His bundle pacing versus right ventricular pacing: A comparative study.

BACKGROUND: Pacing is the most effective and dependable method for treating complete atrioventricular block (AVB). OBJECTIVE: The purpose of this study is to investigate the use of His bundle pacing (HBP) in patients with atrioventricular block. METHODS: Patients who underwent HBP or right ventricular pacing (RVP) were enrolled and divided into two groups: the HBP group and the RVP group, respectively. We compared baseline clinical data, fluoroscopy duration, operation duration, pacing electrode parameters during the operation or follow-up, baseline QRS duration, and pacing QRS duration. RESULTS: HBP was attempted in 48 patients and was successful in 34 patients who were included in the HBP group. In addition, 30 RVP patients were included in the RVP group. Fluoroscopy duration and operation duration were significantly longer in the HBP group compared to the RVP group. Compared to the RVP group, the HBP group had a higher pacing threshold, a lower R wave amplitude, and a shorter pacing QRS duration. At 6 months of follow-up, the pacing threshold remained higher, the R wave amplitude was significantly lower, and the end-diastolic diameter of the left ventricle was smaller in the HBP group. CONCLUSION: HBP was safe and effective for atrioventricular block despite the longer fluoroscopy and operation duration in the HBP group when compared to the RVP group.

Prediction of cardiovascular disease risk based on major contributing features.

The risk of cardiovascular disease (CVD) is a serious health threat to human society worldwide. The use of machine learning methods to predict the risk of CVD is of great relevance to identify high-risk patients and take timely interventions. In this study, we propose the XGBH machine learning model, which is a CVD risk prediction model based on key contributing features. In this paper, the generalisation of the model was enhanced by adding retrospective data of 14,832 Chinese Shanxi CVD patients to the kaggle dataset. The XGBH risk prediction model proposed in this paper was validated to be highly accurate (AUC = 0.81) compared to the baseline risk score (AUC = 0.65), and the accuracy of the model for CVD risk prediction was improved with the inclusion of the conventional biometric BMI variable. To increase the clinical application of the model, a simpler diagnostic model was designed in this paper, which requires only three characteristics from the patient (age, value of systolic blood pressure and whether cholesterol is normal or not) to enable early intervention in the treatment of high-risk patients with a slight reduction in accuracy (AUC = 0.79). Ultimately, a CVD risk score model with few features and high accuracy will be established based on the main contributing features. Of course, further prospective studies, as well as studies with other populations, are needed to assess the actual clinical effectiveness of the XGBH risk prediction model.

C1q/TNF-related protein 3 alleviates heart failure via attenuation of oxidative stress in myocardial infarction rats.

C1q-tumor necrosis factor-related protein 3 (CTRP3), an adipokine, has been reported to be closely related to cardiovascular diseases (CVDs). However, the effect of CTRP3 on heart failure (HF) remains dimness. This study was to explore the role of CTRP3 in HF and its potential interaction mechanism. Heart failure model was established by inducing ischemia myocardial infarction (MI) through ligation of the left anterior descending artery in Sprague-Dawley rats. Four weeks later, the rats were detected by transthoracic echocardiography and masson staining. Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), cardiac troponin I (cTnI) levels, creatine kinase-MB (CK-MB) and oxidative stress levels were recorded. The level of CTRP3 was reduced in the cardiomyocytes (CMs) treated with oxygen-glucose deprivation (OGD) and in the heart of MI rats. CTRP3 overexpression alleviated cardiac dysfunction, attenuated the cardiac fibrosis, and inhibited the increases of ANP, BNP, cTnI and CK-MB in the serum of MI rats. The increases of ANP and BNP in the CMs, and the collagen I and collagen III in the cardiac fibroblasts (CFs) induced by OGD were inhibited by CTRP3 overexpression. The enhancement of oxidative stress in the heart of MI rats was inhibited by CTRP3 overexpression. These results indicated that overexpression of CTRP3 could improve cardiac function and the related cardiac fibrosis in MI-induced HF rats via inhibition of oxidative stress. Upregulation of CTRP3 may be a strategy for HF therapy in the future.

