The fabrication of ZIF-L derived ZnS/MoS2@NC anode materials for remarkable lithium-ion storage.

The enhancement of electrochemical performance in lithium-ion batteries can be achieved through the incorporation of MoS2 with carbon materials and various metal sulfides. In this investigation, a MoS2/ZnS heterostructure was devised incorporating a two-dimensional nitrogen-doped carbon nanosheet (NC) backbone. The synthesis of ZnMo-ZIF-L precursors was achieved by introducing a Mo source in a 1:1 molar ratio during ZIF-L synthesis. Subsequent to high-temperature carbonization and vulcanization treatment, ZnS/MoS2@NC composite materials were successfully synthesized. Compared to the unvulcanized ZnO/MoO3@NC and MoS2 samples, the ZnS/MoS2@NC composite exhibits remarkable lithium storage performance. At a current density of 500 mA g-1, the initial discharge specific capacity is 2547 mAh g-1, with an initial charge specific capacity of 1674 mAh g-1, resulting in a first Coulombic efficiency of 65.76%. Furthermore, this composite material demonstrates optimal rate capabilities and a significant pseudocapacitance contribution. The nitrogen-doped carbon framework effectively mitigates volume effects, while the heterostructural design provides more active sites for lithium ions, thereby enhancing lithium storage performance.

Design, synthesis, and biological evaluation of novel HPK1 inhibitors possessing 3-cyano-quinoline moiety.

Hematopoietic progenitor kinase 1 (HPK1), a negative regulator of T cell receptor signaling, plays a crucial role in multiple cellular immune responses. Emerging researches have demonstrated that inhibiting HPK1 kinase function enhances T cells' ability to recognize tumor antigens and boosts anti-tumor immune responses. As a result, HPK1 has become a promising target for tumor immunotherapy. Herein, we report the design, synthesis, and biological evaluation of a series of novel HPK1 inhibitors featuring a 3-cyano-quinoline scaffold. Among these, compound 3a was identified as the most potent HPK1 inhibitor (HPK1 IC50 = 48 nM). It effectively inhibited SLP76 phosphorylation, enhanced IL-2 cytokine secretion, and reversed PGE2-induced immunosuppression in Jurkat cells. In addition, compound 3a exhibited favorable metabolic stability in mouse liver microsomes and plasma. Overall, this work provides a structurally novel lead compound for the development of HPK1 inhibitors.

Bempedoic Acid can Reduce Cardiovascular Events in Combination with Statins or As Monotherapy: A Systematic Review and Meta-analysis.

AIM: Bempedoic acid has shown noteworthy progress in the prevention and management of atherosclerotic cardiovascular disease (ASCVD) in recent years. However, there has been a lack of high-quality evidence regarding the risk reduction of clinical events with bempedoic acid. Therefore, the aim of this article is to conduct a comprehensive evaluation of the impact of bempedoic acid on the incidence of cardiovascular events. METHODS: A systematic review and meta-analysis of randomized controlled trials pertaining to bempedoic acid was carried out. We conducted a systematic search across the Pubmed, Embase, and Cochrane Central Register of Controlled Trials databases to identify relevant studies published from inception to 23 April 2023. A total of four trials comparing the clinical benefit achieved with bempedoic acid versus placebo were included. RESULTS: Our analysis comprised four trials that encompassed a total of 17,323 patients. In comparison to the placebo, bempedoic acid showed a significant reduction in the risk of major adverse cardiovascular events (MACE) [relative risk (RR), 0.86, 95% confidence interval (CI) 0.87-0.94]. Additionally, bempedoic acid substantially lowered the occurrence of fatal or nonfatal myocardial infarction (RR 0.76, 95% CI 0.66-0.89), hospitalization for unstable angina (RR 0.70, 95% CI 0.55-0.89), and coronary revascularization (RR 0.82, 95% CI 0.73-0.92). There was also a similar reduction in MACE in patients on the maximally tolerated statin therapy. CONCLUSION: Bempedoic acid may reduce the risk of cardiovascular events regardless of whether the patient is taking stains or not. REGISTRATION: PROSPERO registration number CRD42023422932.

