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Xianzhu Tu,1 Juanjuan Wang,2 Xuming Liu,3 Jiyong Zheng4 1Department of Psychiatry, Seventh People’s Hospital of Wenzhou City, Wenzhou, Zhejiang, People’s Republic of China; 2Department of Neurology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 3Department of Radiology, The Third Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou, Zhejiang, People’s Republic of China; 4Department of Medical Imaging, The Affiliated Huai’an No 1 People’s Hospital of Nanjing Medical University, Huai’an, Jiangsu, People’s Republic of China Objective: Whether moderate alcohol consumption has health benefits remains controversial, but the harmful effects of excessive alcohol consumption on behavior and brain function are well recognized. The aim of this study was to investigate alcohol-induced regional brain activities and their relationships with behavioral factors. Subjects and methods: A total of 29 alcohol-dependent subjects (9 females and 20 males) and 29 status-matched healthy controls (11 females and 18 males) were recruited. Severity of alcohol dependence questionnaire (SADQ) and alcohol use disorders identification test (AUDIT) were used to evaluate the severity of alcohol craving. Regional homogeneity (ReHo) analysis was used to explore the alcohol-induced regional brain changes. Receiver operating characteristic (ROC) curve was used to investigate the ability of regional brain activities to distinguish alcohol-dependent subjects from healthy controls. Pearson correlations were used to investigate the relationships between alcohol-induced ReHo differences and behavioral factors. Results: Alcohol-dependent subjects related to healthy controls showed higher ReHo areas in the right superior frontal gyrus (SFG), bilateral medial frontal gyrus (MFG), left precentral gyrus (PG), bilateral middle temporal gyrus (MTG), and right inferior temporal gyrus (ITG) and lower ReHo areas in the right cerebellum posterior lobe (CPL), left rectal gyrus (RG), and right cluster of pons and cerebellum anterior lobe (CAL). ROC curve revealed high area under the curve (AUC) values (mean ± SD: 0.864 ± 0.028; range: 0.828–0.911) of ReHo differences. Diagnostic analysis showed that these areas alone discriminated alcohol-dependent subjects from healthy controls with high degree of sensitivities (mean ± SD: 81.25% ± 11.49%; range: 62.5%–100%) and specificities (mean ± SD: 81.75% ± 12.36%; range: 67.5%–100%). Years of drink showed negative correlation with left RG (r = -0.493, p = 0.007), the same finding was shown between AUDIT and right CPL (r = -0.52, p = 0.004). Conclusion: Alcohol dependence is associated with aberrant regional activities in multiple brain areas. ReHo analysis may be a useful biological indicator for the detection of regional brain activities in individuals with alcohol dependence. Keywords: alcohol dependence, regional homogeneity, receiver operating characteristic

IntroductionThe population is heterogeneous with varying levels of healthcare needs. Clustering individuals into health segments with more homogeneous healthcare needs allows for better understanding and monitoring of health profiles in the population, which can support data-driven resource allocation.MethodsUsing the developed criteria, data from several of Singapore's national administrative datasets were used to classify individuals into the various health segments. Cross-sectional analysis of healthcare utilization charges was conducted. Validation was done for the framework's prognostic ability of clinically relevant outcomes measured in the following year.ResultsThe framework is comprised of twelve segments classed within four broad groups. The segments comprising individuals with cancer, with transitional care needs, and in the last year of their lives had the highest mean per resident healthcare charges. The segments comprising adults and seniors with complex chronic conditions and with transitional care needs had the highest percentage of individuals historically diagnosed with obesity. The framework was able to distinguish varying tiers of healthcare utilization charges and relative risk of death in the following year.DiscussionThe framework was developed using a hybrid approach, with expert input and comprehensive national data that extended beyond the usual hospital patient population. The framework can be directly applied for use in program or policy design, evaluation, and cost-effectiveness analyses.ConclusionThe HealthSCOPES framework was developed to segment the entire population in Singapore with similar healthcare needs.

Summary: Background: The COVID-19 pandemic impacted mental health disorders, affecting both individuals with pre-existing conditions and those with no prior history. However, there is limited evidence regarding the pandemic's impact on mental health visits to primary care physicians. The International Consortium of Primary Care Big Data Researchers (INTRePID) explored primary care visit trends related to mental health conditions in Argentina, Australia, Canada, China, Norway, Peru, Singapore, Sweden, and the USA. Methods: We conducted an interrupted time series analysis in nine countries to examine changes in rates of monthly mental health visits to primary care settings from January 1st, 2018, to December 31st, 2021. Sub-group analysis considered service type (in-person/virtual) and six categories of mental health conditions (anxiety/depression, bipolar/schizophrenia/other psychotic disorders, sleep disorders, dementia, ADHD/eating disorders, and substance use disorder). Findings: Mental health visit rates increased after the onset of the pandemic in most countries. In Argentina, Canada, China, Norway, Peru, and Singapore, this increase was immediate ranged from an incidence rate ratio of 1·118 [95% CI 1.053–1.187] to 2.240 [95% CI 2.057–2.439] when comparing the first month of pandemic with the pre-pandemic trend. Increases in the following months varied across countries. Anxiety/depression was the leading reason for mental health visits in most countries. Virtual visits were reported in Australia, Canada, Norway, Peru, Sweden, and the USA, accounting for up to 40% of the total mental health visits. Interpretation: Findings suggest an overall increase in mental health visits, driven largely by anxiety/depression. During the COVID-19 pandemic, many of the studied countries adopted virtual care in particular for mental health visits. Primary care plays a crucial role in addressing mental ill-health in times of crisis. Funding: Canadian Institutes of Health Research grant #173094 and the Rathlyn Foundation Primary Care EMR Research and Discovery Fund.

Background/Aims Nonalcoholic fatty liver disease (NAFLD) is closely associated with diabetes. The cumulative impact of both diseases synergistically increases risk of adverse events. However, present population analysis is predominantly conducted with reference to non-NAFLD individuals and has not yet examined the impact of prediabetes. Hence, we sought to conduct a retrospective analysis on the impact of diabetic status in NAFLD patients, referencing non-diabetic NAFLD individuals. Methods Data from the National Health and Nutrition Examination Survey 1999–2018 was used. Hepatic steatosis was defined with United States Fatty Liver Index (US-FLI) and FLI at a cut-off of 30 and 60 respectively, in absence of substantial alcohol use. A multivariate generalized linear model was used for risk ratios of binary outcomes while survival analysis was conducted with Cox regression and Fine Gray model for competing risk. Results Of 32,234 patients, 28.92% were identified to have NAFLD. 36.04%, 38.32% and 25.63% were non-diabetic, prediabetic and diabetic respectively. Diabetic NAFLD significantly increased risk of cardiovascular disease (CVD), stroke, chronic kidney disease, all-cause and CVD mortality compared to non-diabetic NAFLD. However, prediabetic NAFLD only significantly increased the risk of CVD and did not result in a higher risk of mortality. Conclusions Given the increased risk of adverse outcomes, this study highlights the importance of regular diabetes screening in NAFLD and adoption of prompt lifestyle modifications to reduce disease progression. Facing high cardiovascular burden, prediabetic and diabetic NAFLD individuals can benefit from early cardiovascular referrals to reduce risk of CVD events and mortality.

Introduction Through the INTernational ConsoRtium of Primary Care BIg Data Researchers (INTRePID), we compared the pandemic impact on the volume of primary care visits and uptake of virtual care in Australia, Canada, China, Norway, Singapore, South Korea, Sweden, the UK and the USA.Methods Visit definitions were agreed on centrally, implemented locally across the various settings in INTRePID countries, and weekly visit counts were shared centrally for analysis. We evaluated the weekly rate of primary care physician visits during 2019 and 2020. Rate ratios (RRs) of total weekly visit volume and the proportion of weekly visits that were virtual in the pandemic period in 2020 compared with the same prepandemic period in 2019 were calculated.Results In 2019 and 2020, there were 80 889 386 primary care physician visits across INTRePID. During the pandemic, average weekly visit volume dropped in China, Singapore, South Korea, and the USA but was stable overall in Australia (RR 0.98 (95% CI 0.92 to 1.05, p=0.59)), Canada (RR 0.96 (95% CI 0.89 to 1.03, p=0.24)), Norway (RR 1.01 (95% CI 0.88 to 1.17, p=0.85)), Sweden (RR 0.91 (95% CI 0.79 to 1.06, p=0.22)) and the UK (RR 0.86 (95% CI 0.72 to 1.03, p=0.11)). In countries that had negligible virtual care prepandemic, the proportion of visits that were virtual were highest in Canada (77.0%) and Australia (41.8%). In Norway (RR 8.23 (95% CI 5.30 to 12.78, p

