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Abstract Background The triglyceride glucose (TyG) index, as a reliable marker of insulin resistance, is associated with the incidence and poor prognosis of various cardiovascular diseases. However, the relationship between the TyG index and clinical outcomes in patients with severe aortic stenosis (AS) who underwent transcatheter aortic valve replacement (TAVR) remains unclear. Methods This study consecutively enrolled 1569 patients with AS underwent TAVR at West China Hospital of Sichuan University between April 2014 and August 2023. The outcomes of interest included all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (MACE). Multivariate adjusted Cox regression and restricted cubic splines (RCS) regression analyses were used to assess the associations between the TyG index and the clinical outcomes. The incremental prognostic value of the TyG index was further assessed by the time-dependent Harrell’s C-index, integrated discrimination improvement (IDI) and the net reclassification improvement (NRI). Results During a median follow-up of 1.09 years, there were 146, 70, and 196 patients experienced all-cause death, cardiovascular death, and MACE, respectively. After fully adjusting for confounders, a per-unit increase of TyG index was associated with a 441% (adjusted HR: 5.41, 95% CI: 4.01–7.32), 385% (adjusted HR: 4.85, 95% CI: 3.16–7.43), and 347% (adjusted HR: 4.47, 95% CI: 3.42–5.85) higher risk of all-cause mortality, cardiovascular mortality and MACE, respectively. The RCS regression analyses revealed a linear association between TyG index and endpoints (all P for non-linearity > 0.05) with 8.40 as the optimal binary cutoff point. Furthermore, adding TyG index to the basic risk model provided a significant incremental value in predicting poor prognosis (Time-dependent Harrell’s C-index increased for all the endpoints; All-cause mortality, IDI: 0.11, P

In the preparation of magnesium by Pidgeon process, the phenomenon slag pellets sticking on the wall of reduction pot always appear, and the glaze sticking on the inner wall of the reduction pot is difficult to remove. The mechanism of this phenomenon is studied in this work by X-ray fluorescence spectrometer (XRF) measurement, electron probe microanalyzer scanning (EPMA) analysis, differential scanning calorimetry (DSC) analysis, and thermodynamic calculations. The main components of the glaze are MgO, Ca12Al14F2O32, CaF2, CaO, and a small amount of Ca4Si2O7F2. The solid-liquid transition temperature of Ca12Al14F2O32 and CaF2 is close to the production temperature of Pidgeon process, which leads to the bonding between the slag pellets and the pot wall. The loss of CaF2 in glaze layer will reduce the total amount of liquid phase and increase the temperature at which Ca12Al14F2O32 is completely transformed into liquid phase, which causes glaze layer sticking on the inner wall of the reduction pot.

Atherosclerosis is a significant contributor to global cardiovascular disease. Reducing the formation of atherosclerotic plaque effectively can lead to a decrease in cardiovascular diseases. Therefore, controlling macrophage function is crucial. This study presents the creation of a bifunctional nanoparticle that is specific to macrophages to achieve intracellular and extracellular synergistic therapy for restoring macrophage functions. The nanoparticle is conjugated with anti-CD47 antibody to modulate extracellular CD47-SIRPα phagocytic signaling axis on the outer surface of macrophages and encapsulates the NLRP3 inhibitor (CY-09) to regulate intracellular inflammation response of macrophages. The results showed that the nanoparticles accumulate in the atherosclerotic plaque, alter macrophage phagocytosis, inhibit NLRP3 inflammasome activation, and decrease the plaque burden in Apoe−/− mice whilst ensuring safety. Examination of single-cell RNA sequencing indicates that this multifunctional nanoparticle decreases the expression of genes linked to inflammation and manages inflammatory pathways in the plaque lesion. This study proposes a synergistic therapeutic approach that utilizes a bifunctional nanoparticle, conjugated with anti-CD47, to regulate the microenvironment of plaques.

Abstract Urinary incontinence is a common disease among middle-aged and elderly women, which not only affects the physical and mental health of patients, but also brings a great medical burden to society. Obesity is a known risk factor for urinary incontinence and is the most common secondary cause of hyperlipidemia. Most obese patients also suffer from hyperlipidemia in the clinic. However, few studies have explored the role of hyperlipidemia in women with urinary incontinence. Using data from the 2005–2018 National Health and Nutrition Examination Survey (NHANES), we aimed to evaluated the independent associations of high body mass index and hyperlipidemia with urinary incontinence in Americans by conducting a weighted multivariate logistic regression model. Additive interactions were also assessed using the relative excess risk due to interaction (RERI), attributed proportion of interaction (AP) and synergy index (S). This study demonstrated that hyperlipidemia was associated with a higher risk of stress urinary incontinence among women with obesity (OR = 1.52, 95% CI = 1.03–2.25), and there was a significant synergistic effect of hyperlipidemia and obesity on stress urinary incontinence(adjusted RERI: 3.75, 95% CI 0.30–7.20; adjusted AP: 0.67, 95% CI 0.54–0.80; adjusted S: 5.49, 95% CI 4.15–7.27). Moreover, fasting serum triglyceride lipids were the most relevant blood lipid indicator for the risk of stress urinary incontinence, especially among obese women younger than 50 years old, which contributes to the development of more refined lipid control protocols for patients with urinary incontinence in different age groups.

Abstract Background Tricuspid regurgitation (TR) is a prevalent disease that triggers systemic pathological changes including cardiac, respiratory, hepatic and digestive, hematopoietic, renal and skin issues. The burden of extra-cardiac manifestations has not been well described in TR patients and the clinical impact is unknown. Methods Patients with severe or more-than-severe TR during hospitalization, who did not have any previous cardiac procedures, hemodynamically significant congenital heart disease or concomitant severe aortic or mitral valve disease, were retrospectively analyzed. Pre-specified criteria and diagnosis of baseline characteristics were used to evaluate the presence of extra-cardiac manifestations secondary to TR after excluding comorbidities that may also lead to corresponding abnormalities. Extra-cardiac involvements encompass respiratory, hepatic and, digestive, renal, hematopoietic and dermatic system. Staging criteria are defined as no extra-cardiac system involvement in Stage 1, one in Stage 2, at least two extra-cardiac involvements in Stage 3 and any end-stage organ failure in Stage 4. A telephone follow-up was conducted to record the composite endpoint namely all-cause death or cardiac rehospitalization after the index hospitalization. Results A total of 258 patients were identified with a median age of 73 (interquartile range [IQR]: 62–83) years and 52.3% were female. Severe TR and more-than-severe TR patients accounted for 92.6% and 7.4% of the cohort. There were 20.5%, 27.5%, 37.6% and 14.3% of patients from Stage 1 to 4 respectively. The follow-up time was at a median of 251 (IQR: 183–324) days. TR Patients in Stage 3&4 were at an increased risk with borderline statistical significance to experience the composite endpoint compared to patients in Stage 1&2 (odds ratio [OR] 1.9, 95% confidence interval [CI] 1.0 to 3.7, P = 0.049). Conclusions Approximately half of patients with at least severe TR presented with two or more extra-cardiac systemic manifestations, which may incur a 1.9-fold higher risk of all-cause death or cardiac rehospitalization than TR patients with one or less extra-cardiac involvement.

