease, and so on. The aim of this review is to assimilate the literature findings from 2011 onwards related to the synthesis and biological potential of MBH adducts, with an emphasis on their structure-activity relationships (SAR). Although insight into the biological mechanisms of action for this recently identified pharmacophore is currently in its nascent stages, the mechanisms described so far are reviewed herein.

The causal relationship between sleep and risk of psychiatric disorders: A two-sample mendelian randomization study.

Introduction: Sleep is associated with psychiatric disorders. However, their causality remains unknown. Methods: The study explored the causal relationship between seven sleep parameters (sleep duration, insomnia, sleep apnea, chronotype, daytime dozing, napping during the day, and snoring) and three psychiatric disorders including major depressive disorder (MDD), schizophrenia, and attention-deficit/hyperactivity disorder (ADHD) using two-sample Mendelian randomization (MR). Genome-wide association study (GWAS) summary data for sleep parameters were obtained from the United Kingdom biobank, FinnGen biobank, and EBI databases. MR-Egger, weighted median, inverse-variance weighted (IVW), simple mode, weighted mode, maximum likelihood, penalized weighted median, and IVW(fixed effects) were used to perform the MR analysis. The heterogeneity was detected by Cochran's Q statistic. The horizontal pleiotropy was detected by MR Egger. The sensitivity was investigated by the leave-one-out analysis. Results: Insomnia (OR = 2.02, 95%CI = 1.34-3.03, p = 0.001, False-discovery rate (FDR) corrected p-value = 0.011) and napping during the day (OR = 1.81, 95%CI = 1.34-2.44, FDR corrected p-value<0.001) were associated with an increased risk of MDD. Longer sleep duration (OR = 2.20, 95%CI = 1.24-3.90, FDR corrected p-value = 0.049) had an association with the increased risk of schizophrenia, while daytime dozing (OR = 4.44, 95%CI = 1.20-16.41, corrected p-value = 0.088)and napping during the day (OR = 2.11, 95%CI = 1.11-4.02, FDR corrected p-value = 0.088) had a suggestive association with an increased risk of schizophrenia. Longer sleep duration had a suggestive association with a decreased risk of ADHD (OR = 0.66, 95%CI = 0.42-0.93, FDR corrected p-value = 0.088). Conclusion: This study provides further evidence for a complex relationship between sleep and psychiatric disorders. Our findings highlight the potential benefits of addressing sleep problems in the prevention of psychiatric disorders.

Personalized evaluation of the passive myocardium in ischemic cardiomyopathy via computational modeling using Bayesian optimization.

Biomechanics-based patient-specific modeling is a promising approach that has proved invaluable for its clinical potential to assess the adversities caused by ischemic heart disease (IHD). In the present study, we propose a framework to find the passive material properties of the myocardium and the unloaded shape of cardiac ventricles simultaneously in patients diagnosed with ischemic cardiomyopathy (ICM). This was achieved by minimizing the difference between the simulated and the target end-diastolic pressure-volume relationships (EDPVRs) using black-box Bayesian optimization, based on the finite element analysis (FEA). End-diastolic (ED) biventricular geometry and the location of the ischemia were determined from cardiac magnetic resonance (CMR) imaging. We employed our pipeline to model the cardiac ventricles of three patients aged between 57 and 66 years, with and without the inclusion of valves. An excellent agreement between the simulated and the target EDPVRs has been reached. Our results revealed that the incorporation of valvular springs typically leads to lower hyperelastic parameters for both healthy and ischemic myocardium, as well as a higher fiber Green strain in the viable regions compared to models without valvular stiffness. Furthermore, the addition of valve-related effects did not result in significant changes in myofiber stress after optimization. We concluded that more accurate results could be obtained when cardiac valves were considered in modeling ventricles. The present novel and practical methodology paves the way for developing digital twins of ischemic cardiac ventricles, providing a non-invasive assessment for designing optimal personalized therapies in precision medicine.

Impact Analysis of COVID-19 Pandemic on Hospital Reviews on Dianping Website in Shanghai, China: Empirical Study.

