Background The health problems of the elderly, especially the elderly women, are increasingly concerned. The prevalence of abnormal liver lipid metabolism in women after menopause is increasing, which is highly related to estrogen and follicle stimulating hormone. However, hormone replacement therapy is highly controversial, and will bring risks such as breast cancer and coronary heart disease. Therefore, this study aims to build an effective and convenient in vitro disease model and perform functional verification to analyze the molecular mechanism of candidate lncRNAs participating in FSH-induced liver lipid metabolism. Result The results indicated the successful preliminary establishment of an in vitro model for FSH-induced lipid metabolism abnormalities. High-throughput sequencing and bioinformatics analysis revealed a total of 174 differentially expressed lncRNAs. Utilizing a comprehensive database, we screened five candidate lncRNAs and conducted interference tests specifically on the upregulated lncRNA ENSMUST00000244884. The findings demonstrated that knocking down this lncRNA led to an increase in the expression of the LXR and ACOX1 genes, which are crucial for lipid metabolism. Consequently, the lipid metabolism abnormality phenotype was alleviated. Conclusion Based on the experimental results, we have determined that bile-derived liver organoids are well-suited for constructing an in vitro disease model of hormone-induced lipid metabolism abnormalities, enabling effective observation of lipid phenotypes. Furthermore, we have screened and identified lncRNAs involved in hormone-regulated lipid metabolism abnormalities at the non-coding regulatory level. These findings offer potential diagnostic markers and therapeutic targets for disorders related to lipid metabolism.

Objective:To systematically evaluate the efficacy and safety of SMLI in patients with HF. Materials and methods:Eight electronic databases were systematically searched from inception up to July 2025 to identify randomized controlled trials (RCTs) comparing SMLI combined with conventional treatment versus conventional treatment alone in patients with HF. Two independent reviewers conducted study selection, data extraction, and risk of bias assessment. Meta-analysis was performed to synthesize efficacy and safety outcomes. Sensitivity analysis was conducted to verify the robustness of the findings, and publication bias was evaluated using funnel plots and Egger's test. Results:A total of 32 RCTs involving 3,077 patients were ultimately included. SMLI significantly improved LVEF (MD = 5.62, 95% CI: 4.42-6.81, P < 0.01), reduced LVEDD (MD = -5.69, 95% CI:-7.46 to-3.92, P < 0.01), and decreased BNP and NT-proBNP levels. It also ameliorated inflammatory markers (CRP, IL-6, TNF-α), endothelial function (ET-1, NO), and increased 6-min walk distance (MD = 60.7, P < 0.01). SMLI reduced cardiovascular adverse events (RR = 0.55, P < 0.01) without increasing overall adverse reactions. Conclusion:Combining SMLI with conventional therapy enhances cardiac function and improves clinical outcomes in patients with HF. However, additional high-quality, large-scale RCTs with long-term follow-up are required to validate the long-term efficacy and safety of SMLI, given the potential limitations of the included studies. Systematic Review Registration:Identifier CRD420251114385.

Background:Cardiovascular disease (CVD) remains the leading cause of mortality and disability globally, with high body mass index (HBMI) playing a pivotal role in its worldwide burden. Gaining a clear understanding and forecasting the effect of HBMI on CVD is crucial for developing effective health policies and interventions. Methods:We used data from the 2021 Global Burden of Disease study to analyze the CVD burden attributable to HBMI. An age-period-cohort (APC) analysis was conducted to investigate trends in CVD-related mortality attributable to HBMI, whereas the Bayesian Age-Period-Cohort (BAPC) model projected the number of deaths and mortality up to 2035. Results:The study revealed a significant increase in CVD deaths and disability-adjusted life years (DALYs) due to HBMI globally, despite slightly decreased age-standardized rates (ASR) for HBMI-related CVD. The ASR of deaths and DALYs decreased from 1990 to 2021 in the high and high-middle Socio-Demographic Index (SDI) regions while increasing in the lower SDI regions. A pinpoint analysis revealed the most significant decline in HBMI-related CVD mortality from 2003 to 2010. The BAPC model projected an increase in global HBMI-related CVD deaths to 2,369,451 by 2035. The ASR of deaths is projected to increase to 37.53 per 100,000, with an increase for females and a decrease for males. Conclusion:This study emphasizes global trends in HBMI-related CVD burden and the importance of targeting HBMI as a modifiable risk factor. It provides crucial information for public health strategies aimed at reducing CVD mortality. Further research is warranted, especially with an aging global population.