Introduction: Mild stenosis [degree of stenosis (DS) < 50%] is commonly labeled as nonobstructive lesion. Some lesions remain stable for several years, while others precipitate acute coronary syndromes (ACS) rapidly. The causes of ACS and the factors leading to diverse clinical outcomes remain unclear.Method: This study aimed to investigate the hemodynamic influence of mild stenosis morphologies in different coronary arteries. The stenoses were modeled with different morphologies based on a healthy individual data. Computational fluid dynamics analysis was used to obtain hemodynamic characteristics, including flow waveforms, fractional flow reserve (FFR), flow streamlines, time-average wall shear stress (TAWSS), and oscillatory shear index (OSI).Results: Numerical simulation indicated significant hemodynamic differences among different DS and locations. In the 20%–30% range, significant large, low-velocity vortexes resulted in low TAWSS (40 dyne/cm2), rapidly expanding the high TAWSS area (averagely increased by 0.46 cm2) in left main artery and left anterior descending artery (LAD), where high OSI areas remained extensive (>0.19 cm2).Discussion: While mild stenosis does not pose any immediate ischemic risk due to a FFR > 0.95, 20%–50% stenosis requires attention and further subdivision based on location is essential. Rapid progression is a danger for lesions with 20%–30% DS near the stenoses and in the proximal LAD, while lesions with 30%–50% DS can cause plaque injury and rupture. These findings support clinical practice in early assessment, monitoring, and preventive treatment.

Microbubble-mediated therapeutic gene or drug delivery is a promising strategy for various cardiovascular diseases (CVDs), but the efficiency and precision need to be improved. Here, we propose a cavitation bubble-driven drug delivery strategy that can be applied to CVDs. A bubble-pulse-driving theory was proposed, and the formula of time-averaged thrust driven by bubble pulses was derived. The continuous motion of particles propelled by cavitation bubbles in the ultrasonic field is investigated experimentally by high-speed photography. The cavitation bubbles grow and collapse continuously, and generate periodic pulse thrust to drive the particles to move in the liquid. Particles attached to bubbles will move in various ways, such as ejection, collision, translation, rotation, attitude variation, and circular motion. The cavity attached to the particle is a relatively large cavitation bubble, which does not collapse to the particle surface, but to the axis of the bubble perpendicular to the particle surface. The cavitation bubble expands spherically and collapses asymmetrically, which makes the push on the particle generated by the bubble expansion greater than the pull on the particle generated by the bubble collapse. The time-averaged force of the cavitation bubble during its growth and collapse is the cavitation-bubble-driven force that propels the particle. Both the cavitation-bubble-driven force and the primary Bjerknes force act in the same position on the particle surface, but in different directions. In addition to the above two forces, particles are also affected by the mass force acting on the center of mass and the motion resistance acting on the surface, so the complex motion of particles can be explained.

This study demonstrated that fibrinogen is an independent risk factor for 10-year mortality in patients with acute coronary syndrome (ACS), with a U-shaped nonlinear relationship observed between the two. These findings underscore the importance of monitoring fibrinogen levels and the consideration of long-term anti-inflammatory treatment in the clinical management of patients with ACS.

Abstract Background Stress urinary incontinence (SUI) is characterized by involuntary urine leakage in response to increased abdominal pressure, such as coughing, laughing, or sneezing. It significantly affects women’s quality of life and imposes a substantial disease burden. While pregnancy and childbirth have been previously identified as risk factors for SUI, educational attainment may also play a role. Therefore, this paper investigates the causal relationship between educational attainment and SUI using two-sample Mendelian randomization (TSMR) analysis, years of schooling (YOS), and college or university degree (CUD) as proxies. Methods Summary statistics of YOS, CUD, and SUI were obtained from genome-wide association studies (GWAS), and TSMR analysis was applied to explore potential causal relationships between them. Causal effects were mainly estimated using the standard inverse variance weighting (IVW) method, and complementary and sensitivity analyses were also performed using multiple methods. Results The results indicate that both YOS (OR = 0.994, 95% CI: 0.992–0.996; P = 7.764E-10) and CUD (OR = 0.987, 95% CI: 0.983–0.991; P = 1.217E-09) may have a negative causal effect on SUI. Conclusions Improving educational attainment may go some way towards reducing the risk of SUI. Therefore, it is important to increase efforts to improve the imbalance in educational development and safeguard women’s health.

Objective Parry⁃Romberg syndrome is a rare disease characterized by unilateral facial progressive atrophy accompanied by ipsilateral intracranial lesions and/or cerebral atrophy, this article is aimed to analyze the clinical, radiological and pathological features of patients with Parry ⁃ Romberg syndrome and explore the microvascular mechanism in the pathogenesis of the disease, to provide reference for understanding the nature of disease. Methods and Results The age of onset was 27 and 17 years old of the 2 patients respectively. Case 1 initially presented with left⁃sided progressive hemifacial atrophy and developed paroxysmal pain, twitch and numbness on the left face. Case 2 presented with a band ⁃ like alopecia in the left fronto⁃parietal area with cutaneous atrophy, and sudden right limb mild hemiplegia. The MRI of Case 1 revealed a space⁃occupying lesion in the left frontal and insular lobes without enhancement. The MRI of Case 2 showed recent lacunar cerebral infarction in left posterior limb of internal capsule. The histopathological examination of Case 1 showed hemorrhage, microvascular thrombosis, fibrinoid necrosis of vascular walls and mild peri⁃microvascular chronic inflammatory cell infiltration, who was irresponsive to prednisone. Case 2 received aspirin and remained free from any cerebrovascular event at his one⁃year⁃ follow up. Conclusions The microvascular mechanism may be the pathogenesis of Parry ⁃ Romberg syndrome, and the antiplatelet therapy may be an optional schedule for stroke prevention and treatment in patients with Parry⁃Romberg syndrome.

