Risk Factors for PVC Induced Cardiomyopathy and Post-Ablation Left Ventricular Systolic Dysfunction Reversibility: A Systematic Review and Meta-Analysis of Observational Studies.

Background: Premature ventricular complex (PVC) induced cardiomyopathy (PVC-CMP) and exacerbated left ventricular systolic dysfunction (LVSD) are common in clinical scenarios. However, their precise risk factors are currently unclear. Methods: We performed a systematic review of PubMed, EMBASE, Web of Science, and Chinese-based literature database (CBM) to identify observational studies describing the factors associated with PVC-CMP and post-ablation LVSD reversibility. A total of 25 and 12 studies, involving 4863 and 884 subjects, respectively, were eligible. We calculated pooled multifactorial odds ratios (OR) and 95% confidence intervals (CI) for each parameter using random-effects and fixed-effects models. Results: The results showed that 3 independent risk factors were associated with PVC-CMP: being asymptomatic (OR and 95% CI: 3.04 [2.13, 4.34]), interpolation (OR and 95% CI: 2.47 [1.25, 4.92]), and epicardial origin (epi-origin) (OR and 95% CI: 3.04 [2.13, 4.34]). Additionally, 2 factors were significantly correlated with post-ablation LVSD reversibility: sinus QRS wave duration (QRSd) (OR and 95% CI: 0.95 [0.93, 0.97]) and PVC burden (OR and 95% CI: 1.09 [0.97, 1.23]). Conclusions: the relatively consistent independent risk factors for PVC-CMP and post-ablation LVSD reversibility are asymptomatic status, interpolation, epicardial origin, PVC burden, and sinus QRS duration, respectively.

Small extracellular vesicles derived from adipose mesenchymal stem cells alleviate intestinal fibrosis by inhibiting the FAK/Akt signaling pathway via MFGE8.

BACKGROUND: Intestinal fibrosis is one of the most frequent and severe complications of Crohn's disease. Accumulating studies have reported that adipose mesenchymal stem cell-derived small extracellular vesicles (AMSC-sEVs) could alleviate renal fibrosis, hepatic fibrosis, etc., while their potential for treating intestinal fibrosis remains uncertain. Therefore, this study aims to determine the therapeutic effects of AMSC-sEVs on intestinal fibrosis and identify the mechanisms underlying these effects. METHODS: AMSC-sEVs were characterized using transmission electron microscopy, nanoparticle tracking analysis, and western blot. Whether AMSC-sEVs exert antifibrotic effects was investigated in two different murine models of intestinal fibrosis. Besides, AMSC-sEVs were co-cultured with primary human fibroblasts and CCD18co during transforming growth factor (TGF)-ß1 stimulation. Label-free proteomics and rescue experiments were performed to identify candidate molecules in AMSC-sEVs. Transcriptome sequencing revealed changes in mRNA levels among different groups. Lastly, proteins related to relevant signaling pathways were identified by western blotting, and their expression and activation status were assessed. RESULTS: AMSC-sEVs positively expressed CD63 and Alix and presented a classical "rim of a cup" and granule shape with approximately 43-100 nm diameter. AMSCs significantly alleviated intestinal fibrosis through secreted sEVs in vitro and in vivo. The milk fat globule-EGF factor 8 (MFGE8) was stably enriched in AMSC-sEVs and was an active compound contributing to the treatment of intestinal fibrosis by AMSCs. Mechanistically, AMSC-sEV-based therapies attenuated intestinal fibrosis by inhibiting the FAK/Akt signaling pathway. CONCLUSIONS: MFGE8-containing AMSC-sEVs attenuate intestinal fibrosis, partly through FAK/Akt pathway inhibition.

Botany, phytochemistry, pharmacologic activities, traditional applications, pharmacokinetics, quality control and toxicity of Zanthoxyli Radix: An updated review.