Abstract Nanoplastics (NPs) are an emerging global environmental concern. While extensive research has focused on the toxicological effects of NPs on microalgae, the post-exposure consequences remain largely unexplored. In this study, Microcystis aeruginosa was exposed to 5 and 50 mg/L of polystyrene (PS) for 15 days, followed by a 15-day post-exposure period in PS-free medium. Exposure to 5 mg/L PS did not significantly affect growth, phycobiliprotein content, or oxidative stress responses. In contrast, 50 mg/L PS significantly inhibited algal growth and impaired photosynthetic capacity. Transcriptomic analysis revealed that this toxicity was underpinned by a broad downregulation of central energy metabolism, including photosynthesis, glycolysis, the tricarboxylic acid (TCA) cycle, and oxidative phosphorylation. Notably, following the removal of PS, M. aeruginosa exhibited a remarkable recovery capacity driven by metabolic rebound. This was manifested as a robust upregulation of previously suppressed pathways, particularly the pentose phosphate pathway and oxidative phosphorylation, facilitating a substantial, though potentially incomplete, restoration of physiological function. These findings highlight the metabolic resilience of M. aeruginosa and underscore the importance of considering post-exposure phases in ecological risk assessments of NPs.

Non-coding RNAs play essential roles during liver regeneration, however, their functions in cholangiocyte-to-hepatocyte differentiation is still unclear. Emerging liver ductal organoids offer a powerful model to replicate the molecular mechanisms of the in vivo cholangiocyte-to-immature hepatocyte transition, potentially accelerating advancements in liver regenerative medicine. Here, we established the liver ductal organoids from three C57BL/6 mice, and induced the differentiation of cholangiocyte into immature hepatocyte to carry out the transcriptome sequencing. Then, the expression profiles of lncRNA, miRNA and mRNA in expansion (EM) and differentiation medium (DM) samples were explored. A total of 529,049,578 and 61,266,130 clean reads were generated from 6 RNA-seq and 6 miRNA-seq libraries, respectively. Through stringent filtering, we identified 24,676 lncRNAs, 1,018 miRNAs and 38,689 mRNAs transcripts. This dataset will contribute to the elucidation of the underlying molecular mechanisms associated with cholangiocyte-to-immature hepatocyte differentiation during liver regeneration, and provides clues for liver regenerative medicine.

BACKGROUND:Ischaemic heart disease (IHD) is a major cause of heart failure (HF), a condition expected to increasingly affect global health and economics. This study evaluates the global burden, trends, and disparities of HF linked to IHD, aiming to inform health policy development. METHODS AND RESULTS:Data from the Global Burden of Disease Study 2021 (GBD2021) are analysed using joinpoint regression, decomposition analysis, and Bayesian age-period-cohort analysis (BAPC). Health disparities are assessed through the Socio-demographic Index (SDI) via the Slope Index of Inequality and the Concentration Index, with future trends projected from 2022 to 2045. In 2021, global HF cases due to IHD were over 19.16 million, with an age-standardized prevalence rate (ASPR) of 228.31 per 100 000 [95% Uncertainty Interval (UI), 188.18-279.55] and age-standardized years lived with disability (ASYLDs) rate of 20.43 per 100 000 [95% UI, 13.55-28.7]. In 2021, there was a 2.87% increase in ASPR and ASYLDs compared with 1990, primarily driven by population growth and aging. Significant reductions in global ASPR and ASYLDs disparities are observed, though the disease burden has intensified in countries with lower SDI levels. Projections indicate that by 2045, while the prevalence and years lived with disability for HF caused by IHD will increase, the ASPR and ASYLDs are expected to decrease. CONCLUSION:The global burden of HF due to IHD remains a significant concern. Urgent improvements in the allocation of medical resources and the implementation of effective prevention and management strategies are necessary to address this issue.

