Induction of COX-2 by feline calicivirus via activation of the MEK1-ERK1/2 pathway, and attenuation of feline lung inflammation and injury by MEK1 inhibitor AZD6244 (selumetinib).

Feline calicivirus (FCV) is an important and highly prevalent pathogen of cats that causes acute infectious respiratory disease. Here it is shown in vitro that FCV induces the production of cyclooxygenase-2 (COX-2) through the MEK1-ERK1/2 signaling pathway. Screening of FCV proteins revealed that FCV non-structural protein VPg enhanced COX-2 mRNA expression and protein production in CRFK cells in a concentration-dependent manner. Regions 24-54aa and 84-111aa in FCV VPg were essential for up-regulation. In vivo, COX-2 and IL-6 production caused by FCV infection of kittens was significantly suppressed by the MEK1 inhibitor AZD6244 (selumetinib) and lung inflammation and injury were practically eliminated, with body temperature being returned to normal. AZD6244 may therefore find application as an effective therapeutic agent for the treatment of FCV infection.

Copper exposure induces inflammation and PANoptosis through the TLR4/NF-κB signaling pathway, leading to testicular damage and impaired spermatogenesis in Wilson disease.

Copper is a toxic heavy metal that causes various damage when it accumulates in the body beyond the physiological threshold. Wilson disease (WD) is an inherited disorder characterized by impaired copper metabolism. Reproductive damage in male patients with WD is gradually attracting attention. However, the underlying mechanisms of copper toxicity are unclear. In this study, we investigated the role of inflammation and PANoptosis in testicular damage and impaired spermatogenesis caused by copper deposition using the WD model toxic milk (TX) mice. Copper chelator-penicillamine and toll-like receptor 4 (TLR4) inhibitor-eritoran were used to intervene in TX mice in our animal experiment methods. Testis samples were collected from mice for further analysis. The results showed that the morphology and ultrastructure of the testis and epididymis in TX mice were damaged, and the sperm counts decreased significantly. The TLR4/nuclear factor kappa-B (NF-κB) signaling pathway was activated by copper deposition, which led to the upregulation of serum and testicular inflammatory factors in TX mice. Meanwhile, pyroptosis, apoptosis, and necroptosis were significant in the testis of TX mice. Both chelated copper or inhibited TLR4 expression markedly suppressed the TLR4/NF-κB signaling pathway, thereby reducing the expression of inflammatory factors. PANoptosis in the testis of TX mice was also reversed. Our study indicated that pathological copper exposure induces inflammation and PANoptosis through the TLR4/NF-κB signaling pathway, leading to toxic testicular damage and impaired spermatogenesis in WD.

Berberine alleviates ovarian tissue damage in mice with hepatolenticular degeneration by suppressing ferroptosis and endoplasmic reticulum stress.

OBJECTIVE: Hepatolenticular degeneration (HLD) is an autosomal recessive disorder that manifests as multiorgan damage due to impaired copper (Cu) metabolism. Female patients with HLD often experience reproductive impairments. This study investigated the protective effect of berberine against ovarian damage in toxic-milk (TX) mice, a murine model for HLD. METHODS: Mice were categorized into control group, HLD TX group (HLD group), penicillamine (Cu chelator)-treated TX group and berberine-treated TX group. Body weight, ovary weight and the number of ovulated eggs were recorded. Follicular morphology and cellular ultrastructure were examined. Total iron, ferrous iron (Fe2+) and trivalent iron (Fe3+) levels, as well as malondialdehyde (MDA), glutathione (GSH) and oxidized glutathione (GSSG), were measured in the ovaries. Western blot analysis was used to analyze the expression of proteins related to ferroptosis and endoplasmic reticulum (ER) stress. RESULTS: Ovarian tissue damage was evident in the HLD group, with a significant increase in ferroptosis and ER stress compared to the control group. This damage was inhibited by treatment with penicillamine, a Cu chelator. Compared with the HLD group, berberine increased the number of ovulations, and improved ovarian morphology and ultrastructure. Further, we found that berberine reduced total iron, Fe2+, MDA and GSSG levels, elevated GSH levels, decreased the expression of the ferroptosis marker protein prostaglandin-endoperoxide synthase 2 (PTGS2), and increased glutathione peroxidase 4 (GPX4) expression. Furthermore, berberine inhibited the expression of ER stress-associated proteins mediated by the protein kinase RNA-like ER kinase (PERK) pathway. CONCLUSION: Ferroptosis and ER stress are involved in Cu-induced ovarian damage in TX mice. Berberine ameliorates ovarian damage in HLD TX mice by inhibiting ferroptosis and ER stress. Please cite this article as: Liu QZ, Han H, Fang XR, Wang LY, Zhao D, Yin MZ, Zhang N, Jiang PY, Ji ZH, Wu LM. Berberine alleviates ovarian tissue damage in mice with hepatolenticular degeneration by suppressing ferroptosis and endoplasmic reticulum stress. J Integr Med. 2024; Epub ahead of print.

Application of biochar and compost improved soil properties and enhanced plant growth in a Pb-Zn mine tailings soil.

