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All‐solid‐state batteries hold great promise for achieving high energy densities. Fabrication of solid‐state electrodes involves cold compaction of the active material—typically an oxide—with a sulfide electrolyte, during which the softer sulfide particles deform and enwrap the harder oxide particles to afford an "active material‐in‐electrolyte" microstructure where the electrolyte forms a continuous ion‐conducting network. This mechanism however does not apply to emerging active materials that promise even higher energy densities like organic and sulfur‐based compounds. These materials are softer than sulfides and form unfavorable "electrolyte‐in‐active material" microstructures where ionic conduction is interrupted. Improvement of these electrodes is challenging in the absence of strategies to overcome the intrinsic material hardnesses. Here, it is demonstrated how the relative hardness difference can be reversed by simultaneously "softening" a sulfide electrolyte Li6PS5Cl by solvent treatment and "hardening" an organic material pyrene‐4,5,9,10‐tetraone (PTO) through partial lithiation. The lithiated PTO ends up harder than the treated Li6PS5Cl, thus forming the favorable "active material‐in‐electrolyte" microstructure. Cell performance improved as a result, including a 91% increase in material utilization compared with electrodes with unfavorable microstructures, as well as enhanced discharge−charge rates and cycling stability. Such a hardness manipulation strategy has broad applications in solid‐state devices and energy storage. [ABSTRACT FROM AUTHOR]

Background: Left bundle branch area pacing (LBBAP) is safe and effective, but studies in older patients are lacking. This study compared the clinical and echocardiographic outcomes of LBBAP and right ventricular pacing (RVP) in patients aged ≥75 years. Methods: This prospective observational study included older patients with symptomatic bradycardia who underwent LBBAP or RVP between 2019 and 2022. Clinical data, including pacing and electrophysiological characteristics, echocardiographic measurements, and device‐related complications were collected. The primary endpoint was a composite of all‐cause mortality, heart failure hospitalization, and upgrade to biventricular pacing. Secondary outcomes included changes in left ventricular ejection fraction (LVEF). Results: Of 267 included patients, 110 underwent LBBAP and 157 underwent RVP. LBBAP was successful in 109 patients (success rate: 99.1%), with one patient eventually undergoing RVP. The pacing parameters of LBBAP were similar to those of RVP, except for a significantly narrower paced QRS duration (112.8 ± 11.6 vs. 138.3 ± 23.9 ms, p <.001). Ventricular lead implanting procedural duration was longer for LBBAP than RVP (14.0 vs. 6.0 min, p <.001), as was the fluoroscopy time (4.0 vs. 2.0 min, p <.001). During a mean follow‐up period of 31.0 ± 16.8 months, the primary outcome incidence was significantly lower following LBBAP than RVP (15.1% vs. 21.1%; hazard ratio, 0.471; 95% confidence interval, 0.215–1.032; p =.036) in 149 patients (55.8%) with ventricular pacing burden > 20%. RVP reduced LVEF from 62.7 ± 4.1% at baseline to 59.8 ± 7.8% at the final follow‐up (p =.001), whereas LBBAP preserved LVEF (61.4 ± 6.3% vs. 60.1 ± 7.4%, p =.429). Conclusion: LBBAP demonstrated improved clinical outcomes compared with RVP and maintained LVEF in older patients with high ventricular pacing burdens. [ABSTRACT FROM AUTHOR]

Aims: To retrospectively compare the long‐term outcomes following atrial fibrillation (AF) ablation between heart failure (HF) with preserved ejection fraction (EF) (HFpEF) and reduced/mildly reduced EF (HFr‐mrEF) patients, and to identify novel predictors of adverse clinical events. Methods: In total, 1402 AF patients with HF who underwent successful ablation were consecutively enrolled. Adverse clinical events including all‐cause death, HF hospitalization, and stroke were followed up. Cox proportional hazards models were used to assess the associations between clinical factors and events. Kaplan–Meier analysis was performed to estimate the cumulative incidences of these events. A receiver operating characteristic curve was used to test the ability of these predictors. Results: During a follow‐up period of 42 ± 15 months, 265 (18.9%) patients experienced adverse clinical events after ablation. The cumulative incidence of adverse clinical events was significantly higher in HFr‐mrEF than in HFpEF (25.4% vs. 15.7%, P < 0.001), the similar tendency was observed on all‐cause death (10.5% vs. 6.5%, P = 0.011) and HF hospitalization (17.2% vs. 10.1%, P < 0.001). After multivariate adjustment, non‐paroxysmal AF [hazard ratio (HR) 1.922, 95% confidence interval (CI) 1.130–3.268, P = 0.016], LAD ≥ 45 mm (HR 2.197, 95% CI 1.206–4.003, P < 0.001), LVEF (HR 0.959, 95% CI 0.946–0.981, P < 0.001), and RAD ≥ 45 mm (HR 2.044, 95% CI 1.362–3.238, P < 0.001) remained the independent predictors for developing adverse clinical events. A predictive model performed with non‐paroxysmal AF, LAD ≥ 45 mm and RAD ≥ 45 mm yielded an area under curve of 0.728 (95% CI 0.696–0.760, P < 0.001). Conclusions: AF patients with HFpEF had better long‐term outcomes than those with HFr‐mrEF, and moderate/severe biatrial dilation could predict adverse clinical events following catheter ablation in AF and HF patients. [ABSTRACT FROM AUTHOR]

Background: Substantial focus has been placed on atrial fibrillation (AF) treatment and associated stroke prevention rather than preventing AF itself. We employed Mendelian randomization (MR) approach to examine the causal relationships between 50 modifiable risk factors (RFs) and AF. Methods: Instrumental variables for genetically predicted exposures were derived from corresponding genome‐wide association studies (GWASs). Summary‐level statistical data for AF were obtained from a GWAS meta‐analysis (discovery dataset, N = 1,030,836) and FinnGen (validation dataset, N = 208,594). Univariable and multivariable MR analyses were performed, primarily using inverse variance weighted method with a series of robust sensitivity analyses. Results: Genetic predisposition to insomnia, daytime naps, apnea, smoking initiation, moderate to vigorous physical activity and obesity traits, including body mass index, waist–hip ratio, central and peripheral fat/fat‐free mass, exhibited significant associations with an increased risk of AF. Coffee consumption and ApoB had suggestive increased risks. Hypertension (odds ratio (OR) 95% confidence interval (CI): 5.26 (4.42, 6.24)), heart failure (HF) (OR 95% CI, 4.77 (2.43, 9.37)) and coronary artery disease (CAD) (OR 95% CI: 1.20 (1.16, 1.24)) were strongly associated with AF, while college degree, higher education attachment and HDL levels were associated with a decreased AF risk. Reverse MR found a bidirectional relationship between genetically predicted AF and CAD, HF and ischemic stroke. Multivariable analysis further indicated that obesity‐related traits, systolic blood pressure and lower HDL levels independently contributed to the development of AF. Conclusions: This study identified several lifestyles and cardiometabolic factors that might be causally related to AF, underscoring the importance of a holistic approach to AF management and prevention. [ABSTRACT FROM AUTHOR]

In this study, we have successfully synthesized two non‐metallic‐based silicon corrole complexes (F10C−Si, F10C−CN−Si) and used them as HER electrocatalysts for the first time. Electrochemical studies indicate the electrocatalytic HER may go via EE‐CEEC (E: electron transfer step, C: chemical step) pathway. Notably, it can be seen that the introduction of electron‐withdrawing cyano group on the meso‐phenyl of the corrole macrocycle may enhance the catalytic activity of silicon corrole complexes. In DMF with TsOH as the proton source, F10C−CN−Si exhibits a turnover frequency (TOF) of 331.48 s−1 and a high catalytic efficiency (C.E) of 1.29. Furthermore, the catalytic prowess of the silicon corrole complexes extends to neutral aqueous solution, with F10C−CN−Si achieving a TOF of 52.72 h−1 at an overpotential of 1188 mV. This study extends the application of non‐metallic‐based silicon corrole molecular catalysts in the electrocatalytic HER field. [ABSTRACT FROM AUTHOR]