Abstract Background The correlation between stable geomagnetic fields and unstable geomagnetic activities with mortality, incidence, and prevalence of cardiovascular diseases (CVDs) remains ambiguous. Method To investigate the correlations between geomagnetic field (GMF) intensity and geomagnetic disturbance (GMD) and CVDs events in global, long-period scale, global and 204 countries and territories were included on the base of 2019 Global Burden of Disease study (GBD 2019). Data of GMF intensity, GMD frequency, CVDs events, weather and health economic indicators from 1996 to 2019 of included locations were collected. Linear regression and panel data modelling were conducted to identify the correlations between GMF intensity and CVDs events, multi-factor panel data analysis was also generated to adjust the effect of confounding factors. Results For the average data during 1996–2019, linear regression model revealed consistent positive correlations between total GMF (tGMF) intensity and mortality of total CVDs [coef = 0.009, (0.006,0.011 95%CI)], whereas negative correlations were found between horizonal GMF (hGMF) intensity and total CVD mortality [coef = -0.010 (-0.013, -0.007 95%CI)]. When considering the time trend, panel data analysis still demonstrated positive correlation between tGMF and total CVDs mortality [coef = 0.009, (0.008,0.009 95%CI)]. Concurrently, the hGMF negatively correlated with total CVDs mortality [coef = -0.008, (-0.009, -0.007 95%CI)]. When the panel models were adjusted for confounding factors, no reverse of correlation tendency was found between tGMF, hGMF and CVDs events. In high-income territories, positive correlation was found between geomagnetic storm (GMS) frequency and mortality of total CVDs [coef = 14.007,(2.785, 25.229 95%CI)], however, this positive trend faded away gradually with the latitude decreasing from polar to equator. Conclusions Stable and long-term horizontal component of GMF may be beneficial to cardiac health. Unstable and short-term GMF called GMD could be a hazard to cardiac health. Our results suggest the importance of regular GMF in maintaining cardio-health state and the adverse impacts of GMD on cardiac health.

Introduction: The synergistic treatment of chemotherapy and photodynamic therapy (PDT) has remarkable potential in cancer therapy. However, challenges remain, such as unstable chemotherapeutic drug release, suboptimal targeting, and reduced efficacy of PDT under hypoxic conditions commonly found in solid tumors.Methods: To address these issues, we use camptothecin (CPT) and pheophorbide a (Pa) incorporated through the functional thioketal, which serves as the reactive oxygen species (ROS)-responsive trigger, to construct a ROS-responsive prodrug (CPT-TK-Pa). Subsequently, we co-loaded it with a platinum nanozyme (PtNP) in distearylphosphatidylethanolamine–polyethylene glycol (DSPE–PEG) to obtain the ROS-responsive prodrug nanoparticle (CPT-TK-Pa/Pt NP).Results and Discussion: Specifically, the incorporated PtNP within CPT-TK-Pa/Pt NP positively catalyzes the conversion of hydrogen peroxide (H2O2) to oxygen, thereby ameliorating the hypoxic state of the tumor. This enhanced oxygen generation could replenish the oxygen that is consumed by Pa during 660 nm exposure, enabling controlled CPT release and amplifying the photodynamic response. In vitro investigations reveal the potency of CPT-TK-Pa/Pt NPs in inhibiting colon tumor cells. Given its ROS-responsive release mechanism and enhanced PDT efficacy, CPT-TK-Pa/Pt NP has the potential to be a promising candidate for cancer therapy.

Heterogeneity in ion flux of electrolyte materials largely dictates the growth of lithium dendrites and performance of lithium metal anode, which is considered “holy grail” to enable safe rechargeable batteries with ultrahigh energy density. This challenge is even more prominent in polymer-based electrolytes, which thereby leads to uneven ion distribution and mobility of ionic charge carriers, disturbing electrodeposition. In this work, we propose an ion-immobilization strategy achieved by an in-situ grafted nanohybrid fluoropolymer electrolyte, which takes advantages of unique weak solvation of fluoropolymers to tether anions to solvation structure of Li+. Such regulation in conjunction with the well dispersed nanometric aggregates, enables polymer electrolytes serving as ion reservoirs with strengthened weakly-solvating effect. As such, we suppressed formation of dendritic lithium by inducing uniform ion distribution, which significantly extended cell lifetime to over 1900 h in electrodeposition and prolonged charge-discharge cycles of in-situ lithium metal batteries up to 4.6 V at ambient temperature. This work demonstrates a new approach to regulate interfacial chemistry of Li anode and access high-performance polymer-based electrolytes.

Introduction Decisions regarding the optimal timing of intervention for asymptomatic aortic stenosis (AS) are controversial. The study aims to identify potential risk factors for asymptomatic patients with severe AS that are associated with worse prognosis and to evaluate the benefits of early interventions for asymptomatic patients presenting with one or more additional risk factors.Methods and analysis This is a non-interventional, prospective, open-label, multicentre registry study across China. A total of 1000 patients will be enrolled and categorised as symptomatic or asymptomatic. The primary endpoint is the occurrence of all-cause mortality, stroke, acute myocardial infarction and heart failure-related hospitalisation at 1-year follow-up. In asymptomatic severe AS patients presenting with one or more risk factors, the occurrence rate of the primary endpoint between those who undergo transcatheter aortic valve replacement (TAVR) and those who do not will be compared. We will also compare the occurrence rate of the primary endpoint for asymptomatic severe AS patients with additional risk factors who undergo TAVR with those presenting with symptoms. This study is believed to provide additional evidence to help clinicians identify and refer severe AS patients who are asymptomatic but present with additional risk factors for early intervention of TAVR.Ethics and dissemination The study protocol has been approved by the local ethics committee of each participating site: West China Hospital, Sichuan University; Sir Run Run Shaw Hospital, Zhejiang University School of Medicine; Second Hospital of Hebei Medical University; Tianjin Chest Hospital; and First Affiliated Hospital of Nanchang University. All participants will provide written informed consent. Study results will be published through academic conferences and peer-reviewed journals.Trial registration This study was registered at the Chinese Clinical Trial Registry (https:// www.chictr.org.cn), with the registration number ChiCTR2200064853.

Abstract Urogenital congenital anomalies (UCAs) is defined as “any live-birth with a urinary or genital condition” and affects millions of men and women worldwide. However, sex differences and related environmental risk factors in UCAs burden on a global scale have not been assessed. Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we estimated prevalence, incidence, mortality and disability-adjusted life years (DALYs) of UCAs from 1990 to 2019 by sex, region, and socio-demographic Index (SDI) in 204 countries and territories. The disease burden of UCAs was also estimated attributable to each risk factor were estimated according to risk exposure. In 2019, UCAs caused 10,200 all-ages deaths (95% UI 7550–13,400). The combined global incidence rate was 8.38 per 1000 (95% UI 5.88–12.0) live births. The ASIR increased slightly, while the ASDR decreased from 1990 to 2019.The UCAs burden varies greatly depending on the development level and geographical location. The UCAs burden was significantly higher in men than in women, and the sex differences showed an enlarging trend. Health risks and issues, including pollution, child and maternal malnutrition, diet habits, unsafe sanitation and water source, were detected to be positively related to UCAs burden. Albeit the age-standardised prevalence, mortality, incidence, and DALYs of UCAs have decreased, they still cause a public health challenge worldwide. The high deaths and DALYs rates in low and low-middle SDI countries highlight the urgent need for improved preventive, diagnostic, and therapeutic measures. Global strategies for enhancing water safety, reducing pollution, and healthy diets are crucial steps in reducing the burden of UCAs.