ETHNOPHARMACOLOGICAL RELEVANCE: Zanthoxyli Radix (ZR), the dry root of Zanthoxylum nitidum (Roxb.) DC (ZN) is known as Liang Mian Zhen in China and has been the preferred Chinese medicine for the treatment of inflammation and cancer disease at home and abroad. ZR has been used as the core ingredient in anti-inflammatory traditional medicines, such as Sanjiuweitai granules and Jinji tablets, etc. AIM OF THE WORK: This review aimed to provide a comprehensive overview of ZR in terms of traditional uses, quality control, botany, phytochemistry, pharmacology, toxicology, and pharmacokinetics. Meanwhile, the anti-inflammatory substances and mechanism of ZR were emphasized, to offer new perspectives and broad scopes for future studies. MATERIALS AND METHODS: The information was retrieved from Web of Science, Researchgate, Google Scholar, SciFinder, X-MOL, PubMed, China National Knowledge Infrastructure (CNKI), Chinese Masters and Doctoral Dissertations, and Elsevier between 1984 and 2024. RESULTS: Till now, a total of 184 chemical components have been identified in ZR, including 91 alkaloids, 22 lignans, 4 flavonoids, 19 coumarins, 17 terpenoids, and 31 other types. Pharmacological studies have proved that ZR had a variety of biological activities, such as anti-tumour, antibacterial, antioxidant and other activities, particularly in anti-inflammation. ZR exerts anti-inflammatory disease effects by modulating various signaling pathways, including MAPK, NF-κB, P13/AKT and JAK/STAT. Pharmacokinetic studies have shown that ZR exhibits low absorption rates, broad distribution, and rapid metabolism. Additionally, this review also revealed the shortcomings of current research on ZR and possible future research directions. CONCLUSION: Extensive literature analysis indicates that ZR and its bioactive constituents possess diverse pharmacological activities, especially anti-inflammation. Moreover, in order to promote the safety and adaptability of ZR in clinical application, it is also strongly recommended that further research should focus on toxicity studies, pharmacokinetic studies of herb-drug interactions, and quality control.

Sophorae tonkinensis radix et rhizoma: A comprehensive review of the ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics, toxicology and detoxification strategy.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophorae tonkinensis Radix et Rhizoma (STR), the dried root and rhizome of Sophora tonkinensis Gagnep., is commonly used in the treatment of tonsillitis and pharyngitis, throat soreness and throat obstruction, swelling and aching of gum, etc. in China or other Asian countries. STR is usually used as the core herb in traditional Chinese medicine preparations, such as "Biyanling Tablets", "Fufang Muji Granules" and "Ganyanling Injections", etc. AIM OF THE REVIEW: This review aimed to provide a comprehensive analysis of STR in terms of botany, traditional use, phytochemistry, ethnopharmacology, pharmacology, pharmacokinetics, toxicology and detoxification strategy, to provide a rational application in future research. MATERIALS AND METHODS: The information involved in the study was gathered from a variety of electronic resources, including China National Knowledge Infrastructure (CNKI), SciFinder, Google Scholar, PubMed, Web of Science, and Chinese Masters and Doctoral Dissertations. RESULTS: Till now, a total of 333 chemical components have been identified in STR, including 85 alkaloids, 124 flavonoids, 24 triterpenes, 27 triterpene saponins, 34 organic acids, 8 polysaccharides, etc. STR and its main active constituents have cardiovascular protection, anti-tumor activity, anti-inflammatory activity, antipyretic activity, analgesic activity, antibacterial activity, antifungal activity, antiviral activity, and hepatoprotective activity, etc. However, toxic effects of STR on the liver, nerves, heart, and gastrointestinal tract have also been observed. To mitigate these risks, STR needs attenuation before use, with the most common detoxification methods being processing and combined use with other drugs. The pharmacokinetics of STR in vivo and traditional and clinical prescriptions containing STR have been sorted out. Despite the potential therapeutic benefits of STR, further research is warranted to elucidate its hepatotoxicity, particularly in vivo, exploring aspects such as in vivo metabolism, distribution, and mechanisms. CONCLUSION: This review serves to emphasize the therapeutic potential of STR and highlights the crucial need to address its toxicity concerns before considering clinical application. Further research is required to comprehensively investigate the toxicological properties of STR, with particular emphasis on its hepatotoxicity and neurotoxicity. Such research endeavors have the potential to standardize the rational application of STR for optimal therapeutic outcomes.

Dissection of potential anti-osteoporosis mechanism of isopsoralen - a quality control marker in Psoraleae Fructus - by metabolite profiling and network pharmacology.

RATIONALE: Isopsoralen (ISO), a quality control marker (Q-marker) in Psoraleae Fructus, is proven to present an obvious anti-osteoporosis effect. Until now, the metabolism and anti-osteoporosis mechanisms of ISO have not been fully elucidated, greatly restricting its drug development. METHODS: The metabolites of ISO in rats were profiled by using ultrahigh-performance liquid chromatography coupled with time-of-flight mass spectrometry. The potential anti-osteoporosis mechanism of ISO in vivo was predicted by using network pharmacology. RESULTS: A total of 15 metabolites were characterized in rats after ingestion of ISO (20 mg/kg/day, by gavage), including 2 in plasma, 12 in urine, 6 in feces, 1 in heart, 3 in liver, 1 in spleen, 1 in lung, 3 in kidney, and 2 in brain. The pharmacology network results showed that ISO and its metabolites could regulate AKT1, SRC, NFKB1, EGFR, MAPK3, etc., involved in the prolactin signaling pathway, ErbB signaling pathway, thyroid hormone pathway, and PI3K-Akt signaling pathway. CONCLUSIONS: This is the first time for revealing the in vivo metabolism features and potential anti-osteoporosis mechanism of ISO by metabolite profiling and network pharmacology, providing data for further verification of pharmacological mechanism.