The impact of social support on the quality of life among older adults in China: An empirical study based on the 2020 CFPS.

Background: As aging issues become serious, how to guarantee and improve the quality of life among older adults has become a hot topic in China. This article is aimed to discuss the impact of formal and informal social support on the quality of life among older adults and the differences in gender and urban-rural areas. Methods: The data used in this article are from the 2020 China Family Panel Studies (CFPS). Quality of life is measured from three dimensions of life: satisfaction, self-rated health, and mental state. This article uses the ordered logistic regression model to analyze the impact of social support on life satisfaction and self-rated health, and the binary logistic regression model to analyze the impact of social support on the mental state. The method of Shapley value decomposition further analyzes the contribution of influencing factors to the quality of life. Results: The activities of daily living (ADL) and income significantly impact the quality of life among older adults. Formal and informal social support positively improved the quality of life among older adults, but the effect of informal social support is greater than that of formal social support. The male older adults are significantly better than the female adults across all three dimensions of quality of life. The mental state of urban older adults is better than that of rural older adults. Conclusion: Formal and informal social support should be strengthened to improve the income of older adults. Older adults should be encouraged to participate in social activities and good interpersonal relationships should be established actively. Female older adults should be paid more attention. The proportion of female older adults participating in insurance should be increased, and the family and intergenerational care burden for female older adults should be reduced. The leisure life of urban older adults should be enriched. The basic social insurance and health service systems in rural areas should be improved.

Alarin moderated myocardial hypertrophy via inhibiting cyclic adenosine monophosphate/protein kinase A signaling pathway to attenuate autophagy.

Alarin could alleviate myocardial infarction-induced heart failure. The present study was to explore whether alarin could alleviate myocardial hypertrophy via inhibiting cyclic adenosine monophosphate/protein kinase A (cAMP/PKA) signaling pathway to attenuate autophagy. Myocardial hypertrophy was induced by angiotensin (Ang) II infusion in vivo in mice and by Ang II treatment of neonatal rat cardiomyocytes (NRCMs) in vitro. The Ang II-induced hypertrophy and fibrosis of the heart were alleviated after alarin administration in mice. The increased atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and beta-myosin heavy chain (ß-MHC), and the decreased alpha-myosin heavy chain (α-MHC) induced by Ang II were reversed by alarin treatment in NRCMs. Alarin inhibited the increases of cAMP and PKA in NRCMs. Treatment with cAMP or overexpression of PKA blocked the attenuating effects of alarin on Ang II-induced hypertrophy in NRCMs. Alarin reduced the Ang II-induced increases of LC3, Beclin 1, autophagy-related gene (Atg)3 and Atg5 in NRCMs. The overexpression of cAMP and PKA reversed the alleviating effects of alarin on the increased autophagy induced by Ang II in NRCMs. These results indicated that alarin could moderate cardiac remodeling. Alarin improved myocardial hypertrophy via inhibiting the cAMP/PKA signaling pathway to attenuate autophagy.

Novel Mode of Noncrystallographic Branching in the Initial Stages of Polymer Fibril Growth.

Spherulites are the most ubiquitous of polycrystalline microstructure of polymers; they develop under a wide range of conditions by the subsequent branching of crystalline lamella that results in an overall spherical shape. Despite significant efforts over decades, the mechanisms behind branching remain unclear. Molecular dynamics simulations in polyethylene reveal the molecular-level origin of noncrystallographic branching and the initial formation of fibrils. We find that the growth of crystalline lamella by reeling in and folding of polymer chains causes surprisingly large local deformation which, in turn, aligns the chains in the neighboring undercooled liquid. Thus, subsidiary grains nucleate with preferred orientations resulting in fibril growth with branching at small angles, consistent with those observed experimentally.