Objectives The COVID-19 outbreak in Singapore has largely centred around migrant worker dormitories, comprising over 90% of all cases in the country. Dormitories are home to a culturally and linguistically distinct, low-income population, without on-site healthcare after-hours. The primary objective of this study was to assess the engagement and utilisation of a simple, low-cost, accessible, mobile health solution for remote self-reporting of vital parameters in dormitory residents with COVID-19.Design Retrospective review of medical care.Setting Two large migrant worker dormitories with a combined population of 31 546.Participants All COVID-19-affected residents housed in dormitories during the study period.Intervention All residents were taught to use a chat assistant to self-report their temperature, heart rate and oxygen saturations. Results flowed into a dashboard, which alerted clinicians of abnormal results.Outcomes The primary outcome measure was engagement rate. This was derived from the total number of residents who registered on the platform over the total number of COVID-19-affected residents in the dormitories during the study period. Secondary outcome measures included outcomes of the alerts and subsequent escalations of care.Results 800 of the 931 COVID-19-affected residents (85.9%) engaged with the platform to log a total of 12 511 discrete episodes of vital signs. Among 372 abnormal readings, 96 teleconsultations were initiated, of which 7 (1.8%) were escalated to emergency services and 18 (4.9%) were triaged to earlier physical medical review on-site.Conclusions A chat-assistant-based self-reporting platform is an effective and safe community-based intervention to monitor marginalised populations with distinct cultural and linguistic backgrounds, living communally and affected by COVID-19. Lessons learnt from this approach may be applied to develop safe and cost-effective telemedicine solutions across similar settings.

Healthcare delivery is a highly complex, deeply personal and costly endeavour that involves multiple specialties and services. There is an imbalance in knowledge between the healthcare provider and consumer that may contribute to doubts and uncertainty over treatment and outcomes. It is unsurprising that conflict and dispute can develop between healthcare providers and patients and their next-of-kin. The use of mediation in the healthcare setting has recently been promoted in many developed countries, including Singapore. We administered a detailed 32-item survey in a large tertiary-care teaching hospital to improve our understanding of the knowledge, attitude and practice of dispute resolution among clinicians to pave the way for better strategies to improve the adoption of mediation in healthcare setting. Ninety-seven respondents had an average of 62% (SD: 12%) knowledge score. The most common misconceptions held by the respondents about mediation were: (1) mediation was about fact-finding, (2) mediation is limited to only certain types of dispute, (3) mediation proceeds by both parties giving their account of the dispute, then a third party decides a settlement, (4) the average time it takes to resolve a dispute through mediation, (5) the cost of mediation, (5) the venue of mediation, (6) the person determining the outcome of mediation, (7) confidentiality of mediation. In general, the respondents were positive about the use of mediation as a dispute resolution tool. When asked to indicate the relative importance of different outcomes of dispute resolution, financial compensation and waiver of hospital bill attracted mixed responses while understanding facts of dispute, assurance that the same error would not recur, and offering corrective treatment were rated as being important. By contrast, seeking an apology from the complainant was considered neutral to somewhat important and the respondents were least concerned with the publicity of the dispute. Direct negotiation with the complainant was considered the most time- and cost-efficient means of resolving a dispute while the opposite was true for litigation. Mediation was considered the approach where the clinicians are most likely to achieve their desired outcome while litigation was considered least likely to produce a favourable outcome. Approximately half of the respondents reported having personal experience or known of a colleague who had been involved in a medico-legal dispute. A quarter of these cases were resolved by direct negotiations with the complainant while lawyers, the judge and mediation, resolved approximately 15% each, respectively. The knowledge base of the clinicians in this study about mediation was moderate and probably reflected the general lack of direct experience in the resolution of a dispute or training in mediation. This further corroborated with the general response that the uptake of mediation in the healthcare setting is currently poor in Singapore due to the lack of awareness and perceived lack of avenue among the surveyed clinicians. Any further work to be done with clinicians may be in the direction of (1) increasing general understanding of mediation, (2) increasing awareness of avenues for mediation, and (3) becoming better aware of when to propose mediation.

[This corrects the article DOI: 10.1371/journal.pone.0199885.].

Background: The S100 protein family comprises 22 members whose protein sequences encompass at least one EF-hand Ca2+ binding motif. They were involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. However, the expression status of S100 family members in gastric cancer was not known yet.Methods: Combined with analysis of series analysis of gene expression, virtual Northern blot and microarray data, the expression levels of S100 family members in normal and malignant stomach tissues were systematically investigated. The expression of S100A3 was further evaluated by quantitative RT-PCR.Results: At least 5 S100 genes were found to be upregulated in gastric cancer by in silico analysis. Among them, four genes, including S100A2, S100A4, S100A7 and S100A10, were reported to overexpressed in gastric cancer previously. The expression of S100A3 in eighty patients of gastric cancer was further examined. The results showed that the mean expression levels of S100A3 in gastric cancer tissues were 2.5 times as high as in adjacent non-tumorous tissues. S100A3 expression was correlated with tumor differentiation and TNM (Tumor-Node-Metastasis) stage of gastric cancer, which was relatively highly expressed in poorly differentiated and advanced gastric cancer tissues (P < 0.05).Conclusion: To our knowledge this is the first report of systematic evaluation of S100 gene expressions in gastric cancers by multiple in silico analysis. The results indicated that overexpression of S100 gene family members were characteristics of gastric cancers and S100A3 might play important roles in differentiation and progression of gastric cancer. [ABSTRACT FROM AUTHOR]

In recent decades, polymeric graphitic carbon nitride (g-C 3 N 4 ) has garnered significant attention as a class of metal-free semiconductor photocatalysts. However, inherent limitations such as inadequate visible light absorption, low specific surface area, moderate charge transfer efficiency, and poor crystallinity restrict its application. To address the constraints, three novel donor-acceptor type covalent heptazine frameworks (CHFs) are constructed through a bottom-up approach by intergrating heptazine and triazine, which are the fundamental active moieties of g-C 3 N 4 , with diverse donor spacers. Compared to g-C 3 N 4 , noteworthy enhancements in photocatalytic activity and hydrogen evolution efficiency are attributed to the increased specific surface areas, broadened visible-light absorption, and accelerated photogenerated charge transfer within the CHFs. Notably, high crystallinity shows a profound influence on the photocatalytic efficiency of the synthesized CHFs. Among the CHFs, highly crystalline CHF-3 stands out to present the highest hydrogen evolution rate of 15284 µmol g -1  h -1 under visible-light irradiation (420-780 nm) with ascorbic acid as the hole sacrificial agent. This remarkable achievement represents a 144-fold improvement over g-C 3 N 4 and a noteworthy sevenfold enhancement compared to the low-crystalline CHF-3. These results not only offer valuable insights for the design of efficient heptazine-based CHF photocatalysts but also contribute toward the advancement of heptazine-based functional materials., (© 2025 Wiley‐VCH GmbH.)

The limited replicability of retention data hinders its application in untargeted metabolomics for small molecule identification. While retention order models hold promise in addressing this issue, their predictive reliability is limited by uncertain generalizability. Here, we present the ROASMI model, which enables reliable prediction of retention order within a well-defined application domain by coupling data-driven molecular representation and mechanistic insights. The generalizability of ROASMI is proven by 71 independent reversed-phase liquid chromatography (RPLC) datasets. The application of ROASMI to four real-world datasets demonstrates its advantages in distinguishing coexisting isomers with similar fragmentation patterns and in annotating detection peaks without informative spectra. ROASMI is flexible enough to be retrained with user-defined reference sets and is compatible with other MS/MS scorers, making further improvements in small-molecule identification., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: The incremental prognostic value of integrating myocardial cine radiomics into predictive models for major adverse cardiovascular events (MACE) risk in patients with ST-elevation myocardial infarction (STEMI) is unclear., Purpose: To determine if myocardial cine radiomics can improve risk assessment for MACE when combined with clinical information and cardiac MRI parameters in STEMI patients., Study Type: Retrospective., Subjects: One thousand twenty-four STEMI patients (83% male; mean age 59 ± 11 years) from two centers, divided into training (819 patients) and external testing (205 patients) cohorts., Field Strength/sequence: 3.0 T/balanced steady-state free precession cine, and phase-sensitive inversion recovery sequences., Assessment: The Rad&#95;score was calculated as a weighted sum of independent radiomic variables derived from the logistic regression model, providing a concise representation of their combined prognostic impact. Six risk models were developed, incorporating varying combinations of MRI parameters, clinical variables, and Rad&#95;score to comprehensively evaluate their prognostic performance. A final risk stratification, integrating left ventricular ejection fraction (LVEF), the extent of late gadolinium enhancement (LGE), and Rad&#95;score, was established and compared with one based on LVEF alone., Statistical Tests: The prognostic implications of the Rad&#95;score were evaluated using univariable and multivariable Cox proportional hazards models. A P value <0.05 was considered significant., Results: During a median follow-up of 3.1 years, 139 patients (17%) in the training set and 30 patients (15%) in the testing set experienced MACE. Rad&#95;score was identified as a significant risk factor for MACE, with a hazard ratio of 1.46 (1.38-1.55) (P < 0.01) in univariate Cox analysis. The risk stratification reclassified the risk for 33% of the study population in the training set and 34% in the testing set., Data Conclusion: Myocardial cine radiomics are associated with MACE risk in STEMI patients and provide incremental improvement in risk stratification when combined with traditional parameters., Plain Language Summary: The development of radiomics has introduced new perspectives in both the diagnosis and prognosis of cardiovascular diseases. However, the incremental prognostic value of incorporating myocardial cine radiomics into predictive models for major adverse cardiovascular events (MACE) risk in patients with ST-elevation myocardial infarction (STEMI) remains unclear. This study integrates radiomics with traditional clinical parameters and cardiac magnetic resonance imaging (MRI) to evaluate its added value in assessing MACE risk in STEMI patients. The results demonstrate that radiomics is significantly associated with MACE and provides incremental value in risk stratification. These findings offer a novel approach to improve personalized risk assessment, making it a valuable addition to the cardiovascular field., Evidence Level: 4 TECHNICAL EFFICACY: Stage 5., (© 2025 International Society for Magnetic Resonance in Medicine.)