[Effect of LY249002 on myocardial structure and cardiac function in rats with dilated cardiomyopathy].

OBJECTIVE: To examine the role of LY294002 in cardiac function and myocardial structure in dilated cardiomyopathy (DCM) rats.
 Methods: Fifty-two male SD rats were randomly assigned to a control group (n=16) and a DCM group (n=36). The DCM rats were induced by intraperitoneal injection of adriamycin, and the control rats were given normal saline. After observation for 2 weeks, 6 rats from each group were killed randomly. In the end of the 8th week, the 24 DCM rats were randomly assigned to a DCM group (n=12) and a LY294002 group (n=12), which were given normal saline and LY294002, respectively. In the end of the 8th week and 16th week, the cardiac function was analyzed by ultrasonic cardiogram (UCG) and the plasma was collected to test the level of N-terminal pro-brain natriuretic peptide (NT-pro BNP). HE and Van Gieson (VG) staining were performed to calculate the collagen volume fraction (CVF).
 Results: Compared with the control group, the left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD) and NT-proBNP level of in the DCM rats were increased obviously, while the left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS) in the DCM rats were decreased obviously (P<0.01). These changes were consistent with DCM characteristics. Compared with the DCM group, the LVEDD, LVESD and NT-proBNP levels in the LY294002 group were decreased, while the LVEF and LVFS were increased (P<0.05). Histopathology showed that the myocardium in the DCM rats was fibrotic and the CVF was increased compared with the control rats (P<0.01). The myocardial structure was improved in the LY294002 group compared to the DCM group.
 Conclusion: LY294002 can reduce the myocardial fibrosis in the DCM rats and improve the cardiac function.

Transesophageal echocardiography measures left atrial appendage volume and function and predicts recurrence of paroxysmal atrial fibrillation after radiofrequency catheter ablation.

AIMS: Paroxysmal atrial fibrillation (PAF) commonly recurs after radiofrequency catheter ablation (RFCA). This study aimed to assess left atrial appendage (LAA) volume and function by transesophageal echocardiography (TEE) and to explore its value in predicting PAF recurrence after RFCA. METHODS: Eighty patients with PAF were recruited. The left atrial (LA) and LAA volume and function were measured by transthoracic echocardiography (TTE) and TEE before ablation. Patients were followed up for 12 months after RFCA, and recurrence was recorded. Odds ratios of candidate risk indicators were determined by logistic regression analysis. Prediction model was constructed using logistic regression with backward selection. Receiver operating characteristic (ROC) curve with area under curve (AUC) was performed to evaluate the prediction efficiency. RESULTS: Twenty-four (30%) PAF patients had recurrence (R group), and 56 (70%) patients had no recurrence (NR group). Compared to NR group, LA dimension (LAD), LA volume index (LAVI), LAA maximum volume (LAAVmax), and LAA minimum volume (LAAVmin) were significantly higher in R group, while LAA peak emptying flow velocity (LAAeV), LAA peak filling flow velocity (LAAfV), and LAA ejection fraction (LAAEF) significantly declined in R group. According to multivariate analysis and backward selection, LAVI, LAAEF, and LAAeV were significant risk factors for PAF recurrence. The LAVI + LAAEF + LAAeV joint model could effectively predict PAF recurrence with AUC of 0.893 (95% confidence interval = 0.816, 0.970), sensitivity of 0.75, and specificity of 0.929. CONCLUSIONS: This study demonstrated that LAVI, LAAEF, and LAAeV were significant predictors of PAF recurrence after RFCA.

[Evaluation of the volume and function of left atrial appendage and left atrium in patients with atrial fibrillation by three-dimensional transesophageal echocardiography and transthoracic echocardiography].