Deep-learning radiomics based on ultrasound can objectively evaluate thyroid nodules and assist in improving the diagnostic level of ultrasound physicians.

Background: The incidence rate of thyroid nodules has reached 65%, but only 5-15% of these modules are malignant. Therefore, accurately determining the benign and malignant nature of thyroid nodules can prevent unnecessary treatment. We aimed to develop a deep-learning (DL) radiomics model based on ultrasound (US), explore its diagnostic efficacy for benign and malignant thyroid nodules, and verify whether it improved the diagnostic level of physicians. Methods: We retrospectively included 1,076 thyroid nodules from 817 patients at three institutions. The radiomics and DL features of the US images were extracted and used to construct radiomics signature (Rad_sig) and deep-learning signature (DL_sig). A Pearson correlation analysis and least absolute shrinkage and selection operator (LASSO) regression analysis were used for feature selection. Clinical US semantic signature (C_US_sig) was constructed based on clinical information and US semantic features. Next, a combined model was constructed based on the above three signatures in the form of a nomogram. The model was constructed using a development set (institution 1: 719 nodules), and the model was evaluated using two external validation sets (institution 2: 74 nodules, and institution 3: 283 nodules). The performance of the model was assessed using decision curve analysis (DCA) and calibration curves. Furthermore, the C_US_sigs of junior physicians, senior physicians, and expers were constructed. The DL radiomics model was used to assist the physicians with different levels of experience in the interpretation of thyroid nodules. Results: In the development and validation sets, the combined model showed the highest performance, with areas under the curve (AUCs) of 0.947, 0.917, and 0.929, respectively. The DCA results showed that the comprehensive nomogram had the best clinical utility. The calibration curves indicated good calibration for all models. The AUCs for distinguishing between benign and malignant thyroid nodules by junior physicians, senior physicians, and experts were 0.714-0.752, 0.740-0.824, and 0.891-0.908, respectively; however, with the assistance of DL radiomics, the AUCs reached 0.858-0.923, 0.888-0.944, and 0.912-0.919, respectively. Conclusions: The nomogram based on DL radiomics had high diagnostic efficacy for thyroid nodules, and DL radiomics could assist physicians with different levels of experience to improve their diagnostic level.

Characterization of metabolic features and potential anti-osteoporosis mechanism of pinoresinol diglucoside using metabolite profiling and network pharmacology.

RATIONALE: Eucommia cortex is the core herb in traditional Chinese medicine preparations for the treatment of osteoporosis. Pinoresinol diglucoside (PDG), the quality control marker and the key pharmacodynamic component in Eucommia cortex, has attracted global attention because of its definite effects on osteoporosis. However, the in vivo metabolic characteristics of PDG and its anti-osteoporotic mechanism are still unclear, restricting its development and application. METHODS: Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to analyze the metabolic characteristics of PDG in rats, and its anti-osteoporosis targets and mechanism were predicted using network pharmacology. RESULTS: A total of 51 metabolites were identified or tentatively characterized in rats after oral administration of PDG (10 mg/kg/day), including 9 in plasma, 28 in urine, 13 in feces, 10 in liver, 4 in heart, 3 in spleen, 11 in kidneys, and 5 in lungs. Furan-ring opening, dimethoxylation, glucuronidation, and sulfation were the main metabolic characteristics of PDG in vivo. The potential mechanism of PDG against osteoporosis was predicted using network pharmacology. PDG and its metabolites could regulate BCL2, MARK3, ALB, and IL6, involving PI3K-Akt signaling pathway, estrogen signaling pathway, and so on. CONCLUSIONS: This study was the first to demonstrate the metabolic characteristics of PDG in vivo and its potential anti-osteoporosis mechanism, providing the data for further pharmacological validation of PDG in the treatment of osteoporosis.

Non-Linear Association between Obstructive Sleep Apnea Risk and Lipid Profile: Data from the 2015-2018 National Health and Nutrition Examination Survey.