A highly efficient chlorobenzene‐degrading strain was isolated from the sludge of a sewage treatment plant associated with a pharmaceutical company. The strain exhibited a similarity of over 99.9% with multiple strains of Paenarthrobacter ureafaciens. Therefore, the strain was suggested to be P. ureafaciens LY. This novel strain exhibited a broad spectrum of pollutant degradation capabilities, effectively degrading chlorobenzene and other organic pollutants, such as 1, 2, 4‐trichlorobenzene, phenol, and xylene. Moreover, P. ureafaciens LY co‐metabolized mixtures of chlorobenzene with 1, 2, 4‐trichlorobenzene or phenol. Evaluation of its degradation efficiency showed that it achieved an impressive degradation rate of 94.78% for chlorobenzene within 8 h. The Haldane–Andrews model was used to describe the growth of P. ureafaciens LY under specific pollutants and its concentrations, revealing a maximum specific growth rate (μmax) of 0.33 h−1. The isolation and characterization of P. ureafaciens LY, along with its ability to degrade chlorobenzene, provides valuable insights for the development of efficient and eco‐friendly approaches to mitigate chlorobenzene contamination. Additionally, investigation of the degradation performance of the strain in the presence of other pollutants offers important information for understanding the complexities of co‐metabolism in mixed‐pollutant environments. Significance statement: The degradation efficiency of chlorobenzene in waste gas is difficult to deal with its high volatility and molecular stability. However, the research on treatment technology of typical chlorine‐containing volatile organic compounds is still concerned. A highly efficient chlorobenzene‐degrading strain, identified as Paenarthrobacter ureafaciens LY, was successfully isolated from the sludge of a sewage treatment plant associated with a pharmaceutical factory. Its degradation efficiency was evaluated and found that it achieved an impressive degradation rate of chlorobenzene within 8 h. We believe that our study makes a contribution to the insight into solving the pollution of chlorobenzene. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the anatomical variations in femoral vasculature and evaluate the clinical value of ultrasound‐guided femoral vein puncture in catheter ablation procedures. Methods: In this retrospective analysis conducted from January 2023 to March 2023, we examined data from patients who underwent catheter ablation with ultrasound‐guided femoral venipuncture. We evaluated the anatomy of the femoral vasculature at both high and low inguinal levels. Based on the relationship between the femoral vein and artery, we classified the anatomy into four types: Type I (vein parallel to artery without overlap), Type II (vein medial to artery with lumen overlap ≤50%), Type III (vein posterior to artery with lumen overlap > 50%), and Type IV (vein lateral to artery). Additionally, we assessed procedure‐related vascular complications that required interventions or prolonged hospital stays. Results: A total of 254 patients were included in this study. At the upper inguinal level, most cases (92.5%) exhibited Type II, followed by Type I (6.5%), while Type III (0.6%) and IV (0.4%) were less common. At the lower inguinal level, Type II accounted for 70.7%, there was a significantly higher proportion of Type III (23.4%) and Type IV (5.9%). The overall complication rate was 0.4%, no pseudoaneurysm or hematoma was observed in our study. Conclusion: Our study revealed significant anatomical variations in the relationship between the femoral vein and femoral artery. Ultrasound‐guided femoral venipuncture significantly reduced vascular complication rate, making it a valuable tool for guiding puncture procedures. [ABSTRACT FROM AUTHOR]

Adverse childhood experiences (ACEs) have been associated with poor HIV testing in adulthood yet, they have not been extensively described in those at increased risk for HIV. Cross‐sectional analysis data (n = 204,231) on ACEs and HIV testing were obtained from the 2019–2020 Behavioural Risk Factor Surveillance Survey. Weighted logistic regression models were used to access the association of ACEs exposure, ACEs score, and ACEs type with HIV testing among adults with HIV risk behaviours, and stratified analysis was also performed to examine gender differences. The results indicated the overall rate of HIV testing was 38.8% and was higher among those with HIV risk behaviours (64.6%) than those without (37.2%). In populations with HIV risk behaviours, the negative association of HIV testing with ACEs exposure, ACEs score, and ACEs type was identified. Relative to those without ACEs, adults who were exposed to ACEs might decrease the rate of HIV testing, participants with ≥4 ACEs scores were less likely to have HIV testing, and childhood exposure to sexual abuse had the greatest impact on HIV testing. For both males and females, childhood exposure to ACEs was associated with lower odds of HIV testing and ACEs score ≥4 had the most robust associations with HIV testing. For males, those who experienced witnessed domestic violence had the lowest odds of HIV testing but the odds of engaging in HIV testing for females were the lowest among those who experienced childhood sexual abuse. [ABSTRACT FROM AUTHOR]

Summary: Plants experience numerous biotic stresses throughout their lifespan, such as pathogens and pests, which can substantially affect crop production. In response, plants have evolved various metabolites that help them withstand these stresses. Here, we show that two specialized metabolites in the herbaceous perennial Belamcanda chinensis, tectorigenin and its glycoside tectoridin, have diverse defensive effects against phytopathogenic microorganisms and antifeeding effects against insect pest. We further functionally characterized a 7‐O‐uridine diphosphate glycosyltransferase Bc7OUGT, which catalyses a novel reversible glycosylation of tectorigenin and tectoridin. To elucidate the catalytic mechanisms of Bc7OUGT, we solved its crystal structure in complex with UDP and UDP/tectorigenin respectively. Structural analysis revealed the Bc7OUGT possesses a narrow but novel substrate‐binding pocket made up by plentiful aromatic residues. Further structure‐guided mutagenesis of these residues increased both glycosylation and deglycosylation activities. The catalytic reversibility of Bc7OUGT was also successfully applied in an one‐pot aglycon exchange reaction. Our findings demonstrated the promising biopesticide activity of tectorigenin and its glycosides, and the characterization and mechanistic study of Bc7OUGT could facilitate the design of novel reversible UGTs to produce valuable glycosides with health benefits for both plants and humans. [ABSTRACT FROM AUTHOR]

Background. Limited randomized controlled studies showed that thoracoscopic surgical left atrial ablation was not superior to catheter ablation (CA) in patients with persistent atrial fibrillation (PerAF). Right atrium might play an important role in triggering and maintaining atrial fibrillation (AF) in patients with PerAF. This study aimed to compare the efficacy of thoracoscopic surgical biatrial ablation versus CA in patients with PerAF. Methods. Patients with PerAF underwent thoracoscopic surgical biatrial ablation or CA were included in this study. Propensity score matching (1 : 2) was applied to select patients in CA group and surgical ablation (SA) group. The primary endpoint was to compare the probability of freedom from atrial tachyarrhythmias between SA and CA. Atrial tachyarrhythmia recurrence was defined as any atrial tachyarrhythmias longer than 30 s documented by 24-hour Holter monitoring after the 3-month blanking period. Results. After propensity score matching, 51 patients in surgical biatrial ablation group and 102 patients in CA group were enrolled (mean left atrial diameter: 45.8 mm). The probability of freedom from atrial tachyarrhythmias on antiarrhythmia drugs was 62.7%, 60.6%, and 60.6% in SA group and 42.0%, 39.6%, and 36.7% in CA group at 12, 24, and 36 months, respectively (p = 0.011), and off antiarrhythmia drugs were 56.9%, 52.5%, and 52.5% in SA group and 36.0%, 31.4%, and 27.5% in CA group at 12, 24, and 36 months, respectively (p = 0.007). After adjustment of age, sex, left atrial diameter, and AF duration history, multivariable Cox regression analysis suggested that SA procedure was an independent factor to reduce the risk of atrial tachyarrhythmia recurrence (HR: 0.589, 95% CI 0.370–0.937, p = 0.025). Conclusion. Compared with CA, thoracoscopic surgical biatrial ablation might achieve superior effectiveness for patients with PerAF. [ABSTRACT FROM AUTHOR]

