TRIM45 facilitates NASH-progressed HCC by promoting fatty acid synthesis via catalyzing FABP5 ubiquitylation.

Non-alcoholic steatohepatitis (NASH) is rapidly surpassing viral hepatitis as the primary cause of hepatocellular carcinoma (HCC). However, understanding of NASH-progressed HCC remains poor, which might impede HCC diagnosis and therapy. In this study, we aim to identify shared transcriptional changes between NASH and HCC, of which we focused on E3 ligase TRIM45. We found TRIM45 exacerbates HCC cells proliferation and metastasis in vitro and in vivo. Further transcriptome analysis revealed TRIM45 predominantly affects fatty acid metabolism and oleic acid restored impaired proliferation and metastasis of TRIM45-deficient HCC cells. IP-tandem mass spectrum and FABP5 depriving experiment indicated that TRIM45 enhance fatty acid synthesis depending on FABP5 presence. Interestingly, we found TRIM45 directly added K33-type and K63-type poly-ubiquitin chains to FABP5 NLS domain, which ultimately promoted FABP5 nuclear translocation. Nuclear FABP5 interacted with PPARγ to facilitate downstream lipid synthesis gene expression. We observed TRIM45 accelerated NASH-to-HCC transition and exacerbated both NASH and NASH-HCC with the enhanced fatty acid production in vivo. Moreover, high concentration of fatty acid increased TRIM45 expression. The established mechanism was substantiated by gene expression correlation in TCGA-LIHC. Collectively, our research revealed a common lipid reprograming process in NASH and HCC and identified the cyclical amplification of the TRIM45-FABP5-PPARγ-fatty acid axis. This signaling pathway offers potential therapeutic targets for therapeutic intervention in NASH and NASH-progressed HCC.

Global Burden and Trends of Primary Liver Cancer Attributable to Comorbid Type 2 Diabetes Mellitus Among People Living with Hepatitis B: An Observational Trend Study from 1990 to 2019.

BACKGROUND: Type 2 diabetes mellitus (T2DM) increases the risk of liver cancer among people living with hepatitis B virus (HBV). Our study aimed to estimate the global burden and trends of liver cancer attributable to comorbid T2DM among people living with HBV from 1990 to 2019. METHODS: We calculated the population attributable fractions (PAFs) of liver cancer attributable to comorbid T2DM among the burden of HBV-related liver cancer. We applied the PAFs to the burden of HBV-related liver cancer derived from the Global Burden of Disease (GBD) 2019 database to obtain the burden of liver cancer attributable to HBV-T2DM comorbidity. The prevalence, disability-adjusted life year (DALY), and deaths of liver cancer attributable to the comorbidity were assessed at the global, regional, and country levels and then stratified by the sociodemographic index (SDI), sex, and age group. Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends. RESULTS: In 2019, the global age-standardized prevalence and DALY rates of liver cancer attributable to HBV-T2DM comorbidity were 9.9 (8.4-11.5) and 182.4 (154.9-212.7) per 10,000,000 individuals, respectively. High-income Asia Pacific and East Asia had the highest age-standardized prevalence and DALY rates of liver cancer attributable to HBV-T2DM comorbidity, respectively. From 1990 to 2019, age-standardized prevalence and DALY rates increased in 16 out of 21 GBD regions. High-income North America had the largest annual increases in both age-standardized prevalence rates (EAPC = 6.07; 95% UI, 5.59 to 6.56) and DALY rates (EAPC = 4.77; 95% UI, 4.35 to 5.20), followed by Australasia and Central Asia. Across all SDI regions, the high SDI region exhibited the most rapid increase in age-standardized prevalence and DALY rates from 1990 to 2019. Additionally, men had consistently higher disease burdens than women across all age groups. The patterns of mortality burden and trends are similar to those of DALYs. CONCLUSIONS: The burden of liver cancer attributable to comorbid T2DM among people living with HBV has exhibited an increasing trend across most regions over the last three decades. Tailored prevention strategies targeting T2DM should be implemented among individuals living with HBV.

