Phage protein Gp11 blocks Staphylococcus aureus cell division by inhibiting peptidoglycan biosynthesis.

Phages and bacteria have a long history of co-evolution. However, these dynamics of phage-host interactions are still largely unknown; identification of phage inhibitors that remodel host metabolism will provide valuable information for target development for antimicrobials. Here, we perform a comprehensive screen for early-gene products of ΦNM1 that inhibit cell growth in Staphylococcus aureus. A small membrane protein, Gp11, with inhibitory effects on S. aureus cell division was identified. A bacterial two-hybrid library containing 345 essential S. aureus genes was constructed to screen for targets of Gp11, and Gp11 was found to interact with MurG and DivIC. Defects in cell growth and division caused by Gp11 were dependent on MurG and DivIC, which was further confirmed using CRISPRi hypersensitivity assay. Gp11 interacts with MurG, the protein essential for cell wall formation, by inhibiting the production of lipid II to regulate peptidoglycan (PG) biosynthesis on the cell membrane. Gp11 also interacts with cell division protein DivIC, an essential part of the division machinery necessary for septal cell wall assembly, to disrupt the recruitment of division protein FtsW. Mutations in Gp11 result in loss of its ability to cause growth defects, whereas infection with phage in which the gp11 gene has been deleted showed a significant increase in lipid II production in S. aureus. Together, our findings reveal that a phage early-gene product interacts with essential host proteins to disrupt PG biosynthesis and block S. aureus cell division, suggesting a potential pathway for the development of therapeutic approaches to treat pathogenic bacterial infections. IMPORTANCE: Understanding the interplay between phages and their hosts is important for the development of novel therapies against pathogenic bacteria. Although phages have been used to control methicillin-resistant Staphylococcus aureus infections, our knowledge related to the processes in the early stages of phage infection is still limited. Owing to the fact that most of the phage early proteins have been classified as hypothetical proteins with uncertain functions, we screened phage early-gene products that inhibit cell growth in S. aureus, and one protein, Gp11, selectively targets essential host genes to block the synthesis of the peptidoglycan component lipid II, ultimately leading to cell growth arrest in S. aureus. Our study provides a novel insight into the strategy by which Gp11 blocks essential host cellular metabolism to influence phage-host interaction. Importantly, dissecting the interactions between phages and host cells will contribute to the development of new and effective therapies to treat bacterial infections.

Electroacupuncture alleviates the symptom of depression in mice by regulating the cGAS-STING-NLRP3 signaling.

PURPOSE: To investigate the therapeutic effect of electroacupuncture (EA) on chronic and unpredictable mild stress (CUMS)-induced depression in mice and the underlying mechanism. METHODS: Male C57BL/6 mice were randomly divided into 6 groups: Control, CUMS, CUMS+EA-placebo, CUMS+EA, CUMS+ ad-NC, CUMS+ ad-cGAS-shRNA. CUMS was utilized to establish the depression model in mice. The behavioral changes were determined by the forced swimming, open field, and sucrose preference experiments. The pathological changes in the hippocampus tissue were evaluated by HE staining. The release of TNF-α, IL-1ß, IL-6, 5-HT, and NE in the hippocampus tissue was determined by ELISA. IBA-1 expression detected by the immunofluorescence was used to represent the activity of microglia. Western blot and RT-PCR were utilized to measure the expression of Bax, bcl-2, cGAS, STING, TBK1, IRF3, and NLRP3. RESULTS: The depression behavior in CUMS mice was significantly alleviated by the treatment of EA and cGAS-shRNA, accompanied by ameliorated hippocampus pathological changes, declined production of TNF-α, IL-1ß, and IL-6, elevated secretion of 5-HT and NE, and inhibition on the activity of microglia. Furthermore, significantly elevated expression level of Bax, cGAS, STING, TBK1, IRF3, and NLRP3 and declined expression level of bcl-2 were observed in the CUMS+EA and CUMS+ ad-cGAS-shRNA groups. CONCLUSIONS: EA significantly mitigated the symptom of depression in mice, which was closely associated with the repressed neuroinflammation, increased monoamine concentration, inactivated microglia, and inhibited cGAS-STING-NLRP3 signaling.

Fire acupuncture for plaque psoriasis case series.