Abstract Background We aim to determine predictors of inadequate left ventricular mass index (LVMi) regression at mid-term after transcatheter aortic valve replacement (TAVR), including the potential role of epicardial adipose tissue (EAT). Methods We retrospectively reviewed patients with both echocardiographic assessments and multi-slice computed tomography (MSCT) obtained one year after TAVR. The change of LVMi, the volume and the average CT attenuation of EAT from baseline to one-year follow-up was calculated. Patients were divided into two groups by the percentage change of LVMi at a cut-off of 15%. Results A total of 152 patients were included with a median age of 74 years (interquartile range [IQR] 69–78 years) and 56.6% being male. LVMi decreased (P mild (P = 0.001) and the change in the average CT attenuation of EAT (P = 0.026) were different between the decrease of LVMi ≥ 15% and mild at baseline was the only statistically significant predictor of a decrease of LVMi

The physical and chemical stabilities of SiC and heat-resistant steel were assessed by the diffusion couple method under vacuum at 1200 °C, which is a commonly used condition in magnesium metallurgy. High-temperature visualization instruments were used and Differential thermal analysis (DTA), X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and thermodynamic analyses were performed to verify the relevant mechanism. The reaction between SiC and heat-resistant steel can be divided into two stages: solid–solid and solid–liquid reactions. The solid–solid interfacial reaction produces graphite, which hinders the interfacial reaction. The interfacial reaction simultaneously generates silicides (NiSi, Ni2Si, and Ni3Si) with low melting points and transforms the reaction interface into a solid–liquid interface. The formation of the liquid phase promotes the dissolution and diffusion of carbon, leading to the accelerated corrosion of SiC and low-temperature melting of steel. Supersaturated carbon precipitates in the melt in the form of nanowires or nanotubes are catalyzed by Fe/Ni. Herein, a general model describing the direct interfacial reaction mechanism of SiC and heat-resistant steel is proposed to explain the reaction process under vacuum.

Abstract Acetic acid and furfural (AF) are two major inhibitors of microorganisms during lignocellulosic ethanol production. In our previous study, we successfully engineered Zymomonas mobilis 532 (ZM532) strain by genome shuffling, but the molecular mechanisms of tolerance to inhibitors were still unknown. Therefore, this study investigated the responses of ZM532 and its wild-type Z. mobilis (ZM4) to AF using multi-omics approaches (transcriptomics, genomics, and label free quantitative proteomics). Based on RNA-Seq data, two differentially expressed genes, ZMO_RS02740 (up-regulated) and ZMO_RS06525 (down-regulated) were knocked out and over-expressed through CRISPR-Cas technology to investigate their roles in AF tolerance. Overall, we identified 1865 and 14 novel DEGs in ZM532 and wild-type ZM4. In contrast, 1532 proteins were identified in ZM532 and wild-type ZM4. Among these, we found 96 important genes in ZM532 involving acid resistance mechanisms and survival rates against stressors. Furthermore, our knockout results demonstrated that growth activity and glucose consumption of mutant strains ZM532∆ZMO_RS02740 and ZM4∆ZMO_RS02740 decreased with increased fermentation time from 42 to 55 h and ethanol production up to 58% in ZM532 than that in ZM532∆ZMO_RS02740. Hence, these findings suggest ZMO_RS02740 as a protective strategy for ZM ethanol production under stressful conditions.

Paravalvular leak (PVL) is a shortcoming that can erode the clinical benefits of transcatheter valve replacement (TAVR) and therefore a readily applicable method (aortography) to quantitate PVL objectively and accurately in the interventional suite is appealing to all operators. The ratio between the areas of the time-density curves in the aorta and left ventricular outflow tract (LVOT-AR) defines the regurgitation fraction (RF). This technique has been validated in a mock circulation; a single injection in diastole was further tested in porcine and ovine models. In the clinical setting, LVOT-AR was compared with trans-thoracic and trans-oesophageal echocardiography and cardiac magnetic resonance imaging. LVOT-AR > 17% discriminates mild from moderate aortic regurgitation on echocardiography and confers a poor prognosis in multiple registries, and justifies balloon post-dilatation. The LVOT-AR differentiates the individual performances of many old and novel devices and is being used in ongoing randomized trials and registries.

Abstract Glutaraldehyde (Glut)-crosslinked porcine pericardium and bovine pericardium are mainly consisted of collagen and widely used for the preparation of heterogenous bioprosthetic heart valves (BHV), which play an important role in the replacement therapy of severe valvular heart disease, while their durability is limited by degeneration due to calcification, thrombus, endothelialization difficulty and prosthetic valve endocarditis. Herein, we develop a novel BHV, namely, TPly-BP, based on natural tannic acid and polylysine to improve the durability of Glut crosslinked bovine pericardium (Glut-BP). Impressively, tannic acid and polylysine could form nanoaggregates via multiple hydrogen bonds and covalent bonds, and the introduction of nanoaggregates not only improved the mechanical properties and collagen stability but also endowed TPly-BP with good biocompatibility and hemocompatibility. Compared to Glut-BP, TPly-BP showed significantly reduced cytotoxicity, improved endothelial cell adhesion, a low hemolysis ratio and obviously reduced platelet adhesion. Importantly, TPly-BP exhibited great antibacterial and in vivo anti-calcification ability, which was expected to improve the in vivo durability of BHVs. These results suggested that TPly-BP would be a potential candidate for BHV. Graphical abstract

Abstract Traditional ceramic materials are generally brittle and not flexible with high production costs, which seriously hinders their practical applications. Multifunctional nanofiber ceramic aerogels are highly desirable for applications in extreme environments, however, the integration of multiple functions in their preparation is extremely challenging. To tackle these challenges, we fabricated a multifunctional SiC@SiO2 nanofiber aerogel (SiC@SiO2 NFA) with a three-dimensional (3D) porous cross-linked structure through a simple chemical vapor deposition method and subsequent heat-treatment process. The as-prepared SiC@SiO2 NFA exhibits an ultralow density (~ 11 mg cm− 3), ultra-elastic, fatigue-resistant and refractory performance, high temperature thermal stability, thermal insulation properties, and significant strain-dependent piezoresistive sensing behavior. Furthermore, the SiC@SiO2 NFA shows a superior electromagnetic wave absorption performance with a minimum refection loss (RL min) value of − 50.36 dB and a maximum effective absorption bandwidth (EAB max) of 8.6 GHz. The successful preparation of this multifunctional aerogel material provides a promising prospect for the design and fabrication of the cutting-edge ceramic materials.