Role of C/EBP Homologous Protein (CHOP) and Nupr1 Interaction in Endoplasmic Reticulum Stress-Induced Apoptosis of Lens Epithelial Cells.

Our study mainly analyzed the mechanism of C/EBP homologous protein (CHOP) and its interacting protein Nupr1 on endoplasmic reticulum stress (ERS) induced lens epithelial cells (LEC) apoptosis. Cell proliferation was detected by CCK-8. Apoptosis was detected by flow cytometry and TUNEL. Nupr1 expression was detected by RT-qPCR. The expressions of CHOP, Nupr1, apoptosis-related protein, and ERS-related protein were detected by Western blot. DCFH-DA probe was used to detect cell ROS. The SOD, GSH-PX, and MDA contents were detected by the kit. Co-IP was used to detect the interaction between CHOP and Nupr1. The morphology of the lens was detected by HE staining. The result shows that Tunicamycin (TU) can induce endoplasmic reticulum stress and apoptosis in LEC in a concentration-dependent manner. TU induction leads to the occurrence of CHOP nuclear translocation. Overexpression of CHOP can further enhance the inhibitory effect of TU on LEC proliferation and the promotion of apoptosis, while knockdown of CHOP has the opposite effect. CHOP and Nupr1 are interacting proteins, and knockdown of Nupr1 or addition of Nupr1 inhibitor ZZW-115 can reverse the effects of TU and overexpression of CHOP, respectively. It has been observed in animal experiments that treatment with oe-CHOP can further aggravate the pathological lesions of the rat lens, while ZZW-115 can reverse the effect of oe-CHOP to a certain extent and improve the lesions of the rat lens. Overall, CHOP interacts with Nupr1 to regulate apoptosis caused by ERS and mediate cataract progression in rats, and this study provides a new potential therapeutic target for the treatment of cataract.

Titration of sedentary behavior with varying physical activity levels reduces mortality in patients with type 2 diabetes.

CONTEXT: Both physical activity (PA) and sedentary behavior (SB) exert important impact on type 2 diabetes, but it remains unclear how maximum impact on improving the mortality and optimized proportion of the two lifestyles combination exists. OBJECTIVE: To explore the impacts of PA/SB combinations on mortality in patients with diabetes. METHODS: Patients with type 2 diabetes patients samplings were collected from the National Health and Nutrition Examination Survey (NHANES) dataset. Their lifestyles were categorized into eight groups based on combinations of the PA and SB levels. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals. RESULTS: During the follow-up period, 1,148 deaths (18.94%) were recorded. High SB (sedentary time ≥6 hours/day) was significantly associated with higher all-cause mortality (HR 1.65). In participants with low SB (<6 hours/day), low PA was associated with lower all-cause mortality (HR 0.43), while further increase of PA level did not show further reduction in either all-cause or cardiovascular mortality. In contrast, in participants with high SB，all levels of PA were associated with lower all-cause mortality (p<0.05), but only moderate PA was associated with lower cardiovascular mortality (HR 0.30). CONCLUSIONS: In patients with type 2 diabetes, different combinations of various levels of PA and SB are associated with different degree of risk for all-cause or cardiovascular mortality.

miRNA-383-5p Regulated Migration and Invasion of Tumor Cells by Inhibiting NCKAP1 Expression in Gastric Cancer.

