Hepatitis B virus–induced imbalance of inflammatory and antiviral signaling by differential phosphorylation of STAT1 in human monocytes

It is not clear how hepatitis B virus (HBV) modulates host immunity during chronic infection. In addition to the key mediators of inflammatory response in viral infection, monocytes also express a high-level IFN-stimulated gene, CH25H, upon response to IFN-a exerting an antiviral effect. In this study, the mechanism by which HBV manipulates IFN signaling in human monocytes was investigated. We observed that monocytes from chronic hepatitis B patients express lower levels of IFN signaling/stimulated genes and higher levels of inflammatory cytokines compared with healthy donors. HBV induces monocyte production of inflammatory cytokines via TLR2/MyD88/NF-kB signaling and STAT1-Ser727 phosphorylation and inhibits IFN-a–induced stat1, stat2, and ch25h expression through the inhibition of STAT1-Tyr701 phosphorylation and in an IL-10–dependent, partially autocrine manner. Further, we found that enhancement of STAT1 activity with a small molecule (2-NP) rescued HBV-mediated inhibition of IFN signaling and counteracted the induction of inflammatory cytokines. In conclusion, HBV contributes to the monocyte inflammatory response but inhibits their IFN-a/b responsiveness to impair antiviral innate immunity. These effects are mediated via differential phosphorylation of Tyr701 and Ser727 of STAT1

The incidence of liver injury in Uyghur patients treated for TB in Xinjiang Uyghur autonomous region, China, and its association with hepatic enzyme polymorphisms nat2, cyp2e1, gstm1 and gstt1.

BACKGROUND AND OBJECTIVE: Of three first-line anti-tuberculosis (anti-TB) drugs, isoniazid is most commonly associated with hepatotoxicity. Differences in INH-induced toxicity have been attributed to genetic variability at several loci, NAT2, CYP2E1, GSTM1and GSTT1, that code for drug-metabolizing enzymes. This study evaluated whether the polymorphisms in these enzymes were associated with an increased risk of anti-TB drug-induced hepatitis in patients and could potentially be used to identify patients at risk of liver injury. METHODS AND DESIGN: In a cross-sectional study, 2244 tuberculosis patients were assessed two months after the start of treatment. Anti-TB drug-induced liver injury (ATLI) was defined as an ALT, AST or bilirubin value more than twice the upper limit of normal. NAT2, CYP2E1, GSTM1 and GSTT1 genotypes were determined using the PCR/ligase detection reaction assays. RESULTS: 2244 patients were evaluated, there were 89 cases of ATLI, a prevalence of 4% 9 patients (0.4%) had ALT levels more than 5 times the upper limit of normal. The prevalence of ATLI was greater among men than women, and there was a weak association with NAT2*5 genotypes, with ATLI more common among patients with the NAT2*5*CT genotype. The sensitivity of the CT genotype for identifying patients with ATLI was 42% and the positive predictive value 5.9%. CT ATLI was more common among slow acetylators (prevalence ratio 2.0 (95% CI 0.95,4.20) )compared to rapid acetylators. There was no evidence that ATLI was associated with CYP2E1 RsaIc1/c1genotype, CYP2E1 RsaIc1/c2 or c2/c2 genotypes, or GSTM1/GSTT1 null genotypes. CONCLUSIONS: In Xinjiang Uyghur TB patients, liver injury was associated with the genetic variant NAT2*5, however the genetic markers studied are unlikely to be useful for screening patients due to the low sensitivity and low positive predictive values for identifying persons at risk of liver injury

Single cell atlas for 11 non-model mammals, reptiles and birds.