BACKGROUND: In the era of the internet, individuals have increasingly accustomed themselves to gathering necessary information and expressing their opinions on public web-based platforms. The health care sector is no exception, as these comments, to a certain extent, influence people's health care decisions. During the onset of the COVID-19 pandemic, how the medical experience of Chinese patients and their evaluations of hospitals have changed remains to be studied. Therefore, we plan to collect patient medical visit data from the internet to reflect the current status of medical relationships under specific circumstances. OBJECTIVE: This study aims to explore the differences in patient comments across various stages (during, before, and after) of the COVID-19 pandemic, as well as among different types of hospitals (children's hospitals, maternity hospitals, and tumor hospitals). Additionally, by leveraging ChatGPT (OpenAI), the study categorizes the elements of negative hospital evaluations. An analysis is conducted on the acquired data, and potential solutions that could improve patient satisfaction are proposed. This study is intended to assist hospital managers in providing a better experience for patients who are seeking care amid an emergent public health crisis. METHODS: Selecting the top 50 comprehensive hospitals nationwide and the top specialized hospitals (children's hospitals, tumor hospitals, and maternity hospitals), we collected patient reviews from these hospitals on the Dianping website. Using ChatGPT, we classified the content of negative reviews. Additionally, we conducted statistical analysis using SPSS (IBM Corp) to examine the scoring and composition of negative evaluations. RESULTS: A total of 30,317 pieces of effective comment information were collected from January 1, 2018, to August 15, 2023, including 7696 pieces of negative comment information. Manual inspection results indicated that ChatGPT had an accuracy rate of 92.05%. The F1-score was 0.914. The analysis of this data revealed a significant correlation between the comments and ratings received by hospitals during the pandemic. Overall, there was a significant increase in average comment scores during the outbreak (P<.001). Furthermore, there were notable differences in the composition of negative comments among different types of hospitals (P<.001). Children's hospitals received sensitive feedback regarding waiting times and treatment effectiveness, while patients at maternity hospitals showed a greater concern for the attitude of health care providers. Patients at tumor hospitals expressed a desire for timely examinations and treatments, especially during the pandemic period. CONCLUSIONS: The COVID-19 pandemic had some association with patient comment scores. There were variations in the scores and content of comments among different types of specialized hospitals. Using ChatGPT to analyze patient comment content represents an innovative approach for statistically assessing factors contributing to patient dissatisfaction. The findings of this study could provide valuable insights for hospital administrators to foster more harmonious physician-patient relationships and enhance hospital performance during public health emergencies.

Surface Carbon Formation and its Impact on Methane Dry Reforming Kinetics on Rhodium-based Catalysts by Operando Raman Spectroscopy.

A mechanism for carbon deposition and its impact on the reaction kinetics of Methane Dry Reforming (MDR) using Rhodium-based catalysts is presented. By integrating Raman spectroscopy with kinetic analysis in an operando-annular chemical reactor under strict chemical conditions, we discovered that carbon deposition on a Rh/α-Al2O3 catalyst follows a nucleation-growth mechanism. The dynamics of carbon aggregates at the surface is found to be ruled by the CO2/CH4 ratio and the inlet CH4 concentration. The findings elucidate the spatiotemporal development of carbon aggregates on the catalyst surface and their effects on catalytic performance. Furthermore, the proposed mechanism for carbon formation shows that the influence of CO2 on MDR kinetics is an indirect result of carbon accumulation over time frames exceeding the turnover frequency, thus reconciling conflicting reports in the literature regarding CO2's kinetic role in MDR.

A Potential Role for MAGI-1 in the Bi-Directional Relationship Between Major Depressive Disorder and Cardiovascular Disease.

PURPOSE OF REVIEW: Major Depressive Disorder (MDD) is characterized by persistent symptoms such as fatigue, loss of interest in activities, feelings of sadness and worthlessness. MDD often coexist with cardiovascular disease (CVD), yet the precise link between these conditions remains unclear. This review explores factors underlying the development of MDD and CVD, including genetic, epigenetic, platelet activation, inflammation, hypothalamic-pituitary-adrenal (HPA) axis activation, endothelial cell (EC) dysfunction, and blood-brain barrier (BBB) disruption. RECENT FINDINGS: Single nucleotide polymorphisms (SNPs) in the membrane-associated guanylate kinase WW and PDZ domain-containing protein 1 (MAGI-1) are associated with neuroticism and psychiatric disorders including MDD. SNPs in MAGI-1 are also linked to chronic inflammatory disorders such as spontaneous glomerulosclerosis, celiac disease, ulcerative colitis, and Crohn's disease. Increased MAGI-1 expression has been observed in colonic epithelial samples from Crohn's disease and ulcerative colitis patients. MAGI-1 also plays a role in regulating EC activation and atherogenesis in mice and is essential for Influenza A virus (IAV) infection, endoplasmic reticulum stress-induced EC apoptosis, and thrombin-induced EC permeability. Despite being understudied in human disease; evidence suggests that MAGI-1 may play a role in linking CVD and MDD. Therefore, further investigation of MAG-1 could be warranted to elucidate its potential involvement in these conditions.

Association between advanced lung cancer inflammation index and in-hospital mortality in ICU patients with community-acquired pneumonia: A retrospective analysis of the MIMIC-IV database.

