The E3 ligase ASB3 downregulates antiviral innate immunity by targeting MAVS for ubiquitin-proteasomal degradation.

E3 ubiquitin ligases are very important for regulating antiviral immunity during viral infection. Here, we discovered that Ankyrin repeat and SOCS box-containing protein 3 (ASB3), an E3 ligase, are upregulated in the presence of RNA viruses, particularly influenza A virus (IAV). Notably, overexpression of ASB3 inhibits type I IFN (IFN-I) responses induced by Sendai virus (SeV) and IAV, and ablation of ASB3 restores SeV and H9N2 infection-mediated transcription of IFN-ß and its downstream interferon-stimulated genes (ISGs). Interestingly, animals lacking ASB3 presented decreased susceptibility to H9N2 and H1N1 infections. Mechanistically, ASB3 interacts with MAVS and directly mediates K48-linked polyubiquitination and degradation of MAVS at K297, thereby inhibiting the phosphorylation of TBK1 and IRF3 and downregulating downstream antiviral signaling. These findings establish ASB3 as a critical negative regulator that controls the activation of antiviral signaling and describe a novel function of ASB3 that has not been previously reported.

Signal mining and analysis of trifluridine/tipiracil adverse events based on real-world data from the FAERS database.

Objective: The objective of this research is to scrutinize adverse events (AEs) linked to Trifluridine/Tipiracil (TFTD/TPI), using data from the FDA Adverse Event Reporting System (FAERS) database. Methods: The AEs data related to TFTD/TPI were collected from the fourth quarter of 2015 through the fourth quarter of 2023. After normalizing the data, multiple signal quantification techniques including Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), Bayesian approaches such as Bayesian Confidence Propagation Neural Network (BCPNN) and the Multi-item Gamma Poisson Shrinker (MGPS) were used for overall and subgroup analysis and visualization analyses were performed. Results: From the FAERS database, we analyzed 13,520,073 reports, identifying 8,331 as primary suspect (PS) AEs for TFTD/TPI, occurring across 27 organ systems. The study retained 99 significant disproportionality Preferred Terms (PTs) across four algorithms and unveiled unexpected serious AEs such as iron deficiency and intestinal perforation, hepatic failure, cholangitis and so on. The median onset of TFTD/TPI-associated AEs was 44 days (IQR 20-97 days), with most occurring within the first 30 days of treatment. Conclusion: This research uncovers critical new safety signals for TFTD/TPI, supporting its clinical monitoring and risk identification.

ASB3 expression aggravates inflammatory bowel disease by targeting TRAF6 protein stability and affecting the intestinal microbiota.

E3 ubiquitin ligase (E3) plays a vital role in regulating inflammatory responses by mediating ubiquitination. Previous studies have shown that ankyrin repeat and SOCS box-containing protein 3 (ASB3) is involved in immunomodulatory functions associated with cancer. However, the impact of ASB3 on the dynamic interplay of microbiota and inflammatory responses in inflammatory bowel disease (IBD) is unclear. Here, we systematically identify the E3 ligase ASB3 as a facilitative regulator in the development and progression of IBD. We observed that ASB3 exhibited significant upregulation in the lesions of patients with IBD. ASB3-/- mice are resistant to dextran sodium sulfate-induced colitis. IκBα phosphorylation levels and production of proinflammatory factors IL-1ß, IL-6, and TNF-α were reduced in the colonic tissues of ASB3-/- mice compared to WT mice. This colitis-resistant phenotype was suppressed after coprophagic microbial transfer and reversed after combined antibiotics removed the gut commensal microbiome. Mechanistically, ASB3 specifically catalyzes K48-linked polyubiquitination of TRAF6 in intestinal epithelial cells. In contrast, in ASB3-deficient organoids, the integrity of the TRAF6 protein is shielded, consequently decelerating the onset of intestinal inflammation. ASB3 is associated with dysregulation of the colitis microbiota and promotes proinflammatory factors' production by disrupting TRAF6 stability. Strategies to limit the protein level of ASB3 in intestinal epithelial cells may help in the treatment of colitis. IMPORTANCE: Ubiquitination is a key process that controls protein stability. We determined the ubiquitination of TRAF6 by ASB3 in intestinal epithelial cells during colonic inflammation. Inflammatory bowel disease patients exhibit upregulated ASB3 expression at focal sites, supporting the involvement of degradation of TRAF6, which promotes TLR-Myd88/TRIF-independent NF-κB aberrant activation and intestinal microbiota imbalance. Sustained inflammatory signaling in intestinal epithelial cells and dysregulated protective probiotic immune responses mediated by ASB3 collectively contribute to the exacerbation of inflammatory bowel disease. These findings provide insights into the pathogenesis of inflammatory bowel disease and suggest a novel mechanism by which ASB3 increases the risk of colitis. Our results suggest that future inhibition of ASB3 in intestinal epithelial cells may be a novel clinical strategy.