OBJECTIVE: To investigate the clinical efficacy of fire acupuncture (FA) on plaque psoriasis (PP), exploring its suitable syndrome types, in order to achieve better therapeutic effects, accelerate the possibility of psoriasis skin lesion recovery, and provide assistance for clinical treatment. METHODS: A total of 8 patients with PP aged between 18 and 60 years were recruited and treated with FA once a week, and the lesion area and severity index (PASI), visual analog scale and pruritus were measured before, 2, 4 and 8 weeks after treatment and at the follow-up period (week 12), respectively. Visual analog scale, and dermoscopy were used for assessment. RESULTS: All patients showed improvement in pruritus after 1 FA treatment, and lesions were reduced to varying degrees after 2 weeks. Except for patients 5 and 8, who only achieved effective results due to severe disease, all other patients with psoriasis achieved significant results at 8 weeks after treatment. CONCLUSION: FA can significantly control the development of lesions, reduce the symptoms of PP lesions and pruritus, and help prevent psoriasis recurrence.

Extract of Gardenia jasminoides Ellis Attenuates High-Fat Diet-Induced Glycolipid Metabolism Disorder in Rats by Targeting Gut Microbiota and TLR4/Myd88/NF-κB Pathway.

Gardenia jasminoides Ellis is abundant in crocin and has a longstanding historical usage both as a dietary and natural ethnic medicine. Enhanced studies have increasingly revealed the intricate interplay between glycolipid metabolism and gut microbiota, wherein their imbalance is regarded as a pivotal indicator of metabolic disorders. Currently, the precise molecular mechanism of the crude extract of crocin from Gardenia jasminoides Ellis (GC) targeting gut microbiota to regulate glycolipid metabolism disorder is still unclear. Firstly, we explored the effect of GC on digestive enzymes (α-amylase and α-glucosidase) in vitro. Secondly, we investigated the effect of GC on the physical and chemical parameters of high-fat diet (HFD) rats, such as body weight change, fasting blood glucose and lipid levels, and liver oxidative stress and injury. Then, 16S rDNA sequencing was used to analyze the effects of GC on the composition and structure of gut microbiota. Finally, the impact of GC on the TLR4/Myd88/NF-κB signaling pathway in the intestine was assessed by Western Blotting. In the present study, GC was found to exhibit a hypoglycemic effect in vitro, by inhibition of digestive enzymes. In animal experiments, we observed that GC significantly reduced fasting blood glucose, TC, and TG levels while increasing HDL-C levels. Additionally, GC demonstrated hepatoprotective properties by enhancing liver antioxidative capacity through the upregulation of SOD, CAT, and GSH-Px, while reducing ROS. 16S rDNA sequencing results showed that GC had a significant effect on the gut microbiota of HFD rats, mainly by reducing the ratio of Firmicutes/Bateroidota, and significantly affected the genera related to glycolipid metabolism, such as Akkermansia, Ligilactobacillus, Lactobacillus, Bacteroides, Prevotellaceae, etc. The Western Blotting results demonstrated that GC effectively downregulated the protein expressions of TLR4, Myd88, and NF-κB in the intestine of HFD rats, indicating that GC could target the TLR4/Myd88/NF-κB pathway to interfere with glycolipid metabolism disorder. Correlation analysis revealed that GC could target the Akkermansia-TLR4/Myd88/NF-κB pathway axis which attenuates glycolipid metabolism disorder. Therefore, this study establishes the foundation for GC as a novel therapeutic agent for glycolipid metabolism disorder chemoprevention, and it introduces a novel methodology for harnessing the potential of natural botanical extracts in the prevention and treatment of metabolic syndrome.

Interventions for psychiatric disorders among university students: An umbrella review of systematic reviews and meta-analyses / Intervenciones para los trastornos psiquiátricos entre estudiantes universitarios: una revisión general de revisiones sistemáticas y metanálisis

Background: Mental disorders are considered to be the main reason for the increase of the disease burden. College students seem to be more vulnerable to the adverse effects of stress, which makes them more at risk of suffering from mental disorders. This umbrella review aimed to evaluate the credibility of published evidence regarding the effects of interventions on mental disorders among university students. Methods: To identify systematic reviews and meta-analyses investigating the effects of interventions on mental disorders in the university student population, extensive searches were carried out in databases including PubMed, Embase, and the Cochrane Database, spanning from inception to July 21, 2023. Subsequently, a thorough reanalysis of crucial parameters such as summary effect estimates, 95 % confidence intervals, heterogeneity I2 statistic, 95 % prediction intervals, small-study effects, and excess significance bias was performed for each meta-analysis found. Results: Nineteen articles involving 74 meta-analyses were included. Our grading of the current evidence showed that interventions based on exercise, Cognitive-behavioural Intervention (CBI), mindfulness-based interventions (MBI), and other interventions like mood and anxiety interventions (MAI) were effective whereas exercise intervention had the highest effect size for both depression and anxiety among university students. However, the credibility of the evidence was weak for most studies. Besides, suggestive evidence was observed for the positive effects of CBI on sleep disturbance(SMD: -0.603, 95 % CI: -0.916, -0.290; P-random effects<0.01) and MAI on anxiety (Hedges'g = -0.198, 95 % CI: -0.302, -0.094; P-random effects<0.01). Conclusion: Based on our findings, it appears that exercise interventions, CBI, and MAI have the potential to alleviate symptoms related to mental disorders...(AU)