OBJECTIVE: To evaluate the volume and function of left atrium and left atrial appendage in patients with atrial fibrillation by three-dimensional transesophageal echocardiography and transthoracic echocardiography.
 Methods: A total of 112 patients with atrial fibrillation were divided into two groups: a paroxysmal atrial fibrillation (ParAF) group (n=80) and a persistent atrial fibrillation (PerAF) group (n=32). Control group was people without atrial fibrillation (n=40). Clinical data of the participants were collected. Left atrial dimension (LAD), left atrial volume (LAV), left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) were measured by transthoracic echocardiography, while left atrial appendage peak emptying flow velocity (LAAeV), left atrial appendage peak filling flow velocity (LAAfV), left atrial appendage maximum volume (LAAVmax) and left atrial appendage minimum volume (LAAVmin) were measured by three-dimensional transesophageal echocardiography. Left atrial volume index (LAVI), left ventricular ejection fraction (LVEF) and left atrial appendage ejection fraction (LAAEF) were calculated. 
 Results: Compared with the control group, LAAEF, LAAeV and LAAfV in the ParAF group were decreased obviously, while LAD, LAV, LAVI, LAAVmax and LAAVmin in the ParAF group were increased obviously (P<0.05). Compared with the ParAF group, LAAEF, LAAeV and LAAfV in the PerAF group were also decreased obviously, and LAD, LAV, LAVI, LAAVmax and LAAVmin in the ParAF group were also increased obviously (P<0.05). There was no statistically significant difference in LVEDV, LVESV, LVEF between the ParAF group and the PerAF group (P<0.05).
 Conclusion: Left atrium and left atrial appendage were enlarged and the function of left atrial appendage was declined in patients with AF, and the changes were more obvious in patients with PerAF compared with patients with ParAF by three-dimensional transesophageal echocardiography and transthoracic echocardiography.

[Evaluation of three-dimensional speckle tracking echocardiography to left ventricular rotation and twist in patients with silent myocardial ischemia].

OBJECTIVE: To analyze the characteristics of left ventricular rotation and twist in patients with silent myocardial ischemia (SMI) by three-dimensional speckle tracking echocardiography (3D-STE), and to explore the diagnostic value of this method for SMI.
 METHODS: According to Gensini score, 66 patients with SMI were divided into 3 subgroups: a mild lesion group (n=16), a moderate lesion group (n=26) and a severe lesion group (n=24). Thirty patients with negative results in selective coronary angiography served as a control group. The parameters of wall motion score index (WMSI), left ventricular ejection fraction (LVEF), peak basal rotation (Ptw-B), peak apical rotation (Prot-A), left ventricular peak apical rotation (LVrot), left ventricular peak apical twist (LVtw) were measured.
 RESULTS: In the SMI group, with an increase in severity of myocardial ischemia, LVEF, Prot-A, Prot-B, LVrot, LVtw showed a decrease trend while WMSI exhibited an opposite phenomenon (P<0.05), and all of them displayed a significant corelation with Gensini score (P<0.05). In the diagnosis of SMI, all of the above-mentioned parameters were highly sensitive and specific. 3D-STE showed the highest diagnostic value for LVtw.
 CONCLUSION: Left ventricular rotation and twisting motion monitered by 3D-STE can evaluate the severity of myocardial ischemia in patients with SMI.

[Advances in genetic modification technologies].

Genetic modification technology is a new molecular tool for targeted genome modification. It includes zinc finger nucleases (ZFN) technology, transcription activator-like effector nucleases (TALEN) technology and clustered regularly interspaced short palindromic repeat (CRISPR)-associated (Cas) (CRISPR-Cas) nucleases technology. All of these nucleases create DNA double-strand breaks (DSB) at chromosomal targeted sites and induce cell endogenous mechanisms that are primarily repaired by the non-homologous end joining (NHEJ) or homologous recombination (HR) pathway, resulting in targeted endogenous gene knock-out or exogenous gene insertion. In recent years, genetic modification technologies have been successfully applied to bacteria, yeast, human cells, fruit fly, zebra fish, mouse, rat, livestock, cynomolgus monkey, Arabidopsis, rice, tobacco, maize, sorghum, wheat, barley and other organisms, showing its enormous advantage in gene editing field. Especially, the newly developed CRISPR-Cas9 system arose more attention because of its low cost, high effectiveness, simplicity and easiness. We reviewed the principles and the latest research progress of these three technologies, as well as prospect of future research and applications.