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Abstract Mycobacterium tuberculosis, which mainly affects the lungs but can also invade other systems, presents a diagnostic challenge when co‐existing with autoimmune disease. We report a case of 31‐year‐old Asian woman with anti‐synthetase syndrome who developed abdominal and subcutaneous lumps during treatment, along with elevated tumor markers, raising suspicion of malignancy. Pathological examination revealed M. tuberculosis infection, changing the diagnosis to multifocal extrapulmonary tuberculosis. This case highlights the need for prompt and detailed evaluations, and the importance of broad differential diagnosis.

Abstract Background Natural tetramates are a family of hybrid polyketides bearing tetramic acid (pyrrolidine-2,4-dione) moiety exhibiting a broad range of bioactivities. Biosynthesis of tetramates in microorganisms is normally directed by hybrid polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) machineries, which form the tetramic acid ring by recruiting trans- or cis-acting thioesterase-like Dieckmann cyclase in bacteria. There are a group of tetramates with unique skeleton of 3-(2H-pyran-2-ylidene)pyrrolidine-2,4-dione, which remain to be investigated for their biosynthetic logics. Results Herein, the tetramate type compounds bripiodionen (BPD) and its new analog, featuring the rare skeleton of 3-(2H-pyran-2-ylidene)pyrrolidine-2,4-dione, were discovered from the sponge symbiotic bacterial Streptomyces reniochalinae LHW50302. Gene deletion and mutant complementation revealed the production of BPDs being correlated with a PKS-NRPS biosynthetic gene cluster (BGC), in which a Dieckmann cyclase gene bpdE was identified by sit-directed mutations. According to bioinformatic analysis, the tetramic acid moiety of BPDs should be formed on an atypical NRPS module constituted by two discrete proteins, including the C (condensation)-A (adenylation)-T (thiolation) domains of BpdC and the A-T domains of BpdD. Further site-directed mutagenetic analysis confirmed the natural silence of the A domain in BpdC and the functional necessities of the two T domains, therefore suggesting that an unusual aminoacyl transthiolation should occur between the T domains of two NRPS subunits. Additionally, characterization of a LuxR type regulator gene led to seven- to eight-fold increasement of BPDs production. The study presents the first biosynthesis case of the natural molecule with 3-(2H-pyran-2-ylidene)pyrrolidine-2,4-dione skeleton. Genomic mining using BpdD as probe reveals that the aminoacyl transthiolation between separate NRPS subunits should occur in a certain population of NRPSs in nature.

Abstract Aims In this study, we aimed to develop and validate a competing risk nomogram for predicting cardiac death and heart transplantation (HT) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Methods We retrospectively enrolled 149 consecutive patients with ARVC diagnosed at our institution between 2008 and 2022. Cox proportional hazards model was primarily used to identify variables associated with cardiac death and HT. On the basis of these indicators, a competing risk nomogram was developed to predict the 1, 3, and 5 year probabilities of cardiac death and HT. The area under the receiver operating characteristic curve (AUC), Harrell's C‐index, and calibration curves were used to evaluate and internally validate the performance of the model. Decision curve analysis was performed to assess the clinical utility of the nomogram. Result Of the 149 patients with ARVC, the mean age was 38.77 ± 15.94 years, and most of the patients were men (67.11%, 100/149). Fourteen patients experienced cardiac death and nine underwent HT, during a median follow‐up period of 5.8 years (interquartile range, 0.62–5.56 years). Multivariable COX analysis revealed that extent of TWI in the anterior and inferior leads (P = 0.0057), right atrial diameter on transthoracic echocardiography (P = 0.0498), RVEF (P = 0.1036), and LVEF (P < 0.001) all showed statistical significance. The 1‐, 3‐, and 5‐year cumulative incidence of cardiac death and HT were 3.35%, 8.05%, and 11.4%, respectively. The area under the receiver operating characteristic curve of the nomogram for predicting cardiac death and HT at 1, 3, and 5 years after diagnosis of ARVC were 0.860, 0.935, and 0.956. The value of Harrell's C‐index is 0.9273 (95% confidence interval 0.8954–0.9590; P

Abstract Background Obesity is a crucial risk factor for obstructive sleep apnea (OSA), but the association between adiposity deposition and OSA risk has not reached a consistent conclusion. This study sought to reveal the association of multiple adiposity indicators with OSA risk. Methods This cross-sectional study included 9,733 participants aged 35–74 years, recruited from an ongoing population-based cohort. OSA was assessed by the Berlin Questionnaire. Six adiposity indicators, including neck circumference (NC), body fat percentage (BF%), waist-to-hip ratio (WHR), visceral adiposity index (VAI), lipid accumulation product (LAP), and resting metabolic rate (RMR), were selected. Multivariate logistic regression models were used to examine the association of adiposity indicators with OSA risk. Results One thousand six hundred twenty-six participants (16.71%) were classified into the OSA group. NC, BF%, WHR, VAI, LAP, and RMR were all positively associated with the risk of OSA after adjusting for confounders, regardless of age, sex, and history of dyslipidemia. Every 1-unit increment of NC, BF%, and VAI was associated with a 13%, 9%, and 14% increased risk of OSA, respectively; every 0.01-unit increment of WHR was associated with a 3% increased risk of OSA; every 10-unit increment of LAP and RMR was associated with 2% and 4% increased risk of OSA, respectively. Conclusions NC, BF%, WHR, VAI, LAP, and RMR were all independently and positively associated with OSA risk, regardless of age, sex, history of dyslipidemia, and menopausal status. Application of these new indicators could help to more comprehensively reflect and predict the risk of OSA in the general population.

The bacterial trialkyl-substituted aromatic polyketides are structurally featured with the unusual aromatic core in the middle of polyketide chain such as TM-123 (1), veramycin A (2), NFAT-133 (3) and benwamycin I (4), which were discovered from Streptomyces species and demonstrated with antidiabetic and immunosuppressant activities. Though the biosynthetic pathway of 1−3 was reported as a type I polyketide synthase (PKS), the PKS assembly line was interpreted inconsistently, and it remains a mystery how the compound 3 was generated. Herein, the PKS assembly logic of 1−4 was revised by site-mutagenetic analysis of the PKS dehydratase domains. Based on gene deletion and complementation, the putative P450 monooxygenase nftE1 and metallo-beta-lactamase (MBL) fold hydrolase nftF1 were verified as essential genes for the biosynthesis of 1−4. The absence of nftE1 led to abolishment of 1−4 and accumulation of new products (5−8). Structural elucidation reveals 5−8 as the non-aromatic analogs of 1, suggesting the NftE1-catalyzed aromatic core formation. Deletion of nftF1 resulted in disappearance of 3 and 4 with the compounds 1 and 2 unaffected. As a rare MBL-fold hydrolase from type I PKSs, NftF1 potentially generates the compound 3 through two strategies: catalyze premature chain-offloading as a trans-acting thioesterase or hydrolyze the lactone-bond of compound 1 as an esterase.

In our continued desire to isolate more bioactive compounds from the Streptomyces sp. MA37 variant, ΔaccJ, three new accramycin derivatives have been successfully characterised. The structures of accramycin L-N (1–3) were established by high-resolution mass spectrometry and 1D and 2D nuclear magnetic resonance. The antimicrobial evaluation of accramycin L-N against Staphylococcus aureus, Klebsiella pneumoniae, and Enterobacter cloacae showed minimum inhibitory concentration (MIC) values ranging from 0.77 to 13.02 µg/mL. Accramycin L exhibited the most significant activity against S. aureus. In addition, accramycin L-N (1–3) displayed significant activity against K. pneumoniae at the MIC values of 0.81, 0.77, and 0.79 µg/mL, respectively.

Background Elevated blood pressure (BP) is reportedly associated with an increased risk of atrial fibrillation (AF). However, the association between cumulative BP exposure in midlife and incident AF in mid‐to‐late life remains unclear. Methods and Results Participants enrolled in the ARIC (Atherosclerosis Risk in Communities) study with 4 consecutive BP measurements and no prevalent AF at baseline were included. Cumulative BP was calculated as the area under the curve from visit 1 to visit 4. Incident AF was identified by study visit ECGs, hospital discharge codes, or death certificates. A total of 9892 participants were included (44.6% men and mean age 62.9±5.7 years at visit 4) with 1550 (15.7%) individuals who developed new‐onset AF during an average follow‐up of 15.4 years. The incidence rates of AF per 1000 person‐years across the 4 quartiles of cumulative systolic BP were 7.9, 9.2, 12.5, and 16.9, respectively. After multivariable adjustment, the hazard ratios for incident AF among participants in the highest quartile of cumulative systolic BP, pulse pressure, and mean arterial pressure were 1.48 (95% CI, 1.27–1.72), 1.81 (95% CI, 1.53–2.13), and 1.22 (95% CI, 1.05–1.41), respectively, compared with those in the lowest quartile. The addition of cumulative systolic BP or pulse pressure slightly improved the ability to predict new‐onset AF. Conclusions Higher exposure to cumulative systolic BP, pulse pressure, and mean arterial pressure was significantly associated with increased risk of incident AF.