Background and ObjectiveThe evidence on the risk of mortality after myocardial infarction (MI) among migrants compared with natives is mixed and limited. The aim of this study is to assess the mortality risk after MI in migrants compared to natives.MethodsThis study protocol is registered with PROSPERO, number CRD42022350876. We searched the Medline and Embase databases, without time and language constraints, for cohort studies that reported the risk of mortality after MI in migrants compared to natives. The migration status is confirmed by country of birth, both migrants and natives are general terms and are not restricted to a particular country or area of destination or origin. Two reviewers separately screened searched studies according to selection criteria, extracted data, and assessed data quality using the Newcastle-Ottawa Scale (NOS) and risk of bias of included studies. Pooled estimates of adjusted and unadjusted mortality after MI were calculated separately using a random-effects model, and subgroup analysis was performed by region of origin and follow-up time.ResultA total of 6 studies were enrolled, including 34,835 migrants and 284,629 natives. The pooled adjusted all-cause mortality of migrants after MI was higher than that of natives (OR, 1.24; 95% CI, 1.10–1.39; I2 = 83.1%), while the the pooled unadjusted mortality of migrants after MI was not significantly different from that of natives (OR, 1.11; 95% CI, 0.69–1.79; I2 = 99.3%). In subgroup analyses, adjusted 5–10 years mortality (3 studies) was higher in the migrant population (OR, 1.27; 95% CI, 1.12–1.45; I2 = 86.8%), while adjusted 30 days (4 studies) and 1–3 years (3 studies) mortality were not significantly different between the two groups. Migrants from Europe (4 studies) (OR, 1.34; 95% CI, 1.16–1.55; I2 = 39%), Africa (3 studies) (OR, 1.50; 95% CI, 01.31–1.72; I2 = 0%), and Latin America (2 studies) (OR, 1.44; 95% CI, 1.30–1.60; I2 = 0%) had significantly higher rates of post-MI mortality than natives, with the exception of migrants of Asian origin (4 studies) (OR, 1.20; 95% CI, 0.99–1.46; I2 = 72.7%).ConclusionsMigrants tend to have lower socioeconomic status, greater psychological stress, less social support, limited access to health care resources, etc., therefore, face a higher risk of mortality after MI in the long term compared to natives. Further research is needed to confirm our conclusions, and more attention should be paid to the cardiovascular health of migrants.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, identifier: r CRD42022350876.

The frequency of mudflow disasters induced by rainfall in the Loess Plateau is increasing with the occurrence of global warming. The initial water content is one of the basic properties of soil, which affects the initiation of loess mudflow. In this work, the field study of the debris flow gullies in Yan’an City, Shaanxi Province, China, was conducted, and the main factors that induce gully loess mudflow were summarized. Based on the investigation results, a flume model was designed to carry out flume tests with different initial soil water contents. The experimental results demonstrate the following. (1) Different initial soil water contents lead to different soil failure models. The damage of soil by water flow when the soil water content is in the range of 0−5% is mainly gully erosion; that within the range of 10−15% is mainly rill surface erosion; that within the range of 20−25% is mainly dam breach failure. (2) When the water content of loess is equal to or less than 5% or equal to or greater than 20%, soil can promote the formation of loess mudflow, and the destruction of soil is more likely to cause mudflow disasters. In contrast, when the water content is within 10−15%, loess mudflow is not easily produced. The research results of the initial water content provide not only theoretical support for the study of loess mudflow disasters, but also a reference for the prevention and control of loess mudflow disasters in the Loess Plateau.

Subarachnoid hemorrhage (SAH) can lead to damage to the myelin sheath in white matter. Through classification and analysis of relevant research results, the discussion in this paper provides a deeper understanding of the spatiotemporal change characteristics, pathophysiological mechanisms and treatment strategies of myelin sheath injury after SAH. The research progress for this condition was also systematically reviewed and compared related to myelin sheath in other fields. Serious deficiencies were identified in the research on myelin sheath injury and treatment after SAH. It is necessary to focus on the overall situation and actively explore different treatment methods based on the spatiotemporal changes in the characteristics of the myelin sheath, as well as the initiation, intersection and common action point of the pathophysiological mechanism, to finally achieve accurate treatment. We hope that this article can help researchers in this field to further clarify the challenges and opportunities in the current research on myelin sheath injury and treatment after SAH.

Reactive oxygen species (ROS) metabolism is essential for the homeostasis of cells. Appropriate production of ROS is an important signaling molecule, but excessive ROS production can damage cells. ROS and ROS-associated proteins can act as damage associated molecular pattern molecules (DAMPs) to activate the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome in cardiovascular diseases. Previous studies have shown that there are connected sites, termed mitochondria-associated membranes (MAMs), between mitochondria and the endoplasmic reticulum. In cardiovascular disease progression, MAMs play multiple roles, the most important of which is the ability to mediate ROS generation, which further activates the NLPR3 inflammasome, exacerbating the progression of disease. In this review, the following topics will be covered: 1. Molecular structures on MAMs that can mediate ROS generation; 2. Specific mechanisms of molecule-mediated ROS generation and the molecules' roles in cardiovascular disease, 3. The effects of MAMs-mediated ROS on the NLRP3 inflammasome in cardiovascular disease. The purpose of this review is to provide a basis for subsequent clinical treatment development.

Aluminum–Vanadium (AlV) alloy is essential for high-performance titanium material. Calcium fluoride (CaF2) is currently used in AlV production and has inevitable drawbacks in terms of product quality and environmental impact. In order to avoid its potential hazards, lime (CaO) as an alternative flux material in producing AlV alloy has been investigated in laboratory and by industrial trials in the present study. The samples were analyzed by Electron Probe X-ray Micro-analyzer (EPMA) and X-ray Diffraction (XRD), regarding the phases formed and corresponding compositions. A slag with good fluidity can protect inner alloy from being oxidized and also promotes the separation between slag and alloy, with a goal to reduce alloy inclusions in slag to enhance the yield. The results showed that using CaO as flux with appropriate amount greatly improved the yield and quality of the AlV alloy and avoided environmental pollution caused by fluoride evaporations.

Abstract Lowering cost will prompt the sustainable development of sugarcane‐based ethanol industry. In this work, we developed a low‐cost process for ethanol production from sugarcane by a genetically engineered Zymomonas mobilis. Fermentation media were first optimized, resulting in a 15.54% increase in ethanol fermentation efficiency as compared to control media. To further reduce the byproduct levan formation, a levansucrase‐encoding gene of Z. mobilis, sacB, was deleted through the type I‐F CRISPR‐Cas system, which resulted in a further elevation of both ethanol conversion ratio and productivity comparing with the starting strain ZMS912 (87.50% vs. 76.77%, 1.95 g/L/h vs. 1.71 g/L/h). Moreover, we conducted fed‐batch fermentation for ethanol production using sugarcane juice in 5 L bioreactors and employing the optimized media and engineered strain. The results showed that maximum ethanol titer of 81.59 g/L and productivity of 5.83 g/L/h were achieved. Finally, preliminary techno‐economic assessment demonstrated that our efforts to modify media and strain could reduce the processing cost of ethanol production from sugarcane juice, which provides the feasibility for economic ethanol production in the future.

