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To explore the effect of acacetin on myocardial mitochondrial dysfunction in spontaneously hypertensive rats (SHR) with insulin resistance (IR), and the possible mechanism. Rapid IR was first induced in fructose-fed SHR, and they were then treated with acacetin (25, 50 mg/kg). After 7 weeks, the rats were tested for hypertension, IR, cardiac function, and mitochondrial damage status. Potential mechanisms of action were explored in terms of oxidative stress, mitochondrial fission and division, apoptosis, and the insulin signaling pathway. Subsequently, the PI3K gene was silenced, after intervention with acacetin (5 μM) for 24 h, and H

The interrelationships among vitamin D, tobacco smoking, and hypertension are currently unknown. This study was conducted to determine the relationship between vitamin D levels and hypertension and the effect of tobacco smoke exposure levels on this relationship among US adults. We performed a cross-sectional analysis of adult participants from the 2001-2016 National Health and Nutrition Examination Survey (NHANES). Serum 25-hydroxyvitamin D concentration was used as a biomarker of vitamin D status, and tobacco smoke exposure levels were objectively evaluated by serum cotinine levels. Among 22,875 eligible adults who were not receiving antihypertensive medications, the prevalence of hypertension, vitamin D deficiency (50 mmol/L), and cotinine ≥3 ng/mL was 13.9%, 34.9%, and 29.4%, respectively. Serum cotinine and vitamin D levels were independently associated with hypertension risk after controlling for confounders (P 0.05). When stratified by the cotinine group (0.05, 0.05-3 and ≥3 ng/mL), we found that the risk of hypertension associated with vitamin D deficiency was higher among subjects with cotinine levels ≥3 ng/mL compared with the other strata [OR (95% CI) 1.30 (1.09, 1.54) vs. 1.53 (1.19, 1.96) vs. 1.64 (1.30, 2.06); P for heterogeneity test0.05]. Furthermore, serum cotinine levels were negatively correlated with vitamin D levels. These findings suggested that the increased risk of hypertension could be partly attributed to low vitamin D levels induced by tobacco smoke exposure, in addition to the effects of tobacco smoke exposure and vitamin D deficiency themselves.

Objective To investigate the feasibility of diagnosing osteoporosis (OP) in women through magnetic resonance image compilation (MAGiC). Methods A total of 110 patients who underwent lumbar magnetic resonance imaging and dual X-ray absorptiometry examinations were collected and divided into two groups according bone mineral density: osteoporotic group (OP) and non-osteoporotic group (non-OP). The variation trends of T1 (longitudinal relaxation time), T2 (transverse relaxation time) and BMD (bone mineral density) with the increase of age, and the correlation of T1 and T2 with BMD were examined by establishing a clinical mathematical model. Results With the increase of age, BMD and T1 value decreased gradually, while T2 value increased. T1 and T2 had statistical significance in diagnosing OP (P ), and there is moderate positive correlation between T1 and BMD values (R = 0.636, P ), while moderate negative correlation between T2 and BMD values (R=-0.694, P ). Receiver characteristic curve test showed that T1 and T2 had high accuracy in diagnosing OP (T1 AUC = 0.982, T2 AUC = 0.978), and the critical values of T1 and T2 for evaluating osteoporosis were 0.625s and 0.095s, respectively. Besides, the combined utilization of T1 and T2 had higher diagnostic efficiency (AUC = 0.985). Combined T1 and T2 had higher diagnostic efficiency (AUC = 0.985). Function fitting results of OP group: BMD=-0.0037* age − 0.0015*T1 + 0.0037*T2 + 0.86, sum of squared error (SSE) = 0.0392, and non-OP group: BMD = 0.0024* age − 0.0071*T1 + 0.0007*T2 + 1.41, SSE = 0.1007. Conclusion T1 and T2 value of MAGiC have high efficiency in diagnosing OP by establishing a function fitting formula of BMD with T1, T2 and age.

Src family protein kinases (SFKs) play a key role in cell adhesion, invasion, proliferation, survival, apoptosis, and angiogenesis during tumor development. In humans, SFKs consists of eight family members with similar structure and function. There is a high level of overexpression or hyperactivity of SFKs in tumor, and they play an important role in multiple signaling pathways involved in tumorigenesis. FYN is a member of the SFKs that regulate normal cellular processes. Additionally, FYN is highly expressed in many cancers and promotes cancer growth and metastasis through diverse biological functions such as cell growth, apoptosis, and motility migration, as well as the development of drug resistance in many tumors. Moreover, FYN is involved in the regulation of multiple cancer-related signaling pathways, including interactions with ERK, COX-2, STAT5, MET and AKT. FYN is therefore an attractive therapeutic target for various tumor types, and suppressing FYN can improve the prognosis and prolong the life of patients. The purpose of this review is to provide an overview of FYN’s structure, expression, upstream regulators, downstream substrate molecules, and biological functions in tumors.