Abstract Objective The microinflammatory state can influence the occurrence of dialysis-related complications in dialysis patients. Chronic periodontitis (CP), in which plaque biofilm is considered to be the initiating factor, is a chronic infectious disease in the oral cavity. It is still uncertain whether CP affects the microinflammatory state in peritoneal dialysis (PD) and the occurrence of dialysis-related complications. The purpose of this study was to investigate the correlation between the periodontal index and clinical parameters in peritoneal dialysis patients with CP and dialysis-related complications, including peritoneal dialysis-associated peritonitis (PDAP) and cardiovascular and cerebrovascular events (CCEs). Methods This was a retrospective cohort study, and 76 patients undergoing PD were enrolled. Clinical parameters, the occurrence of PD-related complications and periodontitis-related indicators, including the gingival index (GI), plaque index (PLI), probing depth (PPD) and clinical attachment loss (CAL), were collected. Correlation analysis was used to explore the correlation between periodontal or clinical parameters and the occurrence of PD-related complications. Results All the patients had different degrees of periodontitis (mild 9.2%, moderate 72.4%, severe 18.4%); PPD was inversely related to serum albumin (r = − 0.235, p = 0.041); CAL has a positive correlation with serum C-reactive protein (rs = 0.242, p = 0.035); PLI was positively correlated with serum calcium (r = 0.314, p = 0.006). ANOVA, multivariate logistic regression analysis and Kaplan-Meier Survival curve suggested that CAL was a risk factor for the occurrence of PDAP. There was no correlation between periodontal parameters and CCEs or poor prognosis. Conclusion CP is universally present in PD patients, and the presentation of periodontitis influences the systemic inflammatory state in PD patients. CP is a risk factor for PDAP.

Fine-grain and weak-texture magnesium alloys are the long-term development targets of lightweight structural materials. In this study, a new composite asymmetric extrusion (CAE) is developed, which, coupling with an asymmetric die and an asymmetric billet, is proposed to improve the strength–ductility of the Mg-3.8Al-1.1Sn-0.4Ca alloy. The influence of the asymmetric billet on the microstructure and mechanical properties was investigated. The findings revealed that the asymmetric billet can induce greater plastic deformation, resulting in an increase in the cumulative strain and an improved nucleation rate. The CAE sheets exhibit fine grains (4.4 μm) and a weak tilted texture (7.57 mrd). Furthermore, the asymmetric billet results in the microstructure not forming a gradient microstructure under gradient strain along the transverse direction (TD) direction. The CAE sheets exhibited good mechanical properties, with a yield strength (YS) of 253 MPa, ultimate tensile strength (UTS) of 331 MPa, and elongation (EL) of 20%. This development shows promise in achieving high-efficiency, low-cost production of magnesium alloys.

Ceramic waste generated by demolition and manufacturing processes is a kind of widely discharged solid waste; its sustainable use can reduce resource extraction, energy consumption, and carbon emissions, thereby reducing the environmental impact. In this study, ceramic powder and ceramic sand were prepared using waste ceramic wall tiles. By using three water-to-binder ratios of 0.30, 0.32, and 0.34, five ceramic powder replacement rates of 10% to 50%, and completely using ceramic sand as the fine aggregate, specimens with large differences in mechanical properties were prepared. Firstly, the compressive strength was investigated. On this basis, hybrid fibers were employed to strengthen the new matrix material, and its bending resistance was experimentally studied. It was found that the incorporation of ceramic powder reduced the compressive strength of the matrix. The water-binder ratio significantly affects compressive strength at an early age. The effect of PVA fiber on improving the ductility of the new composite is distinct. Increasing the amount of steel fiber can effectively enhance the bending bearing capacity.With a ceramic powder dosage of 50%, the new composite has shown ductile failure characteristics, even with low total fiber content. The bending properties of this new composite material, which makes extensive use of ceramic waste, are well adjustable. The bearing capacity and ductility balance can be achieved with the steel fiber content of 1% and the PVA fiber content of 1.2% to 1.50%.

Abstract Background Data are limited on whether several easily measured indices are independent predictors of type 2 diabetes mellitus (T2DM) in hypertensive patients. This study aimed to assess the association of hypertriglyceridemic-waist phenotype, triglyceride glucose (TyG) index, lipid accumulation product (LAP), and visceral adiposity index (VAI) with T2DM risk in hypertensive patients. Methods This cross-sectional study included 5321 hypertensive patients from the baseline survey of the Guangzhou Heart Study. Face-to-face questionnaire survey, physical examination, and fasting blood sample collection were completed for all subjects. Odds ratio (OR) with 95% confidence interval (95% CI) were calculated by using the logistic regression model. The potential nonlinear relationship was examined using restricted cubic spline regression. Results The prevalence of T2DM was 19.98% among hypertensive patients. After adjusting for confounders, participants with elevated triglyceride levels and enlarged waist circumference (HTGW) were associated with a 2.57-fold risk of T2DM (OR 2.57, 95% CI 2.05, 3.23). When comparing with subjects within the lowest quartile of the indices, those in the highest quartile of TyG, LAP, and VAI were associated with 5.35-fold (95% CI 4.33, 6.64), 2.65-fold (95% CI 2.11, 3.34), and 2.17-fold (95% CI 1.77, 2.67) risk of T2DM after adjusting for confounders. Every 1-unit increment of TyG, LAP, and VAI was associated with 81%, 38%, and 31% increased risk of T2DM, respectively. The nonlinear association was observed for TyG, LAP, and VAI (all P Non-linear

Background: The reported anticoagulation rate may be overestimated among Chinese patients with atrial fibrillation (AF). Therefore, we aimed to understand the current status and time trends of anticoagulation among older people in the Chinese community. Methods: Data were obtained from the physical examination program for the elderly (aged ≥65 years) in Guangzhou. During 2017–2020, a total of 31,829, 58,573, 55,483, and 54,845 older people underwent annual physical examinations, respectively, where their general information, AF-related medical history, and use of oral anticoagulants (OACs) were collected for analysis. Results: From 2017 to 2020, the estimated annual prevalence of older people with nonvalvular atrial fibrillation (NVAF) in Guangzhou was 0.99%, 0.92%, 1.05%, and 1.14%, respectively. In patients with high stroke risk (CHA2DS2-VASc score ≥2 for males or ≥3 for females), the annual anticoagulation rates were 2.83%, 2.05%, 5.29%, and 5.82%, respectively. The proportion of NVAF patients prescribed non-vitamin K antagonist oral anticoagulants (NOACs) increased gradually over the same period (p = 0.004). Males (odds ratios (OR), 1.797; 95% confidence interval (CI), 1.169–2.763; p = 0.008), ages over 75 (OR, 1.858; 95% CI, 1.212–2.849; p = 0.005), low education levels (OR, 1.737; 95% CI, 1.132–2.665; p = 0.011), and lacking the ability for self-care (OR, 4.432; 95% CI, 1.067–18.418; p = 0.041) were less likely to receive OAC therapy. Conclusions: The low anticoagulation rate of older people with NVAF in the Chinese community has not significantly improved in recent years, with only 5.82% of patients with high stroke risk being prescribed OACs. Therefore, it is necessary to establish an appropriate mode of anticoagulant management to improve the current situation.

The chemical diversity of peptides from ribosomal origin is a growing field of research. Here, the authors report the discovery, genomic and biosynthetic investigations of kintamdin, a ribosomally synthesized and post-translationally modified peptides featuring a beta-enamino acid and a bis-thioether macrocyclic motif.

