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Background: Hepatocellular carcinoma (HCC) is a serious complication of cirrhosis. Currently, non-selective beta-blockers (NSBBs) are commonly used to treat portal hypertension in patients with cirrhosis. The latest research shows that NSBBs can induce apoptosis and S-phase arrest in liver cancer cells and inhibit the development of hepatic vascular endothelial cells, which may be effective in preventing HCC in cirrhosis patients. Aim: To determine the relationship between different NSBBs and HCC incidence in patients with cirrhosis. Methods: We searched the Cochrane database, MEDLINE, EMBASE, PubMed, and Web of Science. Cohort studies, case‒control studies, and randomized controlled trials were included if they involved cirrhosis patients who were divided into an experimental group using NSBBs and a control group with any intervention. Based on heterogeneity, we calculated odds ratio (OR) and 95% confidence interval (CI) using random-effect models. We also conducted subgroup analysis to explore the source of heterogeneity. Sensitivity analysis and publication bias detection were performed. Results: A total of 47 studies included 38 reporting HCC incidence, 26 reporting HCC-related mortality, and 39 reporting overall mortality. The HCC incidence between the experimental group and the control group was OR = 0.87 (0.69 and 1.10), p = 0.000, and I 2 = 81.8%. There was no significant association between propranolol (OR = 0.94 and 95%CI 0.62–1.44) or timolol (OR = 1.32 and 95%CI 0.44–3.95) and HCC incidence, while the risk of HCC decreased by 26% and 38% with nadolol (OR = 0.74 and 95%CI 0.64–0.86) and carvedilol (OR = 0.62 and 95%CI 0.52–0.74), respectively. Conclusion: Different types of NSBB have different effects on the incidence of patients with cirrhosis of the liver, where nadolol and carvedilol can reduce the risk. Also, the effect of NSBBs may vary in ethnicity. Propranolol can reduce HCC incidence in Europe and America. Systematic Review Registration: identifier https://CRD42023434175 , https://www.crd.york.ac.uk/PROSPERO/ .

Background Schizophrenia is a severe mental disorder with an increasing burden among adolescents and young adults (aged 10–24 years). However, age-specific epidemiological data remains limited. This study aims to analyze the incidence, prevalence, and disability-adjusted life years (DALYs) of schizophrenia in youth (aged 10–24 years) across the Group of Twenty (G20) countries and to project future trends from 2022 to 2035. Methods Data were sourced from the Global Burden of Disease (GBD) 2021 dataset, encompassing information on 369 diseases across 204 countries and regions from 1990 to 2021. Bayesian age-period-cohort (APC) modeling was employed to estimate future burden. Age-standardized incidence rates (ASIRs), prevalence rates (ASPRs), and DALY rates (ASDRs) were analyzed by country, sex, and sociodemographic index (SDI). Result From 1990 to 2021, the burden of schizophrenia among youth has increased across most G20 countries, with particularly sharp rises observed in China and India. The lowest burdens were reported in Canada, Saudi Arabia, and Australia, which also recorded the lowest DALYs. Russia exhibited marked increases in ASIR, ASPR, and ASDR, while the United States and the United Kingdom showed declines. Substantial variations were observed across gender, regions, and SDI levels. Projections indicate that ASPRs will continue to rise in Australia, China, and Japan through 2035, while declines are anticipated in the United States and Italy, and stability is expected in Argentina and Germany. Conclusion The burden of schizophrenia among youth in G20 countries is increasing, accompanied by substantial regional, gender, and socioeconomic disparities. Strengthening early intervention, enhancing diagnostic capacity, and implementing youth-targeted mental health policies are urgently needed.

Background and aims: Hypoglycemic agents are the primary therapeutic approach for the treatment of diabetes and have been postulated to impact pancreatic cancer (PC) incidence in diabetic patients. We conducted a meta-analysis to further evaluate and establish the associations between four common types of hypoglycemic agents [metformin, sulfonylureas, thiazolidinediones (TZDs), and insulin] and PC incidence in individuals with diabetes mellitus (DM). Methods: A comprehensive literature search of PubMed, Web of Science, Embase, and the Cochrane Library identified studies that analyzed the relationship between hypoglycemic agents and PC published between January 2012 and September 2022. Randomized control trials (RCTs), cohorts, and case–control studies were included if there was clear and evaluated defined exposure to the involved hypoglycemic agents and reported PC outcomes in patients with DM. Furthermore, reported relative risks or odds ratios (ORs) or other provided data were required for the calculation of odds ratios. Summary odds ratio estimates with a 95% confidence interval (CI) were estimated using the random-effects model. Additionally, subgroup analysis was performed to figure out the source of heterogeneity. Sensitivity analysis and publication bias detection were also performed. Results: A total of 11 studies were identified that evaluated one or more of the hypoglycemic agents, including three case–control studies and eight cohort studies. Among these, nine focused on metformin, six on sulfonylureas, seven on TZDs, and seven on insulin. Meta-analysis of the 11 observational studies reported no significant association between metformin (OR = 1.04, 95% CI 0.73–1.46) or TZDs (OR = 1.13, 95% CI 0.73–1.75) and PC incidence, while the risk of PC increased by 79% and 185% with sulfonylureas (OR = 1.79, 95% CI 1.29–2.49) and insulin (OR = 2.85, 95% CI 1.75–4.64), respectively. Considerable heterogeneity was observed among the studies and could not be fully accounted for by study design, region, or adjustment for other hypoglycemic agents. Conclusion: Sulfonylureas and insulin may increase the incidence of pancreatic cancer in diabetic patients, with varying effects observed among different ethnicities (Asian and Western). Due to significant heterogeneity across studies, further interpretation of the relationship between hypoglycemic agents and pancreatic cancer incidence in diabetic patients requires well-adjusted data and better-organized clinical trials.