Colchicine is an ancient anti-inflammatory drug. In recent years, an increasing number of studies have shown that colchicine improves the prognosis of patients with coronary artery disease (CAD), while other studies have reported the opposite. The aim of this study was to evaluate the relative efficacy and safety of colchicine in treating CAD.PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov were searched from inception to 20 October 2020 for randomized controlled trials (RCTs) comparing colchicine and placebo in patients with CAD. The primary outcomes were the primary composite outcomes of cardiovascular death, myocardial infarction (MI), ischemic stroke, or ischemia-driven coronary revascularization after colchicine administration. The secondary outcomes were cardiovascular death, death from any cause, noncardiac death, MI, ischemic stroke, coronary revascularization, gastrointestinal (GI) symptoms, and the different effects of colchicine in acute and chronic CAD. We assessed the pooled odds ratio (OR) of all-cause and cardiovascular mortality for CAD in fixed-effects models, the pooled risk ratio (RR) of the primary composite outcomes, MI, ischemic stroke, and ischemia-driven coronary revascularization in fixed-effects models and the pooled RR of GI symptoms in random-effects models. The Cochrane risk of bias tool was used to assess the risk of bias in the included RCTs.Eleven of the 894 identified studies (n = 12,899 patients) were included (6501 subjects in the colchicine group; 6389 subjects in the control group). The colchicine group had significantly lower pooled RRs of the primary composite outcomes (0.73, 95% confidence interval (CI) 0.64-0.84, P 0.0001), MI (0.77, 95% CI 0.64-0.92, P = 0.004), ischemic stroke (0.47, 95% CI 0.30-0.76, P = 0.002), and ischemia-driven coronary revascularization (0.77, 95% CI 0.66-0.89, P = 0.0007), while the pooled RR of adverse GI events (2.15 95% CI 1.40-3.31, P = 0.0005) was significantly higher. Colchicine had a lower pooled RR of ischemic stroke (0.28, 95% CI 0.12-0.65, P = 0.003) for patients with acute compared with chronic CAD.Colchicine treatment significantly decreased the risk of primary cardiovascular composite outcomes, MI, ischemic stroke, and ischemia-driven coronary revascularization in CAD patients but increased adverse GI events. There was no significant difference in all-cause mortality, cardiovascular mortality, and non-cardiovascular death between the colchicine and control groups. Colchicine performs better in acute CAD patients with ischemic stroke than chronic CAD patients. Colchicine might be a new treatment for patients with CAD.

Patients with advanced non-small cell lung cancer (NSCLC) are prone to brain metastases (BM), which essentially include brain parenchymal metastases (PM) and leptomeningeal metastases (LM). We conducted a retrospective study to comprehensively assess the clinical characteristics and risk factors of patients with advanced NSCLC who develop PM and LM. Patients with advanced NSCLC were enrolled. These patients were then divided into three groups for analysis: patients without BM (No-BM), patients with PM and patients with LM. Data on clinical characteristics of each patient at the time of diagnosis advanced NSCLC were extracted and analyzed. In addition, prediction models were developed and evaluated for PM and LM. A total of 592 patients were enrolled in the study. BM was present in 287 patients (48.5%). Among them, 185 and 102 patients had PM or LM. Patients with LM had a higher proportion of EGFR exon 21point mutations (L858R) compared to patients with No-BM and PM (p

Folate may be involved in the detoxification of heavy metals. This has been demonstrated in animal studies, in in vivo and in vitro studies, and clinical evaluations. However, knowledge regarding the associations between serum folate and blood concentrations of cadmium and lead is limited. We aimed to investigate the relationship between serum folate levels and blood concentrations of cadmium and lead in US adults. Data on 15,501 adults were obtained from the 1999–2006 National Health and Nutrition Examination Survey (NHANES) and used for the analysis. Information on serum folate concentrations and blood levels of lead and cadmium was derived from laboratory measurements in the NHANES. Multivariable linear regression was used to examine the relationship between serum folate levels and blood concentrations of cadmium and lead in US adults, controlling for confounders. The serum folate concentration was negatively correlated with blood levels of cadmium and lead (P-trends 60 mL/min/1.73 m2), the association between serum folate concentrations and blood levels of cadmium and lead was found to be more stable in adults with eGFR > 60 mL/min/1.73 m2, both in males and females. These findings warrant future studies to explore the mechanisms responsible for the beneficial role of folate in regulating cadmium and lead concentrations in the blood.