Ethnopharmacological Relevance: Alzheimer's disease (AD) is a common type of neurodegenerative disease with the β-amyloid plaques (Aβ) deposition. Previously, Dengzhan Shengmai capsule (DZSM) has been shown to reduce the pathology associated with AD, but the underlying mechanism is unclear., Aim of Study: This study investigated the potential mechanisms of DZSM against AD., Materials and Methods: The six-month-old wild-type male mice and APP/PS1 double transgenic male mice were administered 0.9 % saline or DZSM for 8 weeks by gavage. Open field test, new object recognition test, and Morris Water maze test were used to assess spatial learning and memory. Aβ plaques in brains were visualized using ThT staining. Nissl staining, TUNEL staining, and Western blot analyses were used to detect the neuronal function and apoptosis level. The superoxide dismutase (SOD), glutathione peroxidase assay kit (GSH-Px), and malondialdehyde (MDA) kits were performed to assess oxidative stress levels. Then, immunofluorescence and Western blot analysis were applied to evaluate ER stress pathway protein levels. Finally, HT22 cells were treated by Aβ 1-42 with or without DZSM medicated serum. Cell viability was assessed using the CCK-8 assay, and Western blot analysis was applied to evaluate ER stress pathway protein levels., Results: Open filed test, new object recognition test and Morris Water maze test showed that DZSM restored cognitive disorders in APP/PS1 mice. Immunohistochemistry and Thioflavin T staining results indicated that DZSM reduced Aβ plaques in the brain. Deeper and denser Nissl bodies were found in APP/PS1 mice after DZSM administration. Besides, APP/PS1 mice treated with DZSM showed a lower level of TUNEL and Bax/Bcl-2 ratio. DZSM improved the acetylcholine (ACh), choline acetyltransferase (ChAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activity while reducing acetylcholinesterase (AChE) and malondialdehyde (MDA) activity. In addition, the levels of ER stress pathway containing Phospho-PKR-like ER kinase (P-PERK), phosphorylate eukaryotic initiation factor 2 (P-eIF2α), activating transcription factor 4 (ATF4), glutamine-rich protein 1 (QRICH1), phosphorylate inositol-requiring protein 1α (P-IRE1α), the spliced form of X-box binding protein 1 (XBP1s), activating transcription factor-6 (ATF6) and C/EBP homologous binding protein (CHOP) were decreased by DZSM. CCK-8 results indicated that DZSM medicated serum played cytoprotective effects on Aβ 1-42 -induced HT22 cells. Western blot results suggested DZSM possibly inhibited ER stress pathways in Aβ 1-42 -induced HT22 cells., Conclusion: The potential protective mechanism of DZSM on cognitive impairment in AD might be related to ER stress pathways., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Trimethylamine (TMA) metabolism comprises choline-containing compounds' metabolization, TMA production and trimethylamine N-oxide (TMAO) generation. However, the presence of numerous compounds in the carnitine and phosphatidylcholine (PC) pool compositions complicates profiling work significantly. This study is aimed at developing an efficient method for profiling TMA metabolic pathways, including quantifying known compounds and semi-quantifying the differential metabolites in the carnitine and PC pool compositions. Pseudo-targeted metabolomics is applicable for characterization. Firstly, multivariate statistics were performed to identify valuable metabolites (variable importance in the projection ＞1) from quality control biological samples. Given that TMA metabolism involved in host-gut microbiota interaction, co-metabolites were defined as the intersections of valuable metabolites from different biological samples (serum, liver, and intestinal contents) and further screened. Finally, alterations in TMA metabolism were observed in dextran sulfate sodium-induced colitis, with semi-quantitative analysis for excavated co-metabolites including 11 PCs, 6 lyso-phosphatidylcholines, and 2 acylcarnitines and quantitative analysis for 10 known metabolites. The findings revealed increased TMA production and accumulation of choline-containing compounds in the gut during ulcerative colitis exacerbation. Correspondingly, the circulating level of TMAO was elevated in the colitis group. A comprehensive understanding of TMA metabolism can contribute to disease differential diagnoses and potential mechanism studies., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interest., (Copyright © 2025. Published by Elsevier B.V.)

Aim: The aim of this study was to explore the relationship between epicardial adipose tissue (EAT), paracardial adipose tissue (PaAT), pericardial adipose tissue (PeAT), and fat ratio with left ventricular (LV) involvement, assessing the prognostic significance of cardiac fat in arrhythmogenic right ventricular cardiomyopathy (ARVC)., Materials and Methods: Ninety-two ARVC patients (mean age: 45.74 years; 63% male) were included and followed up for 92 months. Measured in cardiac magnetic resonance imaging (MRI) cine views, EAT, PaAT, PeAT, and fat ratio (EAT/PaAT) were analyzed to identify the association with major adverse cardiac events (MACEs) (sudden cardiovascular death, aborted cardiac arrest, heart failure hospitalization, and sustained documented ventricular tachycardia)., Results: Among the 92 participants, 28 (30.43%) MACEs occurred during the follow-up. Significantly higher EAT, PaAT, PeAT, and fat ratio were observed in patients with LV involvement than in those without (p = 0.001, p = 0.002, p = 0.001, p = 0.003, respectively) in violin plots. A worse prognosis in ARVC patients was associated with a higher volume of EAT (log rank p = 0.0031). In multivariate Cox regression analysis, EAT (Hazard Ratio [HR]: 1.056, 95% confidence interval [CI]: 1.011-1.103, p = 0.013) and 5-year risk score (HR: 1.018, 95% CI: 1.002-1.034, p = 0.030) were identified as independent prognostic predictors for MACEs. Additional prognostic information over conventional outcome predictors was provided by EAT (Uno C-statistics: 0.645 vs. 0.665, p = 0.007)., Conclusion: higher cardiac fat volume was found to be correlated with LV involvement. Independent risk factors for MACEs in ARVC were identified as EAT and 5-year risk score, and the incremental prognostic value to established predictors in ARVC was provided by EAT., (Copyright © 2024. Published by Elsevier Ltd.)

Aim: Identifying high-risk hypertrophic cardiomyopathy (HCM) patients for heart failure (HF) is a challenge. Previous studies noted left atrial (LA) abnormalities in HCM patients, but the predictive value of LA strain and strain rate for HF in those with left ventricular ejection fraction (LVEF) ≥ 50% remains unclear. Our study aimed to explore if LA strain and strain rate predict HF-related outcomes in HCM patients with LVEF ≥ 50%., Materials and Methods: In this retrospective study, 284 patients aged 51 (range 40-62), 68% male, were studied. 34 experienced HF-related outcomes including death to HF, NYHA III-IV class progression, and HF worsening leading to hospitalization. LA strain and rate were analyzed using cardiac magnetic resonance (CMR) feature tracking technique. ROC curves, Kaplan-Meier curves, violin plot, LASSO analysis, forest plot, and Cox regression were used. The strength of the association was represented as HR∗, where HR∗ is defined as hazard ratio (HR) when the HR > 1 and as 1/HR when HR < 1., Results: After adjusting for the NYHA classification and the extent of LV-LGE, the booster strain (HR∗: 1.094; 95% CI: 0.845-0.989; p = 0.026) and booster strain rate (HR∗: 2.593; 95% CI: 1.369-4.910; p = 0.003) were significantly associated with HF-related events. Reservoir strain, conduit strain, and their respective strain rates did not emerge as independent predictors for HF-related outcomes., Conclusion: LA booster strain and strain rate showed a stronger association with HF-related outcomes, highlighting significant functional changes in the LA. Identifying these parameters as key predictors underscores their importance in managing particularly in HCM patients with LVEF ≥ 50%., (Copyright © 2024 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Hydrogen production via electrocatalytic water splitting has garnered significant attention, due to the growing demand for clean and renewable energy. However, achieving low overpotential and long-term stability of water splitting catalysts at high current densities remains a major challenge. Herein, a CoP@CoNi layered double hydroxide (LDH) electrode was synthesized via a two-step electrodeposition process, demonstrating oxygen evolution reaction, with an overpotential (ƞ 400 ) of 373 mV and a Tafel slope of 64.2 mV/dec. Subsequently, a superhydrophilic CoP@CoNi LDH-Pt electrode was prepared using an in situ oxidation method, with Pt clusters anchored within the CoP@CoNi LDH for the hydrogen evolution reaction, with an overpotential (ƞ 400 ) of 119 mV and a Tafel slope of 33.6 mV/dec. The CoP@CoNi LDH-Pt||CoP@CoNi LDH system achieved a cell voltage of 1.96 V at 1000 mA/cm 2 , maintaining stable performance after water electrolysis for 160 h. These remarkable outcomes stem from the fast charge transfer, improved mass transfer, and superior stability of the catalysts. Heterostructure electrodes were constructed to optimize the electrocatalytic kinetics through strong interfacial electronic interactions, while superhydrophilic electrodes were fabricated to improve the mass transfer process at a high current density. Anchoring high-activity components in catalysts prevents their detachment during water electrolysis, enhancing the structural stability of the electrodes. This study provides a new approach for large-scale preparation of efficient water electrolysis catalysts and offers significant potential for industrial hydrogen production applications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Inc. All rights reserved.)