Apigenin ameliorates HFD-induced NAFLD through regulation of the XO/NLRP3 pathways.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver-related morbidity and mortality disease in the world. However, no effective pharmacological treatment for NAFLD has been found. In this study, we used a high fat diet (HFD)-induced NAFLD model to investigate hepatoprotective effect of apigenin (API) against NAFLD and further explored its potential mechanism. Our results demonstrated that gavage administration of API could mitigate HFD-induced liver injury, enhance insulin sensitivity and markedly reduce lipid accumulation in HFD-fed mice livers. In addition, histological analysis showed that hepatic steatosis and macrophages recruitment in the API treatment group were recovered compared with mice fed with HFD alone. Importantly, API could reverse the HFD-induced activation of the NLRP3 inflammasome, further reduced inflammatory cytokines IL-1ß and IL-18 release, accompanied with the inhibition of xanthine oxidase (XO) activity and the reduction of uric acid and reactive oxygen species (ROS) production. The pharmacological role of API was further confirmed using free fatty acid (FFA) induced cell NAFLD model. Taking together, our results demonstrated that API could protect against HFD-induced NAFLD by ameliorating hepatic lipid accumulation and inflammation. These protective effects may be partially attributed to the regulation of XO by API, which further modulated NLRP3 inflammasome activation and inflammatory cytokines IL-1ß and IL-18 release. Therefore API is a potential therapeutic agent for the prevention of NAFLD.

Activation of the p38/MAPK pathway regulates autophagy in response to the CYPOR-dependent oxidative stress induced by zearalenone in porcine intestinal epithelial cells.

Zearalenone (ZEA) can widely contaminate crops and agricultural products. The ingestion of ZEA-contaminated food or feed affects the integrity and functions of the intestines. In this study, we aimed to find the potential protective mechanism against ZEA ingestion. We found that ZEA induced cell death in IPEC-J2 cells. Meanwhile, the cytoprotective autophagy was activated in ZEA-treated cells. Further studies demonstrated that a p38/MAPK inhibitor down-regulated autophagy and increased cell death compared to those of the controls. Furthermore, ZEA could induce the accumulation of ROS, and eliminating ROS with NAC resulted in a decline in cell death, p38/MAPK phosphorylation, and the expression of LC3-II compared to those of ZEA-group. In addition, cytochrome P450 reductase (CYPOR) was significantly increased in ZEA-treated cells compared to that in the controls, and an inhibitor of CYPOR decreased ROS levels and mitigated cell death compared to those of the ZEA-group. More importantly, we found that blocking both p38/MAPK signalling and autophagy could enhance CYPOR expression and elevate ROS levels. Overall, our study indicated that the p38/MAPK pathway could activate protective autophagy in response to the CYPOR-dependent oxidative stress that was induced by ZEA in IPEC-J2 cells.

Estrogen receptors participate in carcinogenesis signaling pathways by directly regulating NOD-like receptors.

Increasing evidence indicates that the NOD-like receptors (NLRs) family may act as critical back-up defenses and provide synergistic responses when confronted with persistent danger. However, the precise regulatory mechanism of NLRs and the contribution of NLRs to cancer are still unknown. In our previous study, we found that estrogen receptors (ERs) have a close connection with NLRs in the inflammatory response. Here, ERs are first identified as NLRs transcription regulation factors, both regulate NLRs expression and promote inflammasome co-localization. Furthermore, we identified that NLRP3 was differentially expressed in colon normal and cancer cells, selective ERα antagonist could significantly decrease pro-inflammatory cytokines expression, suppress proliferation and promote apoptosis by inhibited NLRP3 expression and inflammasome activity. In short, the research demonstrates that ERs participate in the NLR-associated signaling pathway in cancer by directly regulating NLRs. Our results provide novel insight into ERs as therapeutic targets in NLR-related inflammation and cancer.

Zearalenone can relieve dextran sulfate sodium-induced inflammatory reaction.

In this study, we investigated the influence of zearalenone (ZEA) on the dextran sulfate sodium (DSS)-induced colitis model both in vitro and in vivo. Our results show that the mRNA levels of IL-1ß, IL-18, NLRP3, ASC, and caspase-1 in the DSS+ZEA-treated group are lower than those in either the DSS or ZEA group, and the protein expression trends are similar. Furthermore, colitis, which is characterized by body weight loss, stool consistency, and the presence of bloody feces, was significantly alleviated in the DSS+ZEA group when compared with that in the DSS group. In addition, histological analysis showed that inflammatory cell infiltration and tissue damage of the colon in the DSS+ZEA group were recovered compared with that in the DSS-treated group. These results suggest that, instead of aggravating DSS-induced colitis, ZEA relieves the inflammatory reaction in colon tissue, which may be related to its estrogenic activity.