AhR ligands from LGG metabolites promote piglet intestinal ILC3 activation and IL-22 secretion to inhibit PEDV infection.

In maintaining organismal homeostasis, gut immunity plays a crucial role. The coordination between the microbiota and the immune system through bidirectional interactions regulates the impact of microorganisms on the host. Our research focused on understanding the relationships between substantial changes in jejunal intestinal flora and metabolites and intestinal immunity during porcine epidemic diarrhea virus (PEDV) infection in piglets. We discovered that Lactobacillus rhamnosus GG (LGG) could effectively prevent PEDV infection in piglets. Further investigation revealed that LGG metabolites interact with type 3 innate lymphoid cells (ILC3s) in the jejunum of piglets through the aryl hydrocarbon receptor (AhR). This interaction promotes the activation of ILC3s and the production of interleukin-22 (IL-22). Subsequently, IL-22 facilitates the proliferation of IPEC-J2 cells and activates the STAT3 signaling pathway, thereby preventing PEDV infection. Moreover, the AhR receptor influences various cell types within organoids, including intestinal stem cells (ISCs), Paneth cells, and enterocytes, to promote their growth and development, suggesting that AhR has a broad impact on intestinal health. In conclusion, our study demonstrated the ability of LGG to modulate intestinal immunity and effectively prevent PEDV infection in piglets. These findings highlight the potential application of LGG as a preventive measure against viral infections in livestock.IMPORTANCEWe observed high expression of the AhR receptor on pig and human ILC3s, although its expression was negligible in mouse ILC3s. ILC3s are closely related to the gut microbiota, particularly the secretion of IL-22 stimulated by microbial signals, which plays a crucial regulatory role in intestinal immunity. In our study, we found that metabolites produced by beneficial gut bacteria interact with ILC3s through AhR, thereby maintaining intestinal immune homeostasis in pigs. Moreover, LGG feeding can enhance the activation of ILC3s and promote IL-22 secretion in the intestines of piglets, ultimately preventing PEDV infection.

LGG promotes activation of intestinal ILC3 through TLR2 receptor and inhibits salmonella typhimurium infection in mice.

Salmonella is a foodborne pathogen that causes disruption of intestinal mucosal immunity, leading to acute gastroenteritis in the host. In this study, we found that Salmonella Typhimurium (STM) infection of the intestinal tract of mice led to a significant increase in the proportion of Lacticaseibacillus, while the secretion of IL-22 from type 3 innate lymphoid cells (ILC3) increased significantly. Feeding Lacticaseibacillus rhamnosus GG (LGG) effectively alleviated the infection of STM in the mouse intestines. TLR2-/- mice experiments found that TLR2-expressing dendritic cells (DCs) are crucial for LGG's activation of ILC3. Subsequent in vitro experiments showed that heat-killed LGG (HK-LGG) could promote DCs to secrete IL-23, which in turn further promotes the activation of ILC3 and the secretion of IL-22. Finally, organoid experiments further verified that IL-22 secreted by ILC3 can enhance the intestinal mucosal immune barrier and inhibit STM infection. This study demonstrates that oral administration of LGG is a potential method for inhibiting STM infection.

Epirubicin induces cardiotoxicity through disrupting ATP6V0A2-dependent lysosomal acidification and triggering ferroptosis in cardiomyocytes.