Solid‐state lithium metal batteries have emerged as a promising technology for electric vehicles due to their high specific energy and safety potential. Obtaining intimate contact between Li and electrolyte during cell fabrication, however, remains challenging. Adequate fabrication pressure is required to promote close contact, but this pressure can cause Li deformation and penetration into the electrolyte, resulting in poor battery performance. Here, a strategy for addressing this problem is presented by incorporating 3 at% Mg into Li. Unlike pure Li which obeys the Voce hardening law and allows unconstrained deformation, Li─Mg alloy follows the Swift hardening law and strengthens with strain under compression stress. Because of the constrained deformation of Li─Mg, intimate contact with solid electrolytes is possible even at high fabrication pressure (50–65 MPa), resulting in high critical current densities. These findings underscore the importance of understanding Li metal deformation properties to improve solid‐state battery performance. [ABSTRACT FROM AUTHOR]

Introduction: To investigate the optimal range of quantitative ablation index (AI) value during superior vena cava (SVC) electrical isolation by radiofrequency catheter ablation (RFCA). Methods: First, in a development cohort of patients with atrial fibrillation (AF), the RFCA with 40 W was performed to complete SVC isolation guided by the conduction breakthrough point from the right atrium to SVC. Then, the range of AI value was calculated by offline analysis on different segments of SVC. Lastly, for the validation of AF patients, the safety and effectiveness of SVC isolation with the optimized target range of AI value were evaluated with an additional adenosine test. Results: A total of 101 patients with AF were included in the study (44 patients in the development cohort/57 in the validation cohort). The segmental ablation strategy was applied in 70% of the patients. According to the offline analysis of the AI values in the development cohort, the target AI value range was set as 350–400. The success rate of SVC isolation in the validation cohort was significantly higher than that in the exploration cohort (100% vs. 90.9%, p =.02), and no complications occurred in the exploration cohort. During the adenosine test, the recovery rate of electrical conduction in SVC was significantly lower than that in the pulmonary vein (3.5% vs. 17.5%). Conclusion: The target AI value with a range from 350 to 400 is safe and effective for high‐power RFCA to complete SVC isolation. [ABSTRACT FROM AUTHOR]

Organic electrode materials could revolutionize batteries because of their high energy densities, the use of Earth‐abundant elements, and structural diversity which allows fine‐tuning of electrochemical properties. However, small organic molecules and intermediates formed during their redox cycling in lithium‐ion batteries (LIBs) have high solubility in organic electrolytes, leading to rapid decay of cycling performance. We report the use of three cyclotetrabenzil octaketone macrocycles as cathode materials for LIBs. The rigid and insoluble naphthalene‐based cyclotetrabenzil reversibly accepts eight electrons in a two‐step process with a specific capacity of 279 mAh g−1 and a stable cycling performance with ≈65 % capacity retention after 135 cycles. DFT calculations indicate that its reduction increases both ring strain and ring rigidity, as demonstrated by computed high distortion energies, repulsive regions in NCI plots, and close [C⋅⋅⋅C] contacts between the naphthalenes. This work highlights the importance of shape‐persistency and ring strain in the design of redox‐active macrocycles that maintain very low solubility in various redox states. [ABSTRACT FROM AUTHOR]

The exceptional versatility of carboxylic acids has been extensively exploited in organic synthesis across several decades. There has been a recent upsurge of radical decarboxylative transformations. The process can be initiated under mild conditions, and the resultant radicals have orthogonal reactivities to closed‐shell species, thus providing immense opportunities for streamlining novel reactions. The use of free carboxylic acids is the most desirable owing to its high atom and step economy. Aiming to demonstrate the attractiveness of the strategy and to inspire chemists to tackle existing challenges, this review outlines the recent advances on radical decarboxylative functionalization of free carboxylic acids. [ABSTRACT FROM AUTHOR]

Organic batteries are considered as an appealing alternative to mitigate the environmental footprint of the electrochemical energy storage technology, which relies on materials and processes requiring lower energy consumption, generation of less harmful waste and disposed material, as well as lower CO2 emissions. In the past decade, much effort has been made from fundamental understanding to practical applications in this direction. This Special Collection aims to highlight the current dynamic research environment devoted to the field of organic chemistry and materials as applied to electrochemical energy storage systems and devices. In particular, it reveals how diverse the organic materials are in the context of Li‐ion, but also next‐generation, post‐Li battery technologies. [ABSTRACT FROM AUTHOR]

Introduction: The long‐term efficacy of high‐power (50 W) ablation guided by lesion size index (LSI‐guided HP) for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF) remains undetermined. Our study sought to assess the clinical efficacy of LSI‐guided HP ablation for PVI in patients with AF and explore the potential predictors associated with clinical outcomes. Methods: We consecutively included 186 patients with AF who underwent LSI‐guided HP (50 W) ablation at Fuwai Hospital from June 2019 to October 2021. The target LSI values of 4.5–5.5 and 4.0–4.5 at the anterior and posterior walls, respectively, were used in our study. The baseline clinical characteristics, procedural and ablation data, and clinical outcomes were evaluated. The independent potential predictors associated with AF recurrence were further evaluated. Results: The incidence rate of first‐pass PVI was 83.9% (156/186). A total of 11 883 lesions were analyzed, and compared with posterior walls of pulmonary veins, anterior walls had significantly lower mean contact force (8.2 ± 3.0 vs. 8.3 ± 2.3 g, p =.015), longer mean radiofrequency duration (16.9 ± 7.2 vs. 12.9 ± 4.5 s, p <.001) and higher mean LSI (4.8 ± 0.2 vs. 4.4 ± 0.2, p <.001). The overall incidence of periprocedural complications was 3.7%, and steam pops without pericardial effusion occurred in three patients (1.6%). During a mean follow‐up of 24.0 ± 8.4 months, the overall AF recurrence‐free survival was 87.1% after a single procedure. Patients with paroxysmal AF had a higher incidence of freedom from AF recurrence than those with persistent AF (91.2% vs. 80.8%, log‐rank p =.034). Higher LSI (HR 0.50, p <.001) and paroxysmal AF (HR 0.39, p =.029) were significantly associated with decreased AF recurrence. By receiver operating characteristic analysis, the LSI of 4.7 and 4.3 for the anterior and posterior walls of the PVs had the highest predictive value for AF recurrence, respectively. Conclusion: LSI‐guided HP (50 W) ablation for PVI was an efficient and safe strategy and led to favorable single‐procedure 2‐year AF recurrence‐free survival in patients with AF. Higher LSI and paroxysmal AF were independent predictors of decreased 2‐year AF recurrence. The LSI of 4.7 for the anterior wall and 4.3 for the posterior wall of the PVs were the best cutoff values for predicting AF recurrence after LSI‐guided HP ablation. [ABSTRACT FROM AUTHOR]

Non‐alcoholic fatty liver disease (NAFLD) is a major health problem in Western countries and has become the most common cause of chronic liver disease. Although NAFLD is closely associated with obesity, inflammation, and insulin resistance, its pathogenesis remains unclear. The disease begins with excessive accumulation of triglycerides in the liver, which in turn leads to liver cell damage, steatosis, inflammation, and so on. P38γ is one of the four isoforms of P38 mitogen‐activated protein kinases (P38 MAPKs) that contributes to inflammation in different diseases. In this research, we investigated the role of P38γ in NAFLD. In vivo, a NAFLD model was established by feeding C57BL/6J mice with a methionine‐ and choline‐deficient (MCD) diet and adeno‐associated virus (AAV9‐shRNA‐P38γ) was injected into C57BL/6J mice by tail vein for knockdown P38γ. The results indicated that the expression level of P38γ was upregulated in MCD‐fed mice. Furthermore, the downregulation of P38γ significantly attenuated liver injury and lipid accumulation in mice. In vitro, mouse hepatocytes AML‐12 were treated with free fatty acid (FFA). We found that P38γ was obviously increased in FFA‐treated AML‐12 cells, whereas knockdown of P38γ significantly suppressed lipid accumulation in FFA‐treated AML‐12 cells. Furthermore, P38γ regulated the Janus Kinase‐Signal transducers and activators of transcription (JAK–STAT) signaling pathway. Inhibition of P38γ can inhibit the JAK–STAT signaling pathway, thereby inhibiting lipid accumulation in FFA‐treated AML‐12 cells. In conclusion, our results suggest that targeting P38γ contributes to the suppression of lipid accumulation in fatty liver disease. [ABSTRACT FROM AUTHOR]

