Performance on adsorption of toluene by ionic liquid-modified AC in high-humidity exhaust gas.

Volatile organic compounds (VOCs) frequently pose a threat to the biosphere, impacting ecosystems, flora, fauna, and the surrounding environment. Industrial emissions of VOCs often include the presence of water vapor, which, in turn, diminishes the adsorption capacity and efficacy of adsorbents. This occurs due to the competitive adsorption of water vapor, which competes with target pollutants for adsorption sites on the adsorbent material. In this study, hydrophobic activated carbons (BMIMPF6-AC (L), BMIMPF6-AC (g), and BMIMPF6-AC-H) were successfully prepared using 1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6) to adsorb toluene under humidity environment. The adsorption performance and mechanism of the resulting ionic liquid-modified activated carbon for toluene in a high-humidity environment were evaluated to explore the potential application of ionic liquids as hydrophobic modifiers. The results indicated that BMIMPF6-AC-H exhibited superior hydrophobicity. The toluene adsorption capacity of BMIMPF6-AC-H was 1.53 times higher than that of original activated carbon, while the adsorption capacity for water vapor was only 37.30% of it at 27 °C and 77% RH. The Y-N model well-fitted the dynamic adsorption experiments. To elucidate the microscopic mechanism of hydrophobic modification, the Independent Gradient Model (IGM) method was employed to characterize the intermolecular interactions between BMIMPF6 and toluene. Overall, this study introduces a new modifier for hydrophobic modification of activated carbon, which could enhance the efficiency of activated carbon in treating industrial VOCs.

Efficacy of Catheter Ablation for Ventricular Tachycardia in Ischemic Cardiomyopathy Patients without an ICD Implantation.

BACKGROUND: Implantable cardioverter defibrillator (ICD) prevents sudden cardiac death (SCD) in patients with ischemic cardiomyopathy (ICM). Catheter ablation has been shown to effectively reduce ventricular tachycardia (VT) recurrence, yet its efficacy in patients without an ICD implantation remains uncertain. OBJECTIVE: We aimed to investigate the outcomes of ablation for VT in ICM patients without a backup ICD. METHODS: ICM patients received ablation for VT without an ICD implantation were included in this study. Ablation was guided by either activation mapping or substrate mapping. Endocardial ablation was the primary strategy; epicardial access was considered when endocardial ablation failed. The primary endpoint was VT recurrence during follow-up, with secondary endpoints including cardiovascular rehospitalization, all-cause mortality, and a composite of these events. RESULTS: A total of 114 patients were included, with the mean age of 58.2 ± 11.1 years, 102 of whom (89.5%) were male.Twelve patients (10.5%) underwent endo-epicardial ablation, while the rest received endocardial ablation. With a median follow-up of 53.8 months (24.8-84.2), VT recurred in 45 patients (39.5%), and 6 patients (5.3%) died, including 2 SCD cases. The recurrence rate of VT was significantly lower in patients undergoing endo-epicardial ablation compared to those with endocardial ablation only (8.3% vs 43.1%, Log-rank P = 0.032). After multivariate adjustment, epicardial ablation remained associated with a reduced risk of VT recurrence (hazard ratio: 0.14, 95% confidential interval: 0.02-0.98, P = 0.048). CONCLUSION: ICM patients undergoing VT ablation without a backup ICD experienced a notably low rate of arrhythmic death, with most recurrences proving non-lethal.

CRISPR-Cas genome editing in ex-vivo human lungs to rewire the translational path of genome-targeting therapeutics.