Objective: The objective of the present study was to explore the correlation between the advanced lung cancer inflammation index (ALI) and in-hospital mortality among patients diagnosed with community-acquired pneumonia (CAP). Methods: Data from the Medical Information Mart for Intensive Care-IV database were adopted to analyze the in-hospital mortality of ICU patients with CAP. Upon admission to the ICU, fundamental data including vital signs, critical illness scores, comorbidities, and laboratory results, were collected. The in-hospital mortality of all CAP patients was documented. Multivariate logistic regression (MLR) models and restricted cubic spline (RCS) analysis together with subgroup analyses were conducted. Results: This study includes 311 CAP individuals, involving 218 survivors as well as 93 nonsurvivors. The participants had an average age of 63.57 years, and the females accounted for approximately 45.33%. The in-hospital mortality was documented to be 29.90%. MLR analysis found that ALI was identified as an independent predictor for in-hospital mortality among patients with CAP solely in the Q1 group with ALI ≤ 39.38 (HR: 2.227, 95% CI: 1.026-4.831, P = 0.043). RCS analysis showed a nonlinear relationship between the ALI and in-hospital mortality, with a turning point at 81, and on the left side of the inflection point, a negative correlation was observed between ALI and in-hospital mortality (HR: 0.984, 95% CI: 0.975-0.994, P = 0.002). The subgroup with high blood pressure showed significant interaction with the ALI. Conclusion: The present study demonstrated a nonlinear correlation of the ALI with in-hospital mortality among individuals with CAP. Additional confirmation of these findings requires conducting larger prospective investigations.

The causality between leisure sedentary behaviors, physical activity and obstructive sleep apnea: a bidirectional Mendelian randomization study.

Background: Previous observational studies have shown a correlation between leisure sedentary behaviors (LSB) and physical activity (PA) with the incidence of obstructive sleep apnea (OSA). However, the causal associations remain unknown. Therefore, our study used bidirectional two-sample Mendelian randomization (MR) to identify potential causal relationships between LSB/PA and OSA. Methods: We sourced genetic variation data for LSB and PA from the UK Biobank, while data on OSA were collected from the FinnGen study. The primary analysis method employed was the inverse variance weighted (IVW) approach, complemented by the weighted median and MR-Egger methods. For sensitivity analyses, we conducted Cochran's Q test, the MR-Egger intercept test, the MR-PRESSO global test, and the leave-one-out analysis. Results: IVW analyses showed that genetically predicted leisure television watching (odds ratio [OR] = 1.38, 95% confidence interval [CI] = 1.09-1.75, p = 0.007) and computer use (OR = 1.48, 95% CI = 1.15-1.92, p = 0.002) significantly increased the risk of OSA. Conversely, self-reported vigorous physical activity (VPA) (OR = 0.33, 95% CI = 0.11-0.98, p = 0.046) may reduce the risk of OSA. No causal effects on OSA risk were observed for driving or self-reported moderate-to-vigorous physical activity. Furthermore, the reverse MR analysis indicated no significant causal relationship between OSA and any LSB/PA phenotype. Sensitivity tests showed no significant heterogeneity or horizontal pleiotropy. Conclusion: This study suggests that leisurely television watching and computer use are risk factors for OSA, while VPA may be a protective factor. Additionally, OSA does not affect PA or LSB levels. We recommend reducing sedentary activities, particularly television watching and computer use, and prioritizing VPA to reduce the risk of OSA. Further research in diverse populations and settings is needed to validate these findings.

Trust and quality of life: A study in organizations for individuals with intellectual disability.

BACKGROUND: Based on social exchange within organizations for individuals with intellectual disability, we explore trust between supervisors and team members and its association with organizational performance oriented to the quality of life of service users. AIMS: We examine the mediating role of teams' trust in supervisors in the relationship between supervisors' trust in teams and performance focused on improving the quality of life of service users. We expect teams to reciprocate supervisors' trust by reporting greater levels of trust in supervisors and better performance. METHOD AND PROCEDURES: We tested this trust-mediated model with a sample of 139 supervisors (reporting trust in their teams), 1101 team members (reporting trust in their supervisors), and 1468 family members (reporting performance focused on quality of life). OUTCOMES AND RESULTS: Our findings confirmed a cross-level mediation process. Supervisors' trust in their teams leads to teams' trust in their supervisors. This trust at the team level in turn is positively associated with organizational performance oriented to improving the quality of life of individuals with intellectual disability, reported by family members. CONCLUSIONS AND IMPLICATIONS: Our study builds on and extends an established stream of research on trust theory by considering trust and its association with performance focused on quality of life.