Abstract Objectives This study aimed to investigate the prevalence of congenital heart disease (CHD) among school children in Qinghai province, a high-altitude region in China. Methods A cross-sectional study was conducted among school-aged children in 2019. All subjects completed a survey with a structure questionnaire and underwent CHD screening. CHD was screened by standard physical examination and further confirmed by echocardiography. Multivariate logistic regression were used to estimate the association of CHD prevalence with gender, nationality, and altitude. Results A total of 43,562 children aged 3–19 years participated in the study. The mean (SD) age was 11.2 (3.3) years. 49.7% were boys, and 80.0% were of Tibetan. CHD was identified in 293 children, with an overall prevalence of 6.73 ‰. Among them, 239 were unrecognized CHD, yielding a prevalence of 5.49 ‰. Atrial septal defect accounted for 51.9% of the CHD, followed by patent ductus arteriosus (31.1%), ventricular septal defect (9.9%). The CHD prevalence was significantly higher in female (8 ‰), Han race (18 ‰), children lived in Qumalai county (13 ‰), and children lived in a higher altitude (13 ‰). Female had greater prevalence of total CHD, atrial septal defect, and patent ductus arteriosus, but insignificant difference was observed in ventricular septal defect prvalence than male. In multivariable logistic regression analyses, female (OR, 1.48; 95% CI, 1.17–1.87, P = 0.001), Han population (OR, 3.28; 95% CI, 1.67–6.42, P = 0.001), and higher altitudes (OR, 2.28; 95% CI, 1.74–3.00, P

BackgroundElevated serum total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels are established risk factors for cardiovascular diseases, a leading cause of death in China, especially in aged population. We sought to assess the latest levels of serum lipids, prevalence of dyslipidemia and achievement of LDL-C lowering targets among Chinese aged population.MethodsThe data was obtained from the annual health check and medical records in primary community health institutions of Yuexiu District, Guangzhou, Southern China. A sample of approximately 135,000 participants provides comprehensive estimates of the status of cholesterol level and statins use in older adults in China. Clinical characteristics were compared by different age grades, genders and years. Independent risk factors associated with statin use were determined by stepwise logistic regression analysis.ResultsThe mean levels of TC, HDL-C, LDL-C, TG were 5.39, 1.45, 3.10, and 1.60 mmol/L, respectively, while the prevalence of high TC, high TG, high LDL-C, and low HDL-C were 21.99, 15.52, 13.26, and 11.92%, respectively. Although statin use showed an increasing trend in both participants > 75 years and ≤75 years of age, the achievement of treatment goals fluctuated between 40.94 and 48.47%, and even seemed to have a downward trend. Stepwise multiple logistic regression analysis further indicated that age, medical insurance, ability of self-care, hypertension, stroke, CAD, and high LDL-C were shown to be associated with statins use (P

BackgroundThis study aimed to investigate the associations between multiple glycolipid biomarkers and the risk of obstructive sleep apnea (OSA).MethodsParticipants (10,286) aged from 35 to 74 years old were included in this cross-sectional study from the baseline survey of the Guangzhou Heart Study. OSA was ascertained using both Berlin Questionnaire and STOP-BANG Questionnaire. Fasting blood samples were collected from each participant; fasting blood glucose (FBG) and serum concentrations of high-density lipoprotein cholesterol (HDL-CH), low-density lipoprotein cholesterol (LDL-CH), total cholesterol (TC), and triglyceride (TG) were determined. Odds ratio (OR) with 95% confidence interval (CI) was calculated using the multivariate logistic regression model after adjustment for covariates.ResultsOf the participants included, 15.56% were categorized into the pre-OSA group, and 8.22% into the OSA group. When comparing the highest with the lowest quartiles, HDL-HC was associated with a 22% (OR: 0.78, 95% CI: 0.65–0.94) and 41% (OR: 0.59, 95% CI: 0.45–0.78) reduced risk of pre-OSA and OSA, triglyceride was associated with a 32% (OR 1.32, 95% CI 1.08–1.60) and a 56% (OR 1.56, 95% CI 1.18–2.07) increased risk of pre-OSA and OSA, and FBG was associated with a 1.37-fold (95% CI 1.13–1.67) risk of pre-OSA and 1.38-fold (95% CI 1.03–1.85) risk of OSA. A significant exposure-response trend was observed for HDL-HC, TG, and FBG with both OSA and Pre-OSA (all p

Abstract Background No studies investigated the whole effect of modifiable lifestyle factors on OSA risk. This study aimed to examine the individual and combined effects of lifestyle factors on OSA risk among Chinese adults. Methods This cross-sectional study included 9733 participants aged 35 to 74 years from the baseline survey of Guangzhou Heart Study. OSA was evaluated by Berlin Questionnaire. The healthy lifestyle score (HLS), representing the overall effect of lifestyles, was derived from seven lifestyle factors: active smoking, passive smoking, alcohol, diet, waist-hip ratio, leisure-time physical activity, and mental status. Odds ratio (OR) with 95% confidence interval (CI) was calculated using the multivariate logistic regression model. Results 8107 participants were divided into the non-OSA group and 1626 participants into the OSA group. No passive smoking (OR 0.83, 95% CI 0.74–0.94), healthy waist-hip ratio (OR 0.67, 95% CI 0.58–0.77) and healthy mental status (OR 0.45, 95% CI 0. 29–0.73) were associated with a reduced risk of OSA after adjusting for confounders, while others not. Participants with higher HLS were negatively associated with OSA risk (P -trend

Non-Ribosomal Peptide Synthetases (NRPSs) are responsible for the construction of many types of natural products. Here the authors characterize a key type II thioesterase domain that sheds light on the chain translocation processes of legonmycin NRPSs.

BackgroundTrauma-induced immune dysfunction has been a major barrier to achieving reduced mortality, which is poorly understood. Autophagy is a crucial catabolic mechanism of immune cells during times of stress. Few studies have investigated the immune regulatory effects induced by autophagy after trauma. Here, we use single-cell transcriptomics analysis in a major trauma cohort to demonstrate the dominant role of autophagy in innate immune cells during the early stages of major trauma.MethodSingle-cell transcriptional profiling of peripheral blood mononuclear cells (PBMCs) was performed, which were sampled from three control participants and five major trauma patients within 6 hours of injury. In detail, after single-cell RNA-sequence data processing, cell type annotation and cluster marker identification were performed. A genetic toolbox with 604 autophagy-related genes was used to monitor the autophagy levels in immune cells. In addition, all transcriptome RNA sequencing data obtained from PBMCs in a cohort of 167 major trauma patients were downloaded from gene expression omnibus (GEO) datasets (GSE36809). Key deregulated biological processes and important autophagic hub genes involved in immune cells were identified by weighted gene co-expression network analysis and gene ontology enrichment analysis.ResultsA total of 20,445 differentially expressed genes were identified and five co-expression modules were constructed. Enrichment analysis indicated that activated autophagy is the most important biological process during the early stages of major trauma, and JMY (autophagy-related genes) were identified as hub genes. The single-cell transcriptional profiling of PBMCs demonstrated that all components of adaptive immune cells were significantly decreased, whereas components of innate immune cells (monocytes and neutrophils) were significantly increased in major trauma patients compared with control participants. Activated autophagy was detected in monocytes and neutrophils by monitoring the dynamic transcriptional signature of the autophagy-related genetic toolbox. Biological process analysis shows that antigen uptake, processing presentation, and major histocompatibility complex (MHC) class II protein complex assembly pathways were up-regulated in autophagy-positive monocytes, whereas antigen processing and presentation of endogenous antigen and type I interferon signaling pathways were up-regulated in autophagy-positive neutrophils during the early stages of major trauma.ConclusionOur study demonstrated that autophagy is a biological process crucial to the development of immune disorders in the early stages of major trauma. Furthermore, the results of our study generated a comprehensive single-cell immune landscape for major trauma patients, in which we determined that autophagy profoundly affects the main functions of innate immune cells and provides insight into the cellular basis of immune dysregulation after major trauma.

