Early-life exercise induces immunometabolic epigenetic modification enhancing anti-inflammatory immunity in middle-aged male mice.

Exercise is usually regarded to have short-term beneficial effects on immune health. Here we show that early-life regular exercise exerts long-term beneficial effects on inflammatory immunity. Swimming training for 3 months in male mice starting from 1-month-old curbs cytokine response and mitigates sepsis when exposed to lipopolysaccharide challenge, even after an 11-month interval of detraining. Metabolomics analysis of serum and liver identifies pipecolic acid, a non-encoded amino acid, as a pivotal metabolite responding to early-life regular exercise. Importantly, pipecolic acid reduces inflammatory cytokines in bone marrow-derived macrophages and alleviates sepsis via inhibiting mTOR complex 1 signaling. Moreover, early-life exercise increases histone 3 lysine 4 trimethylation at the promoter of Crym in the liver, an enzyme responsible for catalyzing pipecolic acid production. Liver-specific knockdown of Crym in adult mice abolishes this early exercise-induced protective effects. Our findings demonstrate that early-life regular exercise enhances anti-inflammatory immunity during middle-aged phase in male mice via epigenetic immunometabolic modulation, in which hepatic pipecolic acid production has a pivotal function.

[Inhibition of glutaminolysis alleviates myocardial fibrosis induced by angiotensin II].

The present study was aimed to investigate the role and mechanism of glutaminolysis of cardiac fibroblasts (CFs) in hypertension-induced myocardial fibrosis. C57BL/6J mice were administered with a chronic infusion of angiotensin II (Ang II, 1.6 mg/kg per d) with a micro-osmotic pump to induce myocardial fibrosis. Masson staining was used to evaluate myocardial fibrosis. The mice were intraperitoneally injected with BPTES (12.5 mg/kg), a glutaminase 1 (GLS1)-specific inhibitor, to inhibit glutaminolysis simultaneously. Immunohistochemistry and Western blot were used to detect protein expression levels of GLS1, Collagen I and Collagen III in cardiac tissue. Neonatal Sprague-Dawley (SD) rat CFs were treated with 4 mmol/L glutamine (Gln) or BPTES (5 µmol/L) with or without Ang II (0.4 µmol/L) stimulation. The CFs were also treated with 2 mmol/L α-ketoglutarate (α-KG) under the stimulation of Ang II and BPTES. Wound healing test and CCK-8 were used to detect CFs migration and proliferation respectively. RT-qPCR and Western blot were used to detect mRNA and protein expression levels of GLS1, Collagen I and Collagen III. The results showed that blood pressure, heart weight and myocardial fibrosis were increased in Ang II-treated mice, and GLS1 expression in cardiac tissue was also significantly up-regulated. Gln significantly promoted the proliferation, migration, mRNA and protein expression of GLS1, Collagen I and Collagen III in the CFs with or without Ang II stimulation, whereas BPTES significantly decreased the above indices in the CFs. α-KG supplementation reversed the inhibitory effect of BPTES on the CFs under Ang II stimulation. Furthermore, in vivo intraperitoneal injection of BPTES alleviated cardiac fibrosis of Ang II-treated mice. In conclusion, glutaminolysis plays an important role in the process of cardiac fibrosis induced by Ang II. Targeted inhibition of glutaminolysis may be a new strategy for the treatment of myocardial fibrosis.

Dispersion and Tunable Alignment of Colloidal Silver Nanowires in a Nematic Liquid Crystal for Applications in Electric-Optic Devices.

The dispersion and tunable alignment of colloidal nanomaterials is desirable for practical applications in electric-optic (E-O) devices; however, it remains challenging for large one-dimensional nanomaterials with a large aspect ratio. Here, we demonstrate a large-scale, simple, multi-microdomain, and noncontact photoalignment technology to align colloidal silver nanowires (AgNWs, length ∼4.5 µm, diameter ∼70.6 nm) in a liquid crystal (LC) with a high two-dimensional order parameter (about 0.9). The AgNWs are precisely self-assembled via photomasks with twisted nematic and planar alignment models in microdomain regions. The AgNW orientation is tuned with an electric field, through the rotation of an LC director n, which allows three-dimensional (3D) tunable orientation combined with photoalignment. The colloidal dispersions of AgNWs in the LC cell influenced the ion transfer, elastic constant, dielectric anisotropy, and near LC alignment, changing the E-O properties of the LC devices. The 3D tunable orientation of an AgNW by photoalignment and an electric field could provide a new way to assemble large colloidal nanomaterials and fabricate functional E-O devices.