Background: The relationship between the multivariable apnea prediction (MAP) index and lipid levels was examined using a cross-sectional and retrospective study of National Health and Nutrition Examination Surveys (2015-2018). A total of 3195 participants with MAP scores were included in the analysis. Methods: The MAP index, an algorithm leveraging sleep apnea symptom frequency, body mass index (BMI), age, and sex, estimates the risk of obstructive sleep apnea (OSA). We investigated the associations between the MAP index and lipid profiles-specifically, high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) -using weighted linear regression and restricted cubic splines (RCS) analysis. Additionally, mediation analysis was conducted to explore the potential mediating role of physical activity on the link between OSA risk, hyperlipidemia, and cardiovascular mortality. Results: A non-linear relationship was observed between OSA severity and lipid profiles, including elevated levels of TC, increased LDL-C, higher TG, and decreased HDL-C (All p for non-linearity < 0.05). The findings remained consistent across the stratified sensitivity analyses. Furthermore, physical activity served as a mediator in the association between the MAP index and both hyperlipidemia and cardiovascular mortality, accounting for 16.6% and 16.7% of the indirect effects, respectively. Conclusions: Participants at high risk for OSA demonstrated an increased prevalence of dyslipidemia. Additionally, engagement in physical activity was shown to have beneficial effects on lipid metabolism.

Adipose-derived mesenchymal stromal cells alleviate intestinal fibrosis: The role of tumor necrosis factor-stimulated gene 6 protein.

BACKGROUND: The therapeutic potential of adipose-derived mesenchymal stromal cells (AMSCs) in the treatment of intestinal fibrosis occured in patients with Crohn's disease (CD) remains unclear. Tumor necrosis factor-stimulated gene 6 (TSG6) protein plays a critical role in inflammation regulation and tissue repair. This study aimed to determine if AMSCs attenuate intestinal fibrosis by secreting paracrine TSG6 protein and explore the underlying mechanisms. METHODS: Two murine models for intestinal fibrosis were established using 2,4,6-trinitrobenzene sulfonic acid in BALB/c mice and dextran sulfate sodium in C57BL/6 mice. Primary human fibroblasts and CCD-18co cells were incubated with transforming growth factor (TGF)-ß1 to build two fibrosis cell models in vitro. RESULTS: Intraperitoneally administered AMSCs attenuated intestinal fibrosis in the two murine models, as evidenced by significant alleviation of colon shortening, collagen protein deposits, and submucosal thickening, and also decrease in the endoscopic and fibrosis scores (P < 0.001). Although intraperitoneally injected AMSCs did not migrate to the colon lesions, high levels of TSG6 expression and secretion were noticed both in vivo and in vitro. Similar to the role of AMSCs, injection of recombinant human TSG6 attenuated intestinal fibrosis in the mouse models, which was not observed with the administration of AMSCs with TSG6 knockdown or TSG6 neutralizing antibody. Mechanistically, TSG6 alleviates TGF-ß1-stimulated upregulation of α-smooth muscle actin (αSMA) and collagen I by inhibiting Smad2 phosphorylation. Furthermore, the expression of TSG6 is lower in intestinal fibrosis tissue of patients with Crohn's disease and can reduce pro-fibrotic protein (αSMA) secretion from primary ileal fibrotic tissue. CONCLUSIONS: AMSCs attenuate intestinal fibrosis by secreting paracrine TSG6 protein, which inhibits Smad2 phosphorylation. TSG6, a novel anti-fibrotic factor, could potentially improve intestinal fibrosis treatments.

Conversion of Carbon Dioxide into a Series of CBxOy- Compounds Mediated by LaB3,4O2- Anions: Synergy of the Electron Transfer and Lewis Pair Mechanisms to Construct B-C Bonds.

Converting CO2 into value-added products containing B-C bonds is a great challenge, especially for multiple B-C bonds, which are versatile building blocks for organoborane chemistry. In the condensed phase, the B-C bond is typically formed through transition metal-catalyzed direct borylation of hydrocarbons via C-H bond activation or transition metal-catalyzed insertion of carbenes into B-H bonds. However, excessive amounts of powerful boryl reagents are required, and products containing B-C bonds are complex. Herein, a novel method to construct multiple B-C bonds at room temperature is proposed by the gas-phase reactions of CO2 with LaBmOn- (m = 1-4, n = 1 or 2). Mass spectrometry and density functional theory calculations are applied to investigate these reactions, and a series of new compounds, CB2O2-, CB3O3-, and CB3O2-, which possess B-C bonds, are generated in the reactions of LaB3,4O2- with CO2. When the number of B atoms in the clusters is reduced to 2 or 1, there is only CO-releasing channel, and no CBxOy- compounds are released. Two major factors are responsible for this quite intriguing reactivity: (1) Synergy of electron transfer and boron-boron Lewis acid-base pair mechanisms facilitates the rupture of C═O double bond in CO2. (2) The boron sites in the clusters can efficiently capture the newly formed CO units in the course of reactions, favoring the formation of B-C bonds. This finding may provide fundamental insights into the CO2 transformation driven by clusters containing lanthanide atoms and how to efficiently build B-C bonds under room temperature.