Gastric cancer (GC) is the second deadliest disease in Asia, so it is crucial to find its promising therapeutic targets. The expression profile data of miR383-5p in the Cancer Genome Atlas (TCGA) were analyzed. The expression levels of miR383-5p in the collected clinical tissue samples and peripheral blood samples were examined by qPCR, and the relationship between its expression and the clinical data of patients was evaluated. MiR383-5p was overexpressed in the AGS cells, and cell biology assays, such as Transwell, were performed to detect the cell proliferation, migration, invasion and other cell biology abilities of miR383-5p. Target prediction and dual luciferase reporter gene assay were performed to find and validate the target genes of miR383-5p. The expression and activity of MMP and related proteins after overexpression of miR383-5p and NCKAP1 were detected by WB and gelatin zymography assay. The expression of miR383-5p was down-regulated in GC tissues, and its low expression was associated with lymph node metastasis. Restoration of miR383-5p expression in GC cells can inhibit the invasion and migration abilities of GC cells. MiR383-5p negatively regulated NCKAP1 through direct interaction with the 3'UTR sequence of NCKAP1. The overexpression of NCKAP1 can improve the migration and invasion abilities of GC cells, whereas overexpression of miR383-5p can inhibit growth of the aforementioned abilities of GC cells induced by NCKAP1 overexpression. The overexpression of NCKAP1 can increase the expression level and activity of MMP2, while the overexpression of miR383-5p can inhibit the increase of MMP2 expression level and activity in GC cells induced by NCKAP1 overexpression. NCKAP1 is a target gene of miR383-5p, and miR383-5p could be a valuable therapeutic target for stomach adenocarcinoma.

Effects of Fat and Carnitine on the Expression of Carnitine Acetyltransferase and Enoyl-CoA Hydratase Short-Chain 1 in the Liver of Juvenile GIFT (Oreochromis niloticus).

Carnitine acetyltransferase (CAT) and Enoyl-CoA hydratase short-chain 1 (ECHS1) are considered key enzymes that regulate the ß-oxidation of fatty acids. However, very few studies have investigated their full length and expression in genetically improved farmed tilapia (GIFT, Oreochromis niloticus), an important aquaculture species in China. Here, we cloned CAT and ECHS1 full-length cDNA via the rapid amplification of cDNA ends, and the expressions of CAT and ECHS1 in the liver of juvenile GIFT were detected in different fat and carnitine diets, as were the changes in the lipometabolic enzymes and serum biochemical indexes of juvenile GIFT in diets with different fat and carnitine levels. CAT cDNA possesses an open reading frame (ORF) of 2167 bp and encodes 461 amino acids, and the ECHS1 cDNA sequence is 1354 bp in full length, the ORF of which encodes a peptide of 391 amino acids. We found that juvenile GIFT had higher lipometabolic enzyme activity and lower blood CHOL, TG, HDL-C, and LDL-C contents when the dietary fat level was 2% or 6% and when the carnitine level was 500 mg/kg. We also found that the expression of ECHS1 and CAT genes in the liver of juvenile GIFT can be promoted by a 500 mg/kg carnitine level and 6% fat level feeding. These results suggested that CAT and ECHS1 may participate in regulating lipid metabolism, and when 2% or 6% fat and 500 mg/kg carnitine are added to the feed, it is the most beneficial to the liver and lipid metabolism of juvenile GIFT. Our results may provide a theoretical basis for GIFT feeding and treating fatty liver disease.

Relationships between long-term exposure to major PM2.5 constituents and outpatient visits and hospitalizations in Guangdong, China.

