Association between perivascular spaces burden and future stroke risk in ischemic stroke and transient ischemic attack: A systematic review and meta-analysis.

INTRODUCTION: This meta-analysis aimed to explore the association of perivascular spaces (PVS) burden with the risks of future stroke events and mortality in patients with ischemic stroke and transient ischemic attack (TIA). METHODS: We systematically searched PubMed, Embase and Cochrane database from inception to 31 December 2023. We included eligible studies that reported adjusted estimated effects for future intracranial hemorrhage (ICH), ischemic stroke and mortality with baseline PVS burden in patients with ischemic stroke and TIA. Data were pooled using an inverse-variance method for fixed effect (FE) model and a restricted maximum likelihood (REML) method for random effects (RE) model. RESULTS: Thirteen observational studies (5 prospective, 8 retrospective) were included, comprising 20256 patients. Compared to 0 - 10 PVS at basal ganglia (BG), a higher burden (>10) of BG-PVS was significantly associated with an increased risk of future intracranial hemorrhage (adjusted hazards ratio [aHR] 2.79, 95% confidence interval [CI] 1.16 - 6.73, RE model; aHR 2.14, 95%CI 1.34 - 3.41, FE model; I2 = 64%, n = 17084 from four studies) followed-up for at least one year. There was no significant association between >10 BG-PVS and intracranial hemorrhage within 7 days after reperfusion therapy (adjusted odds ratio [aOR] 1.69, 95%CI 0.74 - 3.88, RE model; aOR 1.43, 95%CI 0.89 - 2.88, FE model; I2 = 67%, n = 1176 from four studies). We did not detect a significant association of recurrent ischemic stroke, mortality or disability with BG-PVS burden. Neither >10 PVS at centrum semiovale (CSO-PVS) nor increasing CSO-PVS burden was significantly associated with the risk of future intracerebral hemorrhage or ischemic stroke recurrence. CONCLUSIONS: Current evidence suggests that a higher BG-PVS burden may be associated with an increased risk of future intracranial hemorrhage in patients with ischemic stroke and TIA. PROSPERO registration number: CRD42021232713 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021232713.

Sex difference in the association between triglyceride and intracerebral bleeding risk after intravenous thrombolysis for acute ischemic stroke, a multi-center retrospective study.

Background: Whether the relationship of intracerebral bleeding risk with lipid profile may vary by sex remains unclear. This study aims to investigate potential sex differences in the association between lipid profile and the risk of symptomatic intracerebral hemorrhage (sICH) in patients with acute ischemic stroke (AIS) who received intravenous thrombolysis using recombinant tissue plasminogen activator (r-tPA). Methods: This multicenter retrospective observational study analyzed patients with AIS treated with intravenous r-tPA. sICH was defined as a worsening of 4 or higher points in the National Institutes of Health Stroke Scale (NIHSS) score within 36 hours after intravenous thrombolysis in any hemorrhage subtype. We assessed the odds ratio (OR) with 95% confidence interval (CI) of lipid profile for sICH for each sex using logistic regression models adjusted for potential confounding factors. Results: Of 957 participants (median age 68 (interquartile range, 59-75), men 628 (65.6%)), 56 sICH events (36 (5.7%) in men and 20 (6.1%) in women) were observed. The risk of sICH in men decreased with increasing serum levels of triglyceride after adjustment for confounding factors (vs lowest tertile, medium tertile OR 0.39, 95% CI [0.17-0.91], top tertile OR 0.33, 95% CI [0.13-0.84], overall p = 0.021; per point increase, adjusted OR 0.29, 95% CI [0.13-0.63], p = 0.002). Neither serum levels of total cholesterol nor low-density lipoprotein (LDL) was associated with sICH in men. In women, there was no association between any of the lipid levels and the risk of sICH. Conclusions: This study indicated that the association between serum levels of triglyceride and sICH may vary by sex. In men, increased triglyceride levels decrease the risk of sICH; in women, this association was lost. Further studies on the biological mechanisms for sex differences in stroke risk associated with triglyceride are needed.

Ultrasound-guided percutaneous transhepatic biliary drainage for distal biliary malignant obstructive jaundice.