[Effect of Microbial Community Structure and Metabolites on Sludge Settling Ability Under Three Different Switching Condition Processes].

Using sodium acetate as the carbon source, sludge settling ability (settleability) was investigated under three processes:AAO nitrogen and phosphorus removal(process Ⅰ), AO nitrification-denitrification (process Ⅱ), and aerobic carbon removal (process Ⅲ). The succession of microbial community structures in sludge was traced, the content and composition of microbial metabolites were monitored, and the effects of operational mode on sludge settleability were analyzed. The results showed that the settleability of process Ⅰ was the best, followed by process Ⅲ and Ⅱ. Under the different operating conditions, the dominant bacteria and microbial community structure of the system changed significantly. The relative amount of Thiothrix was the dominant bacteria affecting the sludge settleability. The abundances of Thiothrix were only 0.08% and 1.51% with fresh sludge and in process Ⅰ; this abundance increased to 9.41% in process Ⅱ and decreased to 4.29% in process Ⅲ. The anaerobic zone of process I had an inhibitory effect on the growth of the bacterium, while the anoxic zone of process Ⅱ stimulated its dominant growth. At the same time, comparison showed that the microbial population diversity was highest in process Ⅰ. followed by processes Ⅱ and Ⅲ. The introduction of anoxic and anaerobic zones led to the increase of system function and environmental complexity, and increased microbial community diversity. Analyses of extracellular polymeric substances (EPS) and fluorescence characteristics showed that the changes in microbial community structure had a significant effect on the composition and content of EPS, which aggravated the process of improving or deteriorating settleability. The sludge settleability was found to be positively correlated with the ratio of protein and polysaccharide in loosely bound EPS.

Zearalenone (ZEA)-induced intestinal inflammation is mediated by the NLRP3 inflammasome.

To ascertain whether zearalenone (ZEA) could induce intestinal inflammation and investigate its possible mechanism, we investigated inflammatory cytokine release and the activation of the NLRP3 inflammasome after ZEA treatment both in vitro or in vivo. First, intestinal porcine enterocyte cell line (IPEC-J2) cells and mouse peritoneal macrophages were treated with ZEA to detect NLRP3 inflammasome activation, and the role of reactive oxygen species (ROS) in ZEA-induced inflammation was investigated. Then, Balb/c mice were fed a gavage of ZEA, and the disease activity indices (DAIs) and histological analysis were used to assess intestinal inflammation. Our study showed that the mRNA expression of NLRP3 inflammasome, pro-interleukin-1ß (pro-IL-1ß), and pro-interleukin-18 (pro-IL-18) was up-regulated 0.5- to 1-fold and that the release of IL-1ß and IL-18 increased from 48 pg mL-1 to 55 pg mL-1 and 110 pg mL-1 to 145 pg mL-1, respectively. However, ROS inhibitor N-acetyl-l-cysteine (NAC) reduced IL-1ß and IL-18 release to 45 pg mL-1 and 108 pg mL-1. Moreover, the same phenomenon was observed in intestinal tissues of ZEA-treated mice. In addition, clinical parameters of treated mice showed stools became loose and contained mucous. In addition, the presence of gross blood stool was found in the last 2 d. Histological analysis showed obvious inflammatory cell infiltration and tissue damage in the colon. These findings uncovered a possible mechanism of intestinal mucosal innate immunity in response to mycotoxin ZEA that ZEA could activate the ROS-mediated NLRP3 inflammasome and, in turn, contribute to the caspase-1-dependent activation of the inflammatory cytokines IL-1ß and IL-18.

Molecular modeling of the microstructure evolution during carbon fiber processing.

