A novel highly virulent nephropathogenic QX-like infectious bronchitis virus originating from recombination of GI-13 and GI-19 genotype strains in China.

Infectious bronchitis virus (IBV) is one of the most widely spread RNA viruses, causing respiratory, renal, and intestinal damage, as well as decreased reproductive performance in hens, leading to significant economic losses in the poultry industry. In this study, a new IBV strain designated as CK/CH/GX/LA/071423 was successfully isolated from the 60-day-old Three-Yellow chicken vaccinated with H120 and QXL87 vaccines. The complete genome sequence analysis revealed that the CK/CH/GX/LA/071423 strain shared a high similarity of 96.7% with the YX10 strain belonging to the GI-19 genotype. Genetic evolution analysis based on the IBV S1 gene showed that the CK/CH/GX/LA/071423 isolate belonged to the GI-19 genotype. Recombination analysis of the virus genome using RDP and Simplot software indicated that CK/CH/GX/LA/071423 was derived from recombination events between the YX10 and 4/91 vaccine strains, which was supported by phylogenetic analysis using gene sequences from the 3 regions. Furthermore, the S1 protein tertiary structure differences were observed between the CK/CH/GX/LA/071423 and the QXL87 and H120 vaccine strains. Pathogenicity studies revealed that the CK/CH/GX/LA/071423 caused death and led to pale and enlarged kidneys with abundant urate deposits, indicative of a nephropathogenic IBV strain. High virus titers were detected in the trachea, kidneys, and cecal tonsils, demonstrating broad tissue tropism. Throughout the experimental period, the virus positive rate in throat swabs of the infected group reached to 100%. These findings highlight the continued predominance of the QX genotype IBV in Guangxi of China and the ongoing evolution of different genotypes through genetic recombination, raising concerns about the efficacy of current IBV vaccines in providing effective protection to poultry.

Subcortical neural mechanisms of childhood trauma impacts on personality traits.

This study aims to explore the relationships between childhood trauma (CT), personality traits, and subcortical structures. 171 healthy individuals completed the Childhood Trauma Questionnaire (CTQ), the Neuroticism-Extraversion-Openness Five-Factor Inventory (NEO-FFI), and underwent 3D T1-weighted MRI scans. Linear regression analyses indicated the complex relationship between CT, personality traits, and subcortical gray matter volume (GMV). Mediation analyses revealed that the right hippocampal GMV partially mediated the effects of CT on neuroticism. These findings suggest that CT affects the development of the Big Five personality traits, and alterations in subcortical structures are closely related to this process. Altered GMV in the right hippocampus may be a key neural mechanism for CT-induced neuroticism.

Inflammasome activation by viral infection: mechanisms of activation and regulation.

Viral diseases are the most common problems threatening human health, livestock, and poultry industries worldwide. Viral infection is a complex and competitive dynamic biological process between a virus and a host/target cell. During viral infection, inflammasomes play important roles in the host and confer defense mechanisms against the virus. Inflammasomes are polymeric protein complexes and are considered important components of the innate immune system. These immune factors recognize the signals of cell damage or pathogenic microbial infection after activation by the canonical pathway or non-canonical pathway and transmit signals to the immune system to initiate the inflammatory responses. However, some viruses inhibit the activation of the inflammasomes in order to replicate and proliferate in the host. In recent years, the role of inflammasome activation and/or inhibition during viral infection has been increasingly recognized. Therefore, in this review, we describe the biological properties of the inflammasome associated with viral infection, discuss the potential mechanisms that activate and/or inhibit NLRP1, NLRP3, and AIM2 inflammasomes by different viruses, and summarize the reciprocal regulatory effects of viral infection on the NLRP3 inflammasome in order to explore the relationship between viral infection and inflammasomes. This review will pave the way for future studies on the activation mechanisms of inflammasomes and provide novel insights for the development of antiviral therapies.