Trimethylamine-N-oxide (TMAO) is a gut microbiota-derived metabolite, the production of which in vivo is mainly regulated by dietary choices, gut microbiota, and the hepatic enzyme flavin monooxygenase (FMO), while its elimination occurs via the kidneys. The TMAO level is positively correlated with the risk of developing cardiovascular diseases. Recent studies have found that TMAO plays an important role in the development of ischemic stroke. In this review, we describe the relationship between TMAO and ischemic stroke risk factors (hypertension, diabetes, atrial fibrillation, atherosclerosis, thrombosis, etc.), disease risk, severity, prognostic outcomes, and recurrence and discuss the possible mechanisms by which they interact. Importantly, TMAO induces atherosclerosis and thrombosis through lipid metabolism, foam cell formation, endothelial dysfunction (via inflammation, oxidative stress, and pyroptosis), enhanced platelet hyper-reactivity, and the upregulation and activation of vascular endothelial tissue factors. Although the pathogenic mechanisms underlying TMAO’s aggravation of disease severity and its effects on post-stroke neurological recovery and recurrence risk remain unclear, they may involve inflammation, astrocyte function, and pro-inflammatory monocytes. In addition, this paper provides a summary and evaluation of relevant preclinical and clinical studies on interventions regarding the gut-microbiota-dependent TMAO level to provide evidence for the prevention and treatment of ischemic stroke through the gut microbe–TMAO pathway.

Analysis of mechanotransduction among ensembles of sensory hair cells in vivo is challenging in many species. To overcome this challenge, we used optical indicators to investigate mechanotransduction among collections of hair cells in intact zebrafish. Our imaging reveals a previously undiscovered disconnect between hair-cell mechanosensation and synaptic transmission. We show that saturating mechanical stimuli able to open mechanically gated channels are unexpectedly insufficient to evoke vesicle fusion in the majority of hair cells. Although synaptically silent, latent hair cells can be rapidly recruited after damage, demonstrating that they are synaptically competent. Therefore synaptically silent hair cells may be an important reserve that acts to maintain sensory function. Our results demonstrate a previously unidentified level of complexity in sculpting sensory transmission from the periphery. Hair cells of the inner ear are mechanosensors that detect sound, and synapse onto afferent neurons. Here, the authors used calcium imaging to find that not all hair cells are synaptically engaged, but after damage these silent cells are synaptically engaged.

Resource, environmental, and ecological issues have become major constraints to the development of many regions. The Yellow River Basin is an important barrier for maintaining ecological security in northern China, but it has been impacted by problems such as severe soil erosion and declining biodiversity. The rational construction of ecological security patterns is important to enhance ecosystem functions and maintain regional ecological security. In this study, a comprehensive ecological security assessment system was constructed by selecting ecosystem service importance, ecological sensitivity, and landscape connectivity to assess the ecological security of Xiliu Ditch, an ecologically fragile region of the Inner Mongolia section of the Yellow River Basin in China. The assessment results showed significant spatial heterogeneity, with medium- and low-security value areas dominating, while high-security value areas accounted for only 18.7% of the study area. Seventeen ecological sources were identified from the high-security areas, which were mainly composed of grassland, woodland, and water bodies, most of which are distributed in the southern part of the study area. Twenty ecological corridors were selected by the minimum cumulative resistance model and gravity model and classified into 15 construction corridors and 5 potential corridors. Forty-six ecological nodes were defined, including twenty strategic points, nine potential strategic points, and seventeen break points. On this basis, we constructed an ecological security pattern of “two belts, three cores, six zones, multiple corridors and multiple nodes” and proposed corresponding ecological governance measures. This study explores the ecological security pattern at the small watershed scale, which helps to realize the fine management of the Xiliu Ditch basin and, on this basis, can provide scientific support for the ecological protection and sustainable development of the Yellow River basin. In addition, the ecological security assessment system proposed in this study can provide new ideas for the construction of ecological security patterns in similar ecologically fragile areas around the globe.