This study evaluated the effect of biochar and compost on physiochemical properties, heavy metal content, microbial biomass, enzyme activities, and plant growth in Pb-Zn mine tailings. In this study, a pot experiment was conducted to evaluate the effects of biochar, compost, and their combination on the availability of heavy metals, physicochemical features, and enzyme activities in mining soil. Compared to separate addition, the combined application of biochar and compost was more effective to improve soil pH, soil organic carbon (SOC), total nitrogen (TN), available phosphorus (AP), and potassium (AK). All amendments significantly decreased CaCl2-extractable Pb, Zn, Cu, and Cd. Soil enzyme activities were activated by biochar and compost. Meanwhile, the addition of biochar and compost decreased heavy metal content in plant tissues and increased plant biomass. Pearson's correlation analysis showed that plant biomass was positively correlated with nutrient levels, microbial biomass, and enzyme activities, whereas it was negatively correlated with CaCl2-extractable heavy metals. These results enhance our understanding of the ecological functions of biochar and compost on the restoration of mining soil and reveal the potential benefit of organic amendments on the improvement of mining soil quality.

A retrospective cohort study: vaccination status and safety analysis of SARS-CoV-2 vaccine in patients with Wilson's disease.

BACKGROUND: Wilson's disease (WD) is a rare hepatic and neurological disorder, which can dramatically worsen by traumatic injuries, surgeries, and infections. No studies have reported safety data of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in WD patients. We aimed to investigate the SARS-CoV-2 vaccination status and post-vaccination adverse events in WD patients. METHODS: This is a multicenter, retrospective, observational study. We investigated the vaccination rates, the type of vaccine, subjective reasons for non-vaccination, and the adverse events following vaccination. Logistic regression analysis was used to assess the correlation between vaccination status and increased Unified Wilson's Disease Rating Scale (UWDRS) scores. RESULTS: A total of 554 WD patients with a mean (SD) age of 25.3 (10.85) years were included in this study, of whom 336 (60.6%) were males and 218 (39.4%) were females. 368 (66.4%) patients received at least one dose of the SARS-CoV-2 vaccine.186 (33.6%) patients were unvaccinated. Logistic regression analysis showed that vaccination against SARS-CoV-2 was not significantly associated with increased UWDRS scores. The safety analysis demonstrated that 21.2% had post-vaccination adverse events. CONCLUSIONS: In this study, vaccination against SARS-CoV-2 was safe in WD patients, providing evidence for the safety of vaccination in WD patients.

Fine nursing intervention relieves the clinical symptoms and decreases the adverse events in acute alcoholism patients.

OBJECTIVE: The purpose of this study is to explore the effect of fine nursing interventions on the clinical efficacy of acute alcoholism patients (AA). METHODS: A total of 100 patients with AA were included in the study. Among them, 51 patients who underwent fine nursing intervention were assigned to the research group (RG), and the remaining 49 patients were treated with routine nursing intervention and were assigned to the control group (CG). The nursing efficacy, the recovery times (consciousness and limb movement), the incidences of adverse events, the nursing compliance, the psychological states (the Symptom Checklist 90 and SCL-90 scores), and the nursing satisfaction levels were observed and compared between the two groups. RESULTS: Compared with the CG, the nursing efficacy, the compliance, and the nursing satisfaction levels in the RG were markedly higher, while the consciousness and limb movement recovery times were significantly shorter; moreover, the RG presented a significantly lower incidence of adverse events and SCL-90 scores than the CG. CONCLUSION: While validly relieving the clinical symptoms and reducing the incidence of adverse events, fine nursing can effectively promote the recovery of patients with AA, and improve their treatment compliance and psychological states.

[Construction of a landscaping-type wetland system for wastewater treatment construction of a landscaping-type wetland system for wastewater treatment and analysis of plant denitrifying effect].

A pilot landscaping-type wetland system for wastewater treatment was constructed by introduction of 15 selected ornamental plant species (including 4 terrestrial plant species). The pilot system consists of 2 sequenced treatment units and 12 sub-units, i.e., a primary treatment unit with 4 parallel cells and a secondary treatment unit with 8 subsurface flow cells. Designed experiments were conducted in the established system to investigate the characteristics of nitrogen accumulation in different plants and the contribution of plant nitrogen uptake to total nitrogen removal of the constructed wetland system. The result shows that the direct contribution by plant uptake to the total nitrogen removal is low, ca. 1%-3% within the nitrogen concentration range 37.5-55.6 mg/L in the influent. Plant uptake does not fully reflect the important role of the plant species in the constructed wetland system for wastewater treatment as the function of the plant should include further its interaction with microorganisms and wetland fillers by enhancing microbial activities and filler adsorption capacities. The plant denitrifying effect, defined as the difference in nitrogen removal rates between units with and without plants, has been used to represent the contribution in nitrogen removal due to presence of plant in the system. The plant denitrifying effect thus includes both the plant nitrogen uptake and the interaction effect of plant with microorganisms and wetland fillers, the later being found to account for more than 80% of the total nitrogen removal in the established treatment system.