The rational design of carbon fibers with desired properties requires quantitative relationships between the processing conditions, microstructure, and resulting properties. We developed a molecular model that combines kinetic Monte Carlo and molecular dynamics techniques to predict the microstructure evolution during the processes of carbonization and graphitization of polyacrylonitrile (PAN)-based carbon fibers. The model accurately predicts the cross-sectional microstructure of the fibers with the molecular structure of the stabilized PAN fibers and physics-based chemical reaction rates as the only inputs. The resulting structures exhibit key features observed in electron microcopy studies such as curved graphitic sheets and hairpin structures. In addition, computed X-ray diffraction patterns are in good agreement with experiments. We predict the transverse moduli of the resulting fibers between 1 GPa and 5 GPa, in good agreement with experimental results for high modulus fibers and slightly lower than those of high-strength fibers. The transverse modulus is governed by sliding between graphitic sheets, and the relatively low value for the predicted microstructures can be attributed to their perfect longitudinal texture. Finally, the simulations provide insight into the relationships between chemical kinetics and the final microstructure; we observe that high reaction rates result in porous structures with lower moduli.

Zearalenone induces ROS-mediated mitochondrial damage in porcine IPEC-J2 cells.

In this study, the mitochondrial damage effect and mechanism of zearalenone (ZEA) in swine small intestine IPEC-J2 cells in vitro were comprehensively characterized. The analyses revealed that ZEA at high doses (8 and 7 µg/mL) can significantly increase P < 0.05 the malondialdehyde levels and decrease antioxidant enzymes activities after 48 h of exposure. Meanwhile, the reactive oxygen species (ROS) accumulation increased in high dose ZEA-treated groups after 2 h treatment, but decreased due to the ROS-induced mitochondrial damage and the caused cell apoptosis after 48 h of high does ZEA treatment. Moreover, the decreasing of mitochondrial membrane potential (MMP; ΔΨ) in high dose ZEA exposure was observed in line with the increasing ROS production in mitochondria. Results suggest that ZEA exposure can induce mitochondrial damage by reducing antioxidant enzyme activities, accumulation of ROS, and decreasing MMP. The mitochondrial damage had a dramatic concentration-effects relationship with ZEA.

Inhibition of bone formation in rats by aluminum exposure via Wnt/ß-catenin pathway.

The previous research found that aluminum trichloride (AlCl3) inhibited rat osteoblastic differentiation through inactivation of Wnt/ß-catenin signaling pathway in vitro. On that basis, the experiment in vivo was conducted in this study. Rats were orally exposed to 0 (control group) and 0.4 g/L AlCl3 (AlCl3-treated group) for 30, 60, 90 or 120 days, respectively. We found that mRNA expressions of type I collagen and insulin-like growth factor-1, mRNA and protein expressions of Runx2 and survivin, ratio of p-GSK3ß/GSK3ß and protein expression of ß-catenin were all decreased, whereas the mRNA and protein expressions Dkk1 and sFRP1 and the mRNA expressions and activity of Caspase-3 were increased in the AlCl3-treated group compared with the control group with time prolonged. These results suggest that AlCl3 inhibits bone formation and induces bone impairment by inhibiting the Wnt/ß-catenin signaling pathway in young growing rats.

Analysis of Evolutionary Processes of Species Jump in Waterfowl Parvovirus.

Waterfowl parvoviruses are classified into goose parvovirus (GPV) and Muscovy duck parvovirus (MDPV) according to their antigenic features and host preferences. A novel duck parvovirus (NDPV), identified as a new variant of GPV, is currently infecting ducks, thus causing considerable economic loss. This study analyzed the molecular evolution and population dynamics of the emerging parvovirus capsid gene to investigate the evolutionary processes concerning the host shift of NDPV. Two important amino acids changes (Asn-489 and Asn-650) were identified in NDPV, which may be responsible for host shift of NDPV. Phylogenetic analysis indicated that the currently circulating NDPV originated from the GPV lineage. The Bayesian Markov chain Monte Carlo tree indicated that the NDPV diverged from GPV approximately 20 years ago. Evolutionary rate analyses demonstrated that GPV evolved with 7.674 × 10-4 substitutions/site/year, and the data for MDPV was 5.237 × 10-4 substitutions/site/year, whereas the substitution rate in NDPV branch was 2.25 × 10-3 substitutions/site/year. Meanwhile, viral population dynamics analysis revealed that the GPV major clade, including NDPV, grew exponentially at a rate of 1.717 year-1. Selection pressure analysis showed that most sites are subject to strong purifying selection and no positively selected sites were found in NDPV. The unique immune-epitopes in waterfowl parvovirus were also estimated, which may be helpful for the prediction of antibody binding sites against NDPV in ducks.