Abstract. The feasibility and safety of intracardiac echocardiography (ICE)-guided catheter ablation for atrial fibrillation (AF) using a minimal/zero-fluoroscopy approach have recently been reported. This approach helps to reduce ionizing radiation exposure and orthopedic complications resulting from using lead aprons. The objectives of this planned prospective, multicenter randomized controlled trial (RCT) (paroxysmal AF (PAF)-ICE trial; ChiCTR2000033624) are to evaluate the efficacy and safety of ICE-guided minimal-fluoroscopy ablation in patients with PAF and the impact on occupational hazards among lab staff. Patients will be randomized in a 1:1 ratio to 2 groups: minimal fluoroscopy group (n = 216) and traditional approach group (n = 216). In the minimal fluoroscopy group, an ICE catheter will be used for geometry/anatomic construction, transseptal puncture, catheter tracking, and effusion monitoring. Pulmonary vein isolation (PVI) will be performed using an open-irrigated radiofrequency SmartTouch Surround Flow or SmartTouch catheter (Biosense Webster, Diamond Bar, California, USA), and confirmed by a multipolar Lasso or PentaRay catheter (Biosense Webster). In the traditional approach group, an ICE catheter will not be used. Transseptal puncture will be performed under fluoroscopic guidance, with all geometries constructed by mapping the catheters. The primary efficacy endpoint is freedom from AF recurrence (without antiarrhythmic medications) at 12 months after ablation. Other endpoints include duration of lead apron use, measures of intra-procedural efficiency, and peri-procedural complications. This RCT will evaluate the efficacy and safety of ICE-guided minimal-fluoroscopy ablation in patients with PAF, also evaluate the benefits to lab staff (regarding reducing occupational hazards) related to this “minimal/zero-fluoroscopy” and “leadless” mode.

Abstract Aims Fabry disease (FD) is an X‐linked genetic disease caused by mutations in the GLA gene that leads to deficient activity of lysosomal enzymes, accumulation of globotriaosylceramide in multi‐organ systems, and variant clinical manifestations. We aimed to detail the clinical and genetic spectrum of FD in Chinese families. Methods and results Five male probands with unexplained left ventricular hypertrophy and their family members were investigated. Genetic screening was available in 11 subjects of the 5 families, 10 of whom proved to be carriers of either GLA gene mutation, including 3 previous reported missense mutations (c.128G > A, c.811G > A, c.950T > C), 1 novel missense mutation (c.37G > C), and 1 novel deletion mutation (c.1241delT). A total of 17 patients were definitely or possibly diagnosed of FD, given their clinical manifestations and hereditary nature of FD. Echocardiography demonstrated normal cardiac structure and function in six female patients. Electrocardiographic pre‐excitation occurred in 80% (4/5) of men and 16.7% (1/6) of women. Six patients (6/14, 42.9%) had chronic kidney disease with decreased renal function and all were male (6/7, 85.7%). Six patients presented with acroparesthesia, hypohidrosis, or both. Three female patients and two male patients experienced sudden death, and one male patient with the mutation (c.128G > A) died of progressive heart failure, between 41 and 66 years of age. Conclusions We reported five unrelated families of FD with different GLA mutations. Clinical manifestations were highly heterogeneous between male and female patients even within the same family. Female patients showed relatively low risks of structural heart disease and renal insufficiency. However, the long‐term outcomes might be adverse in both sexes. Our study underlines the importance of molecular screening of the GLA gene for early identification and clinical decision making in patients with FD.

Abstract Copper ions (Cu2+) disposed to the environment at massive scale pose severe threat to human health and waste of resource. Electrochemical deionization (EDI) which captures ions by electrical field is a promising technique for water purification. However, the removal capacity and selectivity toward Cu2+ are unsatisfying, yet the recycling of the captured copper in EDI systems is yet to be explored. Herein, an efficient electrochemical copper pump (ECP) that can deliver Cu2+ from dilute brackish water into much more concentrated solutions is constructed using carbon nanosheets for the first time, which works based on reversible electrosorption and electrodeposition. The trade‐off between the removal capacity and reversibility is mediated by the operation voltage. The ECP exhibits a removal capacity of 702.5 mg g−1 toward Cu2+ and a high selectivity coefficient of 64 for Cu2+/Na+ in the presence of multiple cations; both are the highest reported to date. The energy consumption of 1.79 Wh g–1 is among the lowest for EDI of copper. More importantly, the Cu species captured can be released into a 20‐fold higher concentrated solution. Such a high performance is attributed to the optimal potential distribution between the two electrodes that allows reversible electrodeposition and efficient electrosorption.

BackgroundAdherence to a healthy lifestyle could reduce the risk of hypertension and diabetes in general populations; however, whether the associations exist in subjects with dyslipidemia remains unclear. This study aimed to investigate the integrated effect of lifestyle factors on the risk of hypertension, type 2 diabetes mellitus (T2DM), and their comorbidity among subjects with dyslipidemia.MethodsIn total of 9,339 subjects with dyslipidemia were recruited from the baseline survey of the Guangzhou Heart Study. A questionnaire survey and medical examination were performed. The healthy lifestyle score (HLS) was derived from five factors: smoking, alcohol drinking, diet, body mass index, and leisure-time physical activity. Odds ratios (ORs) with 95% confidence interval (95% CI) were calculated by using the logistic regression model and the multinomial logistic regression after adjusting for confounders.ResultsThe prevalence of hypertension, T2DM, and their comorbidity was 47.65, 16.02, and 10.10%, respectively. Subjects with a higher HLS were associated with a lower risk of hypertension, T2DM, and their comorbidity. In comparison to the subjects with 0–2 HLS, the adjusted ORs for subjects with five HLS was 0.48 (95% CI: 0.40–0.57) and 0.67 (95% CI: 0.54–0.84) for hypertension and T2DM. Compared with subjects with 0-2 HLS and neither hypertension nor T2DM, those with five HLS had a lower risk of suffering from only one disease (OR: 0.48, 95% CI: 0.40–0.57) and their comorbidity (OR: 0.35, 95% CI: 0.26–0.47).ConclusionsThe results suggest that the more kinds of healthy lifestyle, the lower the risk of hypertension, T2DM, and their comorbidity among subjects with dyslipidemia. Preventive strategies incorporating lifestyle factors may provide a more feasible approach for the prevention of main chronic diseases.

The oil reserves of global basement reservoirs are 248 × 108 t and natural gas reserves are 2681 × 108 m3; they are crucial links in the future oil and natural gas exploration field and play an irreplaceable role in increasing oil and natural gas reserves and production. Based on research on the definition and classification of basement reservoirs, this study dissected three major basement reservoirs in China (i.e., the Dongping region located in the Qaidam Basin, the Bozhong 19-6 gas field located the Bohai Bay Basin, and the Central Uplift area of the Songliao Basin). The geological conditions and controlling factors of oil and natural gas accumulation in basement reservoirs in China are summarized. The results of this study are as follows: (1) Basement reservoirs can be classified into three distinct types, namely, the weathered carapace type, weathered inner type, and weathered composite type. They are characterized by a large burial depth, strong concealment, and huge reserves and are mostly distributed at the margins of continental plates and in zones with stratum intensive tectonic activity; (2) Basement reservoirs in different basins have different controlling factors. The basement reservoir in the Dongping region, located in the Qaidam Basin, has favorable geological conditions with laterally connected sources and reservoirs. In this reservoir, oil and natural gas have transferred along faults and unconformities to accumulate in uplifted areas, forming a weathered carapace-type basement reservoir controlled by structures. The Bozhong 19-6 gas field, which is situated in the Bohai Bay Basin, has favorable multiple hydrocarbon supplies of source rocks. Under the communication of faults and cracks, oil resources form a weathered inner type basement reservoir. In the Central Uplift area of the Songliao Basin, the basement reservoir exhibits a dual-sided hydrocarbon supply condition from the uplift. In this reservoir, oil and natural gas have transferred to traps through the fault and inner fracture system and have been properly preserved thanks to the extensive overlying cap rocks. It can be concluded that, after being attenuated by millions of years of weathering and leaching, basement rocks can form large-scale and medium-scale basement reservoirs with reserves of more than 100 million barrels in the presence of favorable geological conditions, such as a multi-directional hydrocarbon supply, a high brittle mineral content in the reservoirs, diverse reservoir spaces, and high-quality cap rocks.

BackgroundSex hormones are associated with many cardiovascular risk factors, but their effects on atrial fibrillation (AF) incidence remain unclear. This systematic review and meta-analysis aimed to evaluate the association of circulating sex hormones with AF risk by pooling available data from observational studies.MethodsA systematic literature search for pertinent articles with case-control and cohort designs was conducted via five databases up to 7 July 2021. A meta-analysis with six cohort studies was conducted separately on men and women. Adjusted relative risk (RR) with a 95% confidence interval (CI) was derived by comparing the highest with the lowest levels of a specific sex hormone and by using a random-effect or fixed-effect model. Heterogeneity was tested using the I2 statistic and the Q-test.ResultsA total of six cohort studies and four case-control studies were included. In a meta-analysis of cohort studies, dehydroepiandrosterone sulfate (DHEAS) was associated with a decreased risk of AF in men (RR: 0.729, 95% CI: 0.559–0.952, I2 = 50.0%, P–heterogeneity = 0.157) after combining results from two cohort studies; total testosterone was not associated with any risk of AF in men and postmenopausal women, and AF risk was not associated with estradiol in men after synthesizing available studies.ConclusionThis study indicates that a higher endogenous DHEAS level was associated with a lower AF risk in men, whereas total testosterone and estradiol were not associated with AF risk. Longitudinal studies with multiple monitoring are needed to further promulgate the relationship between various circulating sex hormones and AF risk.