Bi-Level Optimization for De-Icing Position Allocation and Unmanned De-Icing Vehicle Fleet Routing Problem.

Aircraft icing due to severe cold and local factors increases the risk of flight delays and safety issues. Therefore, this study focuses on optimizing de-icing allocation and adapting to dynamic flight schedules at medium to large airports. Moreover, it aims to establish a centralized de-icing methodology employing unmanned de-icing vehicles to achieve the dual objectives of minimizing flight delay times and enhancing airport de-icing efficiency. To achieve these goals, a mixed-integer bi-level programming model is formulated, where the upper-level planning guides the allocation of de-icing positions and the lower-level planning addresses the collaborative scheduling of the multiple unmanned de-icing vehicles. In addition, a two-stage algorithm is introduced, encompassing a Mixed Variable Neighborhood Search Genetic Algorithm (MVNS-GA) as well as a Multi-Strategy Enhanced Heuristic Greedy Algorithm (MSEH-GA). Both algorithms are rigorously assessed through horizontal comparisons. This demonstrates the effectiveness and competitiveness of these algorithms. Finally, a model simulation is conducted at a major northwestern hub airport in China, providing empirical evidence of the proposed approach's efficiency. The results show that research offers a practical solution for optimizing the use of multiple unmanned de-icing vehicles in aircraft de-icing tasks at medium to large airports. Therefore, delays are mitigated, and de-icing operations are improved.

Interventions for psychiatric disorders among university students: An umbrella review of systematic reviews and meta-analyses.

Background: Mental disorders are considered to be the main reason for the increase of the disease burden. College students seem to be more vulnerable to the adverse effects of stress, which makes them more at risk of suffering from mental disorders. This umbrella review aimed to evaluate the credibility of published evidence regarding the effects of interventions on mental disorders among university students. Methods: To identify systematic reviews and meta-analyses investigating the effects of interventions on mental disorders in the university student population, extensive searches were carried out in databases including PubMed, Embase, and the Cochrane Database, spanning from inception to July 21, 2023. Subsequently, a thorough reanalysis of crucial parameters such as summary effect estimates, 95 % confidence intervals, heterogeneity I2 statistic, 95 % prediction intervals, small-study effects, and excess significance bias was performed for each meta-analysis found. Results: Nineteen articles involving 74 meta-analyses were included. Our grading of the current evidence showed that interventions based on exercise, Cognitive-behavioural Intervention (CBI), mindfulness-based interventions (MBI), and other interventions like mood and anxiety interventions (MAI) were effective whereas exercise intervention had the highest effect size for both depression and anxiety among university students. However, the credibility of the evidence was weak for most studies. Besides, suggestive evidence was observed for the positive effects of CBI on sleep disturbance(SMD: -0.603, 95 % CI: -0.916, -0.290; P-random effects<0.01) and MAI on anxiety (Hedges'g = -0.198, 95 % CI: -0.302, -0.094; P-random effects<0.01). Conclusion: Based on our findings, it appears that exercise interventions, CBI, and MAI have the potential to alleviate symptoms related to mental disorders. Despite the overall weak credibility of the evidence and the strength of the associations, these interventions offer a promising avenue for further exploration and research in the future. More high-quality randomized controlled trials should be taken into account to verify the effects of these interventions on various mental disorders.