Ambient fine particulate matter (PM2.5) has attracted considerable attention due to its crucial role in the rising global disease burden. Evidence of health risks associated with exposure to PM2.5 and its major constituents is important for advancing hazard assessments and air pollution emission policies. We investigated the relationship between exposure to major constituents of PM2.5 and outpatient visits as well as hospitalizations in Guangdong Province, China, where 127 million residents live in a severe PM2.5 pollution environment. An approach that integrates the generalized weighted quantile sum (gWQS) regression with the difference-in-differences (DID) approach was used to assess the overall mixture effects and relative contributions of each constituent. We observed significant associations between long-term exposure to the mixture of PM2.5 constituents (WQS index) and outpatient visits (IR%, percentage increases in risk per unit WQS index increase:1.73, 95%CI: 1.72, 1.74) as well as hospitalizations (IR%:5.15, 95%CI: 5.11, 5.20). Black carbon (weight: 0.34) and nitrate (weight: 0.60) respectively exhibited the highest contributions to outpatient visits and hospitalizations. The overall mixture effects on outpatient visits and hospitalizations were higher with increased summer air temperatures (IR%: 7.54, 95%CI: 7.33, 7.74 and IR%: 9.55, 95%CI: 8.36, 10.75, respectively) or decreased winter air temperatures (IR%: 1.88, 95%CI: 1.68, 2.08 and IR%: 4.87, 95%CI: 3.73, 6.02, respectively). Furthermore, the overall mixture effects on outpatient visits and hospitalizations were significantly higher in populations with higher socioeconomic status (P < 0.01). It's crucial to address the primary sources of nitrate precursor substances and black carbon (mainly traffic-related and industrial-related air pollutants) and consider the complex interaction effects between air temperature and PM2.5 in the context of climate change. Of particular concern is the need to prioritize healthcare demands in economically disadvantaged regions and to address the health inequalities stemming from the uneven distribution of healthcare resources and PM2.5 pollution.

Research progress of flexible pressure sensor based on MXene materials.

Flexible pressure sensors overcome the limitations of traditional rigid sensors on the surface of the measured object, demonstrating broad application prospects in fields such as sports health and vital sign monitoring due to their excellent flexibility and comfort in contact with the body. MXene, as a two-dimensional material, possesses excellent conductivity and abundant surface functional groups. Simultaneously, MXene's unique layered structure and large specific surface area offer a wealth of possibilities for preparing sensing elements in combination with other materials. This article reviews the preparation methods of MXene materials and their performance indicators as sensing elements, discusses the controllable preparation methods of MXene materials and the impact of their physical and chemical properties on their functions, elaborates on the pressure sensing mechanism and evaluation mechanism of MXene materials. Starting from the four specific application directions: aerogel/hydrogel, ink printing, thin film/electronic skin, and fiber fabric, we introduce the research progress of MXene flexible pressure sensors from an overall perspective. Finally, a summary and outlook for developing MXene flexible pressure sensors are provided.

Effectiveness of a WHO self-help psychological intervention to alleviate stress among healthcare workers in the context of COVID-19 in China: a randomised controlled trial.

AIMS: To examine the effectiveness of Self-Help Plus (SH+) as an intervention for alleviating stress levels and mental health problems among healthcare workers. METHODS: This was a prospective, two-arm, unblinded, parallel-designed randomised controlled trial. Participants were recruited at all levels of medical facilities within all municipal districts of Guangzhou. Eligible participants were adult healthcare workers experiencing psychological stress (10-item Perceived Stress Scale scores of ≥15) but without serious mental health problems or active suicidal ideation. A self-help psychological intervention developed by the World Health Organization in alleviating psychological stress and preventing the development of mental health problems. The primary outcome was psychological stress, assessed at the 3-month follow-up. Secondary outcomes were depression symptoms, anxiety symptoms, insomnia, positive affect (PA) and self-kindness assessed at the 3-month follow-up. RESULTS: Between November 2021 and April 2022, 270 participants were enrolled and randomly assigned to either SH+ (n = 135) or the control group (n = 135). The SH+ group had significantly lower stress at the 3-month follow-up (b = -1.23, 95% CI = -2.36, -0.10, p = 0.033) compared to the control group. The interaction effect indicated that the intervention effect in reducing stress differed over time (b = -0.89, 95% CI = -1.50, -0.27, p = 0.005). Analysis of the secondary outcomes suggested that SH+ led to statistically significant improvements in most of the secondary outcomes, including depression, insomnia, PA and self-kindness. CONCLUSIONS: This is the first known randomised controlled trial ever conducted to improve stress and mental health problems among healthcare workers experiencing psychological stress in a low-resource setting. SH+ was found to be an effective strategy for alleviating psychological stress and reducing symptoms of common mental problems. SH+ has the potential to be scaled-up as a public health strategy to reduce the burden of mental health problems in healthcare workers exposed to high levels of stress.