BackgroundLimited evidence was available on the association of the integrated effect of multidimensional lifestyle factors with mortality among Chinese populations. This cohort study was to examine the effect of combined lifestyle factors on the risk of mortality by highlighting the number of healthy lifestyles and their overall effects.MethodsA total of 11,395 participants from the Guangzhou Heart Study (GZHS) were followed up until 1 January 2020. Individual causes of death were obtained from the platform of the National Death Registry of China. The healthy lifestyle index (HLI) was established from seven dimensions of lifestyle, and lifestyle patterns were extracted from eight dimensions of lifestyle using principal component analysis (PCA). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated using the Cox proportional hazard regression model.ResultsDuring 35,837 person-years of follow-up, 184 deaths (1.61%) were observed, including 64 from cardiovascular disease. After adjustment for confounders, HLI was associated with a 50% (HR: 0.50, 95% CI: 0.25–0.99) reduced risk of all-cause mortality when comparing the high (6–7 lifestyle factors) with low (0–2 lifestyle factors) categories. Three lifestyle patterns were defined and labeled as pattern I, II, and III. Lifestyle pattern II with higher factor loadings of non-smoking and low-level alcohol drinking was associated with a decreased risk of all-cause mortality (HR: 0.63, 95% CI: 0.43–0.92, P–trend = 0.023) when comparing the high with low tertiles of pattern score, after adjustment for confounders. Every 1-unit increment of pattern II score was associated with a decreased risk (HR: 0.97, 95% CI: 0.95–0.99) of all-cause mortality. The other two patterns were not associated with all-cause mortality, and the association of cardiovascular mortality risk was observed with neither HLI nor any lifestyle pattern.ConclusionThe results suggest that the more dimensions of the healthy lifestyle the lower the risk of death, and adherence to the lifestyle pattern characterized with heavier loading of non-smoking and low-level alcohol drinking reduces the risk of all-cause mortality. The findings highlight the need to consider multi-dimensional lifestyles rather than one when developing health promotion strategies.

ObjectiveThis study was conducted to evaluate the association of the risk of all-cause mortality with habitual physical activity (HPA) and its different domains among Chinese adults.MethodsA total of 11,994 participants from the Guangzhou Heart Study were followed up until 1 January 2020. Information on HPA, including leisure-time physical activity (LTPA) and commute activity, was collected using a modified Global Physical Activity Questionnaire. Individual cause of death was obtained from the National Death Registry of China. Cox proportional hazards regression model was used to estimate hazard ratio (HR) and 95% confidence interval (CI) after adjustment for covariates.ResultsDuring 37,715 person-years of follow-up, 208 deaths (1.73%) were observed. When compared with the highest with the lowest exposure tertiles, HPA and LTPA were associated with 34% (HR: 0.66, 95% CI: 0.46–0.95) and 30% (HR: 0.70, 95% CI: 0.49–0.99) reduced risk of all-cause mortality after adjustment for covariates. Commute activity was not associated with mortality risk. For the specific component of LTPA, we found that every 1 MET-h/week increment of the housework was associated with a 1% (HR: 0.99, 95% CI: 0.98–0.99) decreased mortality risk, and performing brisk walking/health exercises/Yangko was associated with a 46% reduced mortality risk (HR: 0.54, 95% CI: 0.29–0.99).ConclusionThis study suggests that a higher level of HPA and LTPA was associated with a lower risk of all-cause mortality. Our findings suggest people to perform HPA, especially LTPA, as a strategy for mortality reduction and health promotion.

Non-ribosomal peptides are a group of structurally diverse natural products with various important therapeutic and agrochemical applications. Bacterial pyrrolizidine alkaloids (PAs), containing a scaffold of two fused five-membered ring system with a nitrogen atom at the bridgehead, have been found to originate from a multidomain non-ribosomal peptide synthetase to generate indolizidine intermediates, followed by multistep oxidation, catalysed by single Bayer-Villiger (BV) enzymes, to yield PA scaffolds. Although bacterial PAs are rare in natural product inventory, bioinformatics analysis suggested that the biosynthetic gene clusters (BGCs) that are likely to be responsible for the production of PA-like metabolites are widely distributed in bacterial genomes. However, most of the strains containing PA-like BGCs are not deposited in the public domain, therefore preventing further assessment of the chemical spaces of this group of bioactive metabolites. Here, we report a genomic scanning strategy to assess the potential of PA metabolites production in our culture collection without prior knowledge of genome information. Among the strains tested, we found fifteen contain the key BV enzymes that are likely to be involved in the last step of PA ring formation. Subsequently one-strain-many-compound (OSMAC) method, supported by a combination of HR-MS, NMR, SMART 2.0 technology, and GNPS analysis, allowed identification and characterization of a new [5 + 7] heterobicyclic carbamate, legoncarbamate, together with five known PAs, bohemamine derivatives, from Streptomyces sp. CT37, a Ghanaian soil isolate. The absolute stereochemistry of legoncarbamate was determined by comparison of measured and calculated ECD spectra. Legoncarbamate displays antibacterial activity against E. coli ATCC 25922 with an MIC value of 3.1 μg/mL. Finally, a biosynthetic model of legoncarbamate and other bohemamines was proposed based on the knowledge we have gained so far.

Abstract Background The relationship between malnutrition-inflammation-atherosclerosis syndrome (MIAS) and self-management ability has not been previously revealed even though both play an important role in the management of peritoneal dialysis (PD) patients. Methods In total, 93 patients were enrolled in this study. A self-management questionnaire was used for the evaluation of self-management ability. The identification of MIAS was based on one or more of the following three conditions: C-reactive protein (CRP)≥10 mg/L, malnutrition–inflammation score (MIS)> 7, and the presence of atherosclerosis-related medical records. The possible association between different self-management abilities and MIAS was analyzed with a Spearman correlation analysis. Results There were 40 (43.0%) patients in the atherosclerosis group, and 38 (40.9%), 38 (40.9%), 10 (10.8%), and 7 (7.5%) patients in the MIAS0, MIAS1, MIAS2, and MIAS3 groups, respectively. The group with a score above the mean score of the Dialysis Effect Evaluation and Monitoring dimension had a fewer number of hospitalizations, higher albumin levels, lower MIS scores, a lower level of IL-6, and a lower number of MIAS factors. The Pearson and Spearman correlation analyses also revealed that this dimension was negatively correlated with the MIAS, MIS, IL-6, BNP, number of hospitalizations, and age and positively associated with albumin and prealbumin. Conclusion The Dialysis Effect Evaluation and Monitoring dimension of the self-management scale for PD patients is closely linked to the MIAS, and a better dialysis effect evaluation and monitoring capacity results in a decreased likelihood of exposure to malnutrition and inflammation. Trial registration Chinese Clinical Trial Registry: ChiCTR2000035525 ( http://www.chictr.org.cn/showproj.aspx?proj=58110 ), registered August 13, 2020.

Currently available mitochondria-targeted fluorescent dyes emit only one color in the visible or NIR-I and their applications are limited. Here, the authors develop upconversion mitochondria-targeted NIR-II fluorophores for synchronous upconversion-mitochondria-targeted cell imaging, in vivo NIR-II osteosarcoma imaging and photothermal efficiency

AimsThe integrated management was evidenced to improve the hospitalization and its associated complications in patients with atrial fibrillation (AF), but the strategies of integrated care varied and results were inconsistent. This systematic review and meta-analysis aimed to evaluate the effect of integrated care on AF-related outcomes with comparison with usual care.MethodsPubMed, Embase, and Web of Science were searched for articles published until 10th January 2022. Eligible studies were randomized controlled trials to study the effect of integrated care on AF-related outcomes. Meta-analysis with a random-effect model was used to calculate risk ratio (RR) and 95% confidence interval (CI) by comparing the integrated care with usual care.ResultsA total of five studies with 6,486 AF patients were selected. By synthesizing available data, integrated care effectively reduced the risk of all-cause mortality (RR = 0.54, 95% CI = 0.42–0.69), cardiovascular hospitalization (RR = 0.72, 95% CI = 0.55–0.94), and cardiovascular mortality (RR = 0.52, 95% CI = 0.36–0.78) when compared with usual care; however, there was no superior effect on preventing AF-related hospitalization (RR = 0.86, 95% CI = 0.72–1.02), cerebrovascular events (RR = 1.13, 95% CI = 0.75–1.70), and major bleeding (RR = 1.29, 95% CI = 0.86–1.94) when comparing integrated care with usual care.ConclusionIntegrated care can reduce the risk of all-cause mortality, cardiovascular mortality, and cardiovascular hospitalizations in AF patients compared with usual care, while the benefit was not observed in other outcomes.