This cross-sectional study aimed to investigate the association between the TyG index and both obesity indicators and hypertension among American adults. Data were drawn from 4,813 adults in the 2013–2018 National Health and Nutrition Examination Survey (NHANES). Multivariate logistic regression models indicated significant associations between TyG and obesity-related indices with hypertension. Using Cox regression analysis, we examined the relationship between TyG and obesity-related indices in relation to hypertensive prognosis, employing threshold effect analysis and fitted smoothed curves for consistency. Subgroup analyses and interaction tests were conducted. Results showed strong correlations between TyG, TyG-BMI, TyG-WHtR, TyG-WC and hypertension, with odds ratios (ORs) of hypertension rising across TyG quartiles (Q1–Q4). Cardiovascular mortality analysis revealed that TyG (HR = 1.89, 95% CI (1.03,3.51), P < 0.05) and the Q2 group (HR = 4.93, 95% CI (1.29,18.80), P < 0.05) were significantly associated with increased risk. A positive correlation between TyG and hypertension was noted below a threshold of 8.1, with inverse associations beyond this point. The TyG-BMI, TyG-WHtR, and TyG-WC exhibited positive correlations with hypertension, although weakened after reaching a certain threshold. These findings suggested that TyG and related indices are associated with hypertension and may aid in understanding risk stratification in this context.

ObjectiveBy using the FAERS database, we aim to identify and assess risk signals of adverse drug events (ADEs) potentially causing pericardial effusion, to inform clinical drug management and promote rational drug use.MethodsWe obtained reports of pericardial effusion events from the FAERS database spanning from the first quarter of 2004 to the second quarter of 2024, and identified the top 50 drugs ranked by report frequency or signal strength. Four algorithms, namely the reported odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS), were employed for signal detection of these drugs. Furthermore, for drugs with positive signals, we conducted sensitivity analyses and employed the Weibull shape parameter test to perform a time to onset (TTO) analysis.ResultsWe identified 20,057 ADEs related to pericardial effusion, involving 19,693 patients for analysis. The patient population comprised 10,187 males (51.7%) and 7,939 females (40.3%). Adults aged 18-65 years were the largest group (7,798 cases, 39.6%). Regarding clinical outcomes, 9,924 patients (50.4%) experienced hospitalization, and 2,770 cases (14.1%) resulted in death. Ranked by the ROR risk signal strength, the top 3 drugs were hydralazine [ROR (95% CI): 27.11 (22.28-33)], dasatinib [ROR (95% CI): 15.62 (14.07-17.33)], and mesalazine [ROR (95% CI): 8.99 (6.84-11.8)]. We conducted a TTO analysis for the 26 drugs with positive signals. The median TTO and interquartile range (IQR) for the top 3 drugs causing the earliest pericardial effusion were: cytarabine 14 (7.5,38), selexipag 14.5 (4.25, 157.75), dabigatran etexilate 29 (9, 229). Most drugs exhibited an early failure type.ConclusionThis study systematically compiled a list of drugs with potential risks of causing pericardial effusion. There is a significant association between pericardial effusion and the use of hydralazine, dasatinib, and mesalazine. Moreover, pericardial effusion is more common in patient groups receiving treatments with antineoplastic and immunomodulating agents.