Aluminum Trichloride Inhibited Osteoblastic Proliferation and Downregulated the Wnt/ß-Catenin Pathway.

Aluminum (Al) exposure inhibits bone formation. Osteoblastic proliferation promotes bone formation. Therefore, we inferred that Al may inhibit bone formation by the inhibition of osteoblastic proliferation. However, the effects and molecular mechanisms of Al on osteoblastic proliferation are still under investigation. Osteoblastic proliferation can be regulated by Wnt/ß-catenin signaling pathway. To investigate the effects of Al on osteoblastic proliferation and whether Wnt/ß-catenin signaling pathway is involved in it, osteoblasts from neonatal rats were cultured and exposed to 0, 0.4 mM (1/20 IC50), 0.8 mM (1/10 IC50), and 1.6 mM (1/5 IC50) of aluminum trichloride (AlCl3) for 24 h, respectively. The osteoblastic proliferation rates; Wnt3a, lipoprotein receptor-related protein 5 (LRP-5), T cell factor 1 (TCF-1), cyclin D1, and c-Myc messenger RNA (mRNA) expressions; and p-glycogen synthase kinase 3ß (GSK3ß), GSK3ß, and ß-catenin protein expressions indicated that AlCl3 inhibited osteoblastic proliferation and downregulated Wnt/ß-catenin signaling pathway. In addition, the AlCl3 concentration was negatively correlated with osteoblastic proliferation rates and the mRNA expressions of Wnt3a, c-Myc, and cyclin D1, while the osteoblastic proliferation rates were positively correlated with mRNA expressions of Wnt3a, c-Myc, and cyclin D1. Taken together, these findings indicated that AlCl3 inhibits osteoblastic proliferation may be associated with the inactivation of Wnt/ß-catenin signaling pathway.

Low-Dose Quinidine Effectively Reduced Shocks in Brugada Syndrome Patients with an Implantable Cardioverter Defibrillator: A Chinese Case Series Report.

BACKGROUND: Only implantable cardioverter defibrillators (ICD) have been proven to prevent sudden cardiac death (SCD) in patients with Brugada syndrome (BrS). However, ICD discharge, whether appropriate or inappropriate, leads to impaired quality of life and even increases rehospitalization. Quinidine might prevent the recurrence of ventricular arrhythmia (VA); however, the effect of low-dose quinidine for preventing spontaneous arrhythmias remains less clear. METHODS: In our cardiology center, 10 confirmed patients with BrS (all men, mean age 38.7 ± 6.72 years) who underwent appropriate ICD shocks due to recurrent VAs were treated with quinidine (≤200 mg/day) and followed regularly. RESULTS: All the patients underwent ICD shocks due to ventricular tachycardia (VT)/ventricular fibrillation (VF) before taking quinidine. A 24-hour distribution of VT/VF demonstrated that most of the events occurred in the sleeping time from 22:00 to 8:00. Quinidine prevented recurrence of VAs in nine patients. The other one patient took quinidine discontinuously because of anxiety suffered from less episodes of VA, and after psychological guidance, he took quinidine 200 mg/day and experienced no VA episodes from then on. In our series, only one patient suffered leukopenia related to quinidine. No other side effect was observed. CONCLUSIONS: Quinidine with a very low dose (≤200 mg/day) well controlled VT/VF recurrence for a long-term period in Chinese patients with BrS. Administration (at 21:00) according to the circadian distribution of VT/VF episodes might increase the efficiency and improve the patient's tolerance.