Epirubicin (EPI) is effective in the treatment of malignant cancers, but its application is limited by life-threatening cardiotoxicity. Iron homeostasis disturbance has been implicated in anthracycline induced cardiotoxicity (AIC), and ferroptosis is involved in AIC which dependent upon intracellular iron. However, the role and exact mechanisms of ferroptosis in the pathogenesis of epirubicin-induced cardiotoxicity (EIC) remain elusive. In this study, we aimed to investigate mechanisms underlying ferroptosis-driven EIC. Epirubicin triggered ferroptosis both in vivo and in cultured cardiomyocytes, and pretreatment with ferroptosis inhibitor, Ferrostatin-1(Fer-1) alleviates EIC. Microarray analysis was performed to screen for potential molecules involved in EIC in neonatal primary mouse ventricular cardiomyocytes (NMVMs). We found that the transcript level of ATP6V0A2, a subunit of vacuolar ATPase (V-ATPase), was significantly downregulated when NMVMs were subjected to EPI, which was verified in vivo and in vitro as measured by real time quantitative reverse transcription PCR (qRT-PCR) and immunoblotting. Intriguingly, overexpression of ATP6V0A2 effectively decreased excessive oxidative stress and lipid-peroxidation accumulation, thereby inhibiting ferroptosis and protecting cardiomyocytes against EIC, as evidenced by functional, enzymatic, and morphological changes. Mechanistically, forced expression of ATP6V0A2 restored lysosomal acidification in EPI-treated cardiomyocytes and protected cardiomyocytes and mice hearts from ferroptosis-driven EIC. In this study, our data elucidate that ferroptosis is involved in EIC, which is ignited by ATP6V0A2-dependent lysosomal acidification dysfunction. Our study provides a new potential therapeutic target for ameliorating EIC.

Establishment of a microspheres-based homogeneous fluorescence immunoassay for the rapid detection of cardiac troponin I.

Myocardial infarction occurs rapidly, and thus the rapid detection of cTnI levels is the key to its diagnosis. Most current assays take 10-30 min. In this study, we developed a method for accurately measuring cardiac troponin I (cTnI) levels in human sera with amplified luminescence neighborhood homogeneous assay (AlphaLISA). The method involves coupling two cTnI antibodies targeting different epitopes to the surface of carboxylated donor and acceptor beads. The final signal values were detected by the double-antibody sandwich method, and the best reaction conditions were obtained by optimizing the experimental conditions. The sensitivity, specificity, accuracy, and precision of the method were evaluated. Results showed that the method requires only 3 min to produce the results, the detection sensitivity is 27.06 ng L-1, and the measurement range is 34.56-62 500 ng L-1. cTnI-AlphaLISA has an intra-assay precision of 2.18-4.57% (<10%) and an inter-assay precision of 5.60-6.95% (<10%). The relative recovery rates are within reasonable limits. In addition, the serum assay results of the method were compared with chemiluminescence immunoassay, and the results are in agreement with one another (ρ = 0.8803; P < 0.0001). The method is expected to be developed as a routine method, but further studies and evaluations are needed.

Serum extracellular vesicle-derived miR-21-5p and miR-26a-5p as non-invasive diagnostic potential biomarkers for gastric cancer: A preliminary study.

PURPOSE: Gastric cancer is the most common malignancy worldwide and is the third leading cause of cancer-related deaths, urgently requiring an early and non-invasive diagnosis. Circulating extracellular vesicles may emerge as promising biomarkers for the rapid diagnosis in a non-invasive manner. METHODS: Using high-throughput small RNA sequencing, we profiled the small RNA population of serum-derived extracellular vesicles from healthy controls and gastric cancer patients. Differentially expressed microRNAs (miRNAs) were randomly selected and validated by reverse transcription-quantitative real-time polymerase chain reaction. Receiver operating characteristic curves were employed to assess the predictive value of miRNAs for gastric cancer. RESULTS: In this study, 193 differentially expressed miRNAs were identified, of which 152 were upregulated and 41 were significantly downregulated. Among the differently expressed miRNA, the expression levels of miR-21-5p, miR-26a-5p, and miR-27a-3p were significantly elevated in serum-derived extracellular vesicles of gastric cancer patients. The miR-21-5p and miR-27a-3p were closely correlated with the tumor size. Moreover, the expression levels of serum miR-21-5p and miR-26a-5p were significantly decreased in gastric cancer patients after surgery. CONCLUSIONS: The present study discovered the potential of serum miR-21-5p and miR-26a-5p as promising candidates for the diagnostic and prognostic markers of gastric cancer.