Objective To compare efficacy and safety of fecal microbiota transplantation (FMT) with glucocorticoid as induction therapy in ulcerative colitis (UC). Methods The patients with active mild to moderate UC were recruited into the single-center, prospective cohort study. The patients were treated with either FMT (FMT group) or glucocorticoids (GCs group). Patients received FMT administration for 3 days. The primary outcome was clinical and endoscopic remission at week 12. Inflammatory parameters were assessed by routine blood tests. Safety was assessed by adverse events recorded. The serum levels of TNF-α, IFN-γ, IL-1β, IL-4, IL-5, IL-6, IL-10 IL-8, IL-12p70, IL-13, IL-17A and IL-23 following FMT were measured by Luminex multiplex assay. Results Of the 122 patients, 62 patients were treated with FMT and 60 with glucocorticoids. 34 patients in FMT group (54.8%) and 29 in GCs group (48.3%) reached the primary outcome (p = 0.30). The incidence of adverse events in GCs group (35/60, 58.3%) was significantly higher than that in FMT group (14/62, 22.6%) and two serious adverse events were observed following GCs. Patients in FMT group were stratified into responders (RE) and non-responders (NR) groups. The level of TNF-α and IL-6 decreased significantly in RE group, while IL-10 decreased significantly in NR group. Conclusion FMT therapy was as effective as glucocorticoids to induce remission in active mild to moderate UC, accompanied by fewer adverse events. The modification of serum TNF-α, IL-6 and IL-10 might be related to the efficacy of FMT in UC. Trial registration This study was registered with ClinicalTrials.gov (NCT02435160). Registered on 6 April, 2015. https://clinicaltrials.gov/ct2/results?cond=&term=NCT02435160&cntry=&state=&city=&dist=

Traditional design, manufacturing and maintenance are run and managed independently under their own rules and regulations in an increasingly time-and-cost ineffective manner. A unified platform for efficient and intelligent design-manufacturing-maintenance of mechanical equipment and systems is highly needed in this rapidly digitized world. In this work, the definition of digital twin and its research progress and associated challenges in the design, manufacturing and maintenance of engineering components and equipment were thoroughly reviewed. It is indicated that digital twin concept and associated technology provide a feasible solution for the integration of design-manufacturing-maintenance as it has behaved in the entire lifecycle of products. For this aim, a framework for information-physical combination, in which a more accurate design, a defect-free manufacturing, a more intelligent maintenance, and a more advanced sensing technology, is prospected.

A universal vaccine protecting against multiple serotypes of Streptococcus suis is urgently needed to improve animal welfare and reduce the consumption of antibiotics. In this study, a dual antigen expression cassette consisting of SS2-SaoA and SS9-Eno was delivered by a recombinant Salmonella Choleraesuis vector to form the vaccine candidate rSC0016(pS-SE). SaoA and Eno were simultaneously synthesized in rSC0016(pS-SE) without affecting the colonization of the recombinant vector in the lymphatic system. In addition, the antiserum of mice immunized with rSC0016(pS-SE) produced a broader and potent opsonophagocytic response against multiple serotypes of S. suis. Finally, rSC0016(pS-SE) provided mice with a 100% protection against a lethal dose of parent S. suis serotype 2 and serotype 9, and provided 90% and 80% protection against heterologous S. suis serotype 7 or 1/2. These values were significantly higher than those obtained with rSC0016(pS-SaoA) or rSC0016(pS-Eno). Together, this study serves as a foundation for developing a universal vaccine against multiple serotypes of S. suis.

Reducing inflammation is a promising therapeutic approach for sepsis-induced cardiomyopathy (SIC). The 5-Methoxytryptophan (5-MTP) is a tryptophan metabolite that demonstrates anti-inflammatory, anti-fibrosis, anti-tumorigenesis, and anti-senescence features. Current investigations aimed to assess the 5-MTP pretreatment impacts on lipopolysaccharide (LPS)-induced cardiac injury and dysfunction. For in vivo studies, the mice were categorized randomly into four groups: control, LPS, LPS+5-MTP (25 mg/kg) and LPS+5-MTP (50 mg/kg). The mice in the LPS+5-MTP groups were given 5-MTP intraperitoneally once a day for 7 days. LPS (10 mg/kg) was then administered intraperitoneally for 24 h. Echocardiography, cardiac injury biomarkers, and H & E staining evaluated heart anatomy and function. The findings indicate that 5-MTP pretreatment significantly reduced LPS-induced heart dysfunction and morphological alterations. Western blot assay was used for investigating molecular mechanisms. After LPS stimulation, the pro-inflammatory cytokines (IL-1β, IL-6, TNF-α and NLRP3) protein levels increased while anti-inflammatory cytokine (IL-10) decreased; however, 5-MTP pretreatment mitigated this response by suppressing the stimulation of the NF-κB signaling pathway. Furthermore, 5-MTP administration reduced LPS-induced cardiac apoptosis, as demonstrated by increased protein levels of cleaved-Casepase-1, cleaved-Casepase-3 and Bax, and decreased protein level of Bcl-2 after LPS stimulation, whereas LPS-induced cardiac apoptosis was reversed by 5-MTP pretreatment. In vitro, 5-MTP pretreatment had a similar cardioprotective effect on cultured cardiac fibroblasts challenged with LPS. In conclusion, 5-MTP pretreatment can reduce LPS-induced cardiac inflammation and apoptosis, implying that 5-MTP is a possible therapeutic option for SIC.