Accurate prediction the curing‐induced deformation is the key to the fabrication of high‐quality composite structures. Aiming at controlling shape distortion of curved‐surface parts during curing process, a layup optimization strategy is proposed based on a variable stiffness (VS) placement method, which uses geodesic curves as fiber‐tow paths. Taking an offset parabolic antenna reflector (PAR) for example, chemical shrinkage and thermal deformation of curved‐surface composites during the curing process and after demolding are modeled. By combining Fourier heat conduction theory, curing kinetics, and generalized Maxwell viscoelastic model, the interactions between chemical cross‐link reaction, heat transfer, and mechanical deformation are taken into account. By comparing the deformation characteristics of VS and traditional constant stiffness structures, the proposed simulation strategy of curing process for composites can predict the factors that influence the curing deformation of VS structures are analyzed. The results show that the maximum of VS PAR decreases by 11.02%, and the average magnitude decreases by 32.35%. [ABSTRACT FROM AUTHOR]

SUMMARY: Benzylisoquinoline alkaloids (BIAs) are a class of plant secondary metabolites with great pharmacological value. Their biosynthetic pathways have been extensively elucidated in the species from the Ranunculales order, such as poppy and Coptis japonica, in which methylation events play central roles and are directly responsible for BIA chemodiversity. Here, we combined BIA quantitative profiling and transcriptomic analyses to identify novel BIA methyltransferases (MTs) from Liriodendron chinense, a basal angiosperm plant. We identified an N‐methyltransferase (LcNMT1) and two O‐methyltransferases (LcOMT1 and LcOMT3), and characterized their biochemical functions in vitro. LcNMT1 methylates (S)‐coclaurine to produce mono‐ and dimethylated products. Mutagenesis experiments revealed that a single‐residue alteration is sufficient to change its substrate selectivity. LcOMT1 methylates (S)‐norcoclaurine at the C6 site and LcOMT3 methylates (S)‐coclaurine at the C7 site, respectively. Two key residues of LcOMT3, A115 and T301, are identified as important contributors to its catalytic activity. Compared with Ranunculales‐derived NMTs, Magnoliales‐derived NMTs were less abundant and had narrower substrate specificity, indicating that NMT expansion has contributed substantially to BIA chemodiversity in angiosperms, particularly in Ranunculales species. In summary, we not only characterized three novel enzymes that could be useful in the biosynthetic production of valuable BIAs but also shed light on the molecular origin of BIAs during angiosperm evolution. Significance Statement: Benzylisoquinoline alkaloids (BIAs) are a class of plant secondary metabolites with great pharmacological value. Our study identified and functionally characterized a BIA N‐methyltransferase (LcNMT1) and two O‐methyltransferases (LcOMT1 and LcOMT3) in Liriodendron chinense, the first to be characterized from Magnoliid species. The magnoliales‐derived NMTs were less abundant and had narrower substrate specificity, suggesting that NMT expansion has contributed substantially to BIA chemodiversity in angiosperms, especially in Ranunculales species. [ABSTRACT FROM AUTHOR]

Nuclear methods, such as the study of the main components of nuclear and the support of vector machines, have gradually evolved into a type of pillar methods for pattern recognition and economic statistics. Therefore, how to choose the inner product function of high-dimensional space is particularly important for the use of such methods. And, because the inner product function of high-dimensional space often determines the structure of high-dimensional space, the superiority of the kernel method is directly affected by using high-dimensional space. Due to its superior performance, the inner product function of Gaussian high-dimensional space has been put into practical use to a large extent. For the processing of unbalanced distribution of BGP data, because the results of BGP usually have multiple results, and the distribution is not uniform, so in the process of training SVM, the process of determining the composition of the hyperplane is generated due to various results The effect of the results will also be different so that the final planning equation has errors and weakens the classification ability. Finally, the BGP test results are displayed. The results show that the operation of the SVM algorithm can complete the supervision and management of BGP abnormal data. If there is any data fluctuation, an alarm will be issued. Under the condition of ensuring the correct rate, the input characteristics of BGP can be reduced in dimensionality, and specific selection methods can be used to complete. A high-level algorithm is used here, so that it has a better SVM classification effect, and abnormal traffic can be more conveniently and quickly checked out of BGP. It can be seen from the results of statistical analysis of urban and rural data that the current gap between urban and rural economic development level is too large, and to some extent, there is a trend of increasing fault, which will undoubtedly affect the stability of urban and rural areas, so the urban-rural income gap should be narrowed. We have also studied the principle of the general preferential economy in rural areas and put forward relevant effective strategy. [ABSTRACT FROM AUTHOR]

Purpose: Whether left bundle branch area pacing (LBBAP) could be achieved in patients with hypertrophic cardiomyopathy (HCM) requiring ventricular pacing remains unknown. The present study aimed to investigate the feasibility and effect of LBBAP in HCM. Methods: Patients with HCM who underwent LBBAP were recruited from November 2018 to September 2021. Clinical characteristics, echocardiographic, and pacing parameters were prospectively collected at baseline and during follow‐up. Results: Eleven consecutive HCM patients who attempted LBBAP were included (mean age 64.0 ± 8.7 years, female 45.5%, mean interventricular septum 16.7 mm). The success rate of LBBAP was 36.4% (4/11) and the reason for failed LBBAP in other seven HCM patients was the inability to screw the lead into the deep septum or capture the left bundle branch. Patients with successful LBBAP had significantly narrower QRS duration than those with failed cases (118.0 ± 3.7 ms vs. 140.9 ± 9.4 ms, p =.01) while the capture thresholds, sensing amplitudes, and pacing impedances were similar. Successful cases presented with less positive late gadolinium enhancement (25.0% vs. 71.4%, p =.02) and thinner interventricular septum thickness (14.5 ± 1.0 mm vs. 18.0 ± 2.5 mm, p =.02) compared with failed cases. Pacing parameters remained stable and no procedure‐related complications occurred during a mean follow‐up of 8.9 ± 7.3 months. Conclusion: LBBAP may be successfully achieved in less than half of HCM patients due to thick interventricular septum and heavy burden of myocardial fibrosis. Pacing strategies should be cautiously considered in patients with HCM. [ABSTRACT FROM AUTHOR]

Legged robot has attracted wide attention because of its outstanding mobility and flexibility in the off‐road environment. Benefitting from the smooth foot trajectory and the discrete footholds, the robot can traverse the rough terrains with a great maneuverability. This paper studies a portable off‐road crawling hexapod robot with a flat structure of Schatz linkage. The proposed crawling hexapod robot could be stacked flatly with a compact size, which is good for storage and transportation. What's more, the robot could play an important role in the search and rescue mission. It could protect the operator from an incident like a collapsing wall. The robot has four locomotion gaits to meet different demands on rough terrains, including the hexapod gait, the tripod gait, the butterfly stroke gait, and the escape gait. A prototype of the robot system is fabricated. A series of experiments and simulated search and rescue missions are conducted, and the results verify that the robot could traverse through the rough terrain and complete the tasks required in the search and rescue mission. [ABSTRACT FROM AUTHOR]