The main cause of distal biliary malignant obstructive jaundice (DBMOJ) is the stricture of the extrahepatic biliary tract by malignant tumors, including pancreatic head and uncinate process cancer, low-grade cholangiocarcinoma, duodenal cancer, papillary duodenal cancer and other malignant tumors. The most effective treatment is radical pancreaticoduodenectomy. However, preoperative obstructive jaundice can affect the patient's liver function and blood coagulation function, increase local inflammation and oedema, and make surgery more difficult. Patients with severe obstructive jaundice require preoperative biliary drainage, which can be achieved by various methods, including ultrasound endoscopic biliary drainage (EUS-EBD) and endoscopic retrograde biliary drainage (ERBD). The latter is mainly divided into endoscopic nasobiliary drainage and endoscopic biliary stent. Some patients underwent percutaneous transhepatic biliary drainage (PTBD) when ERBD and EUS-EBD failed. In this study, we aimed to identify PTBD in DBMOJ and to further investigate the role of the puncture pathway in DBMOJ. The relationship between PTBD and bile duct internal diameter was confirmed by analysing and collating clinical data. In this study, DBMOJ was grouped according to bile duct internal diameter and liver function was used as an indicator to examine the improvement in liver function with PTBD in patients undergoing DBMOJ. Analysis of puncture complications showed that PTBD puncture was safe. DBMOJ with different bile duct internal diameters had different rates of liver function improvement after PTBD. The right-side approaches had significantly lower alanine aminotransferase (ALT) and alanine transaminase (AST) than the left-side approaches. This study showed that PTBD for DBMOJ is associated with a low complication rate and good reduction of jaundice. Liver function recovery was faster in patients with DBMOJ treated with PTBD in the right-sided approach compared with the left-sided approach. PTBD is an effective tool to be used in patients who have failed ERBD and EUS-EBD.

Surveillance for rhabdomyolysis after the consumption of crayfish in Wuhan, China, 2016-2022.

Objectives: To analyze the epidemiological characteristics and etiology of crayfish-related rhabdomyolysis. Methods: Cases of crayfish-related rhabdomyolysis in Wuhan were monitored, and professional training of city's surveillance personnel was conducted. Unified questionnaires were used to collect data. Results: The first case of crayfish-related rhabdomyolysis occurred on July 12, 2016. Subsequently, 423 patients were reported over the next 7 years, with muscle pain, weakness, and chest distress as main symptoms. In total, 64.54% (273/423) of patients were females, and young adults (aged 20-49 years) account for 86.22% (363/423) of patients. The primary clinical presentations were muscle pain, muscle weakness, and chest discomfort. The median incubation time was 6 h. And the number of cases may be related to water levels in Yangzi river. Laboratory tests revealed elevated creatine kinase and myoglobin levels. In total, 95.16% (236/248) of patients had consumed crayfish tail shrimp and 91.53% (227/248) had consumed crayfish liver and pancreas (Female crayfish also contain ovaries). Only 25.00% (62/248) of patients had a history of alcohol consumption. On average, 227 patients consumed 15 (3-50) crayfish, of whom 84.14% (191/227) consumed more than 10 crayfish. All patients had a favorable prognosis. Conclusion: Crayfish-related rhabdomyolysis is a kind of a case or cluster of patients present with severe myalgia or weakness of unknown etiology and mechanism disease in Wuhan, China, 2016-2022. Excessive consumption of crayfish may be a risk factor for the disease. The relationship between the specific parts of crayfish consumed and the onset of the disease is unclear, suggesting further research is needed to identify the relevant risk factors for the disease.

Advanced Anti-Icing Strategies and Technologies by Macrostructured Photothermal Storage Superhydrophobic Surfaces.

Water is the source of life and civilization, but water icing causes catastrophic damage to human life and diverse industrial processes. Currently, superhydrophobic surfaces (inspired by the lotus effect) aided anti-icing attracts intensive attention due to their energy-free property. Here, recent advances in anti-icing by design and functionalization of superhydrophobic surfaces are reviewed. The mechanisms and advantages of conventional, macrostructured, and photothermal superhydrophobic surfaces are introduced in turn. Conventional superhydrophobic surfaces, as well as macrostructured ones, easily lose the icephobic property under extreme conditions, while photothermal superhydrophobic surfaces strongly rely on solar illumination. To address the above issues, a potentially smart strategy is found by developing macrostructured photothermal storage superhydrophobic (MPSS) surfaces, which integrate the functions of macrostructured superhydrophobic materials, photothermal materials, and phase change materials (PCMs), and are expected to achieve all-day anti-icing in various fields. Finally, the latest achievements in developing MPSS surfaces, showcasing their immense potential, are highlighted. Besides, the perspectives on the future development of MPSS surfaces are provided and the problems that need to be solved in their practical applications are proposed.