The global research of artificial intelligence in lung cancer: a 20-year bibliometric analysis.

Background: Lung cancer (LC) is the second-highest incidence and the first-highest mortality cancer worldwide. Early screening and precise treatment of LC have been the research hotspots in this field. Artificial intelligence (AI) technology has advantages in many aspects of LC and widely used such as LC early diagnosis, LC differential classification, treatment and prognosis prediction. Objective: This study aims to analyze and visualize the research history, current status, current hotspots, and development trends of artificial intelligence in the field of lung cancer using bibliometric methods, and predict future research directions and cutting-edge hotspots. Results: A total of 2931 articles published between 2003 and 2023 were included, contributed by 15,848 authors from 92 countries/regions. Among them, China (40%) with 1173 papers,USA (24.80%) with 727 papers and the India(10.2%) with 299 papers have made outstanding contributions in this field, accounting for 75% of the total publications. The primary research institutions were Shanghai Jiaotong University(n=66),Chinese Academy of Sciences (n=63) and Harvard Medical School (n=52).Professor Qian Wei(n=20) from Northeastern University in China were ranked first in the top 10 authors while Armato SG(n=458 citations) was the most co-cited authors. Frontiers in Oncology(121 publications; IF 2022,4.7; Q2) was the most published journal. while Radiology (3003 citations; IF 2022, 19.7; Q1) was the most co-cited journal. different countries and institutions should further strengthen cooperation between each other. The most common keywords were lung cancer, classification, cancer, machine learning and deep learning. Meanwhile, The most cited papers was Nicolas Coudray et al.2018.NAT MED(1196 Total Citations). Conclusions: Research related to AI in lung cancer has significant application prospects, and the number of scholars dedicated to AI-related research on lung cancer is continually growing. It is foreseeable that non-invasive diagnosis and precise minimally invasive treatment through deep learning and machine learning will remain a central focus in the future. Simultaneously, there is a need to enhance collaboration not only among various countries and institutions but also between high-quality medical and industrial entities.

Is cryoablation still suitable for advanced non-small cell lung cancer after failure of first-line chemotherapy? A multicenter, prospective, randomized-controlled trial of eighty-seven patients.

The aim of this study was to investigate the therapeutic effect of cryoablation treatment in advanced NSCLC patients who had failed first-line chemotherapy. Eighty-seven patients from ten hospitals in China were enrolled into the study, forty-four patients received cryoablation treatment plus basic treatment (experimental group), and forty-three patients had basic treatment alone (control group). Follow-up was performed once every three months until the end of the study or the death of the patient. The primary endpoints were overall and post-intervention survival; secondary endpoints included tumor markers, solid tumor efficacy, and symptom changes before and after treatment. There was no significant difference in median OS between the two groups of patients (9.0 months vs 11.2 months, P = 0.583). The disease control rate (DCR) and living quality of the experimental group was higher than that of the control group. In terms of OS, indiscriminate use of cryoablation for such patients was not beneficial, though it could improve symptoms of patients. Cryoablation had a significant effect on selected advanced NSCLC patients after the failure of first-line chemotherapy.

Assessing the impact of comorbid type 2 diabetes mellitus on the disease burden of chronic hepatitis B virus infection and its complications in China from 2006 to 2030: a modeling study.