Anti-Inflammatory Responses Produced with Nippostrongylus brasiliensis-Derived Uridine via the Mitochondrial ATP-Sensitive Potassium Channel and Its Anti-Atherosclerosis Effect in an Apolipoprotein E Gene Knockout Mouse Model.

Atherosclerosis (AS) has become the leading cause of cardiovascular disease worldwide. Our previous study had observed that Nippostrongylus brasiliensis (Nb) infection or its derived products could inhibit AS development by inducing an anti-inflammatory response. We performed a metabolic analysis to screen Nb-derived metabolites with anti-inflammation activity and evaluated the AS-prevention effect. We observed that the metabolite uridine had higher expression levels in mice infected with the Nb and ES (excretory-secretory) products and could be selected as a key metabolite. ES and uridine interventions could reduce the pro-inflammatory responses and increase the anti-inflammatory responses in vitro and in vivo. The apolipoprotein E gene knockout (ApoE-/-) mice were fed with a high-fat diet for the AS modeling. Following the in vivo intervention, ES products or uridine significantly reduced serum and liver lipid levels, alleviated the formation of atherosclerosis, and reduced the pro-inflammatory responses in serum or plaques, while the anti-inflammatory responses showed opposite trends. After blocking with 5-HD (5-hydroxydecanoate sodium) in vitro, the mRNA levels of M2 markers were significantly reduced. When blocked with 5-HD in vivo, the degree of atherosclerosis was worsened, the pro-inflammatory responses were increased compared to the uridine group, while the anti-inflammatory responses decreased accordingly. Uridine, a key metabolite from Nippostrongylus brasiliensis, showed anti-inflammatory and anti-atherosclerotic effects in vitro and in vivo, which depend on the activation of the mitochondrial ATP-sensitive potassium channel.

Expression and characterization of a novel microbial GH9 glucanase, IDSGLUC9-4, isolated from sheep rumen.

OBJECTIVE: This study aimed to identify and characterize a novel endo-ß-glucanase, IDSGLUC9-4, from the rumen metatranscriptome of Hu sheep. METHODS: A novel endo-ß-glucanase, IDSGLUC9-4, was heterologously expressed in Escherichia coli and biochemically characterized. The optimal temperature and pH of recombinant IDSGLUC9-4 were determined. Subsequently, substrate specificity of the enzyme was assessed using mixed-linked glucans including barley ß-glucan and Icelandic moss lichenan. Thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC), matrix assisted laser desorption ionization time of flight mass spectrometry analyses were conducted to determine the products released from polysaccharides and cello-oligosaccharides substrates. RESULTS: The recombinant IDSGLUC9-4 exhibited temperature and pH optima of 40°C and pH 6.0, respectively. It exclusively hydrolyzed mixed-linked glucans, with significant activity observed for barley ß-glucan (109.59±3.61 µmol/mg min) and Icelandic moss lichenan (35.35±1.55 µmol/mg min). TLC and HPLC analyses revealed that IDSGLUC9-4 primarily released cellobiose, cellotriose, and cellotetraose from polysaccharide substrates. Furthermore, after 48 h of reaction, IDSGLUC9-4 removed most of the glucose, indicating transglycosylation activity alongside its endo-glucanase activity. CONCLUSION: The recombinant IDSGLUC9-4 was a relatively acid-resistant, mesophilic endo-glucanase (EC 3.2.1.4) that hydrolyzed glucan-like substrates, generating predominantly G3 and G4 oligosaccharides, and which appeared to have glycosylation activity. These findings provided insights into the substrate specificity and product profiles of rumen-derived GH9 glucanases and contributed to the expanding knowledge of cellulolytic enzymes and novel herbivore rumen enzymes in general.

Correlation between Metabolic Syndrome and Gastric Cancer: Results of an Evidence-Based Strategy in Oriental Populations.