The impact of green credit on environmental quality: empirical evidence from China.

As an innovative financial instrument, green credit is a new driving force for environmental governance. To study the impact of green credit on environmental quality, this paper uses the provincial panel data from 2007 to 2020 to construct a panel model for analysis based on the comprehensive environmental quality index. At the same time, it discusses the mechanism and regional heterogeneity of green credit affecting environmental quality. The results show that green credit significantly improves the overall quality of the environment, which has a significant effect on air quality and green quality but has no significant impact on water quality and soil quality. Green credit improves environmental quality by improving green technology innovation and promoting industrial structure upgrading. At the same time, there is obvious heterogeneity in the environmental effect of green credit. Among them, the environmental quality improvement effect of the eastern region and the carbon emission pilot area is more evident than that of the central and western regions and the non-carbon emission pilot area. This paper has important implications for promoting the development of green credit and giving full play to the environmental effects of green credit to achieve sustainable goals.

Efficacy and safety of levetiracetam vs. oxcarbazepine in the treatment of children with epilepsy: a systematic review and meta-analysis.

Background: Levetiracetam (LEV) and oxcarbazepine (OXC) are new antiseizure medications (ASMs). In recent years, OXC monotherapy is widely used in children with epilepsy; however, no consensus exists on applying LEV monotherapy among children with epilepsy. Objective: The present work focused on comparing the efficacy and safety of LEV and OXC monotherapy in treating children with epilepsy. Methods: We conducted a comprehensive search across multiple databases including PubMed, Cochrane Library, Embase, Web of Science, CNKI, Wanfang Database, VIP, and China Biology Medicine disc, covering studies from inception to August 26, 2023. We included randomized controlled trials (RCTs) and cohort studies evaluating the efficacy and safety of LEV and OXC monotherapy for treating epilepsy in children. We utilized Cochrane Risk of Bias Tool in RevMan 5.3 software for assessing included RCTs quality. In addition, included cohort studies quality was determined using Newcastle-Ottawa Scale (NOS). A random-effects model was utilized to summarize the results. Results: This meta-analysis included altogether 14 studies, including 893 children with epilepsy. LEV and OXC monotherapy was not statistical different among children with epilepsy in seizure-free rate (relative risk [RR] = 1.010, 95% confidence interval [CI] [0.822, 1.242], P > 0.05) and seizure frequency decrease of ≥50% compared with baseline [RR = 0.938, 95% CI (0.676, 1.301), P > 0.05]. Differences in total adverse reaction rate [RR = 1.113, 95% CI (0.710, 1.744), P > 0.05] and failure rate because of serious adverse reaction [RR = 1.001, 95% CI (0.349, 2.871), P > 0.05] were not statistical different between LEV and OXC treatments among children with epilepsy. However, the effects of OXC monotherapy on thyroid among children with epilepsy was statistically correlated than that of LEV (thyroid stimulating hormone: standardized mean difference [SMD] = -0.144, 95% CI [-0.613, 0.325], P > 0.05; free thyroxine: SMD = 1.663, 95% CI [0.179, 3.147], P < 0.05). Conclusion: The efficacy of LEV and OXC monotherapy in treating children with epilepsy is similar. However, OXC having a more significant effect on the thyroid than that of LEV. Therefore, LEV may be safer for children with epilepsy who are predisposed to thyroid disease than OXC. Systematic Review Registration: https://www.crd.york.ac.uk/, PROSPERO (CRD42024514016).

Mitochondrial transfer in tunneling nanotubes-a new target for cancer therapy.

A century ago, the Warburg effect was first proposed, revealing that cancer cells predominantly rely on glycolysis during the process of tumorigenesis, even in the presence of abundant oxygen, shifting the main pathway of energy metabolism from the tricarboxylic acid cycle to aerobic glycolysis. Recent studies have unveiled the dynamic transfer of mitochondria within the tumor microenvironment, not only between tumor cells but also between tumor cells and stromal cells, immune cells, and others. In this review, we explore the pathways and mechanisms of mitochondrial transfer within the tumor microenvironment, as well as how these transfer activities promote tumor aggressiveness, chemotherapy resistance, and immune evasion. Further, we discuss the research progress and potential clinical significance targeting these phenomena. We also highlight the therapeutic potential of targeting intercellular mitochondrial transfer as a future anti-cancer strategy and enhancing cell-mediated immunotherapy.

