Explore the vast range of titles available.

Non-alcoholic fatty liver disease (NAFLD) is an important health issue worldwide. We aimed to develop a simple model to determine the presence of NAFLD in a Chinese population. A cross-sectional study with 9602 subjects was conducted. Potential predictors were entered into a stepwise logistic regression analysis to obtain the model. We used 148 patients with liver biopsy to validate this model. The model, named the ZJU index, was developed based on body mass index (BMI), fasting plasma glucose (FPG), triglycerides (TG) and the serum alanine aminotransferase (ALT) to serum aspartate transaminase (AST) ratio. The area under the receiver operating characteristic curve (AUROC) of the ZJU index to detect NAFLD was 0.822. At a value of <32.0, the ZJU index could rule out NAFLD with a sensitivity of 92.2% and at a value of >38.0, the ZJU index could detect NAFLD with a specificity of 93.4%. In patients with liver biopsy, the ZJU index could detect steatosis with good accuracy, with an AUROC of 0.896. This study revealed that the ZJU index is a helpful model to detect NAFLD for community physicians in China. It was validated not only by a validation cohort but also by pathological data.

ObjectiveAccumulation of free fatty acids (FFAs) in hepatocytes induces lipotoxicity, leading to non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the underlying mechanisms by which FFA contributes to the pathogenesis of NAFLD via the regulation of 3-mercaptopyruvate sulfurtransferase (MPST), a key enzyme that regulates endogenous hydrogen sulfide (H2S) biosynthesis.DesignHepatic MPST expression was evaluated in mice and patients with NAFLD. A variety of molecular approaches were used to study the effects of MPST regulation on hepatic steatosis in vivo and in vitro.ResultsIn vitro treatment of hepatocytes with FFAs upregulated MPST expression, which was partially dependent on NF-κB/p65. Hepatic MPST expression was markedly increased in high fat diet (HFD)-fed mice and patients with NAFLD. Partial knockdown of MPST via adenovirus delivery of MPST short hairpin RNA or heterozygous deletion of the Mpst gene significantly ameliorated hepatic steatosis in HFD-fed mice. Consistently, inhibition of MPST also reduced FFA-induced fat accumulation in L02 cells. Intriguingly, inhibition of MPST significantly enhanced rather than decreased H2S production, whereas MPST overexpression markedly inhibited H2S production. Co-immunoprecipitation experiments showed that MPST directly interacted with and negatively regulated cystathionine γ-lyase (CSE), a major source of H2S production in the liver. Mechanistically, MPST promoted steatosis via inhibition of CSE/H2S and subsequent upregulation of the sterol regulatory element-binding protein 1c pathway, C-Jun N-terminal kinase phosphorylation and hepatic oxidative stress.ConclusionsFFAs upregulate hepatic expression of MPST and subsequently inhibit the CSE/H2S pathway, leading to NAFLD. MPST may be a potential therapeutic target for NAFLD.

In order to study the effect of random pitting defects on the bearing capacity of steel structures in underground engineering, four kinds of samples containing random pitting defects were made and simulated damage tests were carried out. The effects of pitting damage on the failure mode, bearing capacity and deformation capacity of the components were analyzed by compression testing and three-point bending testing of the complete samples and four kinds of prefabricated pitting damage samples. The results show that the existence of pitting damage will change the bending failure mode of the samples, and the four types of pitting damage will reduce the compressive bearing capacity and bending bearing capacity of the members to varying degrees, among which the inclined pitting damage specimens have the highest reduction in compressive and bending bearing capacity. The four types of pitting damage also reduce the compressive deformation ability of the specimen, but the influence of different damage distribution types on the bending deformation ability is very different.

The prevalence and incidence of metabolic-associated fatty liver disease (MAFLD), a clinically heterogeneous disease whose primary clinical therapies include dietary control and exercise therapy, is increasing worldwide and constitutes a significant medical burden. Gut microbes influence the physiopathological processes of the liver through different mechanisms based on the gut-liver axis. Exosomes are essential carriers of intercellular communication. Most previous studies have focused on adipocyte- and hepatocyte-derived exosomes, while the critical role of microbial-derived exosomes and the molecular mechanisms behind them in MAFLD have received little attention. Therefore, we searched and screened the latest relevant studies in the PubMeb database to elucidate the link between microbial-derived exosomes and the pathogenesis of MAFLD, mainly in terms of insulin resistance, intestinal barrier, inflammatory response, lipid metabolism, and liver fibrosis. The aim was to provide a theoretical framework and support for clinical protocols and innovative drug development.

The Nuclear Factor of Activated T-cells cytoplasmic 1 (NFATc1) is identified to be an oncogene in several human cancers. However, its specific role in HCC progression and the relevant mechanisms remain unclear. To investigate this, we analyzed NFATc1 expression in clinical HCC samples ( n  = 289) using RT-qPCR, Western blotting, and immunohistochemistry (IHC). In vitro assays assessed HCC cell proliferation, migration, invasion, apoptosis, and cell cycle, while in vivo studies using BALB/c nude mice evaluated the effects of NFATc1 on HCC growth and metastasis. Mechanistic studies were conducted to explore NFATc1’s downstream signaling pathways. Results revealed that NFATc1 is significantly upregulated in HCC tissues compared to adjacent non-cancerous tissues, correlating with poor prognosis. Overexpression of NFATc1 enhanced HCC cell proliferation, migration, and invasion both in vitro and in vivo, while silencing NFATc1 reduced these malignant traits. Mechanistic analysis indicated that NFATc1 activation correlates with NF-κB/TMP21 signaling and senescence-associated secretory phenotype (SASP) amplification, independent of growth arrest. These findings suggest that NFATc1 plays a pivotal role in HCC progression, potentially through the modulation of SASP activation. Targeting NFATc1 and its signaling pathways could be a promising therapeutic approach for HCC.

Gastric-type mucinous adenocarcinoma (GAS) is an uncommon cervical adenocarcinoma, which is not associated with human papillomavirus (HPV) infection. Compared with HPV-associated cervical adenocarcinoma, GAS has characteristics of larger volume, deep invasion, and easy to metastasize to distant sites. Also, GAS is typically resistant to chemo/radiotherapy. Few studies have reported the molecular genetic characteristics of GAS. In order to investigate the molecular genetic characteristics of GAS and reveal its possible pathogenesis, 15 GAS patients were enrolled from Peking University People’s Hospital (2009–2019) and examined with next-generation sequencing (NGS). Based on the clinicopathologic feature analysis, we found that the presence of lymph node metastasis and extensive lymphovascular invasion were associated with poor survival outcomes of GAS (p = 0.0042 and p = 0.005, respectively). Based on the NGS testing, our results showed that the most frequently mutated gene was TP53 (8/15, 53.3%), followed by STK11, CDKN2A, and ARID1A. STK11 mutations were more frequent in well-differentiated GAS (33.3% vs. 0.0%, p = 0.026) and patients with extensive lymphovascular invasion (33.3% vs. 0.0%, p = 0.044). Survival analysis revealed that STK11 mutations were significantly associated with the poor prognosis of GAS (p = 0.01). Our results also showed that mutations in the target drug were detected in 53.3% of GAS patients. Patients with ERBB2 amplification (13.3%) presented the highest level of evidence according to OncoKB recommendations. These results indicate that the genomic alterations of GAS mainly involved the cell cycle and PI3K/AKT signaling pathways, and some therapeutic candidates were identified in GAS patients.

Background Nonalcoholic fatty liver disease (NAFLD) is a global public health problem. Lifestyle modifications aimed at promoting weight loss and weight maintenance remain the current first‐line treatments for NAFLD. Objective We aim to identify barriers and enabling factors in weight management among patients with NAFLD using the capability, opportunity, motivation, behaviour (COM‐B) model of behaviour. Design This study adopted a qualitative design using semistructured interviews analysed with content analysis and the COM‐B framework. Setting and Participants Interviews were conducted with 27 patients with NAFLD who experienced successful or unsuccessful weight reduction. Results Our study included 27 participants: 15 participants with successful weight loss (successful weight loss refers to a decrease in body weight ≥7% of the initial body weight for patients with NAFLD) and 12 participants with unsuccessful weight loss. Thirty‐five themes (19 barriers and 16 facilitators) were mapped onto the COM‐B model as barriers and facilitators to weight management among patients with NAFLD. The key barriers were lack of time and energy, lack of awareness of weight, lack of attention to NAFLD, treating food as a reward or compensation and social entertainment. The key facilitators were having basic weight loss knowledge and skills, strong motivation, attention to NAFLD, unsuccessful weight loss experiences and positive feedback from phased success. Conclusion In addition to identifying factors consistent with existing studies, this study identified factors that influence weight management in NAFLD patients, such as basic weight loss skills and rational thinking before weight loss, which were not previously reported. This has clinical implications for clinical healthcare providers and health management services for the improvement of education and support regarding lifestyle improvement and weight management in patients with NAFLD. Patient or Public Contribution We recruited potential participants from the Bariatric Clinic, Hepatology Clinic and Physical Examination Center of hospitals between March 2021 and October 2021. Twenty‐seven patients with NAFLD who had successful or unsuccessful weight loss experiences participated in the study and responded to questions on weight management.

The intestinal mucus layer is a barrier that separates intestinal contents and epithelial cells, as well as acts as the \"mucus layer-soil\" for intestinal flora adhesion and colonization. Its structural and functional integrity is crucial to human health. Intestinal mucus is regulated by factors such as diet, living habits, hormones, neurotransmitters, cytokines, and intestinal flora. The mucus layer's thickness, viscosity, porosity, growth rate, and glycosylation status affect the structure of the gut flora colonized on it. The interaction between \"mucus layer-soil\" and \"gut bacteria-seed\" is an important factor leading to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Probiotics, prebiotics, fecal microbiota transplantation (FMT), and wash microbial transplantation are efficient methods for managing NAFLD, but their long-term efficacy is poor. FMT is focused on achieving the goal of treating diseases by enhancing the \"gut bacteria-seed\". However, a lack of effective repair and management of the \"mucus layer-soil\" may be a reason why \"seeds\" cannot be well colonized and grow in the host gut, as the thinning and destruction of the \"mucus layer-soil\" is an early symptom of NAFLD. This review summarizes the existing correlation between intestinal mucus and gut microbiota, as well as the pathogenesis of NAFLD, and proposes a new perspective that \"mucus layer-soil\" restoration combined with \"gut bacteria-seed\" FMT may be one of the most effective future strategies for enhancing the long-term efficacy of NAFLD treatment.

A spatially heterogeneous reaction-diffusion system modelling pre-dator-prey interaction is studied, where the interaction is governed by a Holling type II functional response. Existence of multiple positive steady states and global bifurcation branches are examined as well as related dynamical behavior. It is found that while the predator population is not far from a constant level, the prey population could be extinguished, persist or blow up depending on the initial population distributions, the various parameters in the system, and the heterogeneous environment. In particular, our results show that when the prey growth is strong, the spatial heterogeneity of the environment can play a dominant role for the presence of the Allee effect. Our mathematical analysis relies on bifurcation theory, topological methods, various comparison principles and elliptic estimates. We combine these methods with monotonicity arguments to the system through the use of some new auxiliary scalar equations, though the system itself does not keep an order structure as the competition system does. Among other things, this allows us to obtain partial descriptions of the dynamical behavior of the system.