The biotic stress significantly influences the production of potato (Solanum tuberosum L.) all over the world. Long noncoding RNAs (lncRNAs) play key roles in the plant response to environmental stressors. However, their roles in potato resistance to pathogens, insects, and other biotic stress are still unclear. The PotatoBSLnc is a database for the study of potato lncRNAs in response to major biotic stress. Here, we collected 364 RNA sequencing (RNA-seq) data derived from 12 kinds of biotic stresses in 26 cultivars and wild potatoes. PotatoBSLnc currently contains 18 636 lncRNAs and 44 263 mRNAs. In addition, to select the functional lncRNAs and mRNAs under different stresses, the differential expression analyses and the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses related to the cis/trans-targets of differentially expressed lncRNAs (DElncRNAs) and to the differentially expressed mRNAs (DEmRNAs) were also conducted. The database contains five modules: Home, Browse, Expression, Biotic stress, and Download. Among these, the "Browse" module can be used to search detailed information about RNA-seq data (disease, cultivator, organ types, treatment of samples, and others), the exon numbers, length, location, and sequence of each lncRNA/mRNA. The "Expression" module can be used to search the transcripts per million/raw count value of lncRNAs/mRNAs at different RNA-seq data. The "Biotic stress" module shows the results of differential expression analyses under each of the 12 biotic stresses, the cis/trans-targets of DElncRNAs, the GO and KEGG analysis results of DEmRNAs, and the targets of DElncRNAs. The PotatoBSLnc platform provides researchers with detailed information on potato lncRNAs and mRNAs under biotic stress, which can speed up the breeding of resistant varieties based on the molecular methods.Database URL: https://www.sdklab-biophysics-dzu.net/PotatoBSLnc

In this study, we analyzed publicly available scRNA-seq data from primary tumor tissues of 10 Retinoblastoma (RB) patients to explore tumor microenvironment (TME) heterogeneity. Our findings revealed distinct subpopulations of cone precursor (CP) cells, with higher proportions in invasive RB. Differential gene expression and pathway analysis highlighted functional diversity among CP subpopulations, with CP4 showing elevated TGF-β signaling in invasive RB. Cell-cell interaction analysis further identified rewiring of communication networks, with increased fibroblast-CP interactions in invasive tumors. Bulk RNA-seq identified two molecular subtypes, with subtype 1 showing an immunosuppressive TME. Finally, DOK7 was identified as a key gene associated with invasion, with functional assays confirming its role in promoting tumor progression. These results provide valuable insights into RB progression and potential therapeutic targets.

ObjectiveUtilizing the FDA Adverse Event Reporting System (FAERS) database, this study conducts signal detection for drugs associated with cardiac arrest (CA), aiming to optimize clinical decision-making and ensure safer drug usage.MethodsAdverse event reports related to CA from the first quarter of 2004 to the second quarter of 2024 were extracted from the FAERS database. Signal detection was conducted using the reporting odds ratio (ROR) and proportional reporting ratio (PRR) to identify drugs associated with an increased risk of CA.ResultsA total of 66,431 reports were analyzed, comprising 34,508 males (51.9%) and 31,923 females (48.1%). The majority of cases (71.8%) were reported by healthcare professionals, with adults (≥18 years old) representing the predominant group. Clinical outcomes showed that 67.2% of cases resulted in death. Out of 82 drugs with over 100 CA-related reports, 43 displayed positive signals. The top five drugs identified by ROR were: carisoprodol [ROR (95% CI): 34.13 (29.62–39.32)], sugammadex [ROR (95% CI): 26.93 (22.56–32.16)], regadenoson [ROR (95% CI): 20.00 (17.69–22.60)], alprazolam [ROR (95% CI): 12.82 (12.19–13.48)], and propofol [ROR (95% CI): 11.93 (10.61–13.41)]. In the system drug signal detection, musculo-skeletal system drugs ranked highest [ROR (95% CI): 30.99 (27.74–34.62)], followed by alimentary tract and metabolism drugs [ROR (95% CI): 4.75 (4.59–4.92)], nervous system drugs [ROR (95% CI): 4.51 (4.4–4.61)], anti-infective drugs [ROR (95% CI): 4.13 (3.74–4.57)], cardiovascular drugs [ROR (95% CI): 3.89 (3.78–4.01)], and antineoplastic and immunomodulating agents [ROR (95% CI): 2.16 (2.13–2.2)].ConclusionThis study identifies over 40 drugs potentially associated with an elevated risk of CA based on FAERS data. Healthcare professionals should be particularly vigilant when prescribing these drugs, especially to patients with a history of heart disease, and ensure rigorous monitoring of their cardiac health.

