Prognostic significance of compliance with fractional flow reserve guidance on diverse vessel-related clinical outcomes.

Background: In patients underwent fractional flow reserve (FFR) assessment, a noteworthy proportion of adverse events occur in vessels in which FFR has not been measured. However, the effect of these non-target vessel-related events on the evaluation of FFR-related benefits remains unknown. Methods and results: In this retrospective study, vessels subjected to FFR measurement were grouped as FFR-based approach and non-compliance with FFR based on whether they received FFR-based treatment. Using inverse probability of treatment weighting (IPTW) to account for potential confounding, we investigated the association between compliance with FFR and 5-year target vessel failure (TVF) non-target vessel failure (NTVF) and vessel-oriented composite endpoints (VOCEs). Of the 1,119 vessels, 201 did not receive FFR-based treatment. After IPTW adjustment, a significantly lower hazard of TVF was observed in the FFR-based approach group (HR: 0.56; 95% CI: 0.34-0.92). While, the intergroup difference in hazard of NTVF (HR: 1.02; 95% CI: 0.45-2.31) and VOCEs (HR: 0.69; 95% CI: 0.45-1.05) were nonsignificant. Conclusions: In patients with CAD subjected to FFR, the FFR-based treatment yields a sustained clinical benefit in terms of the risks of target vessel-related events. The dilution of non-target vessel-related events renders the difference favoring the FFR-based approach nonsignificant.

Efficient electrocardiogram generation based on cardiac electric vector simulation model.

This study introduces a novel Cardiac Electric Vector Simulation Model (CEVSM) to address the computational inefficiencies and low fidelity of traditional electrophysiological models in generating electrocardiograms (ECGs). Our approach leverages CEVSM to efficiently produce reliable ECG samples, facilitating data augmentation essential for the computer-aided diagnosis of myocardial infarction (MI). Significantly, experimental results show that our model dramatically reduces computation time compared to conventional models, with the self-adapting regression transformation matrix method (SRTM) providing clear advantages. SRTM not only achieves high fidelity in ECG simulations but also ensures exceptional consistency with the gold standard method, greatly enhancing MI localization accuracy by data augmentation. These advancements highlight the potential of our model to generate dependable ECG training samples, making it highly suitable for data augmentation and significantly advancing the development and validation of intelligent MI diagnostic systems. Furthermore, this study demonstrates the feasibility of applying life system simulations in the training of medical big models.

Percutaneous Coronary Intervention in Acute Coronary Syndrome with Mild-to-Moderate Thrombocytopenia.

BACKGROUND: Baseline thrombocytopenia is commonly observed in patients with acute coronary syndrome (ACS) requiring percutaneous coronary intervention (PCI). AIM: The purpose of this analysis was to investigate safety and effectiveness of PCI in ACS patients with baseline mild-to-moderate thrombocytopenia. METHODS: The data were collected from the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project. A total of 50,009 ACS patients were recruited between July 2017 and December 2019. Among them, there were 6,413 patients with mild-to-moderate thrombocytopenia, defined as a platelet count of ≥50 × 109/L and <150 × 109/L on admission. The primary outcome was in-hospital net adverse clinical events (NACE), consisting of major adverse cardiac events (MACE) and major bleeding events. The associations between PCI and in-hospital outcomes were analyzed by inverse probability treatment weighting (IPTW) method. RESULTS: PCI was performed in 4,023 of 6,413 patients (62.7%). The IPTW analysis showed that PCI was significantly associated with a reduced risk of in-hospital MACE (odd ratio [OR]: 0.45; 95% confidence interval [CI]: 0.31-0.67; p < 0.01) and NACE (OR: 0.59; 95% CI: 0.42-0.83; p < 0.01). PCI was also associated with an increased risk of any bleeding (OR: 1.56; 95% CI: 1.09-2.22; p = 0.01) and minor bleeding (OR: 1.52; 95% CI: 1.00-2.30; p = 0.05), but not major bleeding (OR: 1.51; 95% CI: 0.76-2.98; p = 0.24). CONCLUSION: Compared with medical therapy alone, PCI is associated with better in-hospital outcomes in ACS patients with mild-to-moderate thrombocytopenia. Further studies with long-term prognosis are needed.

Diagnostic accuracy of noninvasive fractional flow reserve derived from computed tomography angiography in ischemia-specific coronary artery stenosis and indeterminate lesions: results from a multicenter study in China.