Pt on Atomic-Layered WO3 Islands: Electronic Tuning of Platinum-Tungsten Heterostructures for Highly Efficient Low-Temperature VOC Combustion.

Adjusting the electronic state of noble metal catalysts on a nanoscale is crucial for optimizing the performance of nanocatalysts in many important environmental catalytic reactions, particularly in volatile organic compound (VOC) combustion. This study reports a novel strategy for optimizing Pt catalysts by modifying their electronic structure to enhance the electron density of Pt. The research illustrates the optimal 0.2Pt-0.3W/Fe2O3 heterostructure with atomic-thick WO3 layers as a bulking block to electronically modify supported Pt nanoparticles. Methods such as electron microscopy, X-ray photoelectron spectroscopy, and in situ Fourier transform infrared spectroscopy confirm Pt's electron-enriched state resulting from electron transfer from atomic-thick WO3. Testing for benzene oxidation revealed enhanced low-temperature activity with moderate tungsten incorporation. Kinetic and mechanistic analyses provide insights into how the enriched electron density benefits the activation of oxygen and the adsorption of benzene on Pt sites, thereby facilitating the oxidation reaction. This pioneering work on modifying the electronic structure of supported Pt nanocatalysts establishes an innovative catalyst design approach. The electronic structure-performance-dependent relationships presented in this study assist in the rational design of efficient VOC abatement catalysts, contributing to clean energy and environmental solutions.

New Perspectives on the Risks of Hydroxylated Polychlorinated Biphenyl (OH-PCB) Exposure: Intestinal Flora α-Glucosidase Inhibition.

Polychlorinated biphenyls (PCBs) are a group of colorless and odorless environmental pollutants with a wide range of toxic effects. Some PCBs, especially less chlorinated ones, will rapidly undergo phase I metabolism after entering the body, and hydroxylated polychlorinated biphenyls (OH-PCBs) are the main metabolites of PCBs. Intestinal flora α-glucosidase is a common carbohydrate-active enzyme which is ubiquitous in human intestinal flora. It can convert complex dietary polysaccharides into monosaccharides, assisting the body in degrading complex carbohydrates and providing energy for the survival and growth of bacterial flora. The present study aims to investigate the inhibition of the activity of intestinal flora α-glucosidase by OH-PCBs. 4-Nitrophenyl-α-D-glucopyranoside (PNPG) was used as a probe substrate for α-glucosidase, and in vitro incubation experiments were conducted to study the inhibition of 26 representative OH-PCBs on α-glucosidase. Preliminary screening of in vitro incubation was performed with 100 µM of OH-PCBs. The results showed that 26 OH-PCBs generally exhibited strong inhibition of α-glucosidase. The concentration-dependent inhibition and half inhibition concentrations (IC50s) of OH-PCBs on α-glucosidase were determined. 4'-OH-PCB 86 and 4'-OH-PCB 106 were chosen as representative OH-PCBs, and the inhibition kinetic parameters (Kis) of inhibitors for α-glucosidase were determined. The inhibition kinetic parameters (Kis) of 4'-OH-PCB 86 and 4'-OH-PCB 106 for α-glucosidase are 1.007 µM and 0.538 µM, respectively. The silico docking method was used to further analyze the interaction mechanism between OH-PCBs and α-glucosidase. All these results will help us to understand the risks of OH-PCB exposure from a new perspective.

Intestinal strictures in Crohn's disease: An update from 2023.

Crohn's disease (CD) is a chronic inflammatory disease that leads to intestinal stricture in nearly 35% of cases within 10 years of initial diagnosis. The unknown pathogenesis, lack of universally accepted criteria, and absence of an effective management approach remain unconquered challenges in structuring CD. The pathogenesis of stricturing CD involves intricate interactions between factors such as immune cell dysbiosis, fibroblast activation, and microecology imbalance. New techniques such as single-cell sequencing provide a fresh perspective. Non-invasive diagnostic tools such as serum biomarkers and novel cross-sectional imaging techniques offer a precise understanding of intestinal fibrostenosis. Here, we provide a timely and comprehensive review of the worthy advancements in intestinal strictures in 2023, aiming to dispense cutting-edge information regarding fibrosis and to build a cornerstone for researchers and clinicians to make greater progress in the field of intestinal strictures.