Tianhuang formula ameliorates liver fibrosis by inhibiting CCL2-CCR2 axis and MAPK/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: In the progression of chronic liver diseases, liver fibrosis is a reversible pathophysiologic event for liver diseases prognosis and risk of cirrhosis. Liver injury factors of different etiologies mediate this process. There is still a lack of effective medications for treating liver fibrosis. Additionally, the ameliorative effects of traditional herbs on liver fibrosis have been commonly reported. Tianhuang formula (THF) is a drug combination consisting of 2 traditional Chinese herbs, which has been showing significant improvement in metabolic liver diseases. However, the hepatoprotective effect and mechanism of THF in ameliorating liver fibrosis are still unclear. AIM OF THE STUDY: This study aimed to investigate the effects of THF on carbon tetrachloride (CCl4)-induced and methionine-choline-deficient (MCD) diet-induced liver fibrosis model and to reveal the potential mechanisms. It can provide experimental evidence for THF as a therapeutic candidate for liver fibrosis. MATERIALS AND METHODS: In this study, CCl4-induced mice were treated with THF (80 mg/kg, 160 mg/kg) or Fuzheng Huayu (FZHY) capsules (4.8 g/kg) for 6 weeks. MCD-induced mice received the same doses of THF or FZHY for 4 weeks. FZHY is used as a comparative study in these two models. Following that, using kit reagents detected changes in relevant serum and liver biochemical indicators. Histological changes in mouse liver were measured by staining of H&E and Sirius Red. The markers expression of liver fibrosis and inflammation were detected using qRT-PCR, western blotting and immunohistochemical staining analysis. The potential regulatory mechanism of THF to ameliorate liver fibrosis was performed by RNA-sequencing analysis. Finally, the analysis results were verified by immunofluorescence co-staining, qRT-PCR and western blotting. RESULTS: Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and hepatic triglyceride (TG) levels in CCl4 and MCD-induced liver fibrosis mice were significantly improved after THF treatment. Meanwhile, the expression of fibrosis and inflammation markers were significantly suppressed. Furthermore, THF downregulated the expression of the macrophage marker CD68. According to RNA-sequencing analysis, we found the CCL2-CCR2 axis and MAPK/NF-κB as the potential signaling pathway for THF against liver fibrosis. CONCLUSION: This study revealed that THF ameliorated liver injury, inflammation and fibrotic process by inhibiting CCL2-CCR2 axis and its downstream MAPK/NF-κB signaling pathway.

Composition of gut microbiota and non-alcoholic fatty liver disease: A systematic review and meta-analysis.

The present systematic review and meta-analysis aimed to summarize the associations between gut microbiota composition and non-alcoholic fatty liver disease. To compare the differences between individuals with or without NAFLD, the standardized mean difference and 95% confidence interval were computed for each α-diversity index and relative abundance of gut microbes. The ß-diversity indices were summarized in a qualitative manner. A total of 54 studies with 8894 participants were included. Overall, patients with NAFLD had moderate reduction in α-diversity indices including Shannon (SMD = -0.36, 95% CI = [-0.53, -0.19], p < 0.001) and Chao 1 (SMD = -0.42, 95% CI = [-0.68, -0.17], p = 0.001), but no significant differences were found for Simpson, observed species, phylogenetic diversity, richness, abundance-based coverage estimator, and evenness (p ranged from 0.081 to 0.953). Over 75% of the included studies reported significant differences in ß-diversity. Although there was substantial interstudy heterogeneity, especially for analyses at the phylum, class, and family levels, the majority of the included studies showed alterations in the depletion of anti-inflammatory microbes (i.e., Ruminococcaceae and Coprococcus) and the enrichment of proinflammatory microbes (i.e., Fusobacterium and Escherichia) in patients with NAFLD. Perturbations in gut microbiota were associated with NAFLD, commonly reflected by a reduction in beneficial species and an increase in the pathogenic species.

DHX33 mediates p53 to regulate mevalonate pathway gene transcription in human cancers.

Tumor suppressor p53 is frequently null or mutated in human cancers. Here in this study, DHX33 protein was found to be induced in p53 null cells in vitro, and in p53 mutant lung tumorigenesis in vivo. Cholesterol metabolism through mevalonate pathway is pivotal for cell proliferation and is frequently altered in human cancers. Mice carrying mutant p53 and KrasG12D alleles showed upregulation of mevalonate pathway gene expression. However upon DHX33 loss, their upregulation was significantly debilitated. Additionally, in many human cancer cells, DHX33 knockdown caused inhibition of mavelonate pathway gene transcription. We propose DHX33 locates downstream of mutant p53 and Ras to regulate mevalonate pathway gene transcription and thereby supports cancer development in vivo.

Efficacy and safety of hepatitis B vaccine: an umbrella review of meta-analyses.