The ongoing advancements in CRISPR-Cas technologies can significantly accelerate the preclinical development of both in vivo and ex-vivo organ genome-editing therapeutics. One of the promising applications is to genetically modify donor organs prior to implantation. The implantation of optimized donor organs with long-lasting immunomodulatory capacity holds promise for reducing the need for lifelong potent whole-body immunosuppression in recipients However, assessing genome-targeting interventions in a clinically-relevant manner prior to clinical trials remains a major challenge due to the limited modalities available. This study introduces a novel platform for testing genome editing in human lungs ex vivo, effectively simulating pre-implantation genetic engineering of donor organs. We identified gene regulatory elements whose disruption via Cas nucleases led to the upregulation of the immunomodulatory gene IL-10. We combined this approach with adenoviral vector (AdV)-mediated IL-10 delivery to create favorable kinetics for early (immediate post-implantation) graft immunomodulation. Using ex-vivo organ machine perfusion and precision-cut tissue slice technology, we demonstrated the feasibility of evaluating CRISPR genome editing in human lungs. To overcome the assessment limitations in ex-vivo perfused human organs, we conducted an in vivo rodent study and demonstrated both early gene induction and sustained editing of the lung. Collectively, our findings lay the groundwork for a first-in-human-organ study to overcome the current translational barriers of genome-targeting therapeutics.

Accelerating Elastic Property Prediction in Fe-C Alloys through Coupling of Molecular Dynamics and Machine Learning.

The scarcity of high-quality data presents a major challenge to the prediction of material properties using machine learning (ML) models. Obtaining material property data from experiments is economically cost-prohibitive, if not impossible. In this work, we address this challenge by generating an extensive material property dataset comprising thousands of data points pertaining to the elastic properties of Fe-C alloys. The data were generated using molecular dynamic (MD) calculations utilizing reference-free Modified embedded atom method (RF-MEAM) interatomic potential. This potential was developed by fitting atomic structure-dependent energies, forces, and stress tensors evaluated at ground state and finite temperatures using ab-initio. Various ML algorithms were subsequently trained and deployed to predict elastic properties. In addition to individual algorithms, super learner (SL), an ensemble ML technique, was incorporated to refine predictions further. The input parameters comprised the alloy's composition, crystal structure, interstitial sites, lattice parameters, and temperature. The target properties were the bulk modulus and shear modulus. Two distinct prediction approaches were undertaken: employing individual models for each property prediction and simultaneously predicting both properties using a single integrated model, enabling a comparative analysis. The efficiency of these models was assessed through rigorous evaluation using a range of accuracy metrics. This work showcases the synergistic power of MD simulations and ML techniques for accelerating the prediction of elastic properties in alloys.

Association of stress hyperglycemia ratio and mortality in patients with sepsis: results from 13,199 patients.

BACKGROUND: The stress hyperglycemia ratio (SHR), adjusted for average glycemic status, is suggested for assessing actual blood glucose levels. Its link with adverse outcomes is known in certain populations, yet its impact on sepsis patients' prognosis is unclear. This study explores the association between SHR and mortality in sepsis. METHODS: We included 13,199 sepsis patients in this study and categorized SHR into distinct groups. Additionally, we utilized restricted cubic spline analysis to evaluate the correlation between SHR as a continuous variable and mortality. The primary outcome was 1-year all-cause mortality. Logistic regression and Cox proportional hazards models were employed to assess the associations between the SHR and both in-hospital mortality and 1-year mortality, respectively. RESULTS: Among the study participants, 4,690 (35.5%) patients died during the 1-year follow-up. After adjusting for confounding variables, we identified a U-shaped correlation between SHR and 1-year mortality. Using an SHR of 0.99 as the reference point, the hazard ratio for predicted 1-year mortality increased by 1.17 (95% CI 1.08 to 1.27) per standard deviation above 0.99, whereas each standard deviation increase predicted the hazard ratio of 0.52 (95% CI 0.39 to 0.69) below 0.99. Furthermore, we found that SHR could enhance the predictive performance of conventional severity scores. CONCLUSION: There exists a U shaped association between SHR and mortality in sepsis patients, where both low and high SHR values are associated with an increased risk of poor outcomes.