To use the FDA Adverse Event Reporting System (FAERS) database to identify drugs associated with orthostatic hypotension. Adverse event reports of orthostatic hypotension from Q1 2004 to Q3 2024 were obtained from the FAERS and JADER databases. We employed algorithms such as the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) for signal detection. JADER database was used to validate the findings from FAERS analysis. We identified 15,737 adverse events associated with orthostatic hypotension, involving 15,480 patients for analysis. The patient demographic included 6,745 males (43.5%) and 7,248 females (46.8%), with the largest group comprising adults over 65 years (7,654 cases, 49.4%). The three drugs with the highest ROR risk signals were terazosin [ROR (95% CI): 153.96 (124.57-190.28)], rasagiline [ROR (95% CI): 37.46 (29.99-46.78)], and doxazosin [ROR (95% CI): 37.06 (31.32-43.86)]. Apomorphine, abalopatine and levodopa were associated with the shortest onset time of orthostatic hypotension. Most of the signal detection results from the FAERS database were verified in the JADER database. Drugs associated with orthostatic hypertension still focused on cardiovascular and nervous system drugs. This study employed the FAERS database to identify 33 drugs that may be potentially linked to orthostatic hypotension. Medical workers should remain vigilant regarding the risk of these drugs causing orthostatic hypotension.

BACKGROUND:Atherosclerosis is the primary cause of cerebrovascular disease, which in turn has substantial deleterious impacts on cognitive abilities. The atherogenic index of plasma (AIP), calculated as the logarithmic transformation of the ratio of triglycerides to high-density lipoprotein cholesterol (log[TG/HDL-C]), has emerged as a novel biomarker reflecting the balance between proatherogenic and antiatherogenic lipoproteins. Nevertheless, the association between AIP and cognitive function has not been examined in a large cohort. This study examined the relationship between AIP and cognitive performance in a nationally representative cohort of adult Americans. METHODS:A cross-sectional study was conducted using data from the 2011-2014 National Health and Nutrition Examination Survey (NHANES). The relationship between AIP and cognitive function was examined using several multivariate regression models with adjustment for arrays of potential confound factors. Fitted smoothed curves and threshold effect analysis were used to characterize possible nonlinear relationships. RESULTS:The study population comprised 995 adults (mean age 63.01 ± 14.93 years; 51.86% female), with 49.65% identifying as non-Hispanic White, 9.15% as Mexican American, and 20.2% as non-Hispanic Black. Higher AIP was associated with greater risk of cognitive impairment. Negative correlations were detected between the AIP and both Animal Fluency Test (AFT) performance (β = -5.54, 95%CI: -9.26, -1.82, p < 0.05) and Digit Symbol Substitution Test (DSST) performance (β = -15.79, 95% CI: -26.32, -5.27, p < 0.05) after adjusting for multiple confounding variables. CONCLUSION:Elevated AIP is associated with cognitive impairment in adult Americans.