Alternative splicing (AS) plays crucial post-transcriptional gene function regulation roles in eukaryotic. Despite progress in studying AS at the RNA level, existing methods for AS event identification face challenges such as inefficiency, lengthy processing times, and limitations in capturing the complexity of RNA sequences. To overcome these challenges, we evaluated 10 AS detection tools and selected rMATS for dataset construction. We then developed a multi-scale convolutional and Transformer-based model (MCTASmRNA) to classify AS events in mRNA sequences without relying on a reference genome. To handle the problem of large intra-class and small inter-class difference in AS event sequences, we incorporated an efficient channel attention mechanism and designed a new joint loss function to optimize MCTASmRNA training. MCTASmRNA outperformed baseline models, with an accuracy improvement and exhibited enhanced cross-species generalizability. This model provides valuable support for AS research across different organisms. Future work will focus on optimizing and expanding the model to further explore the complex mechanisms underlying AS., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Background: Cognitive impairment induced by a high-fat diet (HFD) is common, but its mechanism is largely unknown. Huang-Lian-Jie-Du (HLJD) decoction is a classical and powerful prescription in China. It consists of four medicinal plants and is widely used in traditional Chinese medicines (TCM). Studies have shown that HLJD decoction is effective in treating obesity, depression, and so on. However, the therapeutic mechanism of HLJD is still poorly understood., Purpose: Our study aimed to explore whether inflammatory factors and Trem2/Dap12/Syk pathway are involved in this process and whether HLJD treatment can repair cognitive impairment in HFD-induced obesity., Methods: To obtain the obese mice, male mice were treated with HFD (60 Kcal% fat) for 16 weeks. After an additional eight weeks, HLJD decoction was administered orally at doses of 4 and 8 g/kg daily for eight weeks. The mice were then subjected to four behavior tests. Aβ42, total Tau, inflammatory-related, and microglial dysregulation-related markers expression were measured. Molecular docking analysis was also conducted to predict the interaction of the chemical constituents of HLJD with human TREM2, DAP12, and SYK. HLJD at doses of 12.5, 25, and 50 µg/mL or limonin at concentrations of 12.5, 25, and 50 µM were used to treat BV2 cells for 24 h. CCK8 assay and Trem2, Dap12, Syk, and p-Syk expression were measured., Results: Our study revealed that cognitive impairment was evident in mice treated with HFD, indicating the impact of obesity on cognitive function. The expression of Aβ42 and total Tau in the hippocampus (HIP) was significantly higher in obese (HFD-V) mice compared to normal control (NC-V) mice. The Il6, Il1b, and Il10 mRNA expression levels were also markedly increased in the HIP of obese mice. Furthermore, Trem2, Dap12, p-Syk, and Iba1 expression were elevated in the HIP of obese mice. Importantly, HLJD treatment was found to repair cognitive impairment and lower the protein expression of Aβ42, Tau, Trem2, Dap12, p-Syk, and the expression of Il6, Il1b, and Il10 mRNA in HIP of HFD-V mice. The increased expression of Trem2, Dap12, p-Syk, and Iba1 in HIP after HFD consumption could be reduced after receiving HLJD decoction. The compound Limonin showed a well-predicted binding energy with TREM2, DAP12, and SYK. BV2 cells with HLJD or limonin detected the mRNA expressions of Trem2/Dap12. HLJD at 25 and 50 µg/mL decreased Trem2, Dap12, and p-Syk protein levels in BV2 cells., Conclusion: These results reveal that HLJD treatment could alleviate cognitive impairment in HFD-induced obese mice by controlling the activation of the Trem2/Dap12 pathway and reducing Syk phosphorylation in HIP microglia. HLJD and limonin suppressed Trem2/Dap12/Syk signaling pathway in BV2 cells. HLJD therapy might represent a novel treatment for patients with cognitive impairment induced by obesity., Competing Interests: Declaration of competing interest All the authors declare that this research involves no potential commercial or financial relationships and no conflict of interest., (Copyright © 2024. Published by Elsevier GmbH.)

In our previous research, we reported that administering probiotics Lactobacillus reuteri and Clostridium butyricum (LCs) before cisplatin treatment effectively modifies structures of the gut microbiota and restore ecological balance and significantly increases butyrate levels, a process closely associated with reducing cisplatin-induced nephrotoxicity. This study aims to investigate further whether the elevation of metabolite butyrate in the gut, promoted by probiotics LCs, can effectively mitigate the nephrotoxic effects of cisplatin and the progression of renal senescence in rats. Results show that butyrate administration significantly improved kidney function and decreased renal fibrosis in a dose-dependent manner compared to the cisplatin group. Its effects were associated with reductions in inflammatory responses, evidenced by decreased levels of key inflammatory markers, including KIM-1, MPO, NOX2, F4/80, and TGF-β1, alongside increased production of the anti-inflammatory cytokine IL-10. Furthermore, the butyrate intervention ameliorated cisplatin-induced gut microbiota dysbiosis, preserving the structure and diversity of healthy microbial communities. Specifically, we observed a decrease in the abundance of Escherichia&#95;Shigella and Blautia, alongside an increase in the abundance of the butyrate-producing genus Roseburia. Notably, Escherichia&#95;Shigella exhibited a positive correlation with the pro-inflammatory factor MPO, while displaying a negative correlation with the anti-inflammatory cytokine IL-10. Butyrate also attenuated the cisplatin-induced expression of senescence markers p21 and p16 in kidney tissue. It alleviated the cisplatin-increased senescence-associated beta-galactosidase activity and reactive oxygen species production in SV40 MES-13 cells. These results indicate that butyrate, derived from the gut microbiota, may exert a protective effect against cisplatin-induced kidney damage by regulating microbiota balance and anti-inflammatory effects., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Olfactory dysfunction is increasingly recognized as an early indicator of Alzheimer's disease (AD). Aberrations in GABAergic function and the excitatory/inhibitory (E/I) balance within the olfactory bulb (OB) have been implicated in olfactory impairment during the initial stages of AD. While the neuregulin 1 (NRG1)/ErbB4 signaling pathway is known to regulate GABAergic transmission in the brain and is associated with various neuropsychiatric disorders, its specific role in early AD-related olfactory impairment remains incompletely understood. This study demonstrated that olfactory dysfunction preceded cognitive decline in young adult APP/PS1 mice and was characterized by reduced levels of NRG1 and ErbB4 in the OB. Further investigation revealed that deletion of ErbB4 in parvalbumin interneurons reduced GABAergic transmission and increased hyperexcitability in mitral and tufted cells (M/Ts) in the OB, thereby accelerating olfactory dysfunction in young adult APP/PS1 mice. Additionally, ErbB4 deficiency was associated with increased accumulation of Aβ and BACE1-mediated cleavage of APP, along with enhanced CDK5 signaling in the OB. NRG1 infusion into the OB was found to enhance GABAergic transmission in M/Ts and alleviate olfactory dysfunction in young adult APP/PS1 mice. These findings underscore the critical role of NRG1/ErbB4 signaling in regulating GABAergic transmission and E/I balance within the OB, contributing to olfactory impairment in young adult APP/PS1 mice, and provide novel insights for early intervention strategies in AD. This work has shown that ErbB4 deficiency increased the burden of Aβ, impaired GABAergic transmission, and disrupted the E/I balance of mitral and tufted cells (M/Ts) in the OB, ultimately resulting in olfactory dysfunction in young adult APP/PS1 mice. NRG1 could enhance GABAergic transmission, rescue E/I imbalance in M/Ts, and alleviate olfactory dysfunction in young adult APP/PS1 mice. OB: olfactory bulb, E/I: excitation/inhibition, Pr: probability of release, PV: parvalbumin interneurons, Aβ: β-amyloid, GABA: gamma-aminobutyric acid., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Mitochondrial complex activity controls a multitude of physiological processes by regulating the cellular metabolism. Current methods for evaluating mitochondrial complex activity mainly focus on single metabolic reactions within mitochondria. These methods often require fresh samples in large quantities for mitochondria purification or intact mitochondrial membranes for real-time monitoring. Confronting these limitations, we shifted the analytical perspective toward interactive metabolic networks at the whole-cell level to reflect mitochondrial complex activity. To this end, we compiled a panel of mitochondrial respiratory chain-mapped metabolites (MRCMs), whose perturbations theoretically provide an overall reflection on mitochondrial complex activity. By introducing N-dimethyl-p-phenylenediamine and N -methyl-p-phenylenediamine as a pair of mass spectrometry probes, an ultraperformance liquid chromatography-tandem mass spectrometry method with high sensitivity (LLOQ as low as 0.2 fmol) was developed to obtain accurate quantitative data of MRCMs. Machine learning was then combined to capture the relationship between MRCMs and mitochondrial complex activity. Using Complex I as a proof-of-concept, we identified NADH, alanine, and phosphoenolpyruvate as metabolites associated with Complex I activity based on the whole-cell level. The effectiveness of using their concentrations to reflect Complex I activity was further validated in external data sets. Hence, by capturing the relationship between metabolites and mitochondrial complex activity at the whole-cell level, this study explores a novel analytical paradigm for the interrogation of mitochondrial complex activity, offering a favorable complement to existing methods particularly when sample quantities, type, and treatment timeliness pose challenges. More importantly, it shifts the focus from individual metabolic reactions within mitochondria to a more comprehensive view of an interactive metabolic network, which should serve as a promising direction for future research into the functional architecture between mitochondrial complexes and metabolites.