2D Metal Porphyrin-Based MOFs and ZIF-8 Composite-Derived Carbon Materials Containing M-Nx Active Sites as Bifunctional Electrocatalysts for Zinc-Air Batteries.

The main impediment to the development of zinc-air batteries is the sluggish kinetics of the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER). Transition metal N-doped carbon catalysts offer a promising alternative to noble metal catalysts, with metal-organic framework (MOF)-derived carbon material catalysts being particularly noteworthy. Here, we synthesized MxP-Z-C carbon catalysts by combining two-dimensional (2D) metal porphyrin-based MOFs (MxPMFs, x = Fe, Co, Ni, Mn) and three-dimensional zeolitic imidazole framework-8 (ZIF-8) through electrostatic interaction, followed by carbonization. ZIF-8 was inserted between the layers of MxPMFs to prevent its Π-Π stacking, allowing the active sites to become fully exposed. MxP-Z-C demonstrated an impressive catalytic activity for both the ORR and the OER reactions. Among them, FeP-Z-C showed the best catalytic activity. The half-wave potential for ORR was 0.92 V (vs the reversible hydrogen electrode (RHE)), while the overpotential for the OER was 290 mV. In addition, the zinc-air battery assembled by FeP-Z-C exhibited high power density (133.14 mW cm-2) and significant specific capacity (816 mAh gZn-1), indicating considerable potential as a bifunctional catalyst for electronic devices.

Healable and conductive sulfur iodide for solid-state Li-S batteries.

Solid-state Li-S batteries (SSLSBs) are made of low-cost and abundant materials free of supply chain concerns. Owing to their high theoretical energy densities, they are highly desirable for electric vehicles1-3. However, the development of SSLSBs has been historically plagued by the insulating nature of sulfur4,5 and the poor interfacial contacts induced by its large volume change during cycling6,7, impeding charge transfer among different solid components. Here we report an S9.3I molecular crystal with I2 inserted in the crystalline sulfur structure, which shows a semiconductor-level electrical conductivity (approximately 5.9 × 10-7 S cm-1) at 25 °C; an 11-order-of-magnitude increase over sulfur itself. Iodine introduces new states into the band gap of sulfur and promotes the formation of reactive polysulfides during electrochemical cycling. Further, the material features a low melting point of around 65 °C, which enables repairing of damaged interfaces due to cycling by periodical remelting of the cathode material. As a result, an Li-S9.3I battery demonstrates 400 stable cycles with a specific capacity retention of 87%. The design of this conductive, low-melting-point sulfur iodide material represents a substantial advancement in the chemistry of sulfur materials, and opens the door to the practical realization of SSLSBs.

Research Progress on Biological Evidence Identification in Fire Scenes.

Biological evidence is relatively common evidence in criminal cases, and it has strong probative power because it carries DNA information for individual identification. At the scene of fire-related cases, the complex thermal environment, the escape of trapped people, the firefighting and rescue operations, and the deliberate destruction of criminal suspects will all affect the biological evidence in the fire scene. Scholars at home and abroad have explored and studied the effectiveness of biological evidence identification in fire scenes, and found that the blood stains, semen stains, bones, etc. are the main biological evidence which can be easily recovered with DNA in fire scenes. In order to analyze the research status and development trend of biological evidence in fire scenes, this paper systematically sorts out the relevant research, mainly including the soot removal technology, appearance method of typical biological evidence, and possibility of identifying other biological evidence. This paper also prospects the next step of research direction, in order to provide reference for the identification of biological evidence and improve the value of biological evidence in fire scenes.

Comparisons of long-term clinical outcomes with left bundle branch pacing, left ventricular septal pacing, and biventricular pacing for cardiac resynchronization therapy.