BACKGROUND: There is a lack of synthesis of literature to determine hepatitis B vaccine (HepB) strategies for hepatitis B virus (HBV) supported by quality evidence. We aimed to explore the efficacy and safety of HepB strategies among people with different characteristics. RESEARCH DESIGN AND METHODS: PubMed, Cochrane Library, Embase, and Web of Science were searched for meta-analyses comparing the efficacy and safety of HepB up to July 2023. RESULTS: Twenty-one meta-analyses comparing 83 associations were included, with 16 high quality, 4 moderate, and 1 low quality assessed by AMSTAR 2. Highly suggestive evidence supports HepB booster and HepB with 1018 adjuvant (HBsAg-1018) for improved seroprotection, and targeted and universal HepB vaccination reduced HBV infection Suggestive evidence indicated that targeted vaccination decreased the rate of hepatitis B surface antibody positivity and booster doses increased seroprotection in people aged 10-20. Weak evidence suggests potential local/systemic reaction risk with nucleotide analogs or HBsAg-1018. Convincing evidence shows HLA-DPB1*04:01 and DPB1*04:02 increased, while DPB1*05:01 decreased, hepatitis B antibody response. Obesity may reduce HepB seroprotection, as highly suggested. CONCLUSION: Targeted vaccination could effectively reduce HBV infection, and adjuvant and booster vaccinations enhance seroprotection without significant reaction. Factors such as obesity and genetic polymorphisms may affect the efficacy.

Exploring symptom-level associations between anxiety and depression across developmental stages of adolescence: a network analysis approach.

BACKGROUND: Anxiety and depression often co-occur during adolescence, but the associations between symptoms of these two disorders in this developmental period are not yet fully understood. Network analysis provides a valuable approach to uncover meaningful associations among symptoms and offers insights for prevention and intervention strategies. This study aimed to investigate symptom-level associations between anxiety and depression using network analysis and to identify core symptoms, bridge symptoms, and differences in network structure across different stages of adolescence. METHODS: The cross-sectional study was conducted in March 2022 in Shenzhen, China. Participants completed the Generalized Anxiety Disorder Scale-7 and Patient Health Questionnaire Depression Scale, along with demographic questionnaires assessing age and gender. Chinese adolescents aged 10 to 17 who were in Grades 5 or 6 of elementary school, Grades 1 or 2 of middle school, or Grades 1 or 2 of high school, and who could comprehensively understand and read Chinese were recruited as participants. Students in Grade 3 of middle and high schools were excluded due to their upcoming high school or college entrance examinations. Based on age, participants were categorized into early, middle, and late developmental stages of adolescence. RESULTS: "Loss of control" was among the most central symptoms in the comorbidity network throughout all three developmental stages; "excessive worry" and "anhedonia" emerged as the core symptoms in early adolescence, and "restlessness" as the core symptom in late adolescence. "Anhedonia," "sad mood," and "fatigue" were identified as bridge symptoms between anxiety and depression across all three developmental stages of adolescence. The global strength of the network in middle adolescence was significantly higher compared to the other two stages. CONCLUSION: These findings highlight the core and bridge symptoms that require special attention and intervention at each stage of adolescence. Moreover, significantly higher network connectivity in middle adolescence suggests this is a critical period for intervention to prevent the development of comorbid mental disorders.

Comparative analysis of microbial communities and volatile flavor components in the brewing of Hongqu rice wines fermented with different starters.

As one of the quintessential representatives of Chinese rice wine, Hongqu rice wine is brewed with glutinous rice as the main raw material and Hongqu (Gutian Qu or Wuyi Qu) as the fermentation starter. The present study aimed to investigate the impact of Hongqu on the volatile compositions and the microbial communities in the traditional production of Gutian Hongqu rice wine (GT) and Wuyi Hongqu rice wine (WY). Through the OPLS-DA analysis, 3-methylbutan-1-ol, isobutanol, ethyl lactate, ethyl acetate, octanoic acid, diethyl succinate, phenylethyl alcohol, hexanoic acid and n-decanoic acid were identified as the characteristic volatile flavor components between GT and WY. Microbiome analysis revealed significant enrichments of Lactobacillus, Pediococcus, Aspergillus and Hyphopichia in WY brewing, whereas Monascus, Saccharomyces, Pantoea, and Burkholderia-Caballeronia-Paraburkholderia were significantly enriched in GT brewing. Additionally, correlation analysis showed that Saccharomyces, Lactobacillus, Weissella and Pediococcus were significantly positively correlated wih most characteristic volatile components. Conversely, Picha, Monascus, Franconibacter and Kosakonia showed significant negative correlations with most of the characteristic volatile components. Furthermore, bioinformatical analysis indicated that the gene abundances for enzymes including glucan 1,4-alpha-glucosidase, carboxylesterase, alcohol dehydrogenase, dihydroxy-acid dehydratase and branched-chain-amino-acid transaminase were significantly higher in WY compared to GT. This finding explains the higher content of higher alcohols and characteristic esters in WY relative to GT. Collectively, this study provides a theoretical basis for improving the flavor profile of Hongqu rice wine and establishing a solid scientific foundation for the sustainable development of Hongqu rice wine industry.