Chemical profiling of Zhi-Ke-Bao pills and its potential mechanism against cough by ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry and network pharmacology.

Zhi-Ke-Bao pills (ZKB), a traditional Chinese medicine preparation composed of 13 herbs, is generally used to treat cough caused by external wind cold, phlegm, etc in clinical applications, and it plays a core role in relieving cough caused by COVID-19 and influenza in China. Till now, the understanding of its chemical constituents was dramatically limited due to its chemical complexity, restricting its clinical application or development. In this work, a developed ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS) method, a targeted and non-targeted strategy and network pharmacology were used to comprehensively characterize the chemical compositions in ZKB and predict its mechanism against cough. A total of 164 compounds (148 targeted compounds and 16 non-targeted ones) were identified or tentatively characterized in ZKB, including 65 flavonoids, 25 alkaloids, 19 organic acids, 41 saponins, 9 coumarins, 2 phenylpropanoids, 2 anthraquinones, and 1 other types. Among them, 37 compounds were unambiguously identified by comparison to reference standards. Meanwhile, the fragmentation behaviors of five main chemical structure types were also summarized. 309 targets and two core signaling pathways of ZKB against cough were predicted by network pharmacology, including MAPK and PI3K-Akt signaling pathways. It was the first time to characterize the chemical compounds of ZKB and reveal its potential mechanism against cough, providing the material basis for further quality control or pharmacodynamic evaluation of ZKB.

Completely Methylene-Free Side Chain Enables Significant Microphase Separation at Medium IECs for Fuel-Cell Anion Exchange Membranes.

The introduction of hydrophobic side chain structures in anion exchange membranes (AEMs) to facilitate ion transport has been widely studied; however, low or moderate hydrophobic hydrocarbon and semifluorinated side chains are insufficient to induce a high degree of microphase separation. Herein, we design and prepare poly(aryl piperidinium) AEMs with completely methylene-free perfluorinated side chains, which can maximize the thermodynamic incompatibility between main- and side chains, thus enhancing microphase separation at medium ion exchange capacities (IECs). According to the molecular dynamics study, the methylene-free perfluorinated side chain leads to better hydration of cations. The hydroxide conductivity of the methylene-free perfluorinated side chain-grafted PAP-pF-1 membrane reaches 124.9 mS cm-1 at 80 °C, and the PAP-sF-1 with semifluorinated side chains and PAP-CH-1 with hydrocarbon side chains show lower conductivity (116.8 and 104.0 mS cm-1). The H2/O2 fuel cell using the PAP-pF-1 membrane demonstrates a remarkable peak power density (1651 mW cm-2 at 80 °C) and durability (greater than 300 h). This work provides a novel insight into enhancing microphase separation in AEMs; it opens up new possibilities for developing high-performance AEMs.

Impact of inter-lesion distance and first-pass isolation on outcomes of pulmonary venous isolation for paroxysmal atrial fibrillation.