Background: To determine the diagnostic performance of a novel computational fluid dynamics (CFD)-based algorithm for in situ CT-FFR in patients with ischemia-induced coronary artery stenosis. Additionally, we investigated whether the diagnostic accuracy of CT-FFR differs significantly across the spectrum of disease and analyzed the influencing factors that contribute to misdiagnosis. Methods: Coronary computed tomography angiography (CCTA), invasive coronary angiography (ICA), and FFR were performed on 324 vessels from 301 patients from six clinical medical centers. Local investigators used CCTA and ICA to conduct assessments of stenosis, and CT-FFR calculations were performed in the core laboratory. For CCTA and ICA, CT-FFR ≤ 0.8 and a stenosis diameter ≥ 50% were identified as lesion-specific ischemia. Univariate logistic regression models were used to assess the effect of features on discordant lesions (false negative and false positive) in different CT-FFR categories. The diagnostic performance of CT-FFR was analyzed using an invasive FFR ≤ 0.8 as the gold standard. Results: The Youden index indicated an optimal threshold of 0.80 for CT-FFR to identify functionally ischemic lesions. On a per-patient basis, the diagnostic sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) for CT-FFR were 96% (91%-98%), 92% (87%-96%), 94% (90%-96%), 91% (85%-95%), and 96% (92%-99%), respectively. The diagnostic efficacy of CT-FFR was higher than that of CCTA without the influence of calcification. Closer to the cut point, there was less certainty, with the agreement between the invasive FFR and the CT-FFR being at its lowest in the CT-FFR range of 0.7-0.8. In all lesions, luminal stenosis ≥ 50% significantly affected the risk of reduced false negatives (FN) and false positives (FP) results by CT-FFR, irrespective of the association with calcified plaque. Conclusions: In summary, CT-FFR based on the new parameter-optimized CFD model has a better diagnostic performance than CTA for lesion-specific ischemia. The presence of calcified plaque has no significant effect on the diagnostic performance of CT-FFR and is independent of the degree of calcification. Given the range of applicability of our software, its use at a CT-FFR of 0.7-0.8 requires caution and must be considered in the context of multiple factors.

Diagnostic performance of a novel automated CT-derived FFR technology in detecting hemodynamically significant coronary artery stenoses: A multicenter trial in China.

BACKGROUND AND AIMS: Computed tomography-derived fractional flow reserve (CT-derived FFR) algorithms have emerged as promising noninvasive methods for identifying hemodynamically significant coronary artery disease (CAD). However, its broad adaption is limited by the complex workflow, slow processing, and supercomputer requirement. Therefore, CT-derived FFR solutions capable of producing fast and accurate results could help deliver time-sensitive results rapidly and potentially alter patient management. The current study aimed to determine the diagnostic performance of a novel CT-derived FFR algorithm, esFFR, on patients with CAD was evaluated. METHODS: 329 patients from 6 medical centers in China were included in this prospective study. CT-derived FFR calculations were performed on 350 vessels using the esFFR algorithm using patients' presenting coronary computed tomography angiography (CCTA) images, and results and processing speed were recorded. Using invasive FFR measurements from direct coronary angiography as the reference standard, the diagnostic performance of esFFR and CCTA in detecting hemodynamically significant lesions were compared. Post-hoc analyses were performed for patients with calcified lesions or stenoses within the CT-derived FFR diagnostic "gray zone." RESULTS: The esFFR values correlated well with invasive FFR. The sensitivity, specificity, accuracy, positive and negative predictive value for esFFR were all above 90%. The overall performance of esFFR was superior to CCTA. Coronary calcification had minimal effects on esFFR's diagnostic performance. It also maintained 85% of diagnostic accuracy for "gray zone" lesions, which historically was <50%. The average esFFR processing speed was 4.6 ± 1.3 minutes. CONCLUSIONS: The current study demonstrated esFFR had high diagnostic efficacy and fast processing speed in identifying hemodynamically significant CAD.

Clinical Characteristics, Treatment Patterns, and Effectiveness in Chinese Patients with Angina Pectoris Using Electronic Patient-Reported Outcomes: Protocol for a Multicenter, Prospective, Cohort Study (GREAT).