Network pharmacology: a bright guiding light on the way to explore the personalized precise medication of traditional Chinese medicine.

Network pharmacology can ascertain the therapeutic mechanism of drugs for treating diseases at the level of biological targets and pathways. The effective mechanism study of traditional Chinese medicine (TCM) characterized by multi-component, multi-targeted, and integrative efficacy, perfectly corresponds to the application of network pharmacology. Currently, network pharmacology has been widely utilized to clarify the mechanism of the physiological activity of TCM. In this review, we comprehensively summarize the application of network pharmacology in TCM to reveal its potential of verifying the phenotype and underlying causes of diseases, realizing the personalized and accurate application of TCM. We searched the literature using "TCM network pharmacology" and "network pharmacology" as keywords from Web of Science, PubMed, Google Scholar, as well as Chinese National Knowledge Infrastructure in the last decade. The origins, development, and application of network pharmacology are closely correlated with the study of TCM which has been applied in China for thousands of years. Network pharmacology and TCM have the same core idea and promote each other. A well-defined research strategy for network pharmacology has been utilized in several aspects of TCM research, including the elucidation of the biological basis of diseases and syndromes, the prediction of TCM targets, the screening of TCM active compounds, and the decipherment of mechanisms of TCM in treating diseases. However, several factors limit its application, such as the selection of databases and algorithms, the unstable quality of the research results, and the lack of standardization. This review aims to provide references and ideas for the research of TCM and to encourage the personalized and precise use of Chinese medicine.

CircHERC1 promotes non-small cell lung cancer cell progression by sequestering FOXO1 in the cytoplasm and regulating the miR-142-3p-HMGB1 axis.

BACKGROUND: Noncoding RNAs such as circular RNAs (circRNAs) are abundant in the human body and influence the occurrence and development of various diseases. Non-small cell lung cancer (NSCLC) is one of the most common malignant cancers. Information on the functions and mechanism of circRNAs in lung cancer is limited; thus, the topic needs more exploration. The purpose of this study was to identify aberrantly expressed circRNAs in lung cancer, unravel their roles in NSCLC progression, and provide new targets for lung cancer diagnosis and therapy. METHODS: High-throughput sequencing was used to analyze differential circRNA expression in patients with lung cancer. qRT‒PCR was used to determine the level of circHERC1 in lung cancer tissues and plasma samples. Gain- and loss-of-function experiments were implemented to observe the impacts of circHERC1 on the growth, invasion, and metastasis of lung cancer cells in vitro and in vivo. Mechanistically, dual luciferase reporter assays, fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP) and RNA pull-down experiments were performed to confirm the underlying mechanisms of circHERC1. Nucleocytoplasmic localization of FOXO1 was determined by nucleocytoplasmic isolation and immunofluorescence. The interaction of circHERC1 with FOXO1 was verified by RNA pull-down, RNA immunoprecipitation (RIP) and western blot assays. The proliferation and migration of circHERC1 in vivo were verified by subcutaneous and tail vein injection in nude mice. RESULTS: CircHERC1 was significantly upregulated in lung cancer tissues and cells, ectopic expression of circHERC1 strikingly facilitated the proliferation, invasion and metastasis, and inhibited the apoptosis of lung cancer cells in vitro and in vivo. However, knockdown of circHERC1 exerted the opposite effects. CircHERC1 was mainly distributed in the cytoplasm. Further mechanistic research indicated that circHERC1 acted as a competing endogenous RNA of miR-142-3p to relieve the repressive effect of miR-142-3p on its target HMGB1, activating the MAPK/ERK and NF-κB pathways and promoting cell migration and invasion. More importantly, we found that circHERC1 could bind FOXO1 and sequester it in the cytoplasm, adjusting the feedback AKT pathway. The accumulation of FOXO1 in the cytosol and nuclear exclusion promoted cell proliferation and inhibited apoptosis. CircHERC1 is a new circRNA that promotes tumor function in NSCLC and may serve as a potential prognostic biomarker and therapeutic target for NSCLC. CONCLUSIONS: CircHERC1 is a new circRNA that promotes tumor function in NSCLC and may serve as a potential diagnosis biomarker and therapeutic target for NSCLC. Our findings indicate that circHERC1 facilitates the invasion and metastasis of NSCLC cells by regulating the miR-142-3p/HMGB1 axis and activating the MAPK/ERK and NF-κB pathways. In addition, circHERC1 can promote cell proliferation and inhibit apoptosis by sequestering FOXO1 in the cytoplasm to regulate AKT activity and BIM transcription.