Background: C-reactive protein (CRP), as a non-specific inflammatory marker, is a predictor of the occurrence and prognosis of various arrhythmias. It is still unknown whether electrocardiographic features are altered in patients with inflammation.Objectives: To evaluate the performance of a deep learning model in detection of CRP levels from the ECG in patients with sinus rhythm.Methods: The study population came from an epidemiological survey of heart disease in Guangzhou. 12,315 ECGs of 11,480 patients with sinus rhythm were included. CRP > 5mg/L was defined as high CRP level. A convolutional neural network was trained and validated to detect CRP levels from 12 leads ECGs. The performance of the model was evaluated by calculating the area under the curve (AUC), accuracy, sensitivity, specificity, and balanced F Score (F1 score).Results: Overweight, smoking, hypertension and diabetes were more common in the High CRP group (p < 0.05). Although the ECG features were within the normal ranges in both groups, the high CRP group had faster heart rate, longer QTc interval and narrower QRS width. After training and validating the deep learning model, the AUC of the validation set was 0.86 (95% CI: 0.85–0.88) with sensitivity, specificity of 89.7 and 69.6%, while the AUC of the testing set was 0.85 (95% CI: 0.84–0.87) with sensitivity, specificity of 90.7 and 67.6%.Conclusion: An AI-enabled ECG algorithm was developed to detect CRP levels in patients with sinus rhythm. This study proved the existence of inflammation-related changes in cardiac electrophysiological signals and provided a noninvasive approach to screen patients with inflammatory status by detecting CRP levels.

BackgroundPsychological problems are prevalent in the general population, and their impacts on sleep health deserve more attention. This study was to examine the associations of OSA risk with depression, anxiety, and life events in a Chinese population.MethodsA total of 10,287 subjects were selected from the Guangzhou Heart Study. Berlin Questionnaire (BQ) was used to ascertain the OSA. The Center for Epidemiologic Studies Depression Scale (CES-D) and Zung's self-rating anxiety scale (SAS) were used to define depression and anxiety. A self-designed questionnaire was used to assess life events. Odds ratio (OR) with 95% confidence interval (95% CI) was calculated by using the logistic regression model.ResultsThere were 1,366 subjects (13.28%) classified into the OSA group. After adjusting for potential confounders, subjects with anxiety (OR: 2.60, 95% CI: 1.63–4.04) and depression (OR: 1.91, 95% CI: 1.19–2.97) were more likely to have OSA. Subjects suffering from both anxiety and depression were associated with a 3.52-fold (95% CI: 1.88–6.31) risk of OSA. Every 1-unit increment of CES-D score and SAS index score was associated with 13% (95% CI: 1.11–1.15) and 4% (95% CI: 1.03–1.06) increased risk of OSA. Neither positive life events nor adverse life events were associated with OSA.ConclusionsThe results indicate that depression and anxiety, especially co-occurrence of both greatly, were associated with an increased risk of OSA. Neither adverse life events nor positive life events were associated with any risk of OSA. Screening for interventions to prevent and manage OSA should pay more attention to depression and anxiety.

In the ongoing coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), natural killer T (NKT) cells act as primary initiators of immune responses. However, a decrease of circulating NKT cells has been observed in COVID-19 different stages, of which the underlying mechanism remains to be elucidated. Here, by performing single-cell RNA sequencing analysis in three large cohorts of COVID-19 patients, we found that increased expression of Tim-3 promotes depletion of NKT cells during the progression stage of COVID-19, which is associated with disease severity and outcome of patients with COVID-19. Tim-3+ NKT cells also expressed high levels of CD147 and CD26, which are potential SARS-CoV-2 spike binding receptors. In the study, Tim-3+ NKT cells showed high enrichment of apoptosis, higher expression levels of mitochondrial genes and caspase genes, with a larger pseudo time value. In addition, Tim-3+ NKT cells in COVID-19 presented a stronger capacity to secrete IFN-γ, IL-4 and IL-10 compared with healthy individuals, they also demonstrated high expression of co-inhibitory receptors such as PD-1, CTLA-4, and LAG-3. Moreover, we found that IL-12 secreted by dendritic cells (DCs) was positively correlated with up-regulated expression of Tim-3 in NKT cells in COVID-19 patients. Overall, this study describes a novel mechanism by which up-regulated Tim-3 expression induced the depletion and dysfunction of NKT cells in COVID-19 patients. These findings not only have possible implications for the prediction of severity and prognosis in COVID-19 but also provide a link between NKT cells and future new therapeutic strategies in SARS-CoV-2 infection.

Uncontrolled severe acute respiratory syndrome-coronavirus (SARS-CoV)-2 infection is closely related to disorders of the innate immune and delayed adaptive immune systems. Dendritic cells (DCs) “bridge” innate immunity and adaptive immunity. DCs have important roles in defending against SARS-CoV-2 infection. In this review, we summarize the latest research concerning the role of DCs in SARS-CoV-2 infection. We focus on the complex interplay between DCs and SARS-CoV-2: pyroptosis-induced activation; activation of the renin–angiotensin–aldosterone system; and activation of dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin. We also discuss the decline in DC number, the impaired antigen-presentation capability, and the reduced production of type-I interferon of DCs in severe SARS-CoV-2 infection. In addition, we discuss the potential mechanisms for pathological activation of DCs to understand the pattern of SARS-CoV-2 infection. Lastly, we provide a brief overview of novel vaccination and immunotherapy strategies based on DC targeting to overcome SARS-CoV-2 infection.

ObjectiveThe relationship between physical activity (PA) and the risk of frailty has not reached a conclusive result. This systematic review with meta-analysis aimed to evaluate the effect of PA on the onset of frailty in the community-dwelling middle and older age adults by pooling data from cohort studies.MethodsA systematic literature search was performed via PubMed, Embase, and Web of Science up to June 01, 2021. Pooled adjusted effect estimates (ES) with 95% confidence interval (CI) were calculated by using the random-effect model and by comparing the highest with lowest levels of PA. Heterogeneity was tested using the I2 statistic and Q-test. The quality of evidence was evaluated by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.ResultsA total of ten cohort studies with 14 records were selected, and the GRADE approach classified the quality of evidence as low. In comparison with the lowest level of PA, the highest level of PA was associated with 41% decreased odds of frailty (ES: 0.59, 95% CI: 0.51-0.67; I2 = 70.0%, P-heterogeneity < 0.001) after pooling results from included studies. In stratified analysis by frailty assessment approach, the highest level of PA was significantly associated with 37% (ES 0.63, 95% CI: 0.52-0.77, 49% (ES: 0.51, 95% CI: 0.41-0.63), and 30% (ES: 0.70, 95% CI: 0.65-0.75) reduced odds of frailty when pooling studies using criteria of physical frailty, multidimensional model, and accumulation of disability, respectively. Stratified analyses further by PA indicators and PA assessment tools yielded similar protective effects in any subgroups.ConclusionsThis study with moderate-certainty evidence shows that a higher level of PA was associated with lower odds of frailty, and the benefits of PA for frailty prevention were independent of frailty assessment tools, PA indicators, and PA assessment methods. Findings from this study may help implement active exercise strategies to prevent frailty.

BackgroundCatheter ablation target at the site with large His activation in the left ventricle poses a high risk of atrioventricular (AV) block. We aimed to identify far-field (FF) and near-field (NF) His activation at left upper septum (LUS).MethodsThree-D mapping of the aortic root and left ventricle was performed in 12 dogs. Two sites located at either the base or apex of the triangle interposed between the hinges of the the noncornary coronary cusp (NCC) - right coronary cusp (RCC) were chosen for a single radiofrequency (RF) application. Bipolar and unipolar pacing with different outputs at both sites was attempted to discern NF and FF His activation.ResultsThe sites chosen for NF and FF ablation were located at the base and apex of the triangle, which were 8.03 ± 1.18 mm (group 1) and 3.42 ± 0.61 mm (group 2) away from the RCC-NCC junction. Lower A/V ratios were found in group 1. Pacing could not differentiate NF from FF His activation. In group 1, ablation resulted in III degree AV block in all 6 dogs, whereas neither PR prolongation nor AV block occurred in group 2. Pathologic examination of group 1 showed complete/partial necrosis of the His bundle (HB) and left bundle branch in all 6 dogs. In group 2, no necrosis of the HB was seen in the 6/6 dogs.ConclusionAnatomical localization in the triangle of RCC-NCC junction can help differentiate NF from FF His activation.

Indole-containing acyloins are either key intermediates of many antimicrobial/antiviral natural products or building blocks in the synthesis of biologically active molecules. As such, access to structurally diverse indole-containing acyloins has attracted considerable attention. In this report, we present a pilot study of using biotransformation to provide acyloins that contain various indole substituents. The biotransformation system contains the tryptophan synthase standalone β-subunit variant, PfTrpB6, generated from directed evolution in the literature; a commercially available L-amino acid oxidase (LAAO); and the thiamine-diphosphate (ThDP)-dependent enzyme NzsH, encoded in the biosynthetic gene cluster (nzs) of the bacterial carbazole alkaloid natural product named neocarazostatin A. The utilization of the first two enzymes, the PfTrpB variant and LAAO, is designed to provide structurally diverse indole 3-pyruvate derivatives as donor substrates for NzsH-catalysed biotransformation to provide acyloin derivatives. Our results demonstrate that NzsH displays a considerable substrate profile toward donor substrates for production of acyloins with different indole ring systems, suggesting that NzsH could be further explored as a potential biocatalyst via directed evolution to improve the catalytic efficiency in the future.

Interleukin-7 (IL-7), a molecule known for its growth-promoting effects on progenitors of B cells, remains one of the most extensively studied cytokines. It plays a vital role in health maintenance and disease prevention, and the congenital deficiency of IL-7 signaling leads to profound immunodeficiency. IL-7 contributes to host defense by regulating the development and homeostasis of immune cells, including T lymphocytes, B lymphocytes, and natural killer (NK) cells. Clinical trials of recombinant IL-7 have demonstrated safety and potent immune reconstitution effects. In this article, we discuss IL-7 and its functions in immune cell development, drawing on a substantial body of knowledge regarding the biology of IL-7. We aim to answer some remaining questions about IL-7, providing insights essential for designing new strategies of immune intervention.

Chronic kidney disease (CKD) affects 8–13% of the global population and has become one of the largest burdens on healthcare systems around the world. Peritoneal dialysis is one of the ultimate treatments for patients with severe CKD. Recently, increasing severe periodontal problems have been found in CKD patients. Periodontitis has been identified as a new variable risk factor for CKD. The aim of this study was to investigate the periodontal status and severity of alveolar bone loss in CKD patients with peritoneal dialysis (PD). One hundred and six patients undergoing PD (PD group) and 97 systemically healthy periodontitis patients (control group) were enrolled. The differences in the dimensions of the alveolar bone between two groups were compared, and the distribution of alveolar bone defects was analyzed by cone-beam computed tomography (CBCT). Gingival index (GI), plaque index (PLI), periodontal probing depth (PPD), and attachment loss (AL) were recorded. The levels of inflammatory factors in gingival crevicular fluid were assessed by ELISA. Compared to control group, there was a higher degree of alveolar bone loss in maxillary premolars, maxillary 2nd molar and mandibular 1st molar in patients with PD (p < 0.05). A comparison of bone loss in different sites revealed that the area with the highest degree of bone loss were on the mesial-buccal, mid-buccal, distal-buccal, and mesial-lingual site in PD patients. The expression levels of inflammatory factors were higher in PD group (p < 0.01). In conclusion, PD patients presented more severe periodontal and inflammatory status than systemically healthy periodontitis patients. The loss of the alveolar bone differed between the two groups. Different sites and teeth exhibited a diverse degree of bone loss. This study highlights that clinicians should pay close attention to periodontal status of peritoneal dialysis patients and provides a new thinking to improve healthcare for CKD.

Objectives: To study the benefit of adenosine triphosphate (ATP) in evaluating ablation endpoints of accessory pathways (AP) and subsequent long-term prognosis.Methods: We reviewed consecutive patients with supraventricular tachycardias due to APs that underwent radiofrequency catheter ablation (RFCA) from January 2016 to September 2018 in our center. The patients were divided into two groups: the ATP group (who had passed both the ATP test and PES after ablation as the endpoint) and the non-ATP group (who had passed PES only after ablation as the endpoint). We reviewed the patients' intra-cardiac electrograms and analyzed their long-term outcomes.Results: In total, 1,343 patients underwent successful RFCA. There were 215 patients in the ATP group with one lost to follow-up. There were 1,128 patients in the non-ATP group with 39 lost to follow-up. Twenty-three patients in the ATP group demonstrated additional electrophysiological entities due to ATP administration, including reappearance of the ablated APs in 16 patients, discovery of PES-undetected APs in 5, induction of atrial fibrillation in 5, premature atrial contractions in 1, and premature ventricular contractions in another. During the 7 to 39 months (average 24.4 ± 9.5 months) follow-up, the recurrence rate was 8.41% (18/214) in the ATP group and 6.80% (74/1,084) in the non-ATP group. In subjects with recurrence, 14 patients (14/18 = 77.8%) in the ATP group and 50 patients (50/74 = 67.6%) in the non-ATP group accepted redo ablations. Among the ATP-group, all the 14 redo APs were the old ones as before. Among the non-ATP-group, redo ablations confirmed that 39 APs were the old ones, while 20 APs were newly detected ones which had been missed previously. The difference in recurrent AP locations confirmed by redo procedures between the two groups was significant (p = 0.008). In the non-ATP group, 20 (40%) of redo cases were proven to have multiple APs, while 33 (3.3%) cases who did not suffer from recurrence had multiple APs. Existences of multiple APs in recurred cases were significantly higher than that in non-recurred ones in the non-ATP group (p < 0.001), while there was no such difference in the ATP group (p = 0.114).Conclusions: The existence of multiple APs was more common in recurrent cases if ATP was not used for confirmation of ablation endpoints. ATP probably has additional value over PES alone by detecting weak AP conductions. ATP can evoke atrial and ventricular arrhythmias.

Background: The feasibility and safety of left bundle branch pacing (LBBP) in patients with conduction diseases following prosthetic valves (PVs) have not been well described.Methods: Permanent LBBP was attempted in patients with PVs. Procedural success and intracardiac electrical measurements were recorded at implant. Pacing threshold, complications, and echocardiographic data were assessed at implant and follow-up visit.Results: Twenty-two consecutive patients with atrioventricular (AV) conduction disturbances (10 with AV nodal block and 12 with infranodal block) underwent LBBP. The PVs included aortic valve replacement (AVR) in six patients, mitral valve repair or replacement (MVR) with tricuspid valve ring (TVR) in four patients, AVR with TVR in one patient, AVR with MVR plus TVR in three patients, transcatheter aortic valve replacement (TAVR) in five patients, and MVR alone in three patients. LBBP succeeded in 20 of 22 (90.9%) patients. LBB potential was observed in 15 of 22 (68.2%) patients, including 10 of 15 (66.7%) patients with AVR/TAVR and five of seven (71.4%) patients without AVR/TAVR. AVR and TVR served as good anatomic landmarks for facilitating the LBBP. The final sites of LBBP were 17.9 ± 1.4 mm inferior to the AVR and 23.0 ± 3.2 mm distal and septal to the TVR. The paced QRS duration was 124.5 ± 13.8 ms, while the baseline QRS duration was 120.0 ± 32.5 ms (P = 0.346). Pacing threshold and R-wave amplitude at implant were 0.60 ± 0.16 V at 0.5 ms and 11.9 ± 5.5 mV and remained stable at the mean follow-up of 16.1 ± 10.8 months. No significant exacerbation of tricuspid valve regurgitation was observed compared to baseline.Conclusion: Permanent LBBP could be feasibly and safely obtained in the majority of patients with PVs. The location of the PV might serve as a landmark for guiding the final site of the LBBP. Stable pacing parameters were observed during the follow-up.

Abstract Background To estimate the prevalence of elevated blood glucose level (EBG, including type 2 diabetes mellitus and impaired fasting glucose), and its association with non-valvular atrial fibrillation (NVAF) in Guangzhou, China. Methods The population-based follow-up Guangzhou Heart Study collected baseline data from July 2015 to August 2017 among 12,013 permanent residents aged > 35 from 4 Guangzhou districts. Two streets (Dadong and Baiyun) in the Yuexiu District, and one street (Xiaoguwei) and two towns (Xinzao and Nancun) in the Panyu District were chosen as representative of urban and rural areas, respectively. Each participant completed a comprehensive questionnaire, and underwent physical examination, blood sample collection for laboratory testing, electrocardiography, and other evaluations. Multivariable logistic regression analyses were used to estimate the independent association between hyperglycemia and NVAF prevalence. Results The prevalence of EBG in overall study population was 29.9%. Compared with residents without EBG, the odds ratio (OR) for AF among residents with EBG was significantly higher (1.94, 95% confidence interval [CI]: 1.40–2.70, P 35 years and associated with a multivariate adjusted increase in prevalence of NVAF overall and in women.

Abstract Background Biomarkers have been related to the arrhythmia recurrence following catheter ablation (CA) of atrial fibrillation (AF). We hypothesized that concurrent measurement of several biomarkers would additively improve their predictive value. Methods One thousand four hundred and ten consecutive AF patients (68% male; 57.2 ± 11.6 years) undergoing CA were enrolled. Baseline characteristics, serum B type brain natriuretic peptide (BNP) and high sensitivity C reactive protein (hsCRP), estimated glomerular filtration rate (eGFR), ablation parameters, arrhythmia data at discharge, 1, 3, 6, and then every 6 months post CA were collected. Follow‐up ended when arrhythmia recurred or until 31st December 2016. Results Three hundred and sixty‐five (25.9%) patients had arrhythmia recurrence post‐CA during a mean follow‐up of 20.7 ± 8.8 months. BNP, hsCRP, and eGFR levels and their cut‐off values of 237.45 pg/mL, 1.6 mg/dL, and 82.5 mL/min/1.73 m2 were good predictors for AF recurrence (all P < 0.01). On multivariate analysis, increasing BNP and hsCRP, decreasing eGFR, gender, and early recurrence (ER) were independent predictors of AF recurrence (all P < 0.01). Compared to BNP alone, BNP plus eGFR or both eGFR and CRP showed incrementally better predictive values (ROC comparisons, all P < 0.01). Similar findings were evident in the subgroups of patients with paroxysmal or nonparoxysmal AF. Conclusion Measurement of BNP, CRP, and eGFR were incrementally additive to clinical risk factors in a cumulative manner to improve prediction of arrhythmia recurrence post‐CA of AF. The implications of poor arrhythmia outcome in AF patients with multiple abnormal biomarkers pre‐CA procedure may help with patient selection and inform the likelihood of success or the need of more complicated CA procedure(s).

Background: Left atrial enlargement (LAE) can independently predict the development of a variety of cardiovascular diseases.Objectives: This study sought to develop an artificial intelligence approach for the detection of LAE based on 12-lead electrocardiography (ECG).Methods: The study population came from an epidemiological survey of heart disease in Guangzhou. Elderly people (3,391) over 65 years old who had both 10-s 12 lead ECG and echocardiography were enrolled in this study. The left atrial (LA) anteroposterior diameter >40 mm on echocardiography was diagnosed as LAE, and the LA anteroposterior diameter was indexed by body surface area (BSA) to classify LAE into different degrees. A convolutional neural network (CNN) was trained and validated to detect LAE from normal ECGs. The performance of the model was evaluated by calculating the area under the curve (AUC), accuracy, sensitivity, specificity, and F1 score.Results: In this study, gender, obesity, hypertension, and valvular heart disease seemed to be related to left atrial enlargement. The AI-enabled ECG identified LAE with an AUC of 0.949 (95% CI: 0.911–0.987). The sensitivity, specificity, accuracy, precision, and F1 score were 84.0%, 92.0%, 88.0%, 91.3%, and 0.875, respectively. Physicians identified LAE with sensitivity, specificity, accuracy, precision, and F1 scores of 38.0%, 84.0%, 61.0%, 70.4%, and 0.494, respectively. In classifying LAE in different degrees, the AUCs of identifying normal, mild LAE, and moderate-severe LAE ECGs were 0.942 (95% CI: 0.903–0.981), 0.951 (95% CI: 0.917–0.987), and 0.998 (95% CI: 0.996–1.00), respectively. The sensitivity, specificity, accuracy, positive predictive value, and F1 scores of diagnosing mild LAE were 82.0%, 92.0%, 88.7%, 89.1%, and 0.854, while the sensitivity, specificity, accuracy, positive predictive value, and F1 scores of diagnosing moderate-severe LAE were 98.0%, 84.0%, 88.7%, 96.1%, and 0.969, respectively.Conclusions: An AI-enabled ECG acquired during sinus rhythm permits identification of individuals with a high likelihood of LAE. This model requires further refinement and external validation, but it may hold promise for LAE screening.

Objectives: Although the latest international guidelines recommend the use of uninterrupted non-vitamin K antagonist oral anticoagulants (NOAC) during atrial fibrillation (AF) ablation, it does not reflect current clinical practice, as most centers still use a minimally interrupted NOAC strategy. The purpose of this study was to evaluate the safety and effectiveness of minimally interrupted NOAC compared with bridging therapy and uninterrupted vitamin K antagonist (VKA) for nonvalvular AF ablation.Patients and Methods: A total of 4520 patients who underwent AF ablation between January 2010 and December 2018 were included in the analysis. According to their periprocedural anticoagulation strategies, patients were divided into three groups: Bridging heparin group (n = 1848); Uninterrupted VKA group (n = 796) and Minimally interrupted NOAC group (Total n = 1876; dabigatran: n = 865; rivaroxaban, n = 1011). A combined complication endpoint (CCE) as composed of any bleeding complications and thromboembolic events was analyzed.Results: Rates of thromboembolisms were similar among the three groups (0.22% for Bridging heparin group, 0.25% for Uninterrupted VKA group, and 0.11% for Minimally interrupted NOAC group, p = 0.626). There was a significant difference among the three groups for the incidence of overall bleeding events (8.50% for Bridging heparin group, 4.52% for Uninterrupted VKA group, and 2.67% for Minimally interrupted NOAC group, p < 0.001). A significant difference of CCE rates was shown in the Minimally interrupted NOAC group as compared with the Uninterrupted VKA group (2.77 vs. 4.77%, p = 0.008) and the Bridging heparin group (2.77 vs. 8.71%, p < 0.001). There was no significant difference in CCE rates among the different NOACs (dabigatran 2.89% vs. rivaroxaban 2.67%, p = 0.773).Conclusions: In patients undergoing AF ablation, minimally interrupted NOACs during the periprocedural period appears safer and equally effective when compared to the bridging heparin and uninterrupted VKA therapy.

Background: Obesity or overweight is related to worse outcomes in patients with atrial fibrillation (AF) following catheter ablation (CA). The role of being underweight in relation to recurrent arrhythmias post AF ablation is less certain. We conducted a retrospective study to investigate the association of body mass index (BMI) with arrhythmia outcomes in AF patients undergoing CA. Methods: In a cohort of 1410 AF patients (mean age 57.2 ± 11.6 years; 68% male) undergoing single CA, the association between BMI and AF ablation outcome was analyzed using BMI as a continuous variable and by four BMI categories (

Calcium (Ca), with abundant and cheap reserves, is a potential element to facilitate the further application of Mg-Al-Sn based alloys. Here, effects of Ca content on the microstructure and tensile properties of Mg-2.0Al-0.8Sn (wt.%) alloys were systematically studied. The experimental results illustrated that the strength, ductility and isotropy of the alloys improved simultaneously with the increase of Ca content. The better ductility and isotropy could be contributed to the weakened texture via particle stimulation nucleation mechanism. The higher strength benefited from the combination of finer grains, more precipitates and residual dislocation density. Eventually, the Mg-2.0Al-0.8Sn-0.5Ca (wt.%) alloy showed the best room-temperature balance of strength and ductility with a yield strength of ∼226.0 MPa, an ultimate tensile strength of ∼282.4 MPa and a fracture elongation of ∼20.2%, which has huge potential as an applicable low-cost high-performance magnesium alloy.