BACKGROUND: China bears a high burden of both hepatitis B virus (HBV) infection and type 2 diabetes mellitus (T2DM). T2DM accelerates the progression of liver disease among individuals infected with HBV. This study aims to assess the excess disease burden caused by comorbid T2DM among HBV-infected individuals in China. METHODS: We estimated the disease burden of HBV and its complications in China from 2006 to 2030 using individual-based Markov models. The baseline population consisted of 93 million HBV-infected individuals derived from the 2006 National Serological Epidemiological Survey. We developed two models: one incorporated the impact of T2DM on the disease progression of HBV infection, while the other did not consider the impact of T2DM. By comparing the outcomes between these two models, we estimated the excess disease burden attributable to comorbid T2DM among HBV-infected individuals. RESULTS: The incidence of severe HBV complications, including cirrhosis, hepatocellular carcinoma (HCC), and liver-related deaths, exhibited an increasing trend from 2006 to 2030 among the Chinese HBV-infected population. Comorbid T2DM increased the annual incidence and cumulative cases of severe HBV complications. From 2006 to 2022, comorbid T2DM caused 791,000 (11.41%), 244,000 (9.27%), 377,000 (8.78%), and 796,000 (12.19%) excess cases of compensated cirrhosis, decompensated cirrhosis, HCC, and liver-related deaths, respectively. From 2023 to 2030, comorbid T2DM is projected to result in an 8.69% excess in severe HBV complications and an 8.95% increase in liver-related deaths. Among individuals aged 60 and older at baseline, comorbid T2DM led to a 21.68% excess in severe HBV complications and a 28.70% increase in liver-related deaths from 2006 to 2022, with projections indicating a further 20.76% increase in severe HBV complications and an 18.31% rise in liver-related deaths over the next seven years. CONCLUSIONS: Comorbid T2DM imposes a substantial disease burden on individuals with HBV infection in China. Healthcare providers and health policymakers should develop and implement tailored strategies for the effective management and control of T2DM in individuals with HBV infection.

Preventing post-discharge suicides in psychiatric patients: insights from patients, lay healthcare supporters, and mental health professionals-a qualitative analysis.

BACKGROUND: Discharged psychiatric patients are at higher risk of suicide due to various risk factors in their lives compared to the general population. However, specific problems and needs of these patients after discharge remain unclear. This research constitutes a segment of a broader implementation study designed to formulate an interventional strategy targeting post-discharge suicide among Chinese psychiatric patients. The present study seeks to qualitatively investigate the problems and needs from the perspectives of patients, their lay healthcare supporters (LHSs), and mental health professionals (MPs), aiming to enhance the efficacy of the interventional strategy. METHODS: This study is part of a larger implementation study based on Shenzhen Kangning Hospital (SKH) in Shenzhen, Guangdong, China. Under the community-based participatory research framework, we recruited discharged psychiatric patients, their LHSs, and MPs as a collaborative community team, and we conducted individual in-depth interviews for patients and LSHs and focus group interviews with MPs. We utilized a thematic analysis approach to identify sub-themes and themes from interviews through systematically coding and analyzing the data. RESULTS: A total of 45 participants were recruited for interviews, comprising 17 patients, 8 LHSs, and 20 MPs. We conducted 25 individual in-depth interviews and 3 focus group interviews. Through the interviews, we identified three themes of post-discharge problems: problems related to self, family-related problems, societal and community-related problems. We also identified four themes related to reducing post-discharge suicide: proactive self-management, multifunctional relatives, multifunctional MP group, and a warm society. The tangible support from LHSs and emotional support from MPs are strongly emphasized. Follow-up interventions were identified as the most significant way to addressing these unmet needs. Instrumental support from the community and a caring and non-discriminatory environment for individuals with mental disorders are essential for reducing suicide risk. CONCLUSIONS: Establishing an integrated mental health care service network that connects psychiatric patients, LHSs, and MPs cross community and societal sectors, with patient-centered follow-up care at its core, is a practical approach to better address patients' needs and reduce post-discharge suicide. TRIAL REGISTRATION: Registration number: NCT04907669. Date of registration: May 26th,2021.

Liver Stiffness Measurement is Useful in Predicting Type 2 Diabetes Mellitus Among Nonalcohol Fatty Liver Disease Patients.