Diarrhea is one of the leading causes of death among children, especially in the age under 5, but few studies are available on viral diarrhea in Shenyang. To understand the infection status and the relevant epidemiological characteristics of viral diarrhea and to fill gaps of the distribution of viruses across Shenyang in children under the age of 5 with diarrhea, from 2018 to 2020, stool specimens of children with diarrhea aged 0–59 months and surveillance data were collected in Sentinel Hospital of Shenyang. Specimens were then tested to determine the type of viruses, the seasonal and spatial patterns for major viruses were determined. Viruses were identified in 47.9% of the 897 samples from children with diarrhea. The main viruses of stool samples were rotavirus (16.9%, predominant type G9P[8]), calicivirus (14.7%), adenovirus (11.8%), and astrovirus (4.5%). Viral infections were mainly detected in the age of 0–12 months. In the area of Shenyang, Huanggu had the most cases (198, 22.1%), followed by Dadong (137, 15.3%) and Hunnan (135, 15.1%). The positive rate of viruses varied among patients of different ages, seasons, and regions. Public health entities and the government should develop corresponding measures for different age groups, seasons, and regions. Highlights: Occurrence of enteric virus infections in cases of virus diarrhea.Rotavirus is the predominant viral agents infecting hospitalized children under the age of five.Infection rate of viruses varied over the place in both urban and rural areas of Shenyang. [ABSTRACT FROM AUTHOR]

The size of lipid droplets varies greatly in vivo and is determined by both intrinsic and extrinsic factors. From an RNAi screen in Drosophila, we found that knocking down subunits of COP9 signalosome (CSN) results in enlarged lipid droplets under high‐fat, but not normal, conditions. We identified CG2064, a retinol dehydrogenase (RDH) homolog, as the proteasomal degradation target of CSN in regulating lipid droplet size. RDH/CG2064 interacts with the lipid droplet‐resident protein Plin2 and the RDH/CG2064‐Plin2 axis acts to reduce the overall level and lipid droplet localization of Bmm/ATGL lipase. This axis is important for larval survival under prolonged starvation. Thus, we discovered an RDH‐Plin2 axis modulates lipid droplet size. SYNOPSIS: An RNAi screen identifies subunits of COP9 signalosome (CSN) as negative regulators of lipid droplet formation under high fat conditions. CSN induces proteasomal degradation of RDH, which promotes Plin2 localization to the perinuclear lipid droplets. CSN deficiency causes formation of large lipid droplets under high‐fat conditions.CSN regulates lipid droplet size by proteasomal degradation of RDH/CG2064.RDH/CG2064 interacts with Plin2 and promotes its localization to the perinuclear lipid droplets.The RDH‐Plin2 axis acts to reduce the overall level and lipid droplet localization of Bmm/ATGL lipase. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to assess whether left bundle branch area pacing (LBBAP) can result in favorable clinical and echocardiographic outcomes among patients with persistent atrial fibrillation (PeAF). Methods: We prospectively enrolled consecutive patients with PeAF if they required ventricular pacing and had left ventricular ejection fraction (LVEF) > 35%. During the same period, two experienced operators performed LBBAP and right ventricular pacing (RVP). All‐cause death and heart failure hospitalization (HFH) were routinely followed after procedure. The primary outcome was the composite endpoints of all‐cause death or HFH. Results: LBBAP was successful in 49 of 52 patients (94.2%), whereas 44 patients received RVP. During a mean follow‐up of 13.9 ± 7.0 months, LBBAP group presented with higher ventricular pacing percentage (80% vs. 50.9%, p =.04) and narrower paced QRS duration (117.2 ± 18.8 ms vs. 151.8 ± 13.7 ms, p <.001) than RVP group. The primary endpoint was slightly reduced in LBBAP group than RVP without reaching statistical significance (7.7% vs. 11.4%, p =.48). Compared with baseline, we observed significant changes in LVEF (+0.7% vs. −2.2%, p =.007) and left atrial diameter (−1.63 mm vs. +1.23 mm, p =.011) between LBBAP and RVP. Conclusion: Our results indicate possible effect of LBBAP on reverse remodeling of left atrium and a trend towards favorable clinical outcomes in patients with PeAF requiring high burden of ventricular pacing when compared with RVP. [ABSTRACT FROM AUTHOR]

Sedimentary successions of the Frasnian–Tournaisian (Late Devonian to Earliest Carboniferous) and their spatial distributions in the Hainan Island, South China are critically reviewed based on updated information of the previously published data and newly obtained fossils. The Upper Devonian strata are assigned to the Frasnian Lanyang Formation and Famennian Changjiang Formation, which are distributed in north‐western Hainan Island. The Lanyang Formation is represented by limestone, siltstone, slate, and intercalated with tuff, and yields tentaculites: Polycylindrites sp., stromatoporoids, and tabulate corals. The Changjiang Formation yields abundant conodonts Palmatolepis gracilis sigmoidalis and Polynodosus germanus, typical of Famennian assemblages, and the associated faunas include corals, radiolarians, foraminifers, and calcareous algae of Famennian age. Of these, corals are assignable to the upper Famennian Cystophrentis Zone of South China. The strata of the Tournaisian Jishi Formation are categorized into two types, typically exposed in the Shilu and Jinbo areas, respectively, both of which are located north to the Gancheng‐Wanning Fault. The lower Jishi Formation yields brachiopods Unispirifer (Unispirifer) extensus, Unispirifer sp., Schuchertella magna, and gastropods. The middle Jishi Formation yields conodonts: Siphonodella isosticha and S. levis, brachiopods: Unispirifer (Unispirifer) forbesi, Atylephorus tornacensis, coral: Pseudouralinia irregularis, trilobite: Weberiphillipsia linguiformis, ostracods, bryozoans, and foraminifers. The conodonts are assignable to the zonation equivalent to the Siphonodella sulcata Zone, implying the Devonian–Carboniferous boundary is placed at the base of the middle part of the formation. The upper part of the Jishi Formation yields abundant brachiopods characterized by Mesochorispira subgrandis, Atylephorus tornacensis, and Marginatia huaqiaoensis. The presence of corals Cystophrentis, Pseudouralinia, Zaphrentites, and Kueichowpora, and trilobite Hunanoproetus, endemic to South China from the Changjiang and Jishi formations implies that the Hainan Island was palaeobiogeographically close to the South China Block of the Tethyan Realm, rather than of Gondwana affinity during the Late Devonian and Tournaisian. Identification of Xinanosprifer flabellum and Homotoma sp., typical of early Silurian from the 'Nanhao Formation' previously assigned to the Tournaisian suggests that no Carboniferous strata are distributed in southern Hainan Island and the area south of the Gancheng‐Wanning Fault. [ABSTRACT FROM AUTHOR]

Alteration of tissue inhibitors of matrix metalloproteinases (TIMP)/matrix metalloproteinases (MMP) associated with collagen upregulation has an important role in sustained atrial fibrillation (AF). The expression of miR‐146b‐5p, whose the targeted gene is TIMPs, is upregulated in atrial cardiomyocytes during AF. This study was to determine whether miR‐146b‐5p could regulate the gene expression of TIMP4 and the contribution of miRNA to atrial fibrosis in AF. Collagen synthesis was observed after miR‐146b‐5p transfection in human induced pluripotent stem cell‐derived atrial cardiomyocytes (hiPSC‐aCMs)‐fibroblast co‐culture cellular model in vitro. Furthermore, a myocardial infarction (MI) mouse model was used to confirm the protective effect of miR‐146b‐5p downregulation on atrial fibrosis. The expression level of miR‐146b‐5p was upregulated, while the expression level of TIMP4 was downregulated in the fibrotic atrium of canine with AF. miR‐146b‐5p transfection in hiPSC‐aCMs‐fibroblast co‐culture cellular model increased collagen synthesis by regulating TIMP4/MMP9 mediated extracellular matrix proteins synthesis. The inhibition of miR‐146b‐5p expression reduced the phenotypes of cardiac fibrosis in the MI mouse model. Fibrotic marker MMP9, TGFB1 and COL1A1 were significantly downregulated, while TIMP4 was significantly upregulated (at both mRNA and protein levels) by miR‐146b‐5p inhibition in cardiomyocytes of MI heart. We concluded that collagen fibres were accumulated in extracellular space on miR‐146b‐5p overexpressed co‐culture cellular model. Moreover, the cardiac fibrosis induced by MI was attenuated in antagomiR‐146 treated mice by increasing the expression of TIMP4, which indicated that the inhibition of miR‐146b‐5p might become an effective therapeutic approach for preventing atrial fibrosis. [ABSTRACT FROM AUTHOR]

Background: The effects of epicardial connections (ECs) involving pulmonary veins (PVs) in atrial fibrillation (AF) ablation have been revealed recently. However, no systematic approaches to identify and ablate the ECs were established. Methods: Patients with AF undergoing radiofrequency (RF) catheter ablation were retrospectively analyzed. ECs were identified when (1) PV isolation (PVI) cannot be achieved after first‐pass isolation; (2) PVI was still absent although the conduction gap was detected and ablated; (3) the earliest activation area (EAA) was revealed located within the PV antrum distant from the initial ablation line using high‐density mapping (HDM) technique; (4) focal ablation at the EAA was effective to achieve PVI. Relevant pacing maneuvers were performed to elucidate ECs' bidirectional conduction. Results: Overall, 36 ECs were identified and ablated in 35/597 (5.86%) patients. Among the 35 patients with ECs, at least one PV insertion of ECs was located at the carina region. The most common pattern was a single breakthrough in 31 (88.6%) patients, followed by multiple breakthroughs in 3 and wide breakthroughs in 1. The median distance from EAA to the initial ablation line was 10.0 mm. The average number of RF energy delivery was 1.75 ± 1.00, and single RF delivery was adequate in 16/36 (44.4%) patients. Continuous potentials were present at the EAA in 9/34 (26.5%) patients. Conclusion: ECs were confirmed and ablated successfully in 5.86% (35/597) AF patients using HDM. PV insertions of ECs were mainly located at the carina region. Continuous potentials might assist in the prediction of ECs. [ABSTRACT FROM AUTHOR]

An efficient paired electrosynthesis of functionalized aromatic azo compounds through a diazenyl radical pathway has been developed. The paired electrolysis simultaneously uses the anode and cathode reactions to avoid the electricity expense of oxidation/reduction of sacrificial substances, thereby maximizing energy efficiency and achieving high atom economy. The in vitro cytotoxicity of all compounds was evaluated against four cancer cell lines by MTT assay. Results showed that the aromatic azo compounds exhibited good antitumor activity in vitro, and one of the compounds induced tumor cell apoptosis. [ABSTRACT FROM AUTHOR]

BACKGROUND The present work focuses on a harmless treatment of hazardous substances in spent commercial selective catalytic reduction (SCR) catalyst by using cement as a binder. The spent V2O5‐WO3/TiO2 SCR catalysts were ground and mixed with the cement to prepare the solidified products, according to a simple method in this study. The solidified products were subsequently submitted to a characterization process based on inductively coupled plasma mass spectrometry (ICP‐MS), X‐ray diffraction (XRD), X‐ray fluorescence (XRF), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and N2 adsorption–desorption analysis. The leaching characteristics of hazardous substances, such as V, As, Cr and Pb, in solidified products were studied and the effects of mixed ratio between deactivated SCR catalyst and cement on leaching characteristics of hazardous substances were investigated. RESULTS: The experimental results showed that the cement was effective in immobilizing hazardous substances (V, As, Cr and Pb) present in the spent catalyst. When the cement hardened with 50% spent catalyst addition, the solidified products exhibited extremely low leaching concentrations of V, As, Cr and Pb, which are 0.6, 1.3, 2.3 mg L−1 and 16.5 μg L−1, respectively. CONCLUSION: The leaching toxicity of hazardous substances is far lower than that of the National Standard of China and European regulations. The characterization analysis revealed that the active silicate sand hydroxyl compounds play an important role in immobilizing hazardous substances in spent SCR catalyst. The cement solidification method was expected to achieve the harmless treatment on spent SCR catalyst for the first time. © 2020 Society of Chemical Industry (SCI) [ABSTRACT FROM AUTHOR]

Organic photovoltaic (OPV) devices offer a number of unique advantages over conventional single crystal silicon solar cells, such as simple and low‐cost fabrication, significantly reduced weight, high flexibility, and semitransparency. However, OPV devices exhibit poor durability to mechanical deformations. Here, the use of an elastic semi‐interpenetrating network is studied to improve the mechanical durability of the active layer of OPV devices based on the high‐performance poly[(2,6‐(4,8‐bis(5‐(2‐ethylhexyl‐3‐fluoro)thiophen‐2‐yl)‐benzo[1,2‐b:4,5‐b′]dithiophene))‐alt‐(5,5‐(1′,3′‐di‐2‐thienyl‐5′,7′‐bis(2‐ethylhexyl)benzo[1′,2′‐c:4′,5′‐c′]dithiophene‐4,8‐dione)]:2,2′‐[[6,6,12,12‐tetrakis(4‐hexylphenyl)‐6,12‐dihydrodithieno[2,3‐d:2′,3′‐d′]‐s‐indaceno[1,2‐b:5,6‐b′]dithiophene‐2,8‐diyl]bis[methylidyne(3‐oxo‐1H‐indene‐2,1(3H)‐diylidene)]]bis[propanedinitrile] donor:acceptor blend (PBDBT‐2F:ITIC). The elastic interpenetrating network is synthesized in situ through the UV photoinitiated crosslinking of thiol–ene additives in the active layer. The effects of strain as a function of bending on the network‐stabilized active layer structure are systematically investigated. The elastic interpenetrating network suppresses crack formation and improves durability to high‐curvature and repeated bending deformations. Performance measurements show that network‐stabilized devices outperform pristine devices above a critical bending strain and number of bending deformations. The photovoltaic performance in general decreases with the increase in the network content, and the best performing devices are obtained using network forming reagents that are most compatible with the donor:acceptor system. This work describes an effective route to flexible devices using semi‐interpenetrating polymer networks and provides insight into the design of the networks to maximize photovoltaic performance. [ABSTRACT FROM AUTHOR]

Previous efforts to understand structure‐function relationships in high ionic conductivity materials for solid state batteries have predominantly relied on density functional theory (DFT‐) based ab initio molecular dynamics (MD). Such simulations, however, are computationally demanding and cannot be reasonably applied to large systems containing more than a hundred atoms. Here, an artificial neural network (ANN) is trained to accelerate the calculation of high accuracy atomic forces and energies used during such MD simulations. After carefully training a robust ANN for four and five element systems, nearly identical lithium ion diffusivities are obtained for Li10GeP2S12 (LGPS) when benchmarking the ANN‐MD results with DFT‐MD. Applying the ANN‐MD approach, the effect of chlorine doping on the lithium diffusivity is calculated in an LGPS‐like structure and it is found that a dopant concentration of 1.3% maximizes ionic conductivity. The optimal concentration balances the competing consequences of effective atomic radii and dielectric constants on lithium diffusion and agrees with the experimental composition. Performing simulations at the resolution necessary to model experimentally relevant and optimal concentrations would be infeasible with traditional DFT‐MD. Systems that require a large number of simulated atoms can be studied more efficiently while maintaining high accuracy with the proposed ANN‐MD framework. [ABSTRACT FROM AUTHOR]

Aim: To assess the electrocardiogram patterns of paced QRS narrowing after successful left bundle branch area pacing (LBBAP) and echocardiographic measurements in patients with bradycardia and bundle branch block (BBB). Methods: We prospectively enrolled 55 consecutive bradycardia patients with BBB and left ventricular ejection fraction ≥40% who had attempted LBBAP. Successful LBBAP was defined as paced QRS morphology of a right BBB (RBBB) pattern in lead V1 and a recording of abruptly shortened and then constant stimulus to peak left ventricular activation time with high and low output. Pacing characteristics and echocardiographic measurements were evaluated perioperatively and at 6‐month follow‐up. Results: The success rate of LBBAP was 83.6% in patients with BBB, and median cumulative X‐ray dose‐area product was 100.5 µGym2 (60.0, 179.3). LBBAP was successful in 19 of 26 patients with left BBB (LBBB) (73.1%) and in 27 of 29 patients with RBBB (93.1%). The QRS duration (QRSd) was significantly shortened in patients with LBBB (QRSd 169.4 ± 22.6 to 119.6 ± 9.5 ms), and five forms of QRSd narrowing were observed in patients with RBBB with the mean QRSd shortened from 143.1 ± 16.6 ms to 119.5 ± 11.7 ms. The thresholds for narrowing of QRSd were higher in RBBB than LBBB (1.74 ± 0.36 V/0.4 ms vs 0.79 ± 0.17 V/0.4 ms, P <.001). During the 6‐month follow‐up, both left and right ventricular synchronies were improved, and narrow QRSd persisted in patients with BBB. Conclusion: In most bradycardia patients, RBBB could be completely or partially narrowed by LBBAP at different pacing models in addition to the correction of LBBB with LBBAP. [ABSTRACT FROM AUTHOR]

Aims: This multicentre observational study aimed to prospectively assess the efficacy of left bundle branch area pacing (LBBAP) in heart failure patients with left bundle branch block (LBBB) and compare the 6‐month outcomes between LBBAP and biventricular pacing (BVP). Methods and results: Consecutive patients with LBBB and left ventricular ejection fraction (LVEF) ≤ 35% were prospectively recruited if they had undergone LBBAP as a primary or rescue strategy from three separate centres from March to December 2018. Patients who received BVP in 2018 were retrospectively selected by using 2 to 1 propensity score matching to minimize bias. Implant characteristics and echocardiographic parameters were assessed during the 6‐month follow‐up. LBBAP procedure succeeded in 81.1% (30/37) of patients, with selective LBBAP in 10 patients, and 3 of 20 patients combined non‐selective LBBAP and LV lead pacing for further QRS narrowing. LBBAP resulted in significant QRS narrowing (from 178.2 ± 18.8 to 121.8 ± 10.8 ms, P < 0.001, paced QRS duration ≤ 130 ms in 27 patients) and improved LVEF (from 28.8 ± 4.5% to 44.3 ± 8.7%, P < 0.001) during the 6‐month follow‐up. The comparison between 27 patients with LBBAP alone and 54 of 130 matching patients with BVP showed that LBBAP delivered a greater reduction in the QRSd (58.0 vs. 12.5 ms, P < 0.001), a greater increase in LVEF (15.6% vs. 7.0%, P < 0.001), and greater echocardiographic (88.9% vs. 66.7%, P = 0.035) and super response (44.4% vs. 16.7%, P = 0.007) to cardiac resynchronization therapy. Conclusions: LBBAP could deliver cardiac resynchronization therapy in most patients with heart failure and LBBB, and might be a promising alternative resynchronization approach to BVP. [ABSTRACT FROM AUTHOR]

Developmental processes result from interactions between the external environment and internal factors. Recent discoveries have demonstrated the essential roles of lipid metabolic homeostasis in adapting to environmental changes and fulfilling many cellular requirements during development. Lipids not only constitute biological membranes, but they also provide the most efficient form to store and supply energy upon demand, and they act as signals/messengers in diverse developmental pathways. Lipid metabolism also influences gene transcription by affecting the chromatin state and modulates protein function through post‐translational modification. This review mainly focuses on summarizing recent findings about the critical roles of lipids and lipid metabolism during development. How new lipid imaging or tracing techniques will further strengthen authors' understanding of the tight link between lipid metabolism and diverse developmental processes are also discussed. [ABSTRACT FROM AUTHOR]

Obesity and insulin resistance affect metabolic reactions, but their ensuing contributions to macrophage metabolism remain insufficiently understood. We investigated the contributions of berberine and metformin combination to the inhibition of sebocyte apoptosis in high‐fat diet‐induced diabetic hamsters and an insulin‐treated human cell line. Golden hamsters were fed a high‐glucose high‐fat diet and administered a 6‐week treatment with a combination of metformin and two concentrations of berberine (100 or 50 mg·kg−1). Body weights of treated hamsters were remarkably reduced compared with those of controls. Histological examination indicated that berberine repressed liver fat accumulation. Moreover, insulin and glucose concentrations were noticeably decreased by the combination treatments. In glucose tolerance tests, hamsters receiving berberine displayed higher tolerance to glucose, compared with the control group. Sebocytes isolated from high‐fat diet‐induced diabetic hamsters and insulin‐treated human sebocytes displayed elevated cell death rates, which were attenuated by berberine and metformin treatments. Further studies showed that the effects of metformin and berberine on cellular apoptosis were mediated via the Bik pathway. Thus, berberine may effectively decrease circulating glucose levels, ameliorate insulin resistance, reduce body weight, and attenuate sebocyte apoptosis in diabetic hamsters, potentially decreasing vulnerability to the cardiovascular complications of diabetes. Significance of the study: The present data indicate that insulin stimulates changes in the expression levels of cell death‐associated proteins, which participate in sebaceous gland diseases during obesity or diabetes. The anti‐apoptotic effects of BBR and MET in sebaceous gland cells are regulated partially by Bik expression. To the best of our knowledge, this study is the first to suggest cell death counteracting effects of BBR in hamster and human sebocytes as well as to propose BBR as an innovative therapeutic agent for insulin‐related sebaceous gland diseases, including acne. [ABSTRACT FROM AUTHOR]

Objective. Long noncoding RNA (lncRNA) and circular RNA (circRNA) are receiving increasing attention in diabetes research. However, there are still many unknown lncRNAs and circRNAs that need further study. The aim of this study is to identify new lncRNAs and circRNAs and their potential biological functions in type 2 diabetes mellitus (T2DM). Methods. RNA sequencing and differential expression analysis were used to identify the noncoding RNAs (ncRNAs) and mRNAs that were expressed abnormally between the T2DM and control groups. The competitive endogenous RNA (ceRNA) regulatory network revealed the mechanism of lncRNA and circRNA coregulating gene expression. The biological functions of lncRNA and circRNA were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The candidate hub mRNAs were selected by the protein-protein interaction (PPI) network and validated by using the Gene Expression Omnibus (GEO) database. Results. Differential expression analysis results showed that 441 lncRNAs (366 upregulated and 75 downregulated), 683 circRNAs (354 upregulated and 329 downregulated), 93 miRNAs (63 upregulated and 30 downregulated), and 2923 mRNAs (1156 upregulated and 1779 downregulated) were identified as remarkably differentially expressed in the T2DM group. The ceRNA regulatory network showed that a single lncRNA and circRNA can be associated with multiple miRNAs, and then, they coregulate more mRNAs. Functional analysis showed that differentially expressed lncRNA (DElncRNA) and differentially expressed circRNA (DEcircRNA) may play important roles in the mTOR signaling pathway, lysosomal pathway, apoptosis pathway, and tuberculosis pathway. In addition, PIK3R5, AKT2, and CLTA were hub mRNAs screened out that were enriched in an important pathway by establishing the PPI network. Conclusions. This study is the first study to explore the molecular mechanisms of lncRNA and circRNA in T2DM through the ceRNA network cofounded by lncRNA and circRNA. Our study provides a novel insight into the T2DM from the ceRNA regulatory network. [ABSTRACT FROM AUTHOR]

Aqueous batteries could be potentially used for grid‐scale energy storage owing to the use of nonflammable electrolytes and long cycle life. Recently, quinones have shown examples as redox‐active materials in aqueous batteries under either strong acidic or basic conditions. However, a quinone‐based battery with a less corrosive electrolyte is still rare. Given that quinone‐based batteries are heavily influenced by the pH of electrolytes, we studied the influence of acid dissociation constants (pKa) of hydroquinones on their performance as solid electrode materials. We measured the pKa of anthracene‐9,10‐diol (AQH2) and benzo[1,2‐b:4,5‐b′]dithiophene‐4,8‐diol (BDTDH2) from the Pourbaix diagrams of two para‐quinone monomers [i.e., anthracene‐9,10‐dione (AQ) and benzo[1,2‐b:4,5‐b′]dithiophene‐4,8‐dione (BDTD)]. Subsequently, their polymeric forms [i.e., poly(anthraquinonyl sulfide) (PAQS) and poly(benzo[1,2‐b:4,5‐b′]dithiophene‐4,8‐dione‐2,6‐diyl sulfide) (PBDTDS)] were investigated as electrodes in aqueous lithium‐ion cells. At pH 13, PAQS demonstrates a low capacity and poor cycle life, whereas PBDTDS shows a capacity of 196 mAh g−1 and fade rates of 0.0038 % per cycle over 4200 cycles, 0.77 % per day over 21 days. The differences in capacity and cycle stability can be explained by the difference of corresponding pKa values. A full cell with the configuration of (−)PBDTDS|2.5 m Li2SO4 (pH 13)|LiCoO2(+) shows a voltage of 1.08 V, a capacity of 72 mAh g−1 and ≈99.9 % of Coulombic efficiency for 500 stable cycles. [ABSTRACT FROM AUTHOR]

Long non‐coding RNAs (lncRNAs), which competitively bind miRNAs to regulate target mRNA expression in the competing endogenous RNAs (ceRNAs) network, have attracted increasing attention in breast cancer research. We aim to find more effective therapeutic targets and prognostic markers for breast cancer. LncRNA, mRNA and miRNA expression profiles of breast cancer were downloaded from TCGA database. We screened the top 5000 lncRNAs, top 5000 mRNAs and all miRNAs to perform weighted gene co‐expression network analysis. The correlation between modules and clinical information of breast cancer was identified by Pearson's correlation coefficient. Based on the most relevant modules, we constructed a ceRNA network of breast cancer. Additionally, the standard Kaplan‐Meier univariate curve analysis was adopted to identify the prognosis of lncRNAs. Ultimately, a total of 23 and 5 modules were generated in the lncRNAs/mRNAs and miRNAs co‐expression network, respectively. According to the Green module of lncRNAs/mRNAs and Blue module of miRNAs, our constructed ceRNA network consisted of 52 lncRNAs, 17miRNAs and 79 mRNAs. Through survival analysis, 5 lncRNAs (AL117190.1, COL4A2‐AS1, LINC00184, MEG3 and MIR22HG) were identified as crucial prognostic factors for patients with breast cancer. Taken together, we have identified five novel lncRNAs related to prognosis of breast cancer. Our study has contributed to the deeper understanding of the molecular mechanism of breast cancer and provided novel insights into the use of breast cancer drugs and prognosis. [ABSTRACT FROM AUTHOR]

Multiterritorial atherosclerosis has dramatically increased annual risk of adverse cardiovascular events than atherosclerotic disease with single‐artery affected. Serum uric acid (SUA) is an important predictor of stroke and atherosclerosis; however, which is supported by few direct evidence based on cohort studies. A prospective cohort study including 2644 North Chinese adults aged ≥40 years was performed in 2010‐2012 to investigate the association between SUA and multiterritorial vascular stenosis. Hyperuricaemia was defined as SUA levels >6 and >7 mg/dL for males and females, respectively. All participants underwent twice transcranial Doppler (TCD) and bilateral carotid duplex ultrasound to evaluate intracranial artery stenosis (ICAS) and extracranial arterial stenosis (ECAS) and peripheral arterial disease (PAD) was determined by ankle‐brachial index (ABI) on January 2010 and January 2012 based on regular health check‐ups. The cumulative incidence of vascular stenosis was significantly higher in subjects with hyperuricaemia than in those without hyperuricaemia (54.1% vs. 34.7%, P < 0.001). The adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for new on‐set vascular stenosis due to hyperuricaemia and a 1‐mg/dL change in SUA level were 1.75 (1.32‐2.31) and 1.29 (1.21‐1.38), respectively. Furthermore, in the gender‐stratified analysis, the association between SUA levels and ICAS was statistically significant in males (OR: 2.02; 95% CI: 1.18‐3.46), but not females (OR: 0.85, 95% CI: 0.41‐1.76, P for interaction: 0.026). [ABSTRACT FROM AUTHOR]

Previous studies on long noncoding RNA (lncRNA) have made breakthroughs in the treatment of several tumors, and these findings have brought attention to the lncRNA signature of breast cancer. Increased understanding of genomic architecture and achievement of innovative therapeutic strategies has prompted creation of a novel oncological model for the treatment of solid cancers. In this study, we systematically analyzed the transcriptome of breast cancer tissues to gain more in‐depth knowledge of tumor biology. Gene coexpression relationships were studied in 206 samples from The Cancer Genome Atlas database, and nine coexpression modules were identified. After screening and analysis, we identified four important prognosis‐related lncRNAs (HOTAIR, SNHG16, HCP5, and TINCR), and constructed a prognostic model, one (HCP5) of which has not previously been identified in the context of breast cancer. Importantly, an understanding of prognosis facilitates precise disease risk assessment and advances the selection of strategies for risk‐adaptive management. These findings broaden the landscape of carcinogenic lncRNAs in breast cancer, providing insights into the biological significance and clinical application of lncRNAs in breast cancer. [ABSTRACT FROM AUTHOR]

Background: The optimal sequence of endocrine therapy in a neoadjuvant setting for hormone receptor‐positive (HR+) breast cancer is unclear. Our study evaluated the efficacy and acceptability of neoadjuvant endocrine therapy for HR+ breast cancer. Methods: We identified studies based on titles and abstracts that were published before 22 June 2018 in the following databases: PubMed, EMBASE, and the Cochrane Library. Eligible studies were randomised controlled trials with at least one arm that evaluated the effectiveness of one or a combination of anastrozole, letrozole, palbociclib, tamoxifen, fulvestrant, abemaciclib, everolimus, gefitinib, ribociclib, taselisib, and exemestane. We pooled effect sizes using the odds ratio (OR) and corresponding 95% credibility interval (95% CrI). The primary outcomes were response rate and treatment completion. Results: Our network meta‐analysis included 3,306 participants and 16 eligible studies, which assessed 15 treatments. In terms of response rates, compared with letrozole combined therapy, tamoxifen was associated with a significant reduction in response rate (OR, 0.34; 95% CrI, 0.13–0.85; OR, 0.32; 95% CrI, 0.13–0.80; OR, 0.26; 95% CrI, 0.09–0.83; and OR, 0.30; 95% CrI, 0.09–0.96; for letrozole plus everolimus, letrozole plus taselisib, letrozole plus zoledronic acid, and letrozole plus lapatinib, respectively). Based on the surface under the cumulative ranking curves ranking, letrozole plus zoledronic acid was associated with the highest rate of response (87.6%), followed by letrozole plus lapatinib (85.2%), and letrozole plus taselisib (79.3%). Conclusions: Ultimately, our study established that letrozole plus zoledronic acid may be an optimal treatment based on its current rank in a neoadjuvant setting for HR+ breast cancer. [ABSTRACT FROM AUTHOR]

A series of fluorinated polyurethanes (FPUs) with various contents of fluorinated chain extender (EF) and the same amount of poly(oxytetramethylene glycol) and diphenylmethanediisocyanate were synthesized to explore the relationship between the surface physicochemical properties and bulk microphase separation structures of these FPUs and their antifouling activities against model bacteria and platelets. The bulk microphase separation of FPUs increased with the amount of incorporated EF. It was found that the surfaces of all FPUs were saturated by a layer of fluorocarbon chains which resulted in similar chemical composition and wetting activities for the three kinds of FPUs. The FPUs with lower or similar microphase separation compared with non‐fluorinated polyurethane chain‐extended with 1,4‐butanediol showed similar or even increased adhesion of bacteria and platelets. Notably, FPU with a higher degree of microphase separation than non‐fluorinated polyurethane displayed excellent antifouling activities against both model bacteria and blood platelets. It is therefore concluded that the increased microphase separation of the FPUs results in enhanced antifouling properties. © 2019 Society of Chemical Industry [ABSTRACT FROM AUTHOR]