Colon cancer is one of the most common gastrointestinal tract tumors and is increasing in incidence worldwide each year. Cuproptosis is a novel cell death pathway that is closely related to energy metabolism. Recent studies suggest that cuproptosis-related genes may play important roles in the progression of colon cancer. Therefore, we aimed to construct prognostic models and column plots for overall survival and progression-free survival of colon cancer by cuproptosis-related genes and search their relationship with immune checkpoints and immune infiltration. In this study, we systematically analyzed the expression differences, biological functions, and variants of cuproptosis-related genes in colon cancer tissues using the The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. We analyzed the prognostic characteristics of cuproptosis-related genes in colon cancer using a multifactorial Cox proportional risk regression model and constructed a clinical prognostic model. Subsequently, we analyzed the correlations among cuproptosis-related genes, immune infiltration, and tumor stage. Our results revealed that LIPT1, PDHA1, GLS, CDKN2A, FDX1, DLD, and MTF1 were significantly differentially expressed between colon cancer and normal tissues. There was a broad correlation among cuproptosis-related genes, and their mutations were widely present in colon cancer samples. Analysis of cuproptosis-related genes revealed that their roles were primarily related to the tricarboxylic acid cycle and energy metabolism, whereas DLD, PDHB, DLAT, and PDHA1 were the core genes. Using a Cox proportional risk regression model, we revealed the DLAT, LIAS, and CDKN2A genes were associated with the prognosis of colon cancer. We developed a prognostic model based on the overall and progression-free survival of colon cancer, and the area under the curve (AUC) values for the prognostic score for predicting the 5-year overall and progression-free survival were 0.667 and 0.650, respectively. In regard to the survival analysis in terms of overall survival, a higher the risk score based on the cuproptosis-related gene profile resulted in a lower overall survival (HR = 1.67 [1.13–2.48]; log -rank p = 0.011). Progression-free survival was significantly shorter in high-risk patients (HR = 1.36 [0.96–1.93]; log-rank p = 0.084). To improve the clinical utility of the prediction model, we constructed columnar plots of overall survival and progression-free survival with a C-index of 0.810 for overall survival and 0.773 for progression-free survival. Immune infiltration analysis of colon cancer revealed that the expression levels of LIAS, DLAT, and CDKN2A were closely associated with multiple immune cells. Notably, DLAT expression in colon cancer was positively correlated with the expression levels of the immune checkpoint proteins CD274, HAVCR2, and CTLA4, whereas CDKN2A expression was positively correlated with the expression levels of PDCD1, HAVCR2, and CTLA4. We also observed that CDKN2A expression may be associated with colon cancer progression. Cuproptosis-related genes such as DLAT, LIAS, and CDKN2A possess predictive value in the context of the prognosis and progression of colon cancer, and their relationship with immune checkpoints and immune infiltration may provide a basis for further drug development.

Background Cardiorenal syndrome (CRS) is a complex and severe clinical condition that is gaining increasing attention. Previous studies indicate that insulin resistance (IR) strongly correlates with cardiac diseases (e.g., coronary artery disease, heart failure) and renal disorders (e.g., diabetic nephropathy, chronic kidney disease), with its metrics serving as predictors for cardiovascular and renal risks. However, the concurrent impact of insulin resistance on both organs and its relationship with CRS remain unclear. This study investigates associations between three novel insulin resistance indicators and CRS. Methods This cross-sectional study utilized data from 14,947 participants in the 2005–2020 of the U.S. National Health and Nutrition Examination Survey (NHANES). CRS was defined as coexisting cardiovascular disease and chronic kidney disease (estimated glomerular filtration rate < 60 mL/min/1.73 m²). Three insulin resistance indices were evaluated: estimated glucose disposal rate (eGDR), metabolic insulin resistance score (METS-IR), and triglyceride-glucose index (TyG). Multivariable weighted logistic regression models calculated odds ratios (ORs) and 95% confidence intervals (CIs) for CRS associations. Restricted cubic spline curves assessed nonlinear relationships, while receiver operating characteristic (ROC) analyses evaluated the predictive capacity of these indices for CRS. Results CRS was present in 3.04% of participants. After full covariate adjustment, per standard deviation (SD) increase in eGDR was negatively associated with the presence of CRS (adjusted OR = 0.73, 95% CI: 0.66–0.77); each SD increase in METS-IR was positively associated with the presence of CRS (adjusted OR = 3.62, 95% CI: 2.11–6.20). In contrast, TyG showed no significant association with CRS in fully adjusted models. Subgroup analyses revealed that the associations of eGDR and METS-IR with CRS remained stable across all subgroups. Notably, among the three variables, eGDR had the strongest diagnostic value for CRS (AUC = 0.758). Conclusions Of the three IR indices, eGDR and METS-IR were significantly associated with the presence of patients with CRS. Furthermore, eGDR demonstrated a good predictive value for CRS. Collectively, these findings suggest that eGDR may be a stronger marker of CRS.