Abstract Background Optimal projection is essential for valve deployment during transcatheter aortic valve implantation (TAVI). The purpose of this study was to propose an approach to predict optimal projection in TAVI candidates with different aortic valve anatomies. Methods 331 patients undergoing self-expanding TAVI were included and the so-called non-coronary cusp (NCC)-parallel technique was utilized, which generated the predicted projection by connecting NCC commissures on the transverse plane on the pre-procedural computed tomography images. Results 37.8% of the study cohort were bicuspid aortic valve (BAV) patients. Around 80% of both NCC-parallel views and final views were in the right anterior oblique (RAO) and caudal (CAU) quadrant. There was less than 5° change required from the NCC-parallel view to the final implanted view in 79% of tricuspid aortic valve (TAV) patients but only in 27% (13/48) of type 0 BAV patients with coronary arteries originated from the different cusps. After excluding the above mentioned BAV patients, 62.3% (48/77) of BAV patients needed less than 5° change to achieve optimal projection and only in 8 patients, the angular change was larger than 10° in either left/right anterior oblique or cranial/caudal direction. Conclusions The NCC-parallel technique provides reliable prediction for optimal projection in self-expanding TAVI in all TAV and most BAV patients, with a vast majority of views in the RAO and CAU quadrant.

The snare-assisted technique has been described to facilitate transcatheter aortic valve replacement (TAVR) delivery system advancement in complex aortic anatomies. However, the evidence is limited to case reports. To evaluate the safety profile of the snare-facilitated approach and its impact on self-expanding (SE) TAVR outcomes, we collected consecutive patients who underwent transfemoral SE-TAVR for aortic stenosis, using propensity score matching (PSM) separately in tricuspid and type-0 and type-1 bicuspid aortic valve morphology between the snare and non-snare groups. In 766 patients, despite the snare group having significantly larger annulus angulation and maximal ascending aortic diameter, both groups achieved comparable 30-day device success rates, regardless of first-generation or new-generation valve use. After PSM, the snare group had a significantly lower new permanent pacemaker implantation rate among 193 type-0 patients (3.3% vs. 18.3%, p = 0.01). The ipsilateral group used new-generation valves less frequently (23.0% vs. 75.4%, p < 0.001), but there were no significant inter-group differences in procedure-related events, except for a lower incidence of PVL ≥ mild in the ipsilateral group (14.9% vs. 32.3%, p = 0.01). In conclusion, the snare-assisted technique appears useful in SE-TAVR with angulated aortic root anatomy, and the benefits were comparable between ipsilateral and contralateral snare techniques.

Abstract. Background:. The past decade has witnessed an ever-increasing momentum of transcatheter aortic valve replacement (TAVR) and a subsequent paradigm shift in the contemporary management of severe aortic stenosis (AS). We conducted a multi-centric TAVR registry based on Chinese patients (the China Aortic valve tRanscatheter Replacement registrY [CARRY]) to delineate the clinical characteristics and outcomes of Chinese patients who underwent TAVR and compare the results between different valve types in different Chinese regions. Methods:. CARRY is an all-comer registry of aortic valve disease patients undergoing TAVR across China and was designed as an observational study that retrospectively included all TAVR patients at each participating site. Seven hospitals in China participated in the CARRY, and 1204 patients from April 2012 to November 2020 were included. Categorical variables were compared using the chi-squared test, and continuous variables were analyzed using a t test or analysis of variance (ANOVA) test. The Kaplan–Meier curve was used to estimate the risk of adverse events during follow-up. Results:. The mean age of the patients was 73.8 ± 6.5 years and 57.2% were male. The median Society of Thoracic Surgeon-Predicted Risk of Mortality score was 6.0 (3.7–8.9). Regarding the aortic valve, the proportion of bicuspid aortic valve (BAV) was 48.5%. During the hospital stay, the stroke rate was 0.7%, and the incidence of high-degree atrioventricular block indicating permanent pacemaker implantation was 11.0%. The in-hospital all-cause mortality rate was 2.2%. After 1 year, the overall mortality rate was 4.5%. Compared to patients with tricuspid aortic valve (TAV), those with BAV had similar in-hospital complication rates, but a lower incidence of in-hospital mortality (1.4% vs. 3.3%) and 1 year mortality (2.3% vs. 5.8%). Conclusions:. TAVR candidates in China were younger, higher proportion of BAV, and had lower rates of post-procedural complications and mortality than other international all-comer registries. Given the use of early generation valves in the majority of the population, patients with BAV had similar rates of complications, but lower mortality than those with TAV. These findings further propel the extension of TAVR in low-risk patients. Trial Registration:. https://www.chictr.org.cn/ (No. ChiCTR2000038526).

Recently, a rationally engineered SpCas9 variant (SpCas9-NG) that can recognize a minimal NG protospacer adjacent motif (PAM) was reported to expand the targeting scope in genome editing. However, increased genome-wide off-target mutations with this variant compared with SpCas9 were reported in previous studies. In addition, lower base editing frequencies and higher unintended off-target mutations were also found in Hoxc13-ablated rabbits generated by NG-BE4max in our study. Here, a high-fidelity base editor, NG-HiFi, in comparison to NG-BE4max, showed retention of on-target activity while exhibiting significantly decreased off-target activity in Hoxc13-ablated rabbits. Collectively, the improved specificity and reduced off-target effect of SpCas9-NG assisted in cytidine base editing with the NG-HiFi system, providing a promising tool to precisely model human diseases in rabbits.

AimsTo investigate the risk factors, clinical features, and prognostic factors of patients with premature acute myocardial infarction (AMI).Materials and methodsA retrospective cohort study of patients with AMI included in data from the West China Hospital of Sichuan University from 2011 to 2019 was divided into premature AMI (aged < 55 years in men and < 65 years in women) and non-premature AMI. Patients’ demographics, laboratory tests, Electrocardiography (ECG), cardiac ultrasound, and coronary angiography reports were collected. All-cause death after incident premature MI was enumerated as the primary endpoint.ResultsAmong all 8,942 AMI cases, 2,513 were premature AMI (79.8% men). Compared to the non-premature AMI group, risk factors such as smoking, dyslipidemia, overweight, obesity, and a family history of coronary heart disease (CHD) were more prevalent in the premature AMI group. The cumulative survival rate of patients in the premature AMI group was significantly better than the non-premature AMI group during a mean follow-up of 4.6 years (HR = 0.27, 95% CI 0.22–0.32, p < 0.001). Low left ventricular ejection fraction (LVEF) (Adjusted HR 3.00, 95% CI 1.85–4.88, P < 0.001), peak N-terminal pro-B-type natriuretic peptide (NT-proBNP) level (Adjusted HR 1.34, 95% CI 1.18–1.52, P < 0.001) and the occurrence of in-hospital major adverse cardiovascular and cerebrovascular events (MACCEs) (Adjusted HR 2.36, 95% CI 1.45–3.85, P = 0.001) were predictors of poor prognosis in premature AMI patients.ConclusionAMI in young patients is associated with unhealthy lifestyles such as smoking, dyslipidemia, and obesity. Low LVEF, elevated NT-proBNP peak level, and the occurrence of in-hospital MACCEs were predictors of poor prognosis in premature AMI patients.