BACKGROUND: Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors, including abdominal obesity, hyperglycemia, hypertension, and dyslipidemia. Gastric cancer (GC) is a common malignancy with significant mortality rates. The relationship between MetS and GC risk remains controversial. This systematic review and meta-analysis aimed to evaluate the correlation between MetS and GC. METHODS: Case-control studies investigating the association between MetS and GC were obtained from various databases, including China National Knowledge Infrastructure (CNKI), SinoMed, Embase, Web of Science, The Cochrane Library, and PubMed. The search was performed from the inception of each database up until September, 2023. Two researchers independently screened the literature, extracted data, and assessed the quality of the included studies. A meta-analysis of the included literature was conducted using Stata 12.0 software. The study protocol is registered in PROSPERO (CRD42023490410). RESULTS: A total of eight studies involving a combined sample size of forty-four thousand eight hundred and seventy participants were included in the meta-analysis. The findings revealed that the risk of developing GC was not significantly associated with body mass index, triglycerides, hypertension, high fasting glucose, or MetS. However, it was found to be positively correlated with high-density lipoprotein cholesterol (OR = 1.69, 95%CI: 1.35-2.12). CONCLUSION: This meta-analysis suggests that MetS is not significantly associated with an increased risk of GC. The risk of GC increases with the presence of individual MetS components, such as high-density lipoprotein cholesterol. Therefore, GC prevention strategies should include lifestyle modifications and targeted interventions to manage MetS and its components. TRIAL REGISTRATION: CRD42023490410 (PROSPERO).

Plasma fatty acids and attention deficit hyperactivity disorder: a Mendelian randomization investigation.

Background: Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder of childhood, and pathogenesis is not fully understood. Observational studies suggest an association between fatty acids abnormalities and ADHD, but there are contradictions and differences between these findings. To address this uncertainty, we employed a two-sample bidirectional Mendelian Randomization (MR) analysis to investigate the causal relationship between fatty acids and ADHD. Methods: We conducted a two-sample Mendelian Randomization (MR) study, selecting single nucleotide polymorphisms (SNPs) highly correlated with fatty acid levels from the CHARGE Consortium as our instruments. The outcome data were sourced from the Psychiatric Genomics Consortium (PGC) dataset on ADHD, comprising 225,534 individuals, with 162,384 cases and 65,693 controls. Inverse variance weighting, MR-Egger, and weighted median methods were employed to estimate the causal relationship between fatty acids and ADHD. Cochran's Q-test was used to quantify heterogeneity of instrumental variables. Sensitivity analyses included MR-Egger intercept tests, leave-one-out analyses, and funnel plots. Results: The MR analysis revealed no significant associations between genetically predicted levels of various saturated, monounsaturated, and polyunsaturated fatty acids (including omega-3 and omega-6) and ADHD risk in the CHARGE and PGC cohorts. Notably, an initial association with Dihomo-gamma-linolenic acid (DGLA) (OR = 1.009, p = 0.032 by IVW) did not persist after correction for multiple testing (adjusted p-value = 0.286). Sensitivity analysis supported our findings, indicating robustness. Moreover, there was a lack of evidence supporting a causal link from ADHD to fatty acids. Conclusion: While our study on the basis of genetic data does not provide evidence to support the causal role of fatty acids in ADHD, it does not preclude their potential involvement in reducing the risk of ADHD. Further research is needed to explore this possibility.

The diagnostic efficiency of artificial intelligence based 2 hours Holter monitoring in premature ventricular and supraventricular contractions detection.

BACKGROUND: Electrocardiography (ECG) and 24 hours Holter monitoring (24 h-Holter) provided valuable information for premature ventricular and supraventricular contractions (PVC and PSVC). Currently, artificial intelligence (AI) based 2 hours single-lead Holter (2 h-Holter) monitoring may provide an improved strategy for PSVC/PVC diagnosis. HYPOTHESIS: AI combined with single-lead Holter monitoring improves PSVC/PVC detection. METHODS: In total, 170 patients were enrolled between August 2022 and 2023. All patients wore both devices simultaneously; then, we compared diagnostic efficiency, including the sensitivity/specificity/positive predictive-value (PPV) and negative predictive-value (NPV) in detecting PSVC/PVC by 24 h-Holter and 2 h-Holter. RESULTS: The PPV and NPV in patients underwent 2 h-Holter were 76.00%/87.50% and 96.35%/98.55, respectively, and the sensitivity and specificity were 79.17%/91.30%, and 95.65%/97.84% in PSVC/PVC detection compared with 24 h-Holter. The areas under the ROC curves (AUCs) for PSVC and PVC were 0.885 and 0.741, respectively (p < .0001). CONCLUSIONS: The potential advantages of the 2 h-Holter were shortened wearing period, improved convenience, and excellent consistency of diagnosis.