Background: Arrhythmogenic cardiomyopathy (ACM) is characterized by progressive myocardial fibro-fatty infiltration accompanied by trabecular disarray. Traditionally, two-dimensional (2D) instead of 3D fractal dimension (FD) analysis has been used to evaluate trabecular disarray. However, the prognostic value of trabecular disorder assessed by 3D FD measurement remains unclear., Purpose: To investigate the prognostic value of right ventricular trabecular complexity in ACM patients using 3D FD analysis based on cardiac MR cine images., Study Type: Retrospective., Population: 85 ACM patients (mean age: 45 ± 17 years, 52 male)., Field Strength/sequence: 3.0T/cine imaging, T2-short tau inversion recovery (T2-STIR), and late gadolinium enhancement (LGE)., Assessment: Using cine images, RV (right ventricular) volumetric and functional parameters were obtained. RV trabecular complexity was measured with 3D fractal analysis by box-counting method to calculate 3D-FD. Cox and logistic regression models were established to evaluate the prognostic value of 3D-FD for major adverse cardiac events (MACE)., Statistical Tests: Cox regression and logistic regression to explore the prognostic value of 3D-FD. C-index, time-dependent receiver operating characteristic (ROC) curves and area under the ROC curve (AUC) to evaluate the incremental value of 3D-FD. Intraclass correlation coefficient for interobserver variability. P < 0.05 indicated statistical significance., Results: 26 MACE were recorded during the 60 month follow-up (interquartile range: 48-67 months). RV 3D-FD significantly differed between ACM patients with MACE (2.67, interquartile range: 2.51 ~ 2.81) and without (2.52, interquartile range: 2.40 ~ 2.67) and was a significant independent risk factor for MACE (hazard ratio, 1.02; 95% confidence interval: 1.01, 1.04). In addition, prognostic model fitness was significantly improved after adding 3D-FD to RV global longitudinal strain, LV involvement, and 5-year risk score separately., Data Conclusion: The myocardial trabecular complexity assessed through 3D FD analysis was found associated with MACE and provided incremental prognostic value beyond conventional ACM risk factors., Evidence Level: 4 TECHNICAL EFFICACY: Stage 1., (© 2024 International Society for Magnetic Resonance in Medicine.)