BACKGROUND: Left bundle branch pacing (LBBP) and left ventricular septal pacing (LVSP) are referred to as left bundle branch area pacing. OBJECTIVE: This study investigated whether long-term clinical outcomes differ in patients undergoing LBBP, LVSP, and biventricular pacing (BiVP) for cardiac resynchronization therapy (CRT). METHODS: Consecutive patients with reduced left ventricular ejection fraction (LVEF <50%) undergoing CRT were prospectively enrolled if they underwent successful LBBP, LVSP, or BiVP. The primary composite end point was all-cause mortality or heart failure hospitalization. Secondary end points included all-cause mortality, heart failure hospitalization, and echocardiographic measures of reverse remodeling. RESULTS: A total of 259 patients (68 LBBP, 38 LVSP, and 153 BiVP) were observed for a mean duration of 28.8 ± 15.8 months. LBBP was associated with a significantly reduced risk of the primary end point by 78% compared with both BiVP (7.4% vs 41.2%; adjusted hazard ratio [aHR], 0.22 [0.08-0.57]; P = .002) and LVSP (7.4% vs 47.4%; aHR, 0.22 [0.08-0.63]; P = .004]. The adjusted risk of all-cause mortality was significantly higher in LVSP than in BiVP (31.6% vs 7.2%; aHR, 3.19 [1.38-7.39]; P = .007) but comparable between LBBP and BiVP (2.9% vs 7.2%; aHR, 0.33 [0.07-1.52], P = .155). Propensity score adjustment also obtained similar results. LBBP showed a higher rate of echocardiographic response (ΔLVEF ≥10%: 60.0% vs 36.2% vs 16.1%; P < .001) than BiVP or LVSP. CONCLUSION: LBBP yielded long-term clinical outcomes superior to those of BiVP and LVSP. The role of LVSP for CRT needs to be reevaluated because of its high mortality risk.

Research Progress on the Correlation between Acetaldehyde Dehydrogenase 2 and Hepatocellular Carcinoma Development.

Hepatocellular carcinoma (HCC) is the predominant pathologic type of primary liver cancer. It is a malignant tumor of liver epithelial cells. There are many ways to treat HCC, but the survival rate for HCC patients remains low. Therefore, understanding the underlying mechanisms by which HCC occurs and develops is critical to explore new therapeutic targets. Aldehyde dehydrogenase 2 (ALDH2) is an important player in the redox reaction of ethanol with endogenous aldehyde products released by lipid peroxidation. Increasing evidence suggests that ALDH2 is a crucial regulator of human tumor development, including HCC. Therefore, clarifying the relationship between ALDH2 and HCC is helpful for formulating rational treatment strategies. This review highlights the regulatory roles of ALDH2 in the development of HCC, elucidates the multiple potential mechanisms by which ALDH2 regulates the development of HCC, and summarizes the progress of research on ALDH2 gene polymorphisms and HCC susceptibility. Meanwhile, we envision viable strategies for targeting ALDH2 in the treatment of HCC SIGNIFICANCE STATEMENT: Numerous studies have aimed to explore novel therapeutic targets for HCC, and ALDH2 has been reported to be a critical regulator of HCC progression. This review discusses the functions, molecular mechanisms, and clinical significance of ALDH2 in the development of HCC and examines the prospects of ALDH2-based therapy for HCC.

Clinical Decision Support Requirements for Ventricular Tachycardia Diagnosis Within the Frameworks of Knowledge and Practice: Survey Study.