Rational Design, Synthesis, and Biological Evaluation of Fluorine- and Chlorine-Substituted Pyrazol-5-yl-benzamide Derivatives as Potential Succinate Dehydrogenase Inhibitors.

To develop novel succinate dehydrogenase inhibitors (SDHIs), two series of novel N-4-fluoro-pyrazol-5-yl-benzamide and N-4-chloro-pyrazol-5-yl-benzamide derivatives were designed and synthesized, and their antifungal activities were evaluated against Valsa mali, Sclerotinia sclerotiorum, FusaHum graminearum Sehw, Physalospora piricola, and Botrytis cinerea. The bioassay results showed that some of the target compounds exhibited good antifungal activities in vitro against V. mali and S. sclerotiorum. Remarkably, compound 9Ip displayed good in vitro activity against V. mali with an EC50 value of 0.58 mg/L. This outcome was 21-fold greater than that of fluxapyroxad (12.45 mg/L) and close to that of the commercial fungicide tebuconazole (EC50 = 0.36 mg/L). In addition, in vivo experiments proved that compound 9Ip has good protective fungicidal activity with an inhibitory rate of 93.2% against V. mali at 50 mg/L, which was equivalent to that of the positive control tebuconazole (95.5%). The results of molecular docking indicated that there were obvious hydrogen bonds and p-π interactions between compound 9Ip and succinate dehydrogenase (SDH), which could explain the probable action mechanism. In addition, the SDH enzymatic inhibition assay was carried out to further prove its mode of action. Our studies suggest that compound 9Ip could be a fungicidal lead to discover more potent SDHIs for crop protection.

FGF1ΔHBS ameliorates chronic kidney disease via PI3K/AKT mediated suppression of oxidative stress and inflammation.

Currently, there is a lack of effective therapeutic approaches to the treatment of chronic kidney disease (CKD) with irreversible deterioration of renal function. This study aimed to investigate the ability of mutant FGF1 (FGF1ΔHBS, which has reduced mitogenic activity) to alleviate CKD and to study its associated mechanisms. We found that FGF1ΔHBS exhibited much weaker mitogenic activity than wild-type FGF1 (FGF1WT) in renal tissues. RNA-seq analysis revealed that FGF1ΔHBS inhibited oxidative stress and inflammatory signals in mouse podocytes challenged with high glucose. These antioxidative stress and anti-inflammatory activities of FGF1ΔHBS prevented CKD in two mouse models: a diabetic nephropathy model and an adriamycin-induced nephropathy model. Further mechanistic analyses suggested that the inhibitory effects of FGF1ΔHBS on oxidative stress and inflammation were mediated by activation of the GSK-3ß/Nrf2 pathway and inhibition of the ASK1/JNK signaling pathway, respectively. An in-depth study demonstrated that both pathways are under control of PI3K/AKT signaling activated by FGF1ΔHBS. This finding expands the potential uses of FGF1ΔHBS for the treatment of various kinds of CKD associated with oxidative stress and inflammation.

Sirt6 overexpression suppresses senescence and apoptosis of nucleus pulposus cells by inducing autophagy in a model of intervertebral disc degeneration.

Treatment of intervertebral disc degeneration (IDD) seeks to prevent senescence and death of nucleus pulposus (NP) cells. Previous studies have shown that sirt6 exerts potent anti-senescent and anti-apoptotic effects in models of age-related degenerative disease. However, it is not known whether sirt6 protects against IDD. Here, we explored whether sirt6 influenced IDD. The sirt6 level was reduced in senescent human NP cells. Sirt6 overexpression protected against apoptosis and both replicative and stress-induced premature senescence. Sirt6 also activated NP cell autophagy both in vivo and in vitro. 3-methyladenine (3-MA) and chloroquine (CQ)-mediated inhibition of autophagy partially reversed the anti-senescent and anti-apoptotic effects of sirt6, which regulated the expression of degeneration-associated proteins. In vivo, sirt6 overexpression attenuated IDD. Together, the data showed that sirt6 attenuated cell senescence, and reduced apoptosis, by triggering autophagy that ultimately ameliorated IDD. Thus, sirt6 may be a novel therapeutic target for IDD treatment.