The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs

asilicaimmobilizedpt2catalystfortheselectiveaerobicoxidationofmethaneviaanelectrontransferchain

The combination of Pt2+, benzoquinone and NaNO2 forms an electron-transfer chain, which leads to the oxidation of methane by O-2 in CF3COOH aqueous solution. The overall turnover number per hour (TOF) of methane at 120 degrees C is 0.5 h(-1), however, only about one fourth (23%) of methane is converted to the desired product of methanol in the formation of CF3COOCH3. The over-oxidation of methane to CO2, over the catalyst with the Pt2+ species immobilized via 2,2'-bipyridyl as a ligand on the silica substrate, is depressed distinctly. Under the same conditions, the conversion to methanol dominates, and no CO2 is observed, on account of the over-oxidation of methane, as confirmed by the isotope experiment

asilicaimmobilizedpt2catalystfortheselectiveaerobicoxidationofmethaneviaanelectrontransferchain

The combination of Pt2+, benzoquinone and NaNO2 forms an electron-transfer chain, which leads to the oxidation of methane by O-2 in CF3COOH aqueous solution. The overall turnover number per hour (TOF) of methane at 120 degrees C is 0.5 h(-1), however, only about one fourth (23%) of methane is converted to the desired product of methanol in the formation of CF3COOCH3. The over-oxidation of methane to CO2, over the catalyst with the Pt2+ species immobilized via 2,2'-bipyridyl as a ligand on the silica substrate, is depressed distinctly. Under the same conditions, the conversion to methanol dominates, and no CO2 is observed, on account of the over-oxidation of methane, as confirmed by the isotope experiment

Regulation of bone and fat balance by Fructus Ligustri Lucidi in ovariectomized mice

AbstractContext Fructus Ligustri Lucidi (FLL), a commonly used herb of traditional Chinese medicine (TCM), is the fruit of Ligustrum lucidum Ait. (Oleaceae). The ethanol extract of FLL is a potential candidate for preventing and treating postmenopausal osteoporosis (PMOP) by nourishing the liver and kidneys.Objective This study determines whether an ethanol extract of FLL has anti-osteoporotic effects in ovariectomized (OVX) mice and explores the underlying mechanism.Materials and methods The OVX model of eight-week-old C57BL/6J female mice was taken, and ovariectomy was used as PMOP. Mice were divided into five groups: sham-operated group (n = 10), OVX group (n = 10), OVX + E2 group (n = 10; 0.039 mg/kg), OVX + FLL group (n = 10; 2 g/kg) and OVX + FLL group (n = 10; 4 g/kg). Mice were treated by gavage with FLL or CMCNa once daily for 8 weeks. We harvested uteri, femur, and tibias from mice; bone mineral density (BMD) and bone microstructure were obtained by X-ray absorptiometry and micro-CT. Furthermore, the effect of FLL on the balance of osteoblast and adipocyte differentiation was investigated using bone marrow mesenchymal stem cells (BMMSCs).Results The results indicated that FLL did not affect OVX-induced estradiol reduction. Compared with OVX mice, FLL significantly increased BMD (63.54 vs. 61.96), Conn. D (86.46 vs. 57.00), and left tibial strength (13.91 vs. 11.27), decreased Tb. Sp (0.38 vs. 0.44) and body fat content (4.19% vs. 11.24%). FLL decreased osteoclast activity and enhanced RUNX2 expression; inhibited perilipin peroxisome proliferator-activated receptor gamma (PPARγ) expression and adipocyte differentiation from BMMSCs.Conclusions FLL prevented additional bone loss and improved bone microstructure in OVX mice by modulating bone and fat balance, suggesting that FLL might be a therapeutic agent for PMOP

Prevalence of Developmental Dyslexia in Primary School Children: A Systematic Review and Meta-Analysis