The demand for cloud computing services has increased dramatically. With the promotion of global low-carbon policies, increasing energy savings and efficiency in cloud computing services is important. By improving load prediction capability, reasonable allocation of cloud service management resources can be effectively realized. However, it is difficult to effectively extract features, and the accuracy of load prediction is poor due to large fluctuations and irregular changes in the cloud resource load. Thus, in this study, we propose a parallel cloud resource load prediction model, PCL-RC, that is based on feature optimization and focuses on feature extraction optimization and load forecasting. To address the problem of nonlinear load data feature extraction, a feature extraction optimization method that is based on combining an improved random forest method and complete ensemble empirical modal decomposition with adaptive noise is proposed to realize regular decomposition and feature extraction from fluctuating data. To address the issues of increased data volume due to decomposition and low prediction accuracy due to difficulty in extracting hidden features, a cloud resource load forecasting method based on an improved lightweight attention mechanism long short-term memory network is proposed. Experiments are conducted on data from the AliCloud platform. The proposed model outperforms the AR, SVR, HAR, Informer, Transform, VMDSE-Tformer and XGBoost models and has improved prediction accuracy.

Ophiocordyceps sinensis is a fungus with medicinal value in treating lung diseases, but no study has reported how to prevent acute lung injury using this fungus. The mice were divided into normal, model, positive control, and O . sinensis groups to observe lung histopathological sections and transmission electron microscopy, along with liquid chromatography-mass spectrometry and hematoxylin and eosin (H&E) staining to closely identify structural differences resulting from destruction between the groups. The results of the H&E staining showed that, compared with the normal group, the model group showed alveolar collapse. Compared with the model group, the infiltration of inflammatory cells in the alveolar cavity of the O . sinensis group was significantly reduced. Mitochondrial plate-like cristae were observed in type II alveolar cells of the normal group, with normal coloration of the mitochondrial matrix. Type II alveolar cells in the model group showed obvious edema. The statuses of type II alveolar cells in the O . sinensis and positive groups were similar to that in the normal group. Twenty-nine biomarkers and 10 related metabolic pathways were identified by serum metabolomics screening. The results showed that O . sinensis mycelia had a significant effect on the prevention of lipopolysaccharide-induced inflammation.

Despite advancements in melanoma therapy, the prognosis remains unfavorable for many patients. The proteasome inhibitor MG132 has shown therapeutic potential through pathway regulation, yet its precise mechanisms in melanoma require systematic elucidation. Using A375 melanoma cells, we conducted multi-modal investigations combining cytotoxicity assessment (CCK8), migration analysis (wound healing), apoptosis quantification (flow cytometry), and proteomic profiling (western blot) to dissect MG132’s molecular mechanisms. Our findings revealed MG132’s potent anti-tumor activity with an IC 50 of 1.258 ± 0.06 µM, significantly suppressing cellular migration at therapeutic concentrations. Apoptosis assays demonstrated concentration-dependent effects, with 2 µM treatment inducing early apoptosis in 46.5% and total apoptotic response in 85.5% of cells within 24 h. Mechanistic studies uncovered MG132’s dual regulatory capacity: (1) Through MDM2 inhibition, it activated p53/p21/caspase-3 axis while suppressing CDK2/Bcl2, triggering cell cycle arrest and DNA damage cascades; (2) MAPK pathway activation emerged as a critical apoptosis driver. Notably, western blot analysis established dose-responsive modulation of these molecular targets, confirming pathway specificity. Our results position MG132 as a multi-target agent capable of simultaneously disrupting proliferative signaling and activating apoptotic machinery. The observed MAPK-mediated apoptosis mechanism provides novel insights for melanoma therapeutics, suggesting that combinatorial targeting of proteasomal and MAPK pathways may enhance treatment efficacy.

Prostate stem cell antigen (PSCA) is associated with disease progression, promotion of angiogenesis, invasion, metastasis and immune evasion in cancer. However, its expression pattern and diagnostic and prognostic potential have not been thoroughly analysed from a pan-cancer perspective. This study aimed to examine the effects of PSCA on the prognosis and inflammatory cell infiltration patterns of various cancer types. We analysed the relationship between PSCA expression and immunological subtypes in tumor microenvironment (TME) and the role of molecular subtypes, potentially promising immune biomarkers and tumour-infiltrating lymphocytes (TILs) in various cancer types, especially lung adenocarcinoma (LUAD). In addition, we investigated the prognostic significance of PSCA expression in LUAD. The co-expression network of PSCA was found to be mainly involved in the regulation of immune responses and antigen processing and expression and was significantly enriched in pathological and substance metabolism-related pathways in cancer. Altogether, this study reveals that PSCA is a promising target for immunotherapy in patients with cancer.