Insights into microbial communities and metabolic profiles in the traditional production of the two representative Hongqu rice wines fermented with Gutian Qu and Wuyi Qu based on single-molecule real-time sequencing.

Hongqu rice wine, a famous traditional fermented alcoholic beverage, is brewed with traditional Hongqu (mainly including Gutian Qu and Wuyi Qu). This study aimed to compare the microbial communities and metabolic profiles in the traditional brewing of Hongqu rice wines fermented with Gutian Qu and Wuyi Qu. Compared with Hongqu rice wine fermented with Wuyi Qu (WY), Hongqu rice wine fermented with Gutian Qu (GT) exhibited higher levels of biogenic amines. The composition of volatile flavor components of Hongqu rice wine brewed by different fermentation starters (Gutian Qu and Wuyi Qu) was obviously different. Among them, ethyl acetate, isobutanol, 3-methylbutan-1-ol, ethyl decanoate, ethyl palmitate, ethyl oleate, nonanoic acid, 4-ethylguaiacol, 5-pentyldihydro-2(3H)-furanone, ethyl acetate, n-decanoic acid etc. were identified as the characteristic aroma-active compounds between GT and WY. Microbiome analysis based on high-throughput sequencing of full-length 16S rDNA/ITS-5.8S rDNA amplicons revealed that Lactococcus, Leuconostoc, Pseudomonas, Serratia, Enterobacter, Weissella, Saccharomyces, Monascus and Candida were the predominant microbial genera during the traditional production of GT, while Lactococcus, Lactobacillus, Leuconostoc, Enterobacter, Kozakia, Weissella, Klebsiella, Cronobacter, Saccharomyces, Millerozyma, Monascus, Talaromyces and Meyerozyma were the predominant microbial genera in the traditional fermentation of WY. Correlation analysis revealed that Lactobacillus showed significant positive correlations with most of the characteristic volatile flavor components and biogenic amines. Furthermore, bioinformatical analysis based on PICRUSt revealed that microbial enzymes related to biogenic amines synthesis were more abundant in GT than those in WY, and the enzymes responsible for the degradation of biogenic amines were less abundant in GT than those in WY. Collectively, this study provides important scientific data for enhancing the flavor quality of Hongqu rice wine, and lays a solid foundation for the healthy and sustainable development of Hongqu rice wine industry.

Ketogenic Diet and Multiple Health Outcomes: An Umbrella Review of Meta-Analysis.

Numerous studies have examined the effects of ketogenic diets (KD) on health-related outcomes through meta-analyses. However, the presence of biases may compromise the reliability of conclusions. Therefore, we conducted an umbrella review to collate and appraise the strength of evidence on the efficacy of KD interventions. We conducted a comprehensive search on PubMed, EMBASE, and the Cochrane Database until April 2023 to identify meta-analyses that investigated the treatment effects of KD for multiple health conditions, which yielded 23 meta-analyses for quantitative analyses. The evidence suggests that KD could increase the levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), the respiratory exchange rate (RER), and could decrease total testosterone and testosterone levels (all p-random effects: <0.05). The combination of KD and physical activity can significantly reduce body weight and increase the levels of LDL-C and cortisol. In addition, KD was associated with seizure reduction in children, which can be explained by the ketosis state as induced by the diet. Furthermore, KD demonstrated a better alleviation effect in refractory childhood epilepsy, in terms of median effective rates for seizure reduction of ≥50%, ≥90%, and seizure freedom. However, the strength of evidence supporting the aforementioned associations was generally weak, thereby challenging their credibility. Consequently, future studies should prioritize stringent research protocols to ascertain whether KD interventions with longer intervention periods hold promise as a viable treatment option for various diseases.