Abstract Background With the expanded utilization of transcatheter aortic valve implantation (TAVI) to younger and lower surgical risk patients with severe aortic stenosis (AS), optimal medical therapy after TAVI procedure has become the main concern. Renin-angiotensin system inhibitors (RASi) are widely utilized in the area of cardiovascular disease including heart failure and myocardial infarction and revealed the ability to reverse left ventricular (LV) remodeling. Interests have, thus, been drawn in investigating whether the prescription of RASi after the TAVI procedure can prevent or reverse cardiac remodeling and improve long-term clinical outcomes. No recommendation regarding the prescription of RASi after TAVI is proposed yet due to the lack of evidence from randomized controlled trials, especially in the Chinese population. We, therefore, designed this randomized controlled trial to explore the effect of adding fosinopril to standard care in patients who underwent a successful TAVI procedure on the LV remodeling. Methods A total of 200 post-TAVI patients from seven academic hospitals across China will be recruited and randomized with a ratio of 1:1 to receive standard care or standard care plus fosinopril. Follow-up visits will take place at 30 days, 3 months, 6 months, 12 months, and 24 months from randomization to assess the clinical symptoms, any adverse events, cardiac function, and quality of life. Cardiac magnetic resonance will be performed at baseline and repeated at the 24-month follow-up visit to assess LV remodeling. Discussion This study will provide evidence regarding medical therapy for AS patients who underwent TAVI and filling the gap in the Chinese population. Trial registration Chinese Clinical Trial Registry ChiCTR2100042266 . Registered on 17 January 2021

Polarization conversion metasurfaces are widely used in optical devices, microwave devices and communication systems, owing to their unique polarization modulation characteristics. However, in some applications (such as folded reflectarrays), the unit cell must be capable of polarization conversion and phase modulation. To the best of our knowledge, there are only a few related designs with both the functionalities. In this paper, we propose a well-performing 1-bit reconfigurable coding metasurface with polarization conversion. It realizes linear-to-linear polarization conversion in a 1.32 GHz bandwidth, and the conversion loss is within 1 dB. Simultaneously, the metasurface achieves a phase difference of approximately 180° by switching the working state of the PIN diodes. This metasurface has great potential for radar detection, folded reflectarrays, and other fields.

ObjectiveWe sought to conduct a systematic review and meta-analysis of clinical adverse events in patients undergoing transcatheter aortic valve replacement (TAVR) with bicuspid aortic valve (BAV) vs. tricuspid aortic valve (TAV) anatomy and the efficacy of balloon-expandable (BE) vs. self-expanding (SE) valves in the BAV population. Comparisons aforementioned will be made stratified into early- and new-generation devices. Differences of prosthetic geometry on CT between patients with BAV and TAV were presented. In addition, BAV morphological presentations in included studies were summarized.MethodObservational studies and a randomized controlled trial of patients with BAV undergoing TAVR were included according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline.ResultsA total of 43 studies were included in the final analysis. In patients undergoing TAVR, type 1 BAV was the most common phenotype and type 2 BAV accounted for the least. Significant higher risks of conversion to surgical aortic valve replacement (SAVR), the need of a second valve, a moderate or severe paravalvular leakage (PVL), device failure, acute kidney injury (AKI), and stroke were observed in patients with BAV than in patients with TAV during hospitalization. BAV had a higher risk of new permanent pacemaker implantation (PPI) both at hospitalization and a 30-day follow-up. Risk of 1-year mortality was significantly lower in patients with BAV than that with TAV [odds ratio (OR) = 0.85, 95% CI 0.75–0.97, p = 0.01]. BE transcatheter heart valves (THVs) had higher risks of annular rupture but a lower risk of the need of a second valve and a new PPI than SE THVs. Moreover, BE THV was less expanded and more elliptical in BAV than in TAV. In general, the rates of clinical adverse events were lower in new-generation THVs than in early-generation THVs in both BAV and TAV.ConclusionsDespite higher risks of conversion to SAVR, the need of a second valve, moderate or severe PVL, device failure, AKI, stroke, and new PPI, TAVR seems to be a viable option for selected patients with severe bicuspid aortic stenosis (AS), which demonstrated a potential benefit of 1-year survival, especially among lower surgical risk population using new-generation devices. Larger randomized studies are needed to guide patient selection and verified the durable performance of THVs in the BAV population.

In the context of climate change, enhanced human activities and ecological changes, the danger level for mountain floods has increased significantly, posing direct or potential hazards to local residents. To determine the current status, focus and trends in mountain flood research, in this study, we visualize the number of publications and citations, the countries and institutions engaged in research, co-citations and key literature, keyword categories and research areas, using keyword timeline analysis and burst detection based on the bibliometric software CiteSpace and VOSviewer and the Web of Sciences core collection database. The results show that the total number of publications and citations in the mountain flood field has experienced rapid growth to date. The United States, China, Germany, the United Kingdom, and Switzerland are the main countries driving the development of the field. The field is of great interest within multiple disciplinary categories and is characterized by multiple research hotspots, multiple research objectives, and cross-fertilization of multiple disciplinary categories. Analysis of the keyword timeline network and highlighted words show that disaster risk evaluation based on remote-sensing technology, the alpine region of the Himalayas, the response mechanisms of heavy rainfall to mountain floods, and the construction of hydrological models, will be research hotspots in the future.