BACKGROUND: Angina pectoris (AP) is the initial and the most common manifestation of coronary artery disease (CAD). Therefore, management and control of AP can help prevent further complications associated with CAD. However, there is under-reporting of angina symptoms in clinical practice, resulting in under-treatment and reduced quality of life (QoL). Prospective and standardized monitoring is needed to support timely and appropriate treatment. OBJECTIVES: To establish a large cohort of Chinese patients with AP and compare the effectiveness of different anti-angina regimens with the help of electronic patient-reported outcomes (e-PROs), using the Seattle Angina Questionnaire (SAQ) to assess health status. METHODS: The registry study (GREAT) is a multicenter, prospective, observational, cohort study. Patients diagnosed with AP will be enrolled from 10 hospitals and assessed based on the different anti-anginal regimens. Patients will be followed up every 3 months from baseline to 12 months to observe the difference in the therapeutic effectiveness of the drugs. Data will be collected in the form of e-PROs combined with on-site visit records. PLANNED OUTCOMES: The change in SAQ summary score (SAQ SS) at Month 12 from baseline will be the primary outcome. The secondary measures will include changes in SAQ SS at Months 3, 6, and 9 from baseline, changes in retest results of vascular stenosis imaging at Month 12 from baseline, and medication adherence based on the proportion of days covered. Safety data will be evaluated based on the incidence of adverse events (AEs). CONCLUSION: This study will evaluate the effectiveness of anti-anginal regimens using ePROs in real-world settings in China. The results from this study may provide a new perspective on treatment patterns and the effectiveness of different anti-anginal regimens for patients with AP. STUDY REGISTRATION NUMBER: NCT05050773.

Impact of Pancreatic ß-Cell Function on Clopidogrel Responsiveness and Outcomes in Chinese Nondiabetic Patients Undergoing Elective Percutaneous Coronary Intervention.

PURPOSE: Insulin resistance and ß-cell dysfunction are fundamental defects contributing to type 2 diabetes development. Prior studies indicated that insulin resistance may be correlated with low responsiveness to clopidogrel. This study aimed to investigate the effects of ß-cell function on clopidogrel-induced platelet P2Y12 inhibition and the clinical outcomes of nondiabetic patients undergoing elective percutaneous coronary intervention (PCI). METHODS: Patients scheduled to undergo elective PCI and receive clopidogrel in addition to aspirin were recruited for this study. Homeostatic model assessment 2 of ß-cell function (HOMA2-ß%) was used to classify participants into quartiles. Thromboelastography (TEG) was used to calculate the quantitative platelet inhibition rate to assess clopidogrel-induced antiplatelet reactivity. The clinical outcome was major adverse cardiovascular and cerebrovascular events (MACCEs). RESULTS: Of the 784 participants evaluated, 21.3% of them (169 of 784) had low responsiveness to clopidogrel. According to multivariate linear regression analysis, the first quartile of HOMA2-ß% (19.9-78.1), indicating greater ß-cell dysfunction, was independently associated with low responsiveness to clopidogrel compared with the fourth quartile (126.8-326.2) after adjustment for potential covariates [odds ratio 2.140, 95% confidence interval (CI) (1.336 to 3.570), P = 0.038]. In addition, at one year, the first quartile of HOMA2-ß% was associated with an increased risk of 1-year MACCE occurrence compared with the fourth quartile [adjusted hazard ratio 4.989, 95% CI (1.571 to 15.845), P = 0.006]. CONCLUSION: Increased ß-cell dysfunction, indicated by a low HOMA2-ß%, was associated with low responsiveness to clopidogrel and an increased risk of one-year MACCEs in nondiabetic patients undergoing elective PCI.

An ECG generative model of myocardial infarction.

Background and Objective Computer-aided diagnosis (CAD) of Myocardial Infarction (MI) using machine learning depends on a large amount of clinical Electrocardiogram (ECG) data. Existing infarct ECG databases face the problem of class imbalance. Data augmentation using generative simulation models is a new approach to effectively address this problem. Methods A multiscale ECG generative model was established for ECG data augmentation. In the cellular layer, an ischemic Action Potential (AP) model was established to generate APs in cardiomyocytes with different transmural regions of infraction or different ischemic durations. In the tissue layer, a probability-driven cellular automata excitation propagation model was established to simulate the propagation speed and direction of excitation. An infarct tissue model and a coronary artery model were established to describe the spatiotemporal diversity of MI. A ventricle model, a human torso model, and a computational model of surface ECG based on field source theory were established in the heart-torso layer. Results The model generated pathological 12-lead ECGs of MI with different topography and different extent. When simulating different ventricular wall infarction, the lesions appear in the same leads as the clinical 12-lead ECG. The ST-segment decreases and the T-wave amplitude decreases, similar to the clinical ECG features when simulating subendocardial ischemia. The average fidelity of the 12-lead ECG the model generated is 95.6%, according to the designed DTW-GRA distance algorithm. Conclusions The generative model considers the electrophysiological properties of the natural heart, the pathology of myocardial infarction, and the diversity of clinical ECGs. The model can provide many reliable samples for machine learning of MI.