Digital inclusive finance, industrial structure, and economic growth: An empirical analysis of Beijing-Tianjin-Hebei region in China.

As a product of combining digital technology and traditional finance, digital inclusive finance plays a vital role in economic growth. This paper deeply analyzes the impact of digital inclusive finance on economic growth and the specific transmission path. This research selects the municipal panel data of Beijing-Tianjin-Hebei from 2011 to 2020 and empirically studies the impact of digital inclusive finance on economic growth. From the perspectives of industrial structure transformation speed, industrial structure upgrading, and industrial structure rationalization, this study analyzes the role of industrial structure in the impact of digital inclusive finance on economic growth and tests the heterogeneity of the impact of digital inclusive finance on economic growth. The results show that digital inclusive finance has a significant role in promoting economic growth. The depth of use of digital inclusive finance has the most significant impact, followed by the breadth of coverage, and the degree of digitization is the smallest. The industrial structure transformation speed and the industrial structure rationalization play a significant intermediary role in the economic growth effect of digital inclusive finance, and the industrial structure upgrading has no significant impact on the economic growth effect of digital inclusive finance; the promotion effect of digital inclusive finance on economic growth is bigger in the economically developed group, the higher digital inclusive finance group and the technologically developed group, and the promotion effect is smaller in the economically underdeveloped group, the lower digital inclusive finance group and the technologically underdeveloped group. The results provide a strong reference for policy formulation to promote the development of digital inclusive finance and economic growth.

Rapid and facile detection of largemouth bass ranavirus with CRISPR/Cas13a.

Largemouth bass ranavirus (LMBV) is an epidemic disease that seriously jeopardizes the culture of largemouth bass（Micropterus salmoides）, and it has a very high incidence in largemouth bass. Once an outbreak occurs, it may directly lead to the failure of the culture, resulting in substantial economic losses, but there is no effective vaccine or special effective drug yet. Consequently, it is important to establish an accurate, sensitive, convenient and specific detection approach for preventing LMBV infection. The recombinant enzyme-assisted amplification (RAA) technology was used in combination with clustered regularly interspaced short palindromic repeats (CRISPR), and associated protein 13a (CRISPR/Cas13a) to detect LMBV. We designed RAA primers and CRISPR RNA (crRNA) that targeted the conserved region in the LMBV main capsid protein (MCP) gene, amplified sample nucleic acids using the RAA technology, performed CRISPR/Cas13a fluorescence detection and evaluated the sensitivity and specificity of the established method with qPCR as a control method. This technique was able to determine the results by collecting fluorescence signals, visualizing fluorescence by UV excitation and combining with lateral flow strips (LFS). The sensitivity and specificity of the established method were consistent with the qPCR method. Besides, it was performed at a constant temperature of 37 °C and the sensitivity of the reaction system was 3.1 × 101 copies/µL, with no cross-reactivity with other common aquatic pathogens. Further, the positive detection rate of the proposed method in 32 clinical samples was consistent with that of qPCR. In conclusion, our established RAA-CRISPR/Cas13 method for detecting LMBV is sensitive, simple and specific, which is applicable in the rapid on-site detection and epidemiological monitoring of LMBV.

Characterization of two novel hydrolases from Sphingopyxis sp. DBS4 for enantioselective degradation of chiral herbicide diclofop-methyl.

Diclofop-methyl, an aryloxyphenoxypropionate (AOPP) herbicide, is a chiral compound with two enantiomers. Microbial detoxification and degradation of various enantiomers is garnering immense research attention. However, enantioselective catabolism of diclofop-methyl has been rarely explored, especially at the molecular level. This study cloned two novel hydrolase genes (dcmA and dcmH) in Sphingopyxis sp. DBS4, and characterized them for diclofop-methyl degradation. DcmA, a member of the amidase superfamily, exhibits 26.1-45.9% identity with functional amidases. Conversely, DcmH corresponded to the DUF3089 domain-containing protein family (a family with unknown function), sharing no significant similarity with other biochemically characterized proteins. DcmA exhibited a broad spectrum of substrates, with preferential hydrolyzation of (R)-(+)-diclofop-methyl, (R)-(+)-quizalofop-ethyl, and (R)-(+)-haloxyfop-methyl. DcmH also preferred (R)-(+)-quizalofop-ethyl and (R)-(+)-haloxyfop-methyl degradation while displaying no apparent enantioselective activity towards diclofop-methyl. Using site-directed mutagenesis and molecular docking, it was determined that Ser175 was the fundamental residue influencing DcmA's activity against the two enantiomers of diclofop-methyl. For the degradation of AOPP herbicides, DcmA is an enantioselective amidase that has never been reported in research. This study provided novel hydrolyzing enzyme resources for the remediation of diclofop-methyl in the environment and deepened the understanding of enantioselective degradation of chiral AOPP herbicides mediated by microbes.