Epidemiological characteristics of coronavirus disease 2019 in Wenzhou / 预防医学

Objeetive @#The epidemiological characteristics of confirmed cases of the 2019 novel coronavirus diseases (COVID-19) which was reported in Wenzhou by February 28,2020 were described and analyzed to provide evidence for prevention and control measures in next stage. @*Methods@#The field investigation method was employed on all suspected and confirmed cases. The data of time,spatial and population distribution, source of infection and detective routes of all confirmed cases of COVID-19 in Wenzhou were collected and extracted from the reports of field investigation and the National Diseases Prevention and Control Information System.@*Results@#As of February 20,2020,504 confirmed cases of COVID-19 were diagnosed in Wenzhou, which included one death case. Among all 13 counties, the highest number of confirmed cases were distributed in Yueqing,Ruian and Lucheng. Among 504 cases, the male to female ratio was reported as 1.14:1. The youngest case was 2 years old while the oldest case was 93 years old. Most of the confirmed cases were among people between the ages of 25 and 64 years old. The most common occupation of the confirmed cases was businessman,which accounts for 29.76% (150 cases). Clinical symptoms of the first confirmed case of COVID-19 in Wenzhou occurred on January 4, 2020. Approximately 70% of cases had the first symptoms from January 19 to February 1. The daily number of new cases on January 24 and January 26 were the highest while the number of new cases per day declined significantly after February 2, and there were no new cases after February 14. Among all confirmed cases, the infection source of 61.71% cases were related to Wuhan. As of February 20, 2020, a total of 79 clusters were reported in Wenzhou, which involved 330 cases. Approximately 30% of confirmed cases came to hospitals unaccompanied by community staffs, and cases which confirmed after February 13 were basically found in central isolation locations or by grid checkers. @*Conclusions @#The main reason for the high case numbers of COVID-19 in Wenzhou, in Zhejiang province, was the high number of wenzhou citizens who work in Wuhan. Imported cases account for the most confirmed cases during the early period, while mainly confirmed cases were local cases during the middle and late periods. The outcomes suggest the prevention and control measures employed by Wenzhou government, which included closed-loop control and quantitative control, have achieved remarkable results and the epidemic of COVID-19 in Wenzhou has been initially controlled.

Should synovectomy be performed in primary total knee arthroplasty for osteoarthritis? A meta-analysis of randomized controlled trials.

BACKGROUND: During primary total knee arthroplasty (TKA), synovectomy as a part of the procedure has been recommended to relieve pain and inflammation of the synovium, but there is a controversy about it due to increased bleeding. In this meta-analysis, the aim is to answer whether synovectomy should be performed routinely during TKA for symptomatic knee osteoarthritis (KOA). METHODS: Relevant randomized controlled trials (RCTs) on synovectomy were retrieved through database searches of PubMed, Embase, Web of Science, and Cochrane Library up to February 2019. Studies that compared postoperative pain, clinical Knee Society Score (KSS), functional KSS, range of motion (ROM), drainage, pre- and postoperative hemoglobin difference, transfusion rate, operative time, and/or complications were included in the meta-analysis. Review Manager 5.3.0 was used for meta-analysis. RESULTS: We included 5 RCTs with 542 knees. Pooled results indicated that the synovectomy group was associated with more blood loss via drainage (WMD = - 99.41, 95% CI - 153.75 to - 45.08, P = 0.0003) and pre- and postoperative hemoglobin difference (WMD = - 0.93, 95% CI - 1.33 to - 0.5, P < 0.00001), compared with the non-synovectomy group. No statistically significant differences were demonstrated between both groups in postoperative pain, clinical KSS, functional KSS, ROM, transfusion rate, or complications (P > 0.05). CONCLUSIONS: The current evidence demonstrates that performing synovectomy in primary TKA for symptomatic KOA does not have any clinical benefit. It increases postsurgical blood loss. Surgeons routinely undertaking synovectomy should deliberate whether this is clinically indicated and consider limiting resection, if possible.