Abstract Background Despite substantial research investigating the relationship between Type 2 Diabetes (T2D) and Heart Failure (HF), the specifics and dynamics of this correlation remain a subject of debate. This study seeks to elucidate the genetic determinants underlying the causal relationship between T2D and HF. Methods Genetic analyses were performed utilizing summary statistics derived from recent, extensive Genome-Wide Association Studies (GWASs), focusing on T2D, HF and various mediators. Linkage disequilibrium score regression (LDSC) analysis and both univariable and multivariable Mendelian Randomization (MR) analyses were employed to assess the causal relationships among these conditions. The primary approach for MR analysis was the inverse-variance weighted method. Results LDSC analysis identified a significant genetic correlation between T2D and HF. Univariable MR analyses demonstrated that genetically inferred T2D was causally linked to an increased risk of both HF and chronic heart failure (CHF). Reverse MR analysis indicated a potential genetic causal relationship from CHF to T2D. However, no significant genetic causal relationships were detected between glycemic traits in non-diabetic population and HF. When adjusting for body mass index, waist-hip ratio (WHR), systolic blood pressure (SBP), and coronary artery disease in multivariate MR, the association between T2D and HF was vanished, particularly for SBP, and likely for WHR. The MR findings relating to T2D and left ventricular function traits further reinforced this evidence. Conclusions Our research suggests that SBP is likely a primary mediator in the relationship between T2D and HF, with the influence of WHR on this association also meriting closer examination. Effective management of blood pressure in patients with T2D, dependent of glucose level control, is crucial for reducing the risk of heart failure complication. Moderate weight control strategies targeting WHR may possess certain significance.

The marine flora and fauna along the China seas include the Indo-West Pacific warm-water fauna and the North Pacific temperate fauna. The latitude of 32°N is recognized as the ecological barrier for benthic fauna in the China Seas. However, the ecological barrier on macrobenthos community gradually weakened because of global warming. Microeukaryotes are major components of marine food webs and can quickly response to environmental changes. We hypothesis that microeukaryotic benthos can stride over the ecological barrier of 32°N from the East China Sea (ECS) to the Yellow Sea (YS) under the global change, but their distribution is still limited by depth gradients between the South China Sea (SCS) and the ESC. Therefore, we investigated the distribution of benthic microeukaryotes in the China Seas using RNA metabarcoding. Higher OTU richness and phylogenetic diversity were detected in the SCS than those in the YS and ECS. The YS and ECS communities clustered together firstly and then clustered with the SCS community. Unexpectedly, communities from the 33°N in the YS clustered with those from the ECS. Similar pattern was also detected for Cercozoa, Diatomea, Amoebozoa and Fungi. These findings indicated that microeukaryotic benthos strode over the ecological barrier of 32°N under the global change. Source-sink analyses indicated more than 50% sources of the 33°N community were attributed to the ECS community, while only 12.5% from the YS community. Depth, temperature and latitude showed significant influence on communities in the China Seas. This study highlights the response of active microeukaryotes to the global warming in the coastal sediments.