Background: Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) are closely related conditions. Aim: This study investigated a group of individuals with NAFLD to evaluate if liver fibrosis, identified by FibroScan, correlated with T2DM. Methods: 154 NAFLD patients obtained FibroScan, liver ultrasonography (US), and a thorough assessment of clinical implications and chemical biomarkers. Results: In comparison to the NAFLD without T2DM group, the hemoglobin A1c(HBA1c)(mmol/mol%), homeostasis model of assessment for insulin resistance index (HOMA-IR), gamma-glutamyl transferase (GGT), fibrosis indices, and liver stiffness measurement (LSM) values were all considerably higher in the NAFLD with T2DM group. Patients with NAFLD and T2DM had considerably lower serum uric acid(SUA) levels than those with NAFLD alone.Those with severe fibrosis (79.3%, 23/29) in the NAFLD group showed a greater frequency of T2DM than those with mild fibrosis (45.6%, 21/46) or no fibrosis (27.85%, 22/79) (P=0.000). LSM value and elements of the metabolic syndrome (MetS) were independent risk factors for incident T2DM among NAFLD patients (OR=1.466, 95% CI [1.139-1.888], P=0.003; and OR=0.273, 95% CI [0.081-0.916], P=0.036). Conclusion: FibroScan can identify significant fibrosis, which is independently linked to a higher prevalence of T2DM. As a result, it is crucial to make use of this technology to predict T2DM in NAFLD patients.

Sustainable Aerobic Bromination with Controllable Chemoselectivity.

The formation of C-Br(s) is one of the most fundamental reactions in organic synthesis. Oxidative bromination is a "green" way to achieve it. Aerobic bromination has drawn great interest in the past decades, while the poor substrate scope and selectivity, low efficiency, and the use of metal catalyst still confine its application. In this article, we establish a transition-metal-free aerobic bromination promoted by ionic liquid in a catalytic amount with controllable chemoselectivity toward numbers of C-Br(s) formed, and both NaBr/AcOH and HBr(aq) could be used as the bromine source. This methodology shows high efficiency and has a broad substrate scope for various kinds of C-H(s). We also validate this system by the gram-scale (one-pot) synthesis of functional molecules and direct recycle of the catalyst. The possible radical pathway of this catalysis is also presented with evidence.

Recent progress in biosensor regeneration techniques.

Biosensors are widely used in various applications, from medical diagnostics to environmental monitoring. Their widespread and continuous use necessitates regeneration methods to ensure cost-effectiveness and sustainability. In the realm of advancing human-centric bioelectronics for continuous monitoring, employing these sensors for real-time, in situ detection of biomarkers presents a considerable challenge. This mini-review examines diverse strategies utilized for the regeneration of biosensors, categorizing them based on their underlying mechanisms and discussing representative works. We explore methods ranging from surface engineering/re-functionalization, chemical treatments, allosteric regulation of bioreceptors, to manipulations of electric/magnetic fields, highlighting their working principles and exemplary studies. The advantages of each method, such as simplicity, high regeneration efficiency, and versatility, are discussed alongside their challenges, including degradation over cycles, limited applicability, and potential damage to sensors. As the demand for continuous and real-time biosensing escalates, the development of efficient and reliable regeneration strategies becomes essential. This mini-review offers an overview of the current landscape of biosensor regeneration, aiming to guide future research and innovations in this area.

Beyond low-pass filtering on large-scale graphs via Adaptive Filtering Graph Neural Networks.