BACKGROUND: Contiguity of ablation lesions is a critical determinant of success for paroxysmal atrial fibrillation (PAF) ablation. Evidence supports maintaining an inter-lesional distance (ILD) ≤ 6 mm during pulmonary venous isolation (PVI). Meanwhile, first-pass isolation (FPI) on PVI outcome in follow-up was not deeply studied. The impact of ILD and FPI on PAF ablation outcomes was investigated. METHODS: Consecutive PAF patients who underwent first-time antral PVI were recruited. Coordinates of ablation points were extracted from the electro-anatomical mapping system and analyzed using custom-developed software to determine the ILD. A gap is defined as ILD greater than 6 mm. FPI was defined as the achievement of PVI by encircling the ipsilateral veins while simultaneously recording their electrical activity using a multipolar catheter. The primary endpoint was freedom from documented atrial arrhythmias including AF, atrial tachycardia (AT), or atrial flutter (AFL) lasting longer than 30 s during follow-up. RESULTS: A total of 105 patients underwent first-time antral PVI. During 13.3 ± 0.6 months of follow-up, atrial arrhythmias recurrence was noted in 22.9% of the patients. Atrial arrhythmia recurrence was significantly higher in patients with more gaps (> 2) (37.0% versus 11.9%, P < 0.01), and the number of gaps was an independent predictor of AF/AT/AFL recurrence. (Hazard ratio [HR] 1.20, 95% CI 1.03-1.40, P = 0.02). The group with FPI for at least one ipsilateral pair of PVs exhibited a decreased number of gaps (2.0 versus 7.0, P < 0.01) and demonstrated a significant correlation with a reduction of recurrence (HR 0.26, 95% CI 0.09-0.71, P = 0.01). Among 16 patients who underwent repeat ablation, the number of gaps during the index PVI was associated with PV reconnection (PVR) (P < 0.01). CONCLUSIONS: Gaps created during PVI are a modifiable determinant of AF/AT/AFL recurrence, and avoidance of gaps is crucial to improve clinical outcomes of PAF ablation. In addition, FPI exhibited a strong predictive capability for clinical success in patients with PAF.

Multi-heterostructured MXene/NiS2/Co3S4 with S-Vacancies to Promote Polysulfide Conversion in Lithium-Sulfur Batteries.

The severe shuttle effect of polysulfides (LiPSs) and the slow liquid-solid phase conversion are the main obstacles hindering the practical application of lithium-sulfur (Li-S) batteries. Separator modification with a high-activity catalyst can boost LiPSs conversion and suppress their shuttle effect. In this work, multi-heterostructured MXene/NiS2/Co3S4 with rich S-vacancies was constructed facilely with a hydrothermal and high-temperature annealing strategy for separator modification. The MXene sheet not only provides a physical barrier but also ensures a high conductivity and adsorption capacity of the catalyst; the dual active centers of NiS2 and Co3S4 catalyze LiPSs conversion. In addition, the vacancies and heterostructures can modulate the electronic structure of the catalyst, improve its intrinsic activity, and reduce the polysulfides reaction barrier, thus facilitating ion/electron transport and inhibiting the shuttle effect. Benefiting from these advantages, the Li-S battery with MXene/NiS2/Co3S4 modified separator exhibits exciting discharge capacities (1495.4 mAh g-1 at 0.1C and 549.0 mAh g-1 at 6C) and an excellent ultra-long cycle life (average capacity decay rate of 0.026% for 2000 cycles at 2C); at a high sulfur loading of 10.0 mg cm-2, the battery operates for nearly 80 cycles at 0.2C, giving a capacity retention rate of 75.76%. This work provides a high-activity catalyst for Li-S batteries.

Catheter ablation versus antiarrhythmic drug therapy for sustained ventricular tachycardia in patients with hypertrophic cardiomyopathy.

BACKGROUND: Ventricular tachycardia (VT) is the primary cause of sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM). However, the strategy for VT treatment in HCM patients remains unclear. This study is aimed to compare the effectiveness of catheter ablation versus antiarrhythmic drug (AAD) therapy for sustained VT in patients with HCM. METHODS: A total of 28 HCM patients with sustained VT at 4 different centers between December 2012 and December 2021 were enrolled. Twelve underwent catheter ablation (ablation group) and sixteen received AAD therapy (AAD group). The primary outcome was VT recurrence during follow-up. RESULTS: Baseline characteristics were comparable between two groups. After a mean follow-up of 31.4 ± 17.5 months, the primary outcome occurred in 35.7% of the ablation group and 90.6% of the AAD group (hazard ratio [HR], 0.29 [95%CI, 0.10-0.89]; P = 0.021). No differences in hospital admission due to cardiovascular cause (25.0% vs. 71.0%; P = 0.138) and cardiovascular cause-related mortality/heart transplantation (9.1% vs. 50.6%; P = 0.551) were observed. However, there was a significant reduction in the composite endpoint of VT recurrence, hospital admission due to cardiovascular cause, cardiovascular cause-related mortality, or heart transplantation in ablation group as compared to that of AAD group (42.9% vs. 93.7%; HR, 0.34 [95% CI, 0.12-0.95]; P = 0.029). CONCLUSIONS: In HCM patients with sustained VT, catheter ablation reduced the VT recurrence, and the composite endpoint of VT recurrence, hospital admission due to cardiovascular cause, cardiovascular cause-related mortality, or heart transplantation as compared to AAD.

Severe Periprocedural Complications After Ablation for Atrial Fibrillation: An International Collaborative Individual Patient Data Registry.