Clinical Outcomes After Percutaneous Coronary Intervention Over Time on the Basis of CYP2C19 Polymorphisms.

ABSTRACT: The aim of this study was to investigate the association between CYP2C19 gene polymorphisms and the risk of cardiovascular events in the early stage and subsequent period after percutaneous coronary intervention (PCI) among patients who received clopidogrel. Between October 2015 and January 2017, CYP2C19 genotyped patients who were treated with clopidogrel after PCI were enrolled in this study. Included patients were categorized as non-loss-of-function metabolizers, intermediate metabolizers, and poor metabolizers based on CYP2C19 genotype. The primary outcome was a composite of any-cause mortality, nonfatal myocardial infarction, nonfatal ischemic stroke, and stent thrombosis occurring during exposure to clopidogrel. The rates of clinical outcome events were compared between CYP2C19 phenotypes. Landmark analyses were processed at 90 days and 1 year post-PCI. Of 1341 patients, 161 (12.0%) had 2 copies of loss-of-function (LOF) alleles, 621(46.3%) had one LOF allele, and 559 (41.7%) had no LOF allele. At the 3-month follow-up, the primary outcome events were more frequent in carriers of 2 LOF alleles (5.6%) than in noncarriers (1.8%) [adjusted hazard ratio (HR) 2.944, 95% confidence interval, 1.184-7.321, P = 0.020). A similar finding was observed among in patients with acute coronary syndrome indications at the index PCI (adjusted HR 3.046, 95% confidence interval, 1.237-7.501, P = 0.015). These differences did not persist within the subsequent 9 months of follow-up, among either all comers or subjects with acute coronary syndrome. In conclusion, these data demonstrate a higher risk for ischemic events in patients with 2 CYP2C19 LOF alleles who are prescribed clopidogrel, seen at 3 months after PCI, that is not sustained for 12 months.

Mean Platelet Volume is Associated with Pancreatic ß-Cell Dysfunction in Nondiabetic Patients with Coronary Artery Disease.

PURPOSE: Mean platelet volume (MPV) is an indicator of platelet activation. Pancreatic ß-cell dysfunction is one of the fundamental defects contributing to the development of type 2 diabetes. The aim of this study was to assess the relationship between ß-cell dysfunction and MPV in nondiabetic patients with coronary artery disease (CAD). PATIENTS AND METHODS: A total of 1143 consecutive nondiabetic patients (874 males and 269 females; mean age 60.0±10.3 years) with CAD were recruited for this analysis. All patients were individuals who underwent coronary angiography with a suspicion of CAD. Homeostatic model assessment 2 (HOMA2) of ß-cell function (HOMA2-ß%) was performed, and ß-cell dysfunction was defined by a HOMA2-ß% in the lowest quartile. RESULTS: MPV was significantly higher in CAD patients with ß-cell dysfunction than in controls [(10.6±1.0)fl vs (10.0±1.0)fl, P=0.011]. According to the multiple regression model, pancreatic ß-cell dysfunction was independently associated with MPV (ß=0.210, P=0.006) and age (ß=0.008, P=0.028). CONCLUSION: MPV was significantly elevated in nondiabetic CAD patients with ß-cell dysfunction compared to patients with normal ß-cell function.

Potent and Selective Inhibitors of the Epidermal Growth Factor Receptor to Overcome C797S-Mediated Resistance.

The epidermal growth factor receptor (EGFR) harboring activating mutations is a clinically validated target in non-small-cell lung cancer, and a number of inhibitors of the EGFR tyrosine kinase domain, including osimertinib, have been approved for clinical use. Resistance to these therapies has emerged due to a variety of molecular events including the C797S mutation which renders third-generation C797-targeting covalent EGFR inhibitors considerably less potent against the target due to the loss of the key covalent-bond-forming residue. We describe the medicinal chemistry optimization of a biochemically potent but modestly cell-active, reversible EGFR inhibitor starting point with sub-optimal physicochemical properties. These studies culminated in the identification of compound 12 that showed improved cell potency, oral exposure, and in vivo activity in clinically relevant EGFR-mutant-driven disease models, including an Exon19 deletion/T790M/C797S triple-mutant mouse xenograft model.

Serum Free Triiodothyronine and the Responsiveness to Clopidogrel in Patients Undergoing Elective Percutaneous Coronary Intervention.