Radiation injury to the intestine is one of the most common complications in patients undergoing abdominal or pelvic cavity radiotherapy, limiting the clinical application of this treatment. Evidence shows the potential benefits of dietary restriction in improving metabolic profiles and age-related diseases. The present study investigated the effects and mechanisms of dietary restriction in radiation-induced intestinal injury. The mice were randomly divided into the control group, 10 Gy total abdominal irradiation (TAI) group, and groups pretreated with 30% caloric restriction (CR) for 7 days or 24 h fasting before TAI. After radiation, the mice were returned to ad libitum. The mice were sacrificed 3.5 days after radiation, and tissue samples were collected. CR and fasting reduced radiation-induced intestinal damage and promoted intestinal recovery by restoring the shortened colon length, improving the impaired intestinal structure and permeability, and remodeling gut microbial structure. CR and fasting also significantly reduced mitochondrial damage and DNA damage, which in turn reduced activation of the cyclic GMP-AMP synthase/stimulator of interferon gene (cGAS/STING) pathway and the production of type I interferon and other chemokines in the jejunum. Since the cGAS/STING pathway is linked with innate immunity, we further showed that CR and fasting induced polarization to immunosuppressive M2 macrophage, decreased CD8 + cytotoxic T lymphocytes, and downregulated proinflammatory factors in the jejunum. Our findings indicated that CR and fasting alleviate radiation-induced intestinal damage by reducing cGAS/STING-mediated harmful immune responses., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cerebral ischemia reperfusion injury is a severe neurological impairment that occurs after blood flow reconstruction in stroke, and microglia cell pyroptosis is one of its important mechanisms. Electroacupuncture has been shown to be effective in mitigating and alleviating cerebral ischemia reperfusion injury by inhibiting neuroinflammation, reducing cellular pyroptosis, and improving neurological function. In this experiment, we divided the rats into three groups, including the sham operation (Sham) group, the middle cerebral artery occlusion/reperfusion (MCAO/R) group, and the pre-electroacupuncture (EAC) group. Pre-electroacupuncture group was stimulated with electroacupuncture of a certain intensity on the Baihui (GV 20) and Dazhui (GV 14) of the rat once a day from the 7th day to the 1st day before the MCAO/R operation. The extent of cerebral infarction was detected by TTC staining. A modified Zea-Longa five-point scale scoring system was used to determine neurologic function in MCAO rats. The number of neurons and morphological changes were accessed by Nissl staining and HE staining. The cellular damage was detected by TUNEL staining. In addition, the expression levels of RhoA, pyrin, GSDMD, Caspase1, cleaved-Caspase1, Iba-1, CD206, and ROCK2 were examined by western blotting and immunofluorescence. The results found that pre-electroacupuncture significantly attenuated neurological impairment and cerebral infarction compared to the post-MCAO/R rats. In addition, pre-electroacupuncture therapy promoted polarization of microglia to the neuroprotective (M2) phenotype. In addition, pre-electroacupuncture inhibited microglia pyroptosis by inhibiting RhoA/pyrin/GSDMD signaling pathway, thereby reducing neuronal injury and increasing neuronal survival in the MCAO/R rats. Taken together, these results demonstrated that pre-acupuncture could attenuate cerebral ischemia-reperfusion injury by inhibiting microglial pyroptosis. Therefore, pre-electroacupuncture might be a potential preventive strategy for ischemic stroke patients., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ethnopharmacological Relevance: Taohong Siwu Decoction (TSD), a classic traditional Chinese medicine formula, is used for the treatment of vascular diseases, including vascular dementia (VD). However, the mechanisms remain unclear., Aim of Study: This study aimed to investigate whether TSD has a positive effect on cognitive impairment in VD rats and to confirm that the mechanism of action is related to the Endoplasmic Reticulum stress (ERs) and cell apoptosis signaling pathway., Materials and Methods: A total of 40 male adult Sprague-Dawley rats were divided into four groups: sham-operated group (Sham), the two-vessel occlusion group (2VO), the 2VO treated with 4.5 g/kg/d TSD group (2VO + TSD-L), the 2VO treated with 13.5 g/kg/d TSD group (2VO + TSD-H). The rats underwent either 2VO surgery or sham surgery. Postoperative TSD treatment was given for 4 consecutive weeks. Behavioral tests were initiated at the end of gastrulation. Open-field test (OFT) was used to detect the activity level. The New Object Recognition test (NOR) was used to test long-term memory. The Morris water maze (MWM) test was used to examine the foundation of spatial learning and memory. As a final step, the hippocampus was taken for molecular testing. The protein levels of GRP78 (Bip), p-PERK, PERK, IRE1α, p-IRE1α, ATF6, eIF2α, p-eIF2α, ATF4, XBP1, Bcl-2 and Bax were determined by Western blot. Immunofluorescence visualizes molecular expression., Results: In the OFT, residence time in the central area was significantly longer in both TSD treatment groups compared to the 2VO group. In the NOR, the recognition index was obviously elevated in both TSD treatment groups. The 2VO group had a significantly longer escape latency and fewer times in crossing the location of the platform compared with the Sham group in MWM. TSD treatment reversed this notion. Pathologically, staining observations confirmed that TSD inhibited hippocampal neuronal loss and alleviated the abnormal reduction of the Nissl body. In parallel, TUNEL staining illustrated that TSD decelerated neuronal apoptosis. Western Blot demonstrated that TSD reduces the expression of ERs and apoptotic proteins., Conclusion: In this study, the significant ameliorative effect on cognitive impairment of TSD has been determined by comparing the behavioral data of the 4 groups of rats. Furthermore, it was confirmed that this effect of TSD was achieved by suppressing the ERs-mediated apoptosis signaling pathway., Competing Interests: Declaration of Competing interest There is no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Diquat poisoning is a fatal condition that is becoming increasingly common. The mortality risk of patients taking lethal doses of diquat is extremely high. It typically leads to rapid dysfunction of multiple organs, including the kidneys, heart, lungs, and brain. Acute kidney injury is usually the first manifestation of this poisoning. However, the optimal treatment strategy for diquat poisoning remains uncertain. Additionally, the mechanism of multiple organ dysfunction syndrome caused by diquat poisoning may resemble the progression of sepsis. In this report, we present 3 cases of diquat poisoning, all of which resulted in death. We emphasize that acute kidney injury is the primary cause of death, and suggest that some strategies used in the treatment of sepsis could be beneficial in managing diquat poisoning-induced acute kidney injury., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Microplastics (MPs) pose significant concerns for marine ecological security due to their minuteness and ubiquity. However, comprehensive knowledge on their distribution and fate in seawater columns remains limited. This study investigated the abundances and characteristics of MPs across 3-6 water layers in the South Yellow Sea and East China Sea. Results indicate that high-abundance small MPs (< 100 µm) (average 6567 items/m 3 ) were hidden beneath the sea-surface, predominantly fine-grained particles (< 20 µm) and high-density polymers (> 1.03 g/cm 3 ). The total suspended MPs (5.0-834.2 µm) are estimated at 2.9-3.1 × 10 17 particles, with most of them occurring in upper layers. In profiles, their distribution varied by physical properties with depth; fragment-shaped and high-density MPs increased in proportion at greater depths, contrasting with fibrous MPs. These MPs originated primarily from the Yangtze River and their winter transport was driven by the Yangtze River Dilution Water, East China Sea Coastal Current, and Yellow Sea Warm Current, resulting in their accumulation in coastal and estuarine regions. Consequently, the Yangtze River Estuary ecosystem faces substantial risks from MP pollution throughout the water column. This work unveils the prevalence of small MPs in coastal water columns and intricate interaction between their fate and hydrodynamic conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aims to reveal the effects and mechanisms of different fractions of Polygonati Rhizoma on the reproductive dysfunction in male mice with kidney essence deficiency due to excess of sexual intercourse. Fifty male ICR mice with good sexual function were selected and randomized into normal(NC), model(MC), n-butanol fraction of Polygonati Rhizoma(0.4 g·kg~(-1), HJCT), remaining fraction of Polygonati Rhizoma(0.4 g·kg~(-1), HJSY), and ultra-micro powder of Polygonati Rhizoma(1.0 g·kg~(-1), HJCW) groups. The Coolidge effect was used to induce excess of sexual intercourse in the mice, and a mouse model of reproductive dysfunction with kidney essence deficiency was established. The mice were administrated with corresponding drugs at the same time of modeling for 8 consecutive weeks. The anal temperature, grip strength, locomotor activities, weight-bearing swimming time, and sexual behaviors(catching, straddling, and ejaculation) were measured. Enzyme-linked immunosorbent assay was employed to measure the levels of testosterone(T), luteinizing hormone(LH), follicle-stimulating hormone(FSH), cortisol(COR), gonadotropin-releasing hormone(GnRH), and estradiol(E&#95;2) in the serum and the content of fructose in seminal plasma. Hematoxylin-eosin(HE) staining was employed to observe the pathological changes in the testicular tissue. The sperm quality was evaluated based on the density, viability, survival rate, and deformation rate of sperms. Western blot was employed to determine the expression of proteins involved in proliferation and apoptosis in the testicular tissue. The results showed that HJCT, HJSY, and HJCW significantly increased the grip strength, anal temperature, locomotor activities, weight-bearing swimming time, and sexual behaviors, elevated the serum levels of T, LH, GnRH, and E&#95;2, lowered the levels of COR and FSH, and increased the wet weight of the testicular tissue in the model mice. In addition, they increased the density, viability, and survival and reduced the deformation rate of sperms, increased the content of fructose in the seminal plasma, alleviated the pathological changes and inhibited apoptosis in the testicular tissue in the model mice. HJCT was superior to HJSY and HJCW in ameliorating the hypothalamic-pituitary-gonadal axis(HPGA) disorder, enhancing sexual behaviors, and improving sperm quality. HJCW outperformed HJCT and HJSY in inhibiting apoptosis in the testicular tissue. In conclusion, HJCT, HJSY, and HJCW can improve the reproductive function and inhibit apoptosis in the testicular tissue of the male mice with kidney essence deficiency by ameliorating the HPGA disorder.

Introduction: Ulcerative colitis, a subtype of chronic inflammatory bowel disease (IBD), is characterized by relapsing colonic inflammation and ulcers. The traditional Chinese herbal formulation Huang Lian Jie Du (HLJD) decoction is used clinically to treat diarrhea and colitis. However, the mechanisms associated with the effects of treatment remain unclear. This study aims to elucidate the molecular mechanistic effects of HLJD formulation on colitis., Methods: Chronic colitis in mice was induced by adding 1% dextran sulfate sodium (DSS) to their drinking water continuously for 8 weeks, and HLJD decoction at the doses of 2 and 4 g/kg was administered orally to mice daily from the second week until experimental endpoint. Stool consistency scores, blood stool scores, and body weights were recorded weekly. Disease activity index (DAI) was determined before necropsy, where colon tissues were collected for biochemical analyses. In addition, the fecal microbiome of treated mice was characterized using 16S rRNA amplicon sequencing., Results: HLJD decoction at doses of 2 and 4 g/kg relieved DSS-induced chronic colitis in mice by suppressing inflammation through compromised macrophage activity in colonic tissues associated with the colony-stimulating factor 1 receptor (Csf1r)/Src pathway. Furthermore, the HLJD formula could modify the gut microbiota profile by decreasing the abundance of Bacteroides , Odoribacter , Clostridium&#95;sensu&#95;stricto&#95;1 , and Parasutterella . In addition, close correlations between DAI, colon length, spleen weight, and gut microbiota were identified., Discussion: Our findings revealed that the HLJD formula attenuated DSS-induced chronic colitis by reducing inflammation via Csf1r/Src-mediated macrophage infiltration, as well as modulating the gut microbiota profile., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Su, Liu, Zheng, Wu, Keng, Zhang and Li.)

Aim: To explore the levels of neutrophil extracellular traps (NETs) in patients with periodontitis and examine their effects on keratinization, barrier function of human gingival keratinocytes (HGKs) and the associated mechanisms., Materials and Methods: Saliva, gingival crevicular fluid (GCF), clinical periodontal parameters and gingival specimens were collected from 10 healthy control subjects and 10 patients with stage II-IV periodontitis to measure the NET levels. Subsequently, mRNA and protein levels of keratinization and barrier indicators, as well as intracellular calcium and epithelial barrier permeability, were analysed in HGKs after NET stimulation., Results: The study showed that NET levels significantly elevated in patients with periodontitis, across multiple specimens including saliva, GCF and gingival tissues. Stimulation of HGKs with NETs resulted in a decrease in the expressions of involucrin, cytokeratin 10, zonula occludens 1 and E-cadherin, along with decreased intracellular calcium levels and increased epithelial barrier permeability. Furthermore, the inhibition of keratinization by NETs is ERK-KLF4-dependent., Conclusions: This study indicates that NETs impair the barrier function of HGKs and suppress keratinization through ERK/KLF4 axis. These findings provide potential targets for therapeutic approaches in periodontitis to address impaired gingival keratinization., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Diabetes mellitus (DM), an important public health problem, aggravates the global economic burden. Diabetic encephalopathy (DE) is a serious complication of DM in the central nervous system. Metformin has been proven to improve DE. However, the mechanism is still unclear. In this study, the db/db mice, a common model used for DE, were employed to explore and study the neuroprotective effect of metformin and related mechanisms. Behavioral tests indicated that metformin (100 or 200 mg/kg/day) could significantly improve the learning and memory abilities of db/db mice. The outcomes from the oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) demonstrate that metformin effectively modulates glucose and insulin signaling pathways in db/db mice. The results of body weight and blood lipid panel (total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol) show that metformin promotes the level of lipid metabolism in db/db mice. Furthermore, data from oxidative stress assays, which measured levels of malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase, suggest that metformin suppresses oxidative stress-induced brain damage in db/db mice. In addition, western blot, Nissl staining, and immunofluorescence results showed that metformin increased the expressions of nerve growth factor and postsynaptic density 95 and repaired neuronal structural damage. For the mechanism study, metformin activated SIRT1 and inhibited the expression of NLRP3 inflammasome (NLRP3, ASC, caspase-1, IL-1β, and IL-18) and inflammatory cytokines (TNFα and IL-6). In conclusion, metformin could ameliorate cognitive dysfunction through the SIRT1/NLRP3 pathway, which might be a promising mechanism for DE treatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Central nervous system(CNS) disorders can significantly impact patients' daily lives, impairing their ability to work and imposing a substantial financial burden on their families. In recent years, the incidence of CNS diseases has shown a significant increase with the continuous improvement of the quality of life and the aging problem. Therefore, the search for new preventive and curative drugs has been a research hotspot for this group of diseases. Osthole(OST), isolated from Umbelliferae such as Cnidium monnieri, Angelica sinensis, and Heracleum hemsleyanum, possesses a variety of pharmacological effects such as neuroprotective, antioxidant, anti-inflammatory, and antithrombotic effects. There is increasing evidence that OST has demonstrated significant preventive and curative effects in various CNS disease models. This paper systematically reviewed the research progress of OST in preventing and treating CNS diseases by reviewing domestic and international literature to provide more in-depth theoretical support for the future clinical application of OST in the prevention and treatment of CNS diseases.

Background: Mechanical circulatory support may facilitate high-risk percutaneous coronary intervention (PCI). This study aimed to assess the feasibility, safety and effectiveness of high-risk PCI under the support of venoarterial extracorporeal membrane oxygenation (VA-ECMO) combined with intra-aortic balloon pump (IABP)., Methods: We enrolled patients who received VA-ECMO plus IABP-assisted PCI procedures at our center from April 2012 to June 2018. Major adverse cardiac events (MACEs) included all-cause death, myocardial infarction, and target vessel revascularization., Results: A total of 10 patients were included, with a mean age of 71 years, EuroSCORE II of 19.9%, and SYNTAX score of 39.8. Procedural success was achieved in nine (90%) patients. The mean duration of ECMO support was 1.5 hours, and 2.6 stents were implanted per patient. Major complications included contrast-induced nephropathy needing hemodialysis in one (10%) patient, significant hemoglobin drop requiring blood transfusion in two (20%) patients, pulmonary infection in one (10%) patient, and local surgical incision infection in one (10%) patient. The accumulative mortality rates for the nine patients with procedural success were 0, 22.2%, and 44.4% at 1, 3, and 5 years follow-up, respectively. However, cardiac death occurred in only one (11.1%) patient. In addition, two patients received repeat PCI or coronary artery bypass grafting within two years following the index procedure. The overall incidence rates of MACEs were 11.1%, 44.4%, and 66.7% at 1, 3, and 5 years follow-up, respectively., Conclusions: VA-ECMO plus IABP-assisted high-risk PCI was feasible in patients with complex coronary disease, with a high procedural success rate and acceptable mid-term clinical outcomes., Competing Interests: All the authors declare no conflict of interest.

Objectives: To observe the effect of electroacupuncture (EA) on the intestinal flora-short chain fatty acids (SCFAs) metabolism axis in rats with simple obesity, so as to explore the underlying mechanism of EA in reducing obesity., Methods: Male SD rats were randomly divided into control group, model group and EA group, with 6 rats in each group. The obesity model was established by feeding the rats with high-fat diet. Rats in the EA group were treated with EA at "Quchi" (LI11) and "Zusanli" (ST36) for 15 min, once daily for 21 consecutive days. The changes of body weight were observed every other day. H.E. staining was used to observe the pathological changes of adipose tissue and liver. The blood lipid content was detected by automatic biochemical analyzer. The diversity of intestinal flora in rat feces was analyzed by 16S rRNA high-throughput sequencing. The content of SCFAs in rat feces was detected by ultra-high performance liquid chromatography-electrospray ionization-mass spectrometry (UPLC-ESI-MS/MS). The correlation between the relative abundance of fecal intestinal flora and the content of SCFAs in rats was analyzed by Pearson method., Results: Compared with the control group, the body weight of rats, the serum total cholesterol (TC) and triglyceride (TG) were significantly increased ( P <0.01) in the model group. The results of 16S rRNA sequencing showed that, at the genus level the relative abundance of Bacteroides, Butyrivibrio and Roseburia in were decreased significantly( P <0.05), while that of the Lachnospiraceae&#95;NK4A136&#95;group increased( P <0.05). After the intervention, compared with the model group, the body weight, serum TC and TG contents of rats in the EA group were significantly decreased ( P <0.05, P <0.01)；the results of 16S rRNA sequencing showed that, the relative abundance of the Bacteroidota phylum significantly increased ( P <0.01) and Firmicutes decreased ( P <0.01) at the phylum level, and at the genus level the relative abundances of Bacteroides, Butyrivibrio and Roseburia significantly increased ( P <0.01, P <0.05)；the contents of acetic acid and propionic acid in SCFAs significantly increased ( P <0.01). H.E. staining showed an increase of the diameter of adipocytes, with obvious lipid droplets and inflammatory infiltration in the model group, which was relatively milder in the EA group. PCoA analysis showed that there were significant differences in the structure of intestinal flora between the control group and the model group, as well as the model group and the EA group. At the phylum level, the relative abundance of Bacteroidota was positively correlated with acetic acid and propionic acid contents, with that of Firmicutes negatively correlated with acetic acid and propionic acid contents ( P <0.001). At the genus level, the relative abundances of Bacteroides, Streptococcus and Butyricimonas were positively correlated with acetic acid content ( P <0.01, P <0.05), and the relative abundances of Bacteroides, Streptococcus and Roseburia were positively correlated with propionic acid content ( P <0.001, ( P <0.05)., Conclusions: EA can improve the disorder of lipid metabolism in obese rats by improving the disorder of intestinal flora-SCFAs metabolic axis, thus playing a role in inhibiting obesity.

Background: This study was designed to assess stress levels and related factors during the coronavirus disease 2019 (COVID-19) epidemic among individuals in centralized quarantine camps in Wenzhou, China., Methods: The survey was conducted using a questionnaire. The questionnaire included questions on sociodemographic characteristics, life events related to the COVID-19 and stressful situations, as well as Perceived Stress Scale-14. Participants included close contacts of patients with COVID-19 or at-risk individuals in quarantine camps. Multivariate logistic regression was used to analyze different factors affecting perceived stress., Results: The prevalence of high stress among quarantine camp participants was 37.45%. Of the 881 respondents, 51.99% were concerned about the difficulty of controlling the epidemic, 46.20% were concerned about the health of themselves and their family members and 39.61% were concerned about not being able to leave their homes. Multivariate logistic regression analysis revealed statistically significant differences in the prevalence of stress among different groups for certain variables, including occupation, education level and knowledge of COVID-19 (all P < 0.05). Our study found that at-risk individuals and close contacts experienced high levels of stress in quarantine camps during the COVID-19 pandemic., Conclusions: These findings suggest that centralized quarantine policies should be adapted and optimized to minimize negative psychological effects on quarantined individuals., (© The Author(s) 2024. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Soil organic carbon (SOC) is essential for maintaining soil fertility and promoting sustainable agricultu-ral development. We investigated the impact of long-term tillage practices on soil organic carbon storage (SOCS) and its components in dryland farming areas of the black soil region, based on a 39-year tillage practice experiment. We compared the effects of different tillage practices (conventional rotary and ridge tillage, CT; no-tillage, NT; subsoiling tillage, ST; moldboard plowing, MP) on SOCS, active organic carbon components, and microbial necromass carbon (MNC) content in the 0-40 cm soil layer. The results showed that, compared to CT, NT significantly increased the contents of SOCS, SOC, dissolved organic carbon (DOC), microbial biomass carbon (MBC), easily oxidizable organic carbon (EOC), and MNC in the 0-20 cm soil layer. Both ST and MP significantly improved the contents of SOCS, SOC, and EOC in 0-20 and 20-40 cm soil layers compared to CT and increased MBC content in the 20-40 cm soil layer. Additionally, MP treatment significantly improved the contents of DOC, particulate organic carbon, and MNC in the 20-40 cm soil layer compared to other treatments. ST and MP significantly reduced the contribution rate of MNC to SOC in both soil layers compared to CT and NT treatments. Results of structural equation modeling showed that enhancing the mean weight diameter of soil aggregates, field capacity, and total phosphorus content, along with increasing the activities of β-glucosidase, amylase, and lignin peroxidase, could promote MNC accumulation. MP treatment facilitated the uniform distribution of SOC, active organic carbon, and MNC in the 0-40 cm soil layer, which was more conducive to the fixation of SOC in farmland in the black soil region.