Background: As an emerging arrhythmia monitor, ambulatory smartwatch electrocardiogram (ECG) provides an option for home-based monitoring of delayed new-onset arrhythmic events after transcatheter aortic valve replacement (TAVR). We aimed to validate the diagnostic efficacy of a consumer smartwatch ECG in TAVR recipients, while further explore the occurrence rate of both tachy- and brady-arrhythmia for 30 days after discharge to support risk management. Methods: Consecutive TAVR recipients from February 26th, 2021 to December 13th, 2021 were enrolled prospectively, receiving simultaneous 24-hour Holter and 12-lead ECG compared with smartwatch ECG during hospitalization and daily smartwatch ECG collection for 30 days after discharge. Results: Among 110 patients, the efficacy of smartwatch ECG presented sensitivity and specificity in diagnosing atrial fibrillation (AF) as 1.00 and 0.97, left bundle branch block (LBBB) as 0.61 and 0.88, and right bundle branch block (RBBB) as 0.60 and 0.97, respectively, compared with 24-hour Holter; presented sensitivity and specificity in diagnosing AF as 0.88 and 1.00, LBBB as 0.90 and 0.96, and RBBB as 0.83 and 0.94, respectively, compared with 12-lead ECG. At 30-day follow-up, new-onset arrhythmia included new-onset severe conduction disturbance (SCD) (23.6%), new-onset AF (21.8%), new-onset permanent LBBB (14.5%) and new-onset permanent RBBB (0.9%); 69.2% (36/52) of early new-onset LBBB recovered at 30-day follow-up. Conclusions: The diagnostic efficacy of consumer smartwatch ECG in arrhythmic events among TAVR population was acceptable, which provided a recommendable option for home-based management. Clinical Trial Registration: “Continuously ambulatory rhythm monitoring and predictors of electrocardio-related adverse events in 30 days after transcatheter aortic valve replacement”; Identifier: ChiCTR2000041244; http://www.chictr.org.cn/showproj.aspx?proj=66324.

Niumiangou valley, the epicenter of the 12 May 2008 Wenchuan earthquake (MS 8.0), became an area with frequent and dense debris flow disasters post-earthquake. Based on the in situ investigations after the earthquake on 14 August 2010 and a series of gathered data, characteristics and dynamic analyses of post-earthquake debris flows in Niumiangou valley were conducted, and then their hazard degree was assessed. Some research conclusions are obtained: (1) these post-earthquake debris flows have some typical characteristics, such as rainstorm viscous-type debris flow, happening usually between 11 p.m. and 5 a.m., broken out in the main channel as well as six branch gullies at the same time and also induced in the branches with good vegetation; (2) the dynamic parameters of Niumiangou debris flow (including volumetric weight, velocity, peak discharge, impact force, total amount of debris flow, total amount of solid materials washed out by single debris flow, maximum height of the debris flow rises and super elevation in bend) are relatively significant, and due to which it can be indicated that these debris flow disasters have great destructive power and harmfulness; (3) the hazard degree of debris flow in Niumiangou valley is very high, compared with the debris flows that occurred in the years of 2008 and 2013 in Niumiangou valley post-Wenchuan earthquake, and the comparison result shows that the hazard degree of debris flow in Niumiangou valley is relatively higher, which is consistent with the current situation. Therefore, according to these results, debris flows in Niumiangou valley are in the development phase and large-scale rainfall-induced debris flow disasters, with greater damage and stronger wallop, will easily occur in the rainy seasons of the 20 years after the earthquake.

Loss of T‐type calcium channel (TCC) function has been reported to result in decreased cell viability and impaired muscle regeneration, but the underlying mechanisms remain largely unknown. We previously found that expression of TCC is reduced in aged pelvic floor muscle of multiple vaginal delivery mice, and this is related to endoplasmic reticulum stress (ERS) activation and autophagy flux blockade. In the present work, we further investigated the effects of TCC function loss on C2C12 myotubes and skeletal muscle, which is mediated by promotion of ERS and ultimately contributes to mitochondrial‐related apoptotic cell death. We found that application of a TCC inhibitor induced mitochondria‐related apoptosis in a dose‐dependent manner and also reduced mitochondrial transmembrane potential (MMP), induced mito‐ROS generation, and enhanced expression of mitochondrial apoptosis proteins. Functional inhibition of TCC induced ERS, resulting in disorder of Ca2+ homeostasis in endoplasmic reticulum, and ultimately leading to cell apoptosis in C2C12 myotubes. Tibialis anterior muscles of T‐type α1H channel knockout mice displayed a smaller skeletal muscle fiber size and elevated ERS‐mediated apoptosis signaling. Our data point to a novel mechanism whereby TCC blockade leads to ERS activation and terminal mitochondrial‐related apoptotic events in C2C12 myotubes and skeletal muscles.

CRISPR-Cas9-mediated gene knockout and base-editing-associated induction of STOP codons (iSTOP) have been widely used to exterminate the function of a coding gene, while they have been reported to exhibit side effects. In this study, we propose a novel and practical alternative method referred to as CRISPR Start-Loss (CRISPR-SL), which eliminates gene expression by utilizing both adenine base editors (ABEs) and cytidine base editors (CBEs) to disrupt the initiation codon (ATG). CRISPR-SL has been verified to be a feasible strategy on the cellular and embryonic levels (mean editing efficiencies up to 30.67% and 73.50%, respectively) and in two rabbit models mimicking Otc deficiency (Otc gene) and long hair economic traits (Fgf5 gene).

CRISPR-Cas9 and base editors (BEs) systems are poised to become the gene-editing tool of choice in clinical contexts; however, large-fragment deletion was found in Cas9-mediated mutation cells and mice. In this study, by analyzing 16 gene-edited rabbit lines (including 112 rabbits) generated using SpCas9, BEs, xCas9, and xCas9-BEs with long-range PCR genotyping and long-read sequencing by the PacBio platform, we show the extension of thousands of base fragment deletions in single-guide RNA/Cas9 and xCas9 system mutation rabbits, but no deletions were found in BE-induced mutation rabbits. Thus, we first validated that no large-fragment deletion was induced by the BEs system, suggesting that BE systems can be beneficial tools for the further development of highly accurate and secure gene therapy for the clinical treatment of human genetic disorders.

Objective. The aim of this study is to investigate the characteristics and outcomes of shared bicycle-related injuries from a large emergency medical centre in China in five years from January 2017 to December 2021. Methods. This study was conducted by reviewing the electronic medical record database of a large hospital in China for cases of shared bicycle-related injuries in five years from January 2017 to December 2021. The collected information included demographic data, injury characteristics, and outcomes. Multivariate logistic regression analysis was used to identify risk factors for fatal injury among victims. Results. Most shared bicycle-related injuries occurred in male (60.50%), aged 18–35 (38.81%). Company employees (29.28%) were the majority of victims of shared bicycle-related injuries. Riding in a motor vehicle lane was the most common unsafe riding behaviour (26.52%). The lower limb was the most frequently injured body region (25.28%). Bruising (28.73%) was the most commonly diagnosed injury type. The fatality rate was 9.53%, 72.24% of victims recovered well without permanent disability, and 18.23% of victims had permanent disabilities. The length of hospital stay of most of the victims (67.54%) was less than 7 days, and the hospitalization cost of most of the victims (51.93%) was less than 20,000 Yuan. Riding in a motor vehicle lane, running red lights, and cycling against traffic flow are risk factors for fatal injury. Conclusions. This study indicated that shared bicycle-related injuries make up a sizeable proportion of injuries presenting to the emergency department and with diverse injury characteristics and outcomes. The findings reflect that shared bicycle-related injury has become a public health problem. Therefore, it is necessary to establish injury prevention strategies for the safety of shared bicycle users.