BACKGROUND: Catheter ablation for atrial fibrillation (AF) including pulmonary vein isolation and possibly further substrate ablation is the most common electrophysiological procedure. Severe complications are uncommon, but their detailed assessment in a large worldwide cohort is lacking. OBJECTIVES: The aim of this study was to determine the incidence of periprocedural severe complications and to provide a detailed characterization of the diagnostic evaluation and management of these complications in patients undergoing AF ablation. METHODS: Individual patient data were collected from 23 centers worldwide. Limited data were collected for all patients who underwent catheter ablation, and an expanded series of data points were collected for patients who experienced severe complications during periprocedural follow-up. Incidence, predictors, patient characteristics, management details, and overall outcomes of patients who experienced ablation-related complications were investigated. RESULTS: Data were collected from 23 participating centers at which 33,879 procedures were performed (median age 63 years, 30% women, 71% radiofrequency ablations). The incidence of severe complications (n = 271) was low (tamponade 6.8‰, stroke 0.97‰, cardiac arrest 0.41‰, esophageal fistula 0.21‰, and death 0.21‰). Age, female sex, a dilated left atrium, procedure duration, and the use of radiofrequency energy were independently associated with the composite endpoint of all severe complications. Among patients experiencing tamponade, 13% required cardiac surgery. Ninety-three percent of patients with complications were discharged directly home after a median length of stay of 5 days (Q1-Q3: 3-7 days). CONCLUSIONS: This large worldwide collaborative study highlighted that tamponade, stroke, cardiac arrest, esophageal fistula, and death are rare after AF ablation. Older age, female sex, procedure duration, a dilated left atrium, and the use of radiofrequency energy were associated with severe complications in this multinational cohort. One in 8 patients with tamponade required cardiac surgery.

The phytochemistry, pharmacology, pharmacokinetics, quality control, and toxicity of Forsythiae Fructus: An updated systematic review.

Forsythiae Fructus (FF), the dried fruit of F. suspensa, is commonly used to treat fever, inflammation, etc in China or other Asian countries. FF is usually used as the core herb in traditional Chinese medicine preparations for the treatment of influenza, such as Shuang-huang-lian oral liquid and Yin-qiao powder, etc. Since the wide application and core role of FF, its research progress was summarized in terms of traditional uses, phytochemistry, pharmacology, pharmacokinetics, quality control, and toxicity. Meanwhile, the anti-influenza substances and mechanism of FF were emphasized. Till now, a total of 290 chemical components are identified in F. suspensa, and among them, 248 components were isolated and identified from FF, including 42 phenylethanoid glycosides, 48 lignans, 59 terpenoids, 14 flavonoids, 3 steroids, 24 cyclohexyl ethanol derivatives, 14 alkaloids, 26 organic acids, and 18 other types. FF and their pure compounds have the pharmacological activities of anti-virus, anti-inflammation, anti-oxidant, anti-bacteria, anti-tumor, neuroprotection, hepatoprotection, etc. Inhibition of TLR7, RIG-I, MAVS, NF-κB, MyD88 signaling pathway were the reported anti-influenza mechanisms of FF and phenylethanoid glycosides and lignans are the main active groups. However, the bioavailability of phenylethanoid glycosides and lignans of FF in vivo was low, which needed to be improved. Simultaneously, the un-elucidated compounds and anti-influenza substances of FF strongly needed to be explored. The current quality control of FF was only about forsythoside A and phillyrin, more active components should be taken into consideration. Moreover, there are no reports of toxicity of FF yet, but the toxicity of FF should be not neglected in clinical applications.