Objectives: The present study aimed to investigate the incremental prognostic value of the right ventricular fractal dimension (FD), a novel marker of myocardial trabecular complexity by cardiac magnetic resonance (CMR) in patients with arrhythmogenic cardiomyopathy (ACM)., Methods: Consecutive patients with ACM undergoing CMR were followed up for major cardiac events, including sudden cardiac death, aborted cardiac arrest, and appropriate implantable cardioverter defibrillator intervention. Prognosis prediction was compared by Cox regression analysis. We established a multivariable model supplemented with RV FD and evaluated its discrimination by Harrell's C-statistic. We compared the category-free, continuous net reclassification improvement (cNRI) and integrated discrimination index (IDI) before and after the addition of FD., Results: A total of 105 patients were prospectively included from three centers and followed up for a median of 60 (48, 66) months; experienced 36 major cardiac events were recorded. Trabecular FD displayed a strong unadjusted association with major cardiac events (p < 0.05). In the multivariable Cox regression analysis, RV maximal apical FD maintained an independent association with major cardiac events (hazard ratio, 1.31 (1.11-1.55), p < 0.002). The Hosmer-Lemeshow goodness of fit test displayed good fit (X 2  = 0.68, p = 0.99). Diagnostic performance was significantly improved after the addition of RV maximal apical FD to the multivariable baseline model, and the continuous net reclassification improvement increased 21% (p = 0.001), and the integrated discrimination index improved 16% (p = 0.045)., Conclusions: In patients with ACM, CMR-assessed myocardial trabecular complexity was independently correlated with adverse cardiovascular events and provided incremental prognostic value., Clinical Relevance Statement: The application of FD values for assessing RV myocardial trabeculae may become an accessible and promising parameter in monitoring and early diagnosis of risk factors for adverse cardiovascular events in patients with ACM., Key Points: • Ventricular trabecular morphology, a novel quantitative marker by CMR, has been explored for the first time to determine the severity of ACM. • Patients with higher maximal apical fractal dimension of RV displayed significantly higher cumulative incidence of major cardiac events. • RV maximal apical FD was independently associated with major cardiac events and provided incremental prognostic value in patients with ACM., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Background: The prevalence of dementia around the world is increasing, and these patients are more likely to have cognitive impairments, mood and anxiety disorders (depression, anxiety, and panic disorder), and attention deficit disorders over their lifetime. Previous studies have proven that melatonin could improve memory loss, but its specific mechanism is still confused., Methods: In this study, we used in vivo and in vitro models to examine the neuroprotective effect of melatonin on scopolamine (SCOP)-induced cognitive dysfunction. The behavioral tests were performed. 18 F-FDG PET imaging was used to assess the metabolism of the brain. Protein expressions were determined through kit detection, Western blot, and immunofluorescence. Nissl staining was conducted to reflect neurodegeneration. MTT assay and RNAi transfection were applied to perform the in vitro experiments., Results: We found that melatonin could ameliorate SCOP-induced cognitive dysfunction and relieve anxious-like behaviors or HT22 cell damage. 18 F-FDG PET-CT results showed that melatonin could improve cerebral glucose uptake in SCOP-treated mice. Melatonin restored the cholinergic function, increased the expressions of neurotrophic factors, and ameliorated oxidative stress in the brain of SCOP-treated mice. In addition, melatonin upregulated the expression of silent information regulator 1 (SIRT1), which further relieved endoplasmic reticulum (ER) stress by decreasing the expression of phosphorylate inositol-requiring enzyme (p-IRE1α) and its downstream, X-box binding protein 1 (XBP1)., Conclusions: These results indicated that melatonin could ameliorate SCOP-induced cognitive dysfunction through the SIRT1/IRE1α/XBP1 pathway. SIRT1 might be the critical target of melatonin in the treatment of dementia., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: The CRC-VTE trial conducted in China revealed a significant occurrence of venous thromboembolism (VTE) in patients following colorectal cancer (CRC) surgery, raising concerns about implementing thromboprophylaxis measures. The present study aimed to identify and analyze inappropriate aspects of current thromboprophylaxis practices., Methods: This study performed an analysis of the CRC-VTE trial, a prospective multicenter study that enrolled 1836 patients who underwent CRC surgery. The primary objective was to identify independent risk factors for VTE after CRC surgery using multivariate logistic regression analysis. Furthermore, among the cases in which VTE occurred, the appropriateness of thromboprophylaxis was assessed based on several factors, including pharmacologic prophylaxis, time to initiate prophylaxis, drug selection, drug dosage, and duration of pharmacologic prophylaxis. Based on the analysis of the current state of thromboprophylaxis and relevant clinical guidelines, a modified Delphi method was used to develop a clinical pathway for VTE prophylaxis after CRC surgery., Results: In this analysis of 1836 patients, 205 (11.2%) were diagnosed with VTE during follow-up. The multifactorial analysis identified several independent risk factors for VTE, including age (≥70 years), female sex, varicose veins in the lower extremities, intraoperative blood transfusion, and the duration of immobilization exceeding 24 h. None of the patients diagnosed with VTE in the CRC trial received adequate thromboprophylaxis. The main reasons for this inappropriate practice were the omission of thromboprophylaxis, delayed initiation, and insufficient duration of thromboprophylaxis. We developed a specialized clinical pathway for thromboprophylaxis after CRC surgery to address these issues., Conclusions: This study offers a comprehensive nationwide evaluation of existing thromboprophylaxis practices in patients after CRC surgery in China. A specialized clinical pathway was developed to address the identified gaps and improve the quality of care. This clinical pathway incorporates explicit, tailored, detailed recommendations for thromboprophylaxis after CRC surgery., (© 2024 Pharmacotherapy Publications, Inc.)

The hypothalamic-pituitary-adrenal (HPA) axis is a critical component of the neuroendocrine system, playing a central role in regulating the body's stress response and modulating various physiological processes. Dysregulation of HPA axis function disrupts the neuroendocrine equilibrium, resulting in impaired physiological functions. Acupuncture is recognized as a non-pharmacological type of therapy which has been confirmed to play an important role in modulating the HPA axis and thus favorably targets diseases with abnormal activation of the HPA axis. With numerous studies reporting the promising efficacy of acupuncture for neuroendocrine disorders, a comprehensive review in terms of the underlying molecular mechanism for acupuncture, especially in regulating the HPA axis, is currently in need. This review fills the need and summarizes recent breakthroughs, from the basic principles and the pathological changes of HPA axis dysfunction, to the molecular mechanisms by which acupuncture regulates the HPA axis. These mechanisms include the modulation of multiple neurotransmitters and their receptors, neuropeptides and their receptors, and microRNAs in the paraventricular nucleus, hippocampus, amygdala and pituitary gland, which alleviate the hyperfunctioning of the HPA axis. This review comprehensively summarizes the mechanism of acupuncture in regulating HPA axis dysfunction for the first time, providing new targets and prospects for further exploration of acupuncture. Please cite this article as: Zheng JY, Zhu J, Wang Y, Tian ZZ. Effects of acupuncture on hypothalamic-pituitary-adrenal axis: Current status and future perspectives. J Integr Med. 2024; 22(4): 446-459., (Copyright © 2024 Shanghai Yueyang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine. Published by Elsevier B.V. All rights reserved.)

Background: Current RNA-seq analysis software for RNA-seq data tends to use similar parameters across different species without considering species-specific differences. However, the suitability and accuracy of these tools may vary when analyzing data from different species, such as humans, animals, plants, fungi, and bacteria. For most laboratory researchers lacking a background in information science, determining how to construct an analysis workflow that meets their specific needs from the array of complex analytical tools available poses a significant challenge., Results: By utilizing RNA-seq data from plants, animals, and fungi, it was observed that different analytical tools demonstrate some variations in performance when applied to different species. A comprehensive experiment was conducted specifically for analyzing plant pathogenic fungal data, focusing on differential gene analysis as the ultimate goal. In this study, 288 pipelines using different tools were applied to analyze five fungal RNA-seq datasets, and the performance of their results was evaluated based on simulation. This led to the establishment of a relatively universal and superior fungal RNA-seq analysis pipeline that can serve as a reference, and certain standards for selecting analysis tools were derived for reference. Additionally, we compared various tools for alternative splicing analysis. The results based on simulated data indicated that rMATS remained the optimal choice, although consideration could be given to supplementing with tools such as SpliceWiz., Conclusion: The experimental results demonstrate that, in comparison to the default software parameter configurations, the analysis combination results after tuning can provide more accurate biological insights. It is beneficial to carefully select suitable analysis software based on the data, rather than indiscriminately choosing tools, in order to achieve high-quality analysis results more efficiently., (© 2024. The Author(s).)