Lactiplantibacillus plantarum surface-displayed VP6 (PoRV) protein can prevent PoRV infection in piglets.

Porcine rotavirus (PoRV) poses a threat to the development of animal husbandry and human health, leading to substantial economic losses. VP6 protein is the most abundant component in virus particles and also the core structural protein of the virus. Firstly, this study developed an antibiotic-resistance-free, environmentally friendly expression vector, named asd-araC-PBAD-alr (AAPA). Then Recombinant Lactiplantibacillus plantarum (L. plantarum) strains induced by arabinose to express VP6 and VP6-pFc fusion proteins was constructed. Subsequently, This paper discovered that NC8/Δalr-pCXa-VP6-S and NC8/Δalr-pCXa-VP6-pFc-S could enhance host immunity and prevent rotavirus infection in neonatal mice and piglets. The novel recombinant L. plantarum strains constructed in this study can serve as oral vaccines to boost host immunity, offering a new strategy to prevent PoRV infection.

Effect of ultrasonic treatment during fermentation on the quality of fortified sweet wine.

The present study aimed to investigate the potential of ultrasonic treatment during fermentation for enhancing the quality of fortified wines with varying time and power settings. Chemical analysis and sensory evaluation were conducted to assess the impact of ultrasonic treatment on wine quality. Results showed that ultrasonic treatment could increase total anthocyanin and total phenol content, reduce anthocyanin degradation rate, and improve color stability. Moreover, ethyl carbamate content was lower in the ultrasonic group after aging compared to non-ultrasonic group. A combination of 200 W for 20 min resulted in higher sensory scores and more coordinated taste, while a combination of 400 W for 40 min produced higher levels of volatile compounds (21860.12 µg/L) leading to a richer and more elegant aroma. Therefore, ultrasound can be used as a potential technology to improve the quality of wine.

impHFrEF trial: study protocol for an open-label, multicentre study of improvement the outcome of patients with heart failure in China using a mobile hEalth-supported platForm.

BACKGROUND: Patients with chronic heart failure (CHF) often have a long duration of illness, difficulty in attending follow-up visits, and poor adherence to treatment. As a result, they frequently cannot receive guideline-directed medical therapy (GDMT) at the desired or maximum tolerable drug dosage. This leads to high hospitalisation and mortality rates for HF patients. Therefore, effective management and monitoring of patients with HF to ensure they receive GDMT is crucial for improving the prognosis. DESIGN AND METHODS: This is a multicentre, open-label, randomised, parallel-group study involving patients with CHF across five centres. The study aims to assess the impact of an optimised GDMT model for HF patients, established on a mobile health (mHealth) platform, compared with a control group. Patients must have a left ventricular ejection fraction of less than 50% and be receiving medication titration therapy that has not yet reached the target dose, with a modest increase in N-terminal pro-B-type natriuretic peptide level. The primary composite outcome is worsening HF events (hospitalisation or emergency treatment with intravenous fluids) or cardiovascular death. ETHICS AND DISSEMINATION: On 22 December 2021, this study received ethical approval from the Ethics Review Board of the First Affiliated Hospital of Nanjing Medical University, with the ethics number 2021-SR-530. All study participants will be informed of the research purpose and their participation will be voluntary. Informed consent will be obtained by providing and signing an informed consent form. We will ensure compliance with relevant laws and regulations regarding privacy and data protection. The results of this study will be published in a peer-reviewed academic journal. We will ensure that the dissemination of study results is accurate, clear and timely. TRIAL REGISTRATION NUMBER: ChiCTR2200056527.

Delay estimation for cortical-muscular interaction with wavelet coherence time lag.