INTRODUCTION: Both thyroid dysfunction and low responsiveness to clopidogrel have been reported to be associated with increased cardiovascular risk. Our study aims at determining the relationship between free triiodothyronine (FT3) and low responsiveness to clopidogrel in patients undergoing elective percutaneous coronary intervention (PCI). METHODS: Consecutive patients undergoing elective PCI were enrolled. All patients received a loading dose of 300 mg clopidogrel, and platelet function was assessed by thromboelastography at least 12 h later. Low responsiveness to clopidogrel was defined by an adenosine diphosphate-induced platelet-fibrin clot strength > 47 mm and adenosine diphosphate-induced platelet inhibition rate < 50%. Major adverse cardiovascular events (MACEs) were defined as a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and ischemia-driven revascularization. RESULTS: Of 812 patients included in the study, 289 showed low responsiveness to clopidogrel. The FT3 level was significantly lower in low responders (4.61 ± 0.60 pmol/l versus 4.94 ± 4.66 pmol/l, p = 0.002). Moreover, the percentage of low responders was greater among patients with low FT3 level than among those without (56.1% versus 34.5%, p = 0.007). Logistic regression analysis showed that a FT3 level was independently associated with the risk of low responsiveness to clopidogrel (odds ratio 0.720, 95% confidence interval [CI] 0.533-0.973, p = 0.033). In patients with low responsiveness to clopidogrel, low FT3 was independently associated with increased risk of MACEs (adjusted hazard ratio 3.040, 95% CI 1.077-8.580, p = 0.036) at a median of 19-month follow-up. CONCLUSIONS: Low FT3 was independently associated with increased risks of both low responsiveness to clopidogrel and cardiovascular events in patients undergoing elective PCI.

Efficacy and safety of balloon-assisted microdissection with Sapphire® II 1.0-mm balloon in balloon-uncrossable chronic total occlusion lesions.

OBJECTIVE: Earlier studies have shown that the balloon-assisted microdissection (BAM) technique is feasible using a 1.2- to 1.5-mm small balloon in balloon-uncrossable chronic total occlusion (CTO) lesions. This study was performed to assess the efficacy and safety of the BAM technique with a Sapphire® II 1.0-mm balloon. METHODS: In this retrospective study, patients undergoing percutaneous coronary intervention for CTO were consecutively screened for balloon-uncrossable CTO lesions using BAM with the Sapphire® II 1.0-mm balloon. The patients' clinical and angiographic characteristics and procedural outcomes were collected for analyses. RESULTS: Twenty-four balloon-uncrossable CTO lesions were identified. Most of the CTO lesions were located in the right coronary artery, followed by the left anterior descending artery and left circumflex artery. The mean Japanese Multicenter CTO Registry (J-CTO) and Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS CTO) scores were 1.96 and 1.38, respectively. The total technical success rates were 91.6% (22/24) and 75.00% (18/24) for the lesions that were successfully treated with BAM. No patients developed major complications with the exception of one patient who developed a femoral hematoma. CONCLUSION: BAM with the Sapphire® II 1.0-mm balloon may be an effective and safe technique for balloon-uncrossable CTO lesions.

Elevated Serum Levels of Alkaline Phosphatase and the Risk of Low Responsiveness to Clopidogrel.

The elevated serum levels of alkaline phosphatase (ALP) serve as independent predictors of stent thrombosis after percutaneous coronary intervention (PCI). Our study aims at investigating the relationship between the serum ALP and the responsiveness to clopidogrel. Patients undergoing elective PCI were enrolled for the study, and all participants received a 300-mg clopidogrel loading dose. The responsiveness to clopidogrel was determined by thromboelastography (TEG), and low responsiveness to clopidogrel was defined based on two aspects: (1) adenosine diphosphate (ADP) -induced platelet-fibrin clot strength (MAADP) of > 47 mm and (2) ADP-induced platelet inhibition rate of < 50%. A logistic regression model analysis was used to calculate the risks of responsiveness to clopidogrel as odd ratios (OR) and 95% confidence intervals (CIs). Overall, 809 patients were considered for the study. They were divided into four quartile groups based on the serum ALP levels. A positive linear trend was observed in MAADP across the ALP quartiles (P for linear trend < 0.001), whereas ADP-induced platelet inhibition rate decreased across the ALP quartiles (P for linear trend = 0.007). When multiple confounders were adjusted, the highest ALP quartile correlated with an increased risk of low responsiveness to clopidogrel compared to the lowest ALP quartile (OR, 1.423; 95% CI, 1.017-1.991; P = 0.039). In the sensitivity analysis, the association remained significant for different definitions of low responsiveness to clopidogrel. The elevated serum levels of ALP are independently associated with an increased risk of low responsiveness to clopidogrel.