Graph Neural Networks (GNNs) have emerged as a crucial deep learning framework for graph-structured data. However, existing GNNs suffer from the scalability limitation, which hinders their practical implementation in industrial settings. Many scalable GNNs have been proposed to address this limitation. However, they have been proven to act as low-pass graph filters, which discard the valuable middle- and high-frequency information. This paper proposes a novel graph neural network named Adaptive Filtering Graph Neural Networks (AFGNN), which can capture all frequency information on large-scale graphs. AFGNN consists of two stages. The first stage utilizes low-, middle-, and high-pass graph filters to extract comprehensive frequency information without introducing additional parameters. This computation is a one-time task and is pre-computed before training, ensuring its scalability. The second stage incorporates a node-level attention-based feature combination, enabling the generation of customized graph filters for each node, contrary to existing spectral GNNs that employ uniform graph filters for the entire graph. AFGNN is suitable for mini-batch training, and can enhance scalability and efficiently capture all frequency information from large-scale graphs. We evaluate AFGNN by comparing its ability to capture all frequency information with spectral GNNs, and its scalability with scalable GNNs. Experimental results illustrate that AFGNN surpasses both scalable GNNs and spectral GNNs, highlighting its superiority.

Cavin1 activates the Wnt/ß-catenin pathway to influence the proliferation and migration of hepatocellular carcinoma.

INTRODUCTION AND OBJECTIVES: Cavin1 is a cell membrane caveolin, with controversial function in different tumors. Meanwhile, the role of Cavin1 in hepatocellular carcinoma (HCC) progression remains unclear. In this study, we attempted to elucidate the significance of Cavin1 in HCC occurrence and progression. MATERIALS AND METHODS: Cavin1 content was examined in HCC tissues and paired adjacent normal liver tissues by qRT-PCR and IHC among 81 HCC patients. The Cavin1-mediated regulation of HCC proliferation and metastasis was assessed through in vitro and in vivo experiments. Finally, using GSEA, we found out Cavin1 could be a potential regulator of the Wnt pathway. The alterations of the Wnt pathway-related proteins were identified by Western Blot analysis. RESULTS: Cavin1 was lower expressed in HCC, which implied poor survival outcomes in HCC patients. Phenotypic experiments revealed that Cavin1 strongly suppressed HCC proliferation and migration in vitro and in vivo. Besides, altered epithelial-mesenchymal transition (EMT)-related protein expressions were detected. Based on our GSEA analysis, Cavin1 activated the Wnt pathway, and Western Blot analysis revealed diminished ß-catenin, c-Myc, and MMP9 contents upon Cavin1 overexpression. CONCLUSIONS: Cavin1 suppresses HCC progression by modulating HCC proliferation and migration via inhibiting the Wnt/ß-catenin axis activation.

LIM domain only 7 negatively controls nonalcoholic steatohepatitis in the setting of hyperlipidemia.

BACKGROUND AND AIMS: Hyperlipidemia has been extensively recognized as a high-risk factor for NASH; however, clinical susceptibility to NASH is highly heterogeneous. The key controller(s) of NASH susceptibility in patients with hyperlipidemia has not yet been elucidated. Here, we aimed to reveal the key regulators of NASH in patients with hyperlipidemia and to explore its role and underlying mechanisms. APPROACH AND RESULTS: To identify the predominant suppressors of NASH in the setting of hyperlipidemia, we collected liver biopsy samples from patients with hyperlipidemia, with or without NASH, and performed RNA-sequencing analysis. Notably, decreased Lineage specific Interacting Motif domain only 7 (LMO7) expression robustly correlated with the occurrence and severity of NASH. Although overexpression of LMO7 effectively blocked hepatic lipid accumulation and inflammation, LMO7 deficiency in hepatocytes greatly exacerbated diet-induced NASH progression. Mechanistically, lysine 48 (K48)-linked ubiquitin-mediated proteasomal degradation of tripartite motif-containing 47 (TRIM47) and subsequent inactivation of the c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) cascade are required for the protective function of LMO7 in NASH. CONCLUSIONS: These findings provide proof-of-concept evidence supporting LMO7 as a robust suppressor of NASH in the context of hyperlipidemia, indicating that targeting the LMO7-TRIM47 axis is a promising therapeutic strategy for NASH.