Panax quinquefolium saponin inhibits endoplasmic reticulum stress-induced apoptosis and the associated inflammatory response in chondrocytes and attenuates the progression of osteoarthritis in rat.

Treatments for osteoarthritis (OA) seek to restore chondrocyte function and inhibit cell apoptosis. Panax quinquefolium saponin (PQS) is the major active ingredient of Radix panacis quinquefolii (American ginseng), and has been demonstrated to exert anti-inflammatory and anti-apoptotic effects in various diseases. However, any potential effect of PQS on the pathological process of OA remains unclear. This work aimed to explore the role of PQS in chondrocytes and to clarify its potential mechanisms. We showed that PQS treatment could protect chondrocytes against endoplasmic reticulum (ER) stress and associated apoptosis induced by interleukin (IL)-1ß. Also, PQS further attenuated triglyceride (TG)-induced ER stress and associated apoptosis. Moreover, PQS may inhibit the ER stress-activated NF-κB pathway and associated inflammatory response in chondrocytes. Finally, PQS abolished rat cartilage degeneration in an in-vivo OA model of the knee joint. Our results indicate that PQS may be a potential novel treatment for OA.

[Polycyclic Aromatic Hydrocarbons in the Atmosphere of Dajiuhu, Shennongjia, China].

The concentration, potential source and health risks of 16 polycyclic aromatic hydrocarbons (PAHs) in the atmosphere of Dajiuhu, Shennongjia, China, were studied. Polyurethane foam (PUF) Passive air samplers (PAS) were settled. The results indicated that the total concentrations of 16 PAHs in different samples ranged from 6.94 to 184.23 ng·m-3, with the mean of 30.36 ng·m-3. The dominant compounds were low rings PAHs, such as Phe, Nap, Pyr, Fla, Flu and Ant. Compared with other regions, the PAHs pollution of Dajiuhu atmosphere was at a low level. Higher PAHs concentrations were detected in nearby Deer farm, Dajiuhu peat area and Dajiuhu Wetland Authority. Higher PAHs concentrations were detected in autumn and winter, whereas lower concentrations were detected in spring and summer. Potential pollution sources of PAHs were investigated by diagnostic ratios and backward trajectory analysis, which indicated that coal and biofuel combustion, vehicle emissions and petroleum were the main sources. PAHs of Dajiuhu in air not only came from local emission, but also originated from Hubei, Henan and Hunan's atmosphere transport for most part and long range transport from northwest direction for small part. Health risks assessment results showed that the annual average concentration of total Benzo(a)pyrene-equivalent carcinogenic potency (∑BaPeq) was 0.208 ng·m-3, lower than the value recommended by Ambient Air Quality Standard of China(GB 3095-2012, 1 ng·m-3), indicating a low carcinogenic risk for the local residents.

Silver/chitosan-based Janus particles: Synthesis, characterization, and assessment of antimicrobial activity in vivo and vitro.

Janus particles containing chitosan and silver were synthesized in an eco-friendly manner and were confirmed using transmission electron microscopy. Based on the data of the antimicrobial activity assessment, this material exhibited a higher antimicrobial activity than virgin chitosan with long-lasting antibacterial effectiveness against Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Salmonella choleraesuis bacteria, as well as Botrytis cinerea fungi. The results showed that the Janus polymer could completely suppress the growth and germination of B. cinerea at a concentration of 0.02mg/mL in vitro and in vivo. This Janus polymer is an advanced functional material that combines the suitable properties of both components and could be an alternative new antimicrobial agent due to its unique chemical properties and pronounced antimicrobial activity. This material is a potential candidate for use in the food industry to prevent microbial contamination and to inhibit the growth of microorganisms, enhancing product quality and, extend shelf-life of fresh and processed agri-food products.