BACKGROUND: Ventricular tachycardia (VT) diagnosis is challenging due to the similarity between VT and some forms of supraventricular tachycardia, complexity of clinical manifestations, heterogeneity of underlying diseases, and potential for life-threatening hemodynamic instability. Clinical decision support systems (CDSSs) have emerged as promising tools to augment the diagnostic capabilities of cardiologists. However, a requirements analysis is acknowledged to be vital for the success of a CDSS, especially for complex clinical tasks such as VT diagnosis. OBJECTIVE: The aims of this study were to analyze the requirements for a VT diagnosis CDSS within the frameworks of knowledge and practice and to determine the clinical decision support (CDS) needs. METHODS: Our multidisciplinary team first conducted semistructured interviews with seven cardiologists related to the clinical challenges of VT and expected decision support. A questionnaire was designed by the multidisciplinary team based on the results of interviews. The questionnaire was divided into four sections: demographic information, knowledge assessment, practice assessment, and CDS needs. The practice section consisted of two simulated cases for a total score of 10 marks. Online questionnaires were disseminated to registered cardiologists across China from December 2022 to February 2023. The scores for the practice section were summarized as continuous variables, using the mean, median, and range. The knowledge and CDS needs sections were assessed using a 4-point Likert scale without a neutral option. Kruskal-Wallis tests were performed to investigate the relationship between scores and practice years or specialty. RESULTS: Of the 687 cardiologists who completed the questionnaire, 567 responses were eligible for further analysis. The results of the knowledge assessment showed that 383 cardiologists (68%) lacked knowledge in diagnostic evaluation. The overall average score of the practice assessment was 6.11 (SD 0.55); the etiological diagnosis section had the highest overall scores (mean 6.74, SD 1.75), whereas the diagnostic evaluation section had the lowest scores (mean 5.78, SD 1.19). A majority of cardiologists (344/567, 60.7%) reported the need for a CDSS. There was a significant difference in practice competency scores between general cardiologists and arrhythmia specialists (P=.02). CONCLUSIONS: There was a notable deficiency in the knowledge and practice of VT among Chinese cardiologists. Specific knowledge and practice support requirements were identified, which provide a foundation for further development and optimization of a CDSS. Moreover, it is important to consider clinicians' specialization levels and years of practice for effective and personalized support.

Correlations between the peripheral coronary fat attenuation index based on computed tomography images, high-risk plaque and degree of coronary artery stenosis in patients with coronary atherosclerosis.

BACKGROUND: Coronary artery disease can be quantified by measuring the fat attenuation index (FAI). OBJECTIVE: To explore the correlations between FAI, high-risk plaque and the degree of coronary artery stenosis. METHODS: The clinical data of patients with coronary atherosclerosis who underwent a coronary computed tomography (CT) angiography examination between July 2020 and June 2023 were selected for retrospective analysis. These patients were classified into a high-risk plaque group and non-high-risk plaque group according to the presence of CT high-risk plaque. The diagnostic value of FAI and FAI combined with the degree of stenosis was evaluated for CT high-risk plaque. RESULTS: Differences in age, body mass index, smoking history, FAI and the degree of stenosis between the two groups were statistically significant (all P< 0.05). The results of a binary logistic regression analysis revealed that FAI (odds ratio (OR): 1.131, 95% confidence interval (CI): 1.101-1.173, P< 0.001) and the degree of stenosis (OR: 1.021, 95% CI: 1.012-1.107, P< 0.001) were risk factors for high-risk plaque. CONCLUSION: The FAI can be used to monitor the inflammation level of the coronary artery; the higher the FAI is, the higher the risk of plaque and degree of stenosis.

Reduction characteristic of chlorobenzene by a newly isolated Paenarthrobacter ureafaciens LY from a pharmaceutical wastewater treatment plant.

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.

Prognostic potency of plasma LRG1 measurement at multiple time points in acute ischemic stroke patients.

Objective: This study aimed to investigate the prognostic potency of LRG1 in acute ischemic stroke (AIS) patients. Methods: Plasma LRG1 levels were detected at admission and on days 3, 7 and 30 in 150 AIS patients. Results: LRG1 positively correlated with total cholesterol (p = 0.016), triglycerides (p = 0.046), C-reactive protein (p < 0.001), TNF-α (p = 0.001) and IL-6 (p = 0.004). After admission, LRG1 showed a decreasing trend (p < 0.001). Interestingly, LRG1 levels at admission (p = 0.014), day 3 (p = 0.027), day 7 (p = 0.008) and day 30 (p = 0.002) were higher in patients with modified Rankin scale score ≥2 versus those with scores <2. The LRG1 levels at day 7 (p = 0.032) and day 30 (p = 0.023) were higher in patients with recurrence versus no recurrence. Conclusion: LRG1 correlates with blood lipids, inflammation and short-term prognosis of AIS.

Associations of 50 modifiable risk factors with atrial fibrillation using Mendelian randomization analysis.

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.

Experimental determination of the partitioning of representative organic pollutants to the air-water interface.

Using glancing-angle laser-induced fluorescence (GALIF) spectroscopy as a probe, the partitioning of naphthalene, fluoranthene, pyrene, umbelliferone, phenol red, and bisphenol A from bulk solution to the air-water interface was examined in both pure water and aqueous solutions of 6 mM octanol. Previous studies provided similar Langmuir adsorption isotherms for anthracene and imidazole 2-carboxaldehyde. The surface partitioning behaviour of each compound in both environments was well described using a Langmuir adsorption model; partitioning coefficients were derived from the fits to such isotherms. Only the PAH molecules, naphthalene, fluoranthene and pyrene, saw an enhancement in the surface partitioning in octanol solution compared to pure water. The surface partitioning to pure water surfaces could be fairly well described using a one parameter linear free energy relationship based on either solubility or KOW.

Catheter ablation of ventricular tachycardia in patients with arrhythmogenic right ventricular cardiomyopathy and biventricular involvement.

AIMS: Catheter ablation of ventricular tachycardia (VT) improves VT-free survival in 'classic' arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to investigate electrophysiological features and ablation outcomes in patients with ARVC and biventricular (BiV) involvement. METHODS AND RESULTS: We assembled a retrospective cohort of definite ARVC cases with sustained VTs. Patients were divided into the BiV (BiV involvement) group and the right ventricular (RV) (isolated RV involvement) group based on the left ventricular systolic function detected by cardiac magnetic resonance. All patients underwent electrophysiological mapping and VT ablation. Acute complete success was non-inducibility of any sustained VT, and the primary endpoint was VT recurrence. Ninety-eight patients (36 ± 14 years; 87% male) were enrolled, including 50 in the BiV group and 48 in the RV group. Biventricular involvement was associated with faster clinical VTs, a higher VT inducibility, and more extensive arrhythmogenic substrates (all P < 0.05). Left-sided VTs were observed in 20% of the BiV group cases and correlated with significantly reduced left ventricular systolic function. Catheter ablation achieved similar acute efficacy between these two groups, whereas the presence of left-sided VTs increased acute ablation failure (40 vs. 5%, P = 0.012). Over 51 ± 34 months [median, 48 (22-83) months] of follow-up, cumulative VT-free survival was 52% in the BiV group and 58% in the RV group (P = 0.353). A multivariate analysis showed that younger age, lower RV ejection fraction (RVEF), and non-acute complete ablation success were associated with VT recurrence in the BiV group. CONCLUSION: Biventricular involvement implied a worse arrhythmic phenotype and increased the risk of left-sided VTs, while catheter ablation maintained its efficacy for VT control in this population. Younger age, lower RVEF, and non-acute complete success predicted VT recurrence after ablation.

FARS2 Deficiency Causes Cardiomyopathy by Disrupting Mitochondrial Homeostasis and the Mitochondrial Quality Control System.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a common heritable heart disease. Although HCM has been reported to be associated with many variants of genes involved in sarcomeric protein biomechanics, pathogenic genes have not been identified in patients with partial HCM. FARS2 (the mitochondrial phenylalanyl-tRNA synthetase), a type of mitochondrial aminoacyl-tRNA synthetase, plays a role in the mitochondrial translation machinery. Several variants of FARS2 have been suggested to cause neurological disorders; however, FARS2-associated diseases involving other organs have not been reported. We identified FARS2 as a potential novel pathogenic gene in cardiomyopathy and investigated its effects on mitochondrial homeostasis and the cardiomyopathy phenotype. METHODS: FARS2 variants in patients with HCM were identified using whole-exome sequencing, Sanger sequencing, molecular docking analyses, and cell model investigation. Fars2 conditional mutant (p.R415L) or knockout mice, fars2-knockdown zebrafish, and Fars2-knockdown neonatal rat ventricular myocytes were engineered to construct FARS2 deficiency models both in vivo and in vitro. The effects of FARS2 and its role in mitochondrial homeostasis were subsequently evaluated using RNA sequencing and mitochondrial functional analyses. Myocardial tissues from patients were used for further verification. RESULTS: We identified 7 unreported FARS2 variants in patients with HCM. Heart-specific Fars2-deficient mice presented cardiac hypertrophy, left ventricular dilation, progressive heart failure accompanied by myocardial and mitochondrial dysfunction, and a short life span. Heterozygous cardiac-specific Fars2R415L mice displayed a tendency to cardiac hypertrophy at age 4 weeks, accompanied by myocardial dysfunction. In addition, fars2-knockdown zebrafish presented pericardial edema and heart failure. FARS2 deficiency impaired mitochondrial homeostasis by directly blocking the aminoacylation of mt-tRNAPhe and inhibiting the synthesis of mitochondrial proteins, ultimately contributing to an imbalanced mitochondrial quality control system by accelerating mitochondrial hyperfragmentation and disrupting mitochondrion-related autophagy. Interfering with the mitochondrial quality control system using adeno-associated virus 9 or specific inhibitors mitigated the cardiac and mitochondrial dysfunction triggered by FARS2 deficiency by restoring mitochondrial homeostasis. CONCLUSIONS: Our findings unveil the previously unrecognized role of FARS2 in heart and mitochondrial homeostasis. This study may provide new insights into the molecular diagnosis and prevention of heritable cardiomyopathy as well as therapeutic options for FARS2-associated cardiomyopathy.

Notes on species of Talaus Simon, 1886 (Araneae, Thomisidae) from China, with descriptions of two new species.

Taxonomic notes on the Talaus species from China are provided. Two new species, T.yuyang Yao & Liu, sp. nov. and T.zhangjiangkou Yao & Liu, sp. nov. are described and illustrated, and a further three species are redescribed based on their genitalic characters: T.dulongjiang Tang, Yin, Ubick & Peng, 2008, T.niger Tang, Yin, Ubick & Peng, 2008, and T.sulcus Tang & Li, 2010. The species T.xiphosus Zhu & Ono, 2007 is considered a junior synonym of T.triangulifer Simon, 1886 based on an examination of many recently collected female and male specimens from Guangxi Province, China. Diagnoses, detailed illustrations and a map of distributional records of the six treated species of Talaus in China are provided.

Midget cave spiders (Araneae, Leptonetidae) from Jiangxi and Fujian Province, China.

Eleven leptonetid species belonging to four genera collected in Jiangxi and Fujian Provinces, China are presented. Ten new species of midget cave spiders from southern China are diagnosed, described, and illustrated: Leptoneteladawu Yao & Liu, sp. nov., L.yuanhaoi Yao & Liu, sp. nov. and L.zuojiashanensis Yao & Liu, sp. nov. from Jiangxi; Longileptonetaguadunensis Yao & Liu, sp. nov., L.huboliao Yao & Liu, sp. nov., L.jiaxiani Yao & Liu, sp. nov., L.letuensis Yao & Liu, sp. nov., L.renzhouensis Yao & Liu, sp. nov., L.tianmenensis Yao & Liu, sp. nov., and Pararanamingxuani Yao & Liu, sp. nov. from Fujian. Furthermore, Falcileptonetamonodactyla (Yin, Wang & Wang, 1984) is recorded from Jiangxi province for the first time. Distributions records are given for all investigated species.