Interfacial ice sprouting during salty water droplet freezing.

Icing of seawater droplets is capable of causing catastrophic damage to vessels, buildings, and human life, yet it also holds great potential for enhancing applications such as droplet-based freeze desalination and anti-icing of sea sprays. While large-scale sea ice growth has been investigated for decades, the icing features of small salty droplets remain poorly understood. Here, we demonstrate that salty droplet icing is governed by salt rejection-accompanied ice crystal growth, resulting in freezing dynamics different from pure water. Aided by the observation of brine films emerging on top of frozen salty droplets, we propose a universal definition of freezing duration to quantify the icing rate of droplets having varying salt concentrations. Furthermore, we show that the morphology of frozen salty droplets is governed by ice crystals that sprout from the bottom of the brine film. These crystals grow until they pierce the free interface, which we term ice sprouting. We reveal that ice sprouting is controlled by condensation at the brine film free interface, a mechanism validated through molecular dynamics simulations. Our findings shed light on the distinct physics that govern salty droplet icing, knowledge that is essential for the development of related technologies.

ASIC1 promotes migration and invasion of hepatocellular carcinoma via the PRKACA/AP-1 signaling pathway.

Hepatocellular carcinoma (HCC) exhibits a high mortality rate due to its high invasion and metastatic nature, and the acidic microenvironment plays a pivotal role. Acid-sensing ion channel 1 (ASIC1) is upregulated in HCC tissues and facilitates tumor progression in a pH-dependent manner, while the specific mechanisms therein remain currently unclear. Herein, we aimed to investigate the underlying mechanisms by which ASIC1 contributes to the development of HCC. Using bioinformatics analysis, we found a significant association between ASIC1 expression and malignant transformation of HCC, such as poor prognosis, metastasis and recurrence. Specifically, ASIC1 enhanced the migration and invasion capabilities of Li-7 cells in the in vivo experiment using an HCC lung metastasis mouse model, as well as in the in vitro experiments such as wound healing assay and Transwell assay. Furthermore, our comprehensive gene chip and molecular biology experiments revealed that ASIC1 promoted HCC migration and invasion by activating the PRKACA/AP-1 signaling pathway. Our findings indicate that targeting ASIC1 could have therapeutic potential for inhibiting HCC progression.

Spherical Bi2O3/ATO catalyst with N2 pre-reduction electrocatalytic reduction of CO2 to formic acid.

Bi2O3 catalyst with Bi-O bond crystal structure has more active sites, which shows better CO2 catalytic performance than pure Bi catalysts in many catalytic reactions. How to strengthen the Bi-O bond in Bi2O3 to obtain higher selectivity and catalytic activity is a problem worthy of consideration. Here, we develop a N2 pre-reduced spherical Bi2O3/ATO catalyst that has a high formate Faradaic efficiency of 92.7%, which is superior to the existing tin oxide catalyst. Detailed electrocatalytic analysis shows that N2 pre-reduction and spherical structure are helpful for Sn to stabilize the oxidation state of Bi, thus retaining part of the Bi-O structure. The existence of the Bi-O structure can reduce the energy barrier of the CO2 production *OCHO reaction and promote the reaction rate of the CO2-*OCHO-HCOOH path, thus promoting the formation of formate.

Advanced oxidation protein products attenuate the autophagy-lysosome pathway in ovarian granulosa cells by modulating the ROS-dependent mTOR-TFEB pathway.