Unravelling the intricacies between gaming motivations and internet gaming disorder symptoms in adolescents: a network analysis of 2-year healthy and deteriorating transition profiles.

BACKGROUND: The increasing prevalence of internet gaming disorder (IGD) among adolescents has become a global concern, while gaming plays a large role in many adolescents' lives. While prior research emphasised the significance of investigating IGD through an etiological lens, the interconnections between diverse gaming motivations and IGD symptoms in adolescents remain inadequately understood. This study explored the associations between distinct gaming motivations and IGD symptoms by conducting network analysis in adolescents. METHODS: Data from a two-year longitudinal school-based survey (N = 2148) was utilized. LPA was used to offer a straightforward and interpretable solution for identifying adolescents with two-year healthy and deteriorating transitions of IGD profiles. Subsequently, we conducted a network analysis to explore and compare the associations between gaming motivations and IGD symptoms in adolescents with two-year healthy transition profiles and deteriorating transition profiles. RESULTS: Three profiles were delineated: 'low IGD' (T1: n = 808, 37.62%; T2: n = 731; 34.03%), 'middle IGD' (T1: n = 1063, 49.49%; T2: n = 1103, 51.35%), and 'severe IGD' (T1: n = 277, 12.89%; T2: n = 314, 14.62%), classifying adolescents with healthy transitions and those with deteriorating transitions. Three gaming motivations (i.e., 'Daily entertainment', 'I am good at it', and 'Improvement of ability and mindset') were identified as protective motivations. Two others, 'Enjoy being in the gaming world' and 'Preoccupation', were identified as bridge nodes in adolescents with deteriorating transitions. Three core nodes (i.e., 'Sense of victory', 'Enjoy being in the gaming world', and 'Sense of achievement') were identified in both adolescents with healthy profile transitions and deteriorating transitions. CONCLUSION: Findings suggest that not all gaming motivations contribute to the development of IGD in adolescents. Adolescents with deteriorating transitions showed specific gaming motivation and IGD symptom that is closely connected. Future interventions should consider corresponding gaming motivation when addressing IGD among adolescents.

Self-Competitive Adsorption Behavior of Arsenic on the TiO2 Surface.

TiO2 is a commonly used material to remove arsenic from drinking water by adsorption as well as photocatalytic oxidation (PCO). In the present paper, arsenic adsorption and PCO at different pH environments are studied on the (1 1 0) facet of rutile TiO2 (r-TiO2). A self-competitive adsorption (SCA) behavior of arsenic is observed; i.e., arsenic species compete to adsorb on the surface. Related DFT calculations are carried out to simulate adsorption. SCA behavior is the key to connecting calculation results with experimental results. Furthermore, PCO of arsenite is performed at different pH values. Of note, PCO is related to adsorption; namely, the adsorption process determines the whole PCO reaction speed. Therefore, SCA is also helpful for the PCO reaction. The SCA behavior is useful not only for arsenic on r-TiO2 but also for arsenic on anatase TiO2 (a-TiO2). It may be helpful to further study arsenic adsorption and PCO on other materials such as Fe2O3 and MnO2. The SCA behavior extends our understanding of arsenic and provides new insights into arsenic removal and its cycle in nature.

The Interaction of Dietary Patterns and Genetic Variants on the Risk of Cardiovascular Diseases in Chinese Patients with Type 2 Diabetes.

SCOPE: Diabetes is an important risk factor for cardiovascular disease (CVD), which in turn is the most common and serious complication of diabetes. This study analyzes dietary patterns and single nucleotide polymorphisms (SNPs) in 543 diabetes patients with new-onset cardiovascular events and 461 diabetic patients without. METHODS AND RESULTS: SNPs are determined and analyzed using real time PCR and gene chip method. Factor analysis and logistic regression are used to determine dietary patterns and evaluate the level of associations and interaction effects, respectively. The legumes and edible fungi pattern and vegetable pattern show a significant negative correlation with complication risk. ADIPOQ rs37563 and legumes and edible fungi pattern have a significant interactive effect on disease, and patients with a high score of C polymorphism genotype (GC + CC) have a lower risk of disease. 5-10-Methylenetetrahydrofolate reductase (MTHFR) rs1801131 and vegetable pattern have a borderline interaction effect on disease, and those patients with TT genotype have a lower risk of disease. CONCLUSION: These findings provide new insights into the role of the interactive protection of dietary patterns and SNPs. And participants with specific alleles show a lower risk of cardiovascular complications.