BACKGROUND: Cortico-muscular coherence (CMC) between the cerebral cortex and muscle activity is an effective tool for studying neural communication in the motor control system. To accurately evaluate the coherence between electroencephalogram (EEG) and electromyogram (EMG) signals, it is necessary to accurately calculate the time delay between physiological signals to ensure signal synchronization. NEW METHOD: We proposed a new delay estimation method, named wavelet coherence time lag (WCTL) and the significant increase areas (SIA) index as a measure of the specific region enhancement effect of the magnitude squared coherence (MSC) image. RESULTS: The grip strength level had a small effect on the information transmission time from the cortex to the muscles, while the transmission time from the cortex to different muscle channels was different for the same task. A positive correlation was found between the grip strength level and the SIA index on the ß band of C3-B and the α and ß bands of C3-FDS. COMPARISON WITH EXISTING METHOD: The WCTL method was found to accurately calculate the delay time even when the number of repeated segments was low in a simple motor control model, and the results were more accurate than the rate of voxels change (RVC) and CMC with time lag (CMCTL) methods. CONCLUSIONS: The WCTL is an effective method for detecting the transmission time of information between the cortex and muscles, laying the foundation for future rehabilitation treatment for stroke patients.

Gut microbiota-derived LCA mediates the protective effect of PEDV infection in piglets.

BACKGROUND: The gut microbiota is a critical factor in the regulation of host health, but the relationship between the differential resistance of hosts to pathogens and the interaction of gut microbes is not yet clear. Herein, we investigated the potential correlation between the gut microbiota of piglets and their disease resistance using single-cell transcriptomics, 16S amplicon sequencing, metagenomics, and untargeted metabolomics. RESULTS: Porcine epidemic diarrhea virus (PEDV) infection leads to significant changes in the gut microbiota of piglets. Notably, Landrace pigs lose their resistance quickly after being infected with PEDV, but transplanting the fecal microbiota of Min pigs to Landrace pigs alleviated the infection status. Macrogenomic and animal protection models identified Lactobacillus reuteri and Lactobacillus amylovorus in the gut microbiota as playing an anti-infective role. Moreover, metabolomic screening of the secondary bile acids' deoxycholic acid (DCA) and lithocholic acid (LCA) correlated significantly with Lactobacillus reuteri and Lactobacillus amylovorus, but only LCA exerted a protective function in the animal model. In addition, LCA supplementation altered the distribution of intestinal T-cell populations and resulted in significantly enriched CD8+ CTLs, and in vivo and in vitro experiments showed that LCA increased SLA-I expression in porcine intestinal epithelial cells via FXR receptors, thereby recruiting CD8+ CTLs to exert antiviral effects. CONCLUSIONS: Overall, our findings indicate that the diversity of gut microbiota influences the development of the disease, and manipulating Lactobacillus reuteri and Lactobacillus amylovorus, as well as LCA, represents a promising strategy to improve PEDV infection in piglets. Video Abstract.

Prognosis and clinical significance of Piezo2 in tumor: a meta-analysis and database validation.

OBJECTIVE: The objective of this study is to assess the correlation between Piezo2 and tumors through a comprehensive meta-analysis and database validation. METHODS: Case-control studies investigating the association between Piezo2 and tumors were obtained from various databases, including China National Knowledge Infrastructure (CNKI), SinoMed, Embase, Web of Science, The Cochrane Library, and PubMed. The search was performed from the inception of each database up until May 2023. Two researchers independently screened the literature, extracted data, and assessed the quality of the included studies. Metaanalysis of the included literature was conducted using Stata 12.0 software. Additionally, the Gene Expression Profiling Interactive Analysis (GEPIA) database predicted a correlation between Piezo2 expression and prognostic value in tumor patients. RESULTS: A total of three studies, involving a combined sample size of 392 participants, were included in the meta-analysis. The findings revealed that the expression level of Piezo2 in tumor patients was not significantly associated with age, gender, or tumor size. However, it was found to be positively correlated with lymphatic invasion (OR = 7.89, 95%CI: 3.96-15.73) and negatively correlated with invasion depth (OR = 0.17, 95%CI: 0.06-0.47), TNM stage (OR = 0.48, 95%CI: 0.27-0.87), and histological grade (OR = 0.40, 95%CI: 0.21-0.77). Confirming these findings, the GEPIA database indicated that high expression of Piezo2 was associated with poor prognosis of disease-free survival in patients with colon adenocarcinoma (HR = 1.6, P = 0.049) and gastric cancer (HR = 1.6, P = 0.017). CONCLUSION: Piezo2 may be associated with poor prognosis and clinicopathological parameters in tumor patients.