Multi-omics and chemical profiling approaches to understand the material foundation and pharmacological mechanism of sophorae tonkinensis radix et rhizome-induced liver injury in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophorae tonkinensis Radix et Rhizoma (STR) is an extensively applied traditional Chinese medicine (TCM) in southwest China. However, its clinical application is relatively limited due to its hepatotoxicity effects. AIM OF THE STUDY: To understand the material foundation and liver injury mechanism of STR. MATERIALS AND METHODS: Chemical compositions in STR and its prototypes in mice were profiled by ultra-performance liquid chromatography coupled quadrupole-time of flight mass spectrometry (UPLC-Q/TOF MS). STR-induced liver injury (SILI) was comprehensively evaluated by STR-treated mice mode. The histopathologic and biochemical analyses were performed to evaluate liver injury levels. Subsequently, network pharmacology and multi-omics were used to analyze the potential mechanism of SILI in vivo. And the target genes were further verified by Western blot. RESULTS: A total of 152 compounds were identified or tentatively characterized in STR, including 29 alkaloids, 21 organic acids, 75 flavonoids, 1 quinone, and 26 other types. Among them, 19 components were presented in STR-medicated serum. The histopathologic and biochemical analysis revealed that hepatic injury occurred after 4 weeks of intragastric administration of STR. Network pharmacology analysis revealed that IL6, TNF, STAT3, etc. were the main core targets, and the bile secretion might play a key role in SILI. The metabolic pathways such as taurine and hypotaurine metabolism, purine metabolism, and vitamin B6 metabolism were identified in the STR exposed groups. Among them, taurine, hypotaurine, hypoxanthine, pyridoxal, and 4-pyridoxate were selected based on their high impact value and potential biological function in the process of liver injury post STR treatment. CONCLUSIONS: The mechanism and material foundation of SILI were revealed and profiled by a multi-omics strategy combined with network pharmacology and chemical profiling. Meanwhile, new insights were taken into understand the pathological mechanism of SILI.

Selecting Monoclonal Cell Lineages from Somatic Reprogramming Using Robotic-Based Spatial-Restricting Structured Flow.

Somatic cell reprogramming generates induced pluripotent stem cells (iPSCs), which serve as a crucial source of seed cells for personalized disease modeling and treatment in regenerative medicine. However, the process of reprogramming often causes substantial lineage manipulations, thereby increasing cellular heterogeneity. As a consequence, the process of harvesting monoclonal iPSCs is labor-intensive and leads to decreased reproducibility. Here, we report the first in-house developed robotic platform that uses a pin-tip-based micro-structure to manipulate radial shear flow for automated monoclonal iPSC colony selection (~1 s) in a non-invasive and label-free manner, which includes tasks for somatic cell reprogramming culturing, medium changes; time-lapse-based high-content imaging; and iPSCs monoclonal colony detection, selection, and expansion. Throughput-wise, this automated robotic system can perform approximately 24 somatic cell reprogramming tasks within 50 days in parallel via a scheduling program. Moreover, thanks to a dual flow-based iPSC selection process, the purity of iPSCs was enhanced, while simultaneously eliminating the need for single-cell subcloning. These iPSCs generated via the dual processing robotic approach demonstrated a purity 3.7 times greater than that of the conventional manual methods. In addition, the automatically produced human iPSCs exhibited typical pluripotent transcriptional profiles, differentiation potential, and karyotypes. In conclusion, this robotic method could offer a promising solution for the automated isolation or purification of lineage-specific cells derived from iPSCs, thereby accelerating the development of personalized medicines.

Sesamin alleviates lipid accumulation induced by oleic acid via PINK1/Parkin-mediated mitophagy in HepG2 cells.

Sesamin, a special compound present in sesame and sesame oil, has been reported a role in regulating lipid metabolism, while the underlying mechanisms remain unclear. Autophagy has been reported associated with lipid metabolism and regarded as a key modulator in liver steatosis. The present work aimed to investigate whether sesamin could exert its protective effects against lipid accumulation via modulating autophagy in HepG2 cells stimulated with oleic acid (OA). Cell viability was evaluated using the CCK-8 method, and triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein, cholesterol (LDL-C), alanine aminotransferase (ALT), along with aspartate aminotransferase (AST) were assessed by oil red O staining, transmission electron microscopy (TEM), and biochemical kits to investigate the lipid-lowering effects of sesamin. Differentially expressed genes were screened by RNA sequencing and validated using real-time quantitative PCR and Western blot. Autophagy and mitophagy related molecules were analyzed employing TEM, Western blot, and immunofluorescence. The data shows that in HepG2 cells stimulated by OA, sesamin reduces levels of TG, TC, LDL-C, ALT, and AST while elevating HDL-C, alleviates the lipid accumulation and improves fatty acid metabolism through modulating the levels of fat metabolism related genes including PCSK9, FABP1, CD36, and SOX4. Sesamin restores the suppressed autophagy in HepG2 cells caused by OA, which could be blocked by autophagy inhibitors. This indicates that sesamin improves fatty acid metabolism by enhancing autophagy levels, thereby mitigating the intracellular lipid accumulation. Furthermore, sesamin significantly enhances the mitophagy and improves mitochondrial homeostasis via activating the PINK/Parkin pathway. These data suggest that sesamin alleviates the excessive lipid accumulation in HepG2 caused by OA by restoring the impaired mitophagy via the PINK1/Parkin pathway, probably playing a preventive or therapeutic role in hepatic steatosis.