Oxidative stress dysfunction has recently been found to be involved in the pathogenesis of premature ovarian insufficiency (POI). Previously, we found that advanced oxidation protein products (AOPPs) in plasma were elevated in women with POI and had an adverse effect on granulosa cell proliferation. However, the mechanism underlying the effects of AOPPs on autophagy-lysosome pathway regulation in granulosa cells remains unclear. In this study, the effect of AOPPs on autophagy and lysosomal biogenesis and the underlying mechanisms were explored by a series of in vitro experiments in KGN and COV434 cell lines. AOPP-treated rat models were employed to determine the negative effect of AOPPs on the autophagy-lysosome systems in vivo. We found that increased AOPP levels activated the mammalian target of rapamycin (mTOR) pathway, and inhibited the autophagic response and lysosomal biogenesis in KGN and COV434 cells. Furthermore, scavenging of reactive oxygen species (ROS) with N-acetylcysteine and blockade of the mTOR pathway with rapamycin or via starvation alleviated the AOPP-induced inhibitory effects on autophagy and lysosomal biogenesis, suggesting that these effects of AOPPs are ROS-mTOR dependent. The protein expression and nuclear translocation of transcription factor EB (TFEB), the key regulator of lysosomal and autophagic function, were also impaired by the AOPP-activated ROS-mTOR pathway. In addition, TFEB overexpression attenuated the AOPP-induced impairment of autophagic flux and lysosomal biogenesis in KGN and COV434 cells. Chronic AOPP stimulation in vivo also impaired autophagy and lysosomal biogenesis in granulosa cells of rat ovaries. The results highlight that AOPPs lead to impairment of autophagic flux and lysosomal biogenesis via ROS-mTOR-TFEB signaling in granulosa cells and participate in the pathogenesis of POI.

Effect of vegetable consumption on risk of gastric cancer: a systematic review and multi-level meta-analysis of prospective studies.

Vegetables are known to be beneficial to human health, but the association between vegetable consumption and gastric cancer remains uncertain. To synthesise knowledge about the relationship between vegetable group consumption and gastric cancer risk, update present meta-analyses and estimate associations between vegetable consumption and gastric cancer risk based solely on prospective studies, we perform a PRISMA-compliant three-level meta-analysis. Systematic search identified thirteen prospective studies with fifty-two effect sizes that met all inclusion criteria and no exclusion criteria for our meta-analysis. Pooled risk ratios (RRs) showed a positive association between high vegetable consumption and low gastric cancer risk (pooled RR 0·93, 95% confidence interval 0·90-0·97, P = 0·06). In moderator analyses for indicators of gender, region and quantity of vegetable intake, there was no significant difference between subgroups. However, the effect became significant in populations with lower than the minimum risk exposure level (TMREL) of vegetable consumption (P < 0·05). Higher vegetable intake is associated with a decreased risk of gastric cancer. This effect may be limited to specific populations, such as ones with lower vegetable consumption. Evidence from our study has important public health implications for dietary recommendations.

Comprehensive molecular analyses of a 7-m6A-related lncRNAs signature for prognosis, tumor immunity and therapeutic effect in patients with hepatocellular carcinoma.

Hepatocellular carcinoma is the most common form of liver tumor. m6A modification and noncoding RNA show indispensable roles in HCC. We sought to establish and verify an appropriate m6A-related long noncoding RNA prognostic tool for predicting hepatocellular carcinoma progression. We extracted the RNA expression levels and the clinicopathologic data from GTEx and TCGA databases. Multivariate Cox regression analysis and receiver operating characteristic curves were performed to test the model's predictive ability. We further built a nomogram for overall survival according to the risk score and clinical features. A competing endogenous RNA network and Gene Ontology assessment were implemented to identify related biological mechanisms and processes. By bioinformatics analysis, a risk model comprising GABPB1-AS1, AC025580.1, LINC01358, AC026356.1, AC009005.1, HCG15, and AC026368.1 was built to offer a prognostic prediction for hepatocellular carcinoma independently. The prognostic tool could better prognosticate hepatocellular carcinoma patients' survival than other clinical characteristics. Then, a nomogram with risk score and clinical characteristics was created, which had strong power to calculate the survival probability in hepatocellular carcinoma. The immune-associated processes involving the differentially expressed genes between the two subgroups were displayed. Analyses of prognosis, clinicopathological characteristics, tumor mutation burden, immune checkpoint molecules, and drug response showed significant differences among the two risk subtypes, hinting that the model could appraise the efficacy of immunotherapy and chemotherapy. The tool can independently predict the prognosis in patients with hepatocellular carcinoma, which benefits drug selection in hepatocellular carcinoma patients.