Background: Developmental dyslexia (DD) is a specific learning disorder concerning reading acquisition that may has a lifelong negative impact on individuals. A reliable estimate of the prevalence of DD serves as the basis for diagnosis, intervention, and evidence-based health resource allocation and policy-making. Hence, the present meta-analysis aims to generate a reliable prevalence estimate of DD worldwide in primary school children and explore the potential variables related to that prevalence. Methods: Studies from the 1950s to June 2021 were collated using a combination of search terms related to DD and prevalence. Study quality was assessed using the STROBE guidelines according to the study design, with study heterogeneity assessed using the I2 statistic, and random-effects meta-analyses were conducted. Variations in the prevalence of DD in different subgroups were assessed via subgroup meta-analysis and meta-regression. Results: The pooled prevalence of DD was 7.10% (95% CI: 6.27–7.97%). The prevalence in boys was significantly higher than that in girls (boys: 9.22%, 95%CI, 8.07–10.44%; girls: 4.66%, 95% CI, 3.84–5.54%; p < 0.001), but no significant difference was found in the prevalence across different writing systems (alphabetic scripts: 7.26%, 95%CI, 5.94–8.71%; logographic scripts: 6.97%, 95%CI, 5.86–8.16%; p > 0.05) or across different orthographic depths (shallow: 7.13%, 95% CI, 5.23–9.30%; deep: 7.55%, 95% CI, 4.66–11.04%; p > 0.05). It is worth noting that most articles had small sample sizes with diverse operational definitions, making comparisons challenging. Conclusions: This study provides an estimation of worldwide DD prevalence in primary school children. The prevalence was higher in boys than in girls but was not significantly different across different writing systems

The circulating IL‐35+ regulatory B cells are associated with thyroid associated opthalmopathy

Abstract Background Thyroid‐associated ophthalmopathy (TAO) is the most common orbital disease in adults, potentially leading to disfigurement and visual impairment. However, the causes of TAO are not fully understood. IL‐35+B cells are a newly identified regulatory B cells (Bregs) in maintaining immune balance in various autoimmune diseases. Yet, the influence of IL‐35+Bregs in TAO remains unexplored. Methods This study enrolled 36 healthy individuals and 14 TAO patients. We isolated peripheral blood mononuclear cells and stimulated them with IL‐35 and CpG for 48 h. Flow cytometry was used to measure the percentages of IL‐35+Bregs. Results The percentage of circulating IL‐35+Bregs was higher in TAO patients, and this increase correlated positively with disease activity. IL‐35 significantly increased the generation of IL‐35+Bregs in healthy individuals. However, B cells from TAO patients exhibited potential impairment in transitioning into IL‐35+Breg phenotype under IL‐35 stimulation. Conclusions Our results suggest a potential role of IL‐35+Bregs in the development of TAO, opening new avenues for understanding disease mechanisms and developing therapeutic approaches

Norcantharidin regulates ERα signaling and tamoxifen resistance via targeting miR-873/CDK3 in breast cancer cells.

MiR-873/CDK3 has been shown to play a critical role in ERα signaling and tamoxifen resistance. Thus, targeting this pathway may be a potential therapeutic approach for the treatment of ER positive breast cancer especially tamoxifen resistant subtype. Here we report that Norcantharidin (NCTD), currently used clinically as an ani-cancer drug in China, regulates miR-873/CDK3 axis in breast cancer cells. NCTD decreases the transcriptional activity of ERα but not ERβ through the modulation of miR-873/CDK3 axis. We also found that NCTD inhibits cell proliferation and tumor growth and miR-873/CDK3 axis mediates cell proliferation suppression of NCTD. More important, we found that NCTD sensitizes resistant cells to tamoxifen. NCTD inhibits tamoxifen induced the transcriptional activity as well ERα downstream gene expressions in tamoxifen resistant breast cancer cells. In addition, we found that NCTD restores tamoxifen induced recruitments of ERα co-repressors N-CoR and SMRT. Knockdown of miR-873 and overexpression of CDK3 diminish the effect of NCTD on tamoxifen resistance. Our data shows that NCTD regulates ERα signaling and tamoxifen resistance by targeting miR-873/CDK3 axis in breast cancer cells. This study may provide an alternative therapy strategy for tamoxifen resistant breast cancer