Abstract Long noncoding RNAs (lncRNAs) have emerged as crucial regulators across diverse biological processes and diseases. While high-throughput sequencing has enabled lncRNA discovery, functional characterization remains limited. The EVLncRNAs database is the first and exclusive repository for all experimentally validated functional lncRNAs from various species. After previous releases in 2018 and 2021, this update marks a major expansion through exhaustive manual curation of nearly 25 000 publications from 15 May 2020, to 15 May 2023. It incorporates substantial growth across all categories: a 154% increase in functional lncRNAs, 160% in associated diseases, 186% in lncRNA-disease associations, 235% in interactions, 138% in structures, 234% in circular RNAs, 235% in resistant lncRNAs and 4724% in exosomal lncRNAs. More importantly, it incorporated additional information include functional classifications, detailed interaction pathways, homologous lncRNAs, lncRNA locations, COVID-19, phase-separation and organoid-related lncRNAs. The web interface was substantially improved for browsing, visualization, and searching. ChatGPT was tested for information extraction and functional overview with its limitation noted. EVLncRNAs 3.0 represents the most extensive curated resource of experimentally validated functional lncRNAs and will serve as an indispensable platform for unravelling emerging lncRNA functions. The updated database is freely available at https://www.sdklab-biophysics-dzu.net/EVLncRNAs3/.

Objective To systematically evaluate the efficacy and safety of seven oral Chinese patent medicines for clearing heat and removing dampness in the treatment of non-alcoholic fatty liver disease(NAFLD).Methods The randomized controlled trials(RCTs)of seven Chinese patent medicines for clearing heat and removing dampness in the treatment of NAFLD were retrieved from databases including CNKI,Sinomed,Wanfang,VIP,PubMed,Cochrane Library and Embase,and the time range for searching was from the establishment of databases to October 1,2022.The literature quality evaluation and network Meta-analysis were then conducted for the included studies.Results A total of 37 RCTs with 3472 patients were finally included.The experimental group was treated with a combination of Chinese patent medicine for clearing heat and removing dampness and conventional therapy,and the control group was treated with conventional therapy.Network Meta-analysis results showed that,in terms of total effective rate,Danning Tablets(胆宁片)+conventional therapy,Kezhi Capsules(壳脂胶囊)+conventional therapy,Qianggan Capsules(强肝胶囊)+conventional therapy,Huazhi Rougan Granules(化滞柔肝颗粒)+conventional therapy,Dahuang Lidan Capsules(大黄利胆胶囊)+conventional therapy,Dangfei Liganning Capsules(当飞利肝宁胶囊)+conventional therapy were all superior to conventional therapy.In terms of reducing alanine aminotransferase(ALT),Huazhi Rougan Granules+conventional therapy,Danning Tablets+conventional therapy,Qianggan Capsules+conventional therapy,Kezhi Capsules+conventional therapy were all superior to conventional therapy.In terms of reducing aspartate aminotransferase(AST),Huazhi Rougan Granules+conventional therapy,Danning Tablets+conventional therapy,Qianggan Capsules+conventional therapy,Kezhi Capsules+conventional therapy were all superior to conventional therapy.In terms of reducing blood total cholesterol(TC),Huazhi Rougan Granules+conventional therapy,Kezhi Capsules+conventional therapy,Qianggan Capsules+conventional therapy were all superior to conventional therapy.In terms of reducing blood triglycerides(TG),Kezhi Capsule+conventional therapy,Huganning Tablets(护肝宁片)+conventional therapy,Danning Tablets+conventional therapy,Huazhi Rougan Granules+conventional therapy,Qianggan Capsules+conventional therapy were all superior to conventional therapy.The surface under the cumulative ranking curve(SUCRA)probability ranking showed that Dangfei Liganning Capsules+conventional therapy and Kezhi Capsules+conventional therapy were the best regimens to improve the total efficiency and reduce TG respectively,and Huazhi Rougan Granules+conventional therapy was the best regimen to reduce ALT,AST and TC.Conclusion Chinese patent medicines for clearing heat and removing dampness combined with conventional therapy has obvious advantages in the treatment of NAFLD.However,because of the low methodological quality of some included studies,the results of the study still need to be further verified by high-quality RCTs.