High glycated albumin is an independent predictor of low response to clopidogrel in ACS patients: a cross-sectional study.

BACKGROUND: Glycated albumin (GA) is a marker of short-term glycemic control and is strongly associated with the occurrence of diabetes. Previous studies have shown an association between GA and the effect of clopidogrel therapy on ischemic stroke. However, limited information is available regarding this relationship in acute coronary syndrome (ACS) patients. In this study, we evaluated the effect of GA on platelet P2Y12 inhibition by clopidogrel in patients with ACS. METHODS: Consecutive Chinese patients with ACS who received loading or maintenance doses of clopidogrel in addition to aspirin were recruited. At least 12 h after the patient had taken the clopidogrel dose, thromboelastography (TEG) and light transmittance aggregometry (LTA) were used to calculate the quantitative platelet inhibition rate to determine clopidogrel-induced antiplatelet reactivity. A prespecified cutoff of the maximum amplitude of adenosine diphosphate (ADP)-induced platelet-fibrin clot strength > 47 mm plus an ADP-induced platelet inhibition rate < 50% assessed by TEG or ADP-induced platelet aggregation > 40% assessed by LTA to indicate low responsiveness to clopidogrel were applied for evaluation. Patients were categorized into two groups based on a GA level of 15.5%, the cutoff point indicating the development of early-phase diabetes. Multivariate linear regression analysis was used to assess the interaction of GA with clopidogrel antiplatelet therapy. RESULTS: A total of 1021 participants were evaluated, and 28.3% of patients (289 of 1021) had low responsiveness to clopidogrel assessed by TEG. In patients with elevated GA levels, low responsiveness to clopidogrel assessed by TEG was observed in 33.7% (139 of 412) of patients, which was a significantly higher rate than that in the lower-GA-level group (24.6%, P = 0.002). According to multivariate linear regression analysis, a GA level > 15.5% was independently associated with low responsiveness to clopidogrel after adjustment for age, sex and other conventional confounding factors. This interaction was not mediated by a history of diabetes mellitus. A GA level ≤ 15.5% was associated with a high positive value [75.4%, 95% CI 73.0-77.6%] for predicting a normal responsiveness to clopidogrel. CONCLUSIONS: GA could be a potential biomarker to predict the effects of clopidogrel antiplatelet therapy in ACS patients and might be a clinical biomarker to guide DAPT de-escalation.

Identification of candidate genes in ischemic cardiomyopathy by gene expression omnibus database.

BACKGROUND: Ischemic cardiomyopathy (ICM) is one of the most usual causes of death worldwide. This study aimed to find the candidate gene for ICM. METHODS: We studied differentially expressed genes (DEGs) in ICM compared to healthy control. According to these DEGs, we carried out the functional annotation, protein-protein interaction (PPI) network and transcriptional regulatory network constructions. The expression of selected candidate genes were confirmed using a published dataset and Quantitative real time polymerase chain reaction (qRT-PCR). RESULTS: From three Gene Expression Omnibus (GEO) datasets, we acquired 1081 DEGs (578 up-regulated and 503 down-regulated genes) between ICM and healthy control. The functional annotation analysis revealed that cardiac muscle contraction, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and dilated cardiomyopathy were significantly enriched pathways in ICM. SNRPB, BLM, RRS1, CDK2, BCL6, BCL2L1, FKBP5, IPO7, TUBB4B and ATP1A1 were considered the hub proteins. PALLD, THBS4, ATP1A1, NFASC, FKBP5, ECM2 and BCL2L1 were top six transcription factors (TFs) with the most downstream genes. The expression of 6 DEGs (MYH6, THBS4, BCL6, BLM, IPO7 and SERPINA3) were consistent with our integration analysis and GSE116250 validation results. CONCLUSIONS: The candidate DEGs and TFs may be related to the ICM process. This study provided novel perspective for understanding mechanism and exploiting new therapeutic means for ICM.

Sb nanoparticle decorated rGO as a new anode material in aqueous chloride ion batteries.

An aqueous chloride ion battery (CIB) is an emerging technology for electrochemical energy storage as well as battery desalination systems. However, the instability and decomposition of electrode materials in an aqueous medium is a major issue in CIBs. Herein, