Prognostic biomarker NRG2 correlates with autophagy and epithelial­mesenchymal transition in breast cancer.

Breast cancer (BRCA) is a leading cause of death in women worldwide, accounting for 31% of female cancer. Autophagy plays a crucial role in cancer progression, however, the function of autophagy-related gene neuroregulatory protein 2 (NRG2) in BRCA and its underlying molecular mechanisms remain unclear. In the present study, the expression of the NRG2 gene in BRCA was significantly down-regulated compared with the normal controls. The low expression level of NRG2 was related to poor survival rate of BRCA. The receiver operating characteristic curve of NRG2 showed a good diagnostic value for distinguishing BRCA from normal tissues (AUC=0.932). GO-KEGG analysis and GSEA enrichment analysis showed that NRG2 and its regulated genes were enriched in autophagy-related and immune-related pathways, and NRG2 was positively correlated with a number of immune cells and immune checkpoint genes. In addition, knockdown of NRG2 significantly promoted the proliferation, invasion and migration of BRCA cells. The autophagy marker, LC3-II and epithelial-mesenchymal transition (EMT) marker, vimentin were increased, while P62 and E-cadherin were decreased in response to NRG2 depletion. The findings of the present study demonstrated that NRG2 acts as a tumor suppressor factor that contributes to the immune escape and anti-tumor immunity inhibition by regulating the pathological process of autophagy and EMT, suggesting that NRG2 could be used as a prognostic biomarker and clinical target for BRCA therapy.

Changes in the etiology of liver cirrhosis and the corresponding management strategies.

We read with interest the article by Xing Wang, which was published in the recent issue of the World Journal of Hepatology 2023; 15: 1294-1306. This article focuses particularly on the prevalence and trends in the etiology of liver cirrhosis (LC), prognosis for patients suffering from cirrhosis-related complications and hepatocellular carcinoma (HCC), and management strategies. The etiology of cirrhosis varies according to geographical, economic, and population factors. Viral hepatitis is the dominant cause in China. Vaccination and effective treatment have reduced the number of people with viral hepatitis, but the overall number is still large. Patients with viral hepatitis who progress over time to LC and HCC remain an important population to manage. The increased incidence of metabolic syndrome and alcohol consumption is likely to lead to a potential exponential increase in metabolic dysfunction-associated steatotic liver disease (MASLD)-associated LC and alcoholic liver disease in the future. Investigating the evolution of the etiology of LC is important for guiding the direction of future research and policy development. These changing trends indicate a need for greater emphasis on tackling obesity and diabetes, and implementing more effective measures to regulate alcohol consumption in order to reduce the occurrence of MASLD. In an effort to help cope with these changing trends, the authors further proposed countermeasures for healthcare authorities doctors, and patients.

KRT19 is a Promising Prognostic Biomarker and Associates with Immune Infiltrates in Serous Ovarian Cystadenocarcinoma.

Background: Ovarian cancer (OV) is the highest prevalent gynecologic tumor with complicated pathogenesis; high-grade serous ovarian cystadenocarcinoma (HGSOC) is the most epidemiological and malignant subtype of OV. Keratin type I cytoskeleton 19 (KRT19) is an intermediate filament protein which plays essential roles in the maintenance of epithelial cells. However, its role in OV remains largely unknown. Methods: Bioinformatic analysis with various databases was conducted in this study. In details, KRT19 expression was assessed using databases including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Gene Expression Omnibus (GEO) and Human Protein Atlas (HPA). GO-KEGG and GSEA analysis were performed by R packages. The biological function of KRT19 was analyzed based on the single-cell sequencing information from CancerSEA database. The association of KRT19 expression with immunomodulator and chemokine was predicted via the TISIDB database. Results: The expression of KRT19 was significantly upregulated in ovarian samples compared with normal controls. KRT19 expression was negatively associated with prognosis in OV, and further analysis revealed that KRT19 had promising diagnostic significance in distinguishing OV cancer from normal samples. GO-KEGG and GSEA analysis indicated that KRT19 was associated with multiple biological functions and pathways including epidermis development, apical junction, inflammatory response, and epithelial mesenchymal transition. By using different GEO series, we found that KRT19 was differentially expressed in OV-associated tissues. Furthermore, the increased KRT19 expression was positively correlated with the immune infiltration levels of the most immune cells in OV. Conclusion: This study demonstrated that KRT19 is a promising prognosis and diagnosis biomarker that determines cancer progression and is correlated with tumor immune cells infiltration in OV, suggesting being a molecular target for immunotherapies.

Global trends and hotspots of treatment for nonalcoholic fatty liver disease: A bibliometric and visualization analysis (2010-2023).

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is chronic, with its progression leading to liver fibrosis and end-stage cirrhosis. Although NAFLD is increasingly common, no treatment guideline has been established. Many mechanistic studies and drug trials have been conducted for new drug development to treat NAFLD. An up-to-date overview on the knowledge structure of NAFLD through bibliometrics, focusing on research hotspots, is necessary to reveal the rational and timely directions of development in this field. AIM: To research the latest literature and determine the current trends in treatment for NAFLD. METHODS: Publications related to treatment for NAFLD were searched on the Web of Science Core Collection database, from 2010 to 2023. VOSviewers, CiteSpace, and R package "bibliometrix" were used to conduct this bibliometric analysis. The key information was extracted, and the results of the cluster analysis were based on network data for generating and investigating maps for country, institution, journal, and author. Historiography analysis, bursts and cluster analysis, co-occurrence analysis, and trend topic revealed the knowledge structure and research hotspots in this field. GraphPad Prism 9.5.1.733 and Microsoft Office Excel 2019 were used for data analysis and visualization. RESULTS: In total, 10829 articles from 120 countries (led by China and the United States) and 8785 institutions were included. The number of publications related to treatment for NAFLD increased annually. While China produced the most publications, the United States was the most cited country, and the United Kingdom collaborated the most from an international standpoint. The University of California-San Diego, Shanghai Jiao Tong University, and Shanghai University of Traditional Chinese Medicine produced the most publications of all the research institutions. The International Journal of Molecular Sciences was the most frequent journal out of the 1523 total journals, and Hepatology was the most cited and co-cited journal. Sanyal AJ was the most cited author, the most co-cited author was Younossi ZM, and the most influential author was Loomba R. The most studied topics included the epidemiology and mechanism of NAFLD, the development of accurate diagnosis, the precise management of patients with NAFLD, and the associated metabolic comorbidities. The major cluster topics were "emerging drug," "glucagon-like peptide-1 receptor agonist," "metabolic dysfunction-associated fatty liver disease," "gut microbiota," and "glucose metabolism." CONCLUSION: The bibliometric study identified recent research frontiers and hot directions, which can provide a valuable reference for scholars researching treatments for NAFLD.

Investigating the impact of inter-limb asymmetry in hamstring strength on jump, sprint, and strength performance in young athletes: comparing the role of gross force.

The main purpose of this cross-sectional study was to examine the impact of the inter-limb asymmetry of hamstring strength on jump, sprint and strength performance and to compare the effects of inter-limb asymmetry of hamstring strength with gross force (GF) of the hamstring on these physical qualities in youth volleyball athletes. Eighty-one youth volleyball players (age: 16.6 ± 1.9 years; training experience: 3.0 ± 0.9 years; height: 191.4 ± 7.1 cm; body mass: 78.5 ± 12.9 kg; lean body mass: 63.5 ± 10.5 kg; body fat rate: 18.6% ± 6.1%) performed a mid-season battery of tests consisting of morphological test, depth jump (DJ), counter movement jump (CMJ), squat jump (SJ), 10 m sprint, isometric mid-thigh pull (IMTP) and hamstring strength test. All tests reported good to excellent reliability (ICC range = 0.815-0.996) and acceptable variability (CV range = 3.26-7.84%). Results show a significant negative relationship between inter-limb asymmetry of hamstring strength and all physical qualities (r = -0.271 to -0.445; p < 0.05), and a significant positive relationship between GF of hamstring and all physical qualities (r = 0.303 to 0.664; p < 0.05). Additionally, GF of hamstring was more relevant to IMTP-PF (peak force) (r = 0.664) and inter-limb asymmetry of hamstring strength was more relevant to 10 m sprint (r = -0.445). The findings from this study indicate that, for youth athletes, the GF of the hamstring is crucial for overall lower limb strength performance, and the importance of inter-limb symmetry of hamstring strength increases with the complexity of the task.

Metabolic Risk Factors Are Associated with the Disease Severity and Prognosis of Hepatitis B Virus-Related Acute on Chronic Liver Failure.

Background/Aims: Metabolic risk factors could accelerate hepatitis B virus (HBV)-related mortality; however, their impacts on disease severity in HBV-related acute on chronic liver failure (HBV-ACLF) patients remain unexplored. In this study, we assessed the effects of metabolic risk factors on the outcome of HBV-ACLF patients. Methods: This study retrospectively enrolled antiviral therapy naïve HBV-ACLF patients from a single center in China. Patients were evaluated according to Child-Turcotte-Pugh score, Model for End-Stage Liver Disease (MELD) score, 30-day, 90-day mortality and survival rate to estimate the prognosis of HBV-ACLF. The impacts of different metabolic risk factors were further analyzed. Results: A total of 233 patients, including 158 (67.8%) with metabolic risk factors and 75 (32.2%) without metabolic risk factors, were finally analyzed. Patients with metabolic risk factors had significantly higher MELD score (22.6±6.1 vs 19.8±3.8, p<0.001), 90-day mortality rate (56.3% vs 38.7%, p=0.017), and shorter median survival time (58 days vs 75 days: hazard ratio, 1.553; 95% confidence interval, 1.061 to 2.274; p=0.036) than patients without them. Moreover, metabolic risk factors were independently associated with patients' 90-day mortality (hazard ratio, 1.621; 95% confidence interval, 1.016 to 2.585; p=0.043). Prediabetes/diabetes and hypertension were related to higher rates of infection and worse renal function in HBV-ACLF patients. Conclusions: HBV-ACLF patients with metabolic risk factors, especially prediabetes/diabetes or hypertension, could have more severe disease and lower survival rates. In addition, the existence of metabolic disorder is an independent risk factor for HBV-ACLF patients' 90-day mortality.

Effects of different external cooling placements prior to and during exercise on athletic performance in the heat: A systematic review and meta-analysis.

Background: Nowadays, many high-profile international sport events are often held in warm or hot environments, hence, it is inevitable for these elite athletes to be prepared for the challenges from the heat. Owing to internal cooling may cause gastrointestinal discomfort to athletes, external cooling technique seems to be a more applicable method to deal with thermal stress. Central cooling mainly refers to head, face, neck and torso cooling, can help to reduce skin temperature and relieve thermal perception. Peripheral cooling mainly refers to four limbs cooling, can help to mitigate metabolic heat from muscular contrac to effectively prevent the accumulation of body heat. Hence, we performed a meta-analysis to assess the effectiveness of different external cooling placements on athletic performance in the heat Methods: A literatures search was conducted using Web of Science, MEDLINE and SPORTDiscus until September 2022. The quality and risk of bias in the studies were independently assessed by two researchers. Results: 1,430 articles were initially identified (Web of Science = 775; MEDLINE = 358; SPORTDiscus = 271; Additional records identified through other sources = 26), 60 articles (82 experiments) met the inclusion criteria and were included in the final analysis, with overall article quality being deemed moderate. Central cooling (SMD = 0.43, 95% CI 0.27 to 0.58, p < 0.001) was most effective in improving athletic performance in the heat, followed by central and peripheral cooling (SMD = 0.38, 95% CI 0.23 to 0.54, p < 0.001), AND peripheral cooling (SMD = 0.32, 95% CI 0.07 to 0.57, p = 0.013). For the cooling-promotion effects on different sports types, the ranking order in central cooling was ETE (exercise to exhaustion), TT (time-trial), EWT (exercise within the fixed time or sets), IS (intermittent sprint); the ranking order in peripheral cooling was EWT, TT, ETE and IS; the ranking order in central and peripheral cooling was ETE, IS, EWT and TT. Conclusion: Central cooling appears to be an more effective intervention to enhance performance in hot conditions through improvements of skin temperature and thermal sensation, compared to other external cooling strategies. The enhancement effects of peripheral cooling require sufficient re-warming, otherwise it will be trivial. Although, central and peripheral cooling seems to retain advantages from central cooling, as many factors may influence the effects of peripheral cooling to offset the positive effects from central cooling, the question about whether central and peripheral cooling method is better than an isolated cooling technique is still uncertain and needs more researchs to explore it.

[Enhanced Membrane Anti-fouling Ability of Anaerobic Membrane Bioreactor Equipped with Bio-electrochemical System Using Nano-zero-valent Iron and Its Regulation Mechanism].

Membrane fouling is the biggest challenge of membrane bioreactor industrialization. In this study, a bio-electrochemical system (BES)-anaerobic membrane bioreactor (AnMBR) system was constructed, and the effect of nano-zero-valent iron (nZVI) on membrane anti-fouling ability and methane production was investigated. The results showed that the BES-AnMBR system was stable and the chemical oxygen demand (COD) removal rate was maintained at approximately 95%. The optimum condition was observed to be nZVI 0.1 g·g-1(VS). Under this condition, transmembrane pressure (TMP) was reduced by 28.1%, the membrane flux had a slight improvement, and methane production was up to 81.3 mL·g-1(CODremoved). This was 12.1% higher than that of the control. In addition, a further analysis of extracellular polymeric substances (EPS) fraction and membrane resistance showed that nZVI enhanced EPS decomposition, promoted the formation of an iron-rich layer of inorganic and organic matters on the membrane surface, and changed the distribution of organics and inorganics, thereby significantly alleviating membrane fouling. This study will enrich basic theory of conventional AnMBR and provide a new solution for efficient sludge treatment and resource utilization.

[Performance of Anaerobic Membrane Bioreactors for the Co-digestion of Sewage Sludge and Food Waste].

A laboratory-scale anaerobic membrane bioreactor (AnMBR) was used for the co-digestion of sewage sludge and food waste to investigate its organic matter removal characteristics, biogas production performance, and microbial community composition. The results showed that the degradation rate of volatile solids (VS) increased from 17.5% for a single digestion to 40% for the total digestion, and that the COD removal was 95.3% when the organic loading rate (OLR) was stabilized at 0.59-0.64 kg·(m3·d)-1. The solids content of the digested sludge increased by a factor of 3.9. The final CH4 content was 60% and the CH4 yield was 78.7 mL·g-1 of CODadded. The transmembrane pressure (TMP) and average flux were maintained at between -3.1 and -2.7 kPa and 0.106 L·(m2·h)-1, respectively, and membrane fouling was not serious. According to an analysis of the microbial diversity using 16S rRNA, the anaerobic bacterium in the AnMBR were mainly phylum Proteobacteria, Bacteroidetes, and Cloacimonetes, and the dominant methanogens included the Methanobacterium family, Methanosaeta genus, and Methanolinea genus. This study provides a strong theoretical basis for research into the stability and performance of AnMBRs for the co-treatment of sludge and other high-solid waste streams, and provided an effective solution for biomass resource utilization and the energy crisis.

[Impact of dopamine receptor modulation on reduced anxiety-like behavior in neonatal rats after hypoxic-ischemic brain damage].

OBJECTIVE: To observe the long-term changes in anxiety-like behavior and tyrosine hydroxylase (TH) expression in the substantia nigra (SN) after hypoxic-ischemic brain damage (HIBD) in a neonatal rat model and to further explore the relationship between dopamine (DA) level and long-term anxiety-like behavior using the DA receptor (DAR) antagonist. METHODS: Seven-day-old (P7) neonatal Sprague-Dawley (SD) rats were randomized into normal control, sham-operated, HIBD and HIBD+DAR antagonist groups. HIBD model was prepared by ligating the right common carotid artery and 8% hypoxia exposure. The rats in the sham-operated group were sham-operated and were not subjected to right common carotid artery ligation and hypoxia exposure. The DAR antagonist was injected intraperitoneally before and after inducing HIBD. The same amount of normal saline was given to the other three groups as a control. Anxiety-like behavior was evaluated by elevated plus maze test, and TH expression in the SN was measured by immunohistochemistry on P14, P21, and P28. RESULTS: On P21 and P28, the time spent in the open arms and the percentage of open arms entries in the HIBD group were significantly increased compared with those in the normal control, sham-operated and HIBD+DAR antagonist groups (P<0.05); in addition, the HIBD+DAR antagonist group showed a significantly longer time spent in the open arms than the normal control group (P<0.05). On P14, P21, and P28, TH expression in the HIBD and HIBD+DAR antagonist groups was significantly lower than that in the normal control and sham-operated groups, and TH level in the HIBD group was significantly lower than that in the HIBD+DAR antagonist group (P<0.05). CONCLUSIONS: DAR antagonist allows the restoration of anxiety-like behavior and alleviates the damage to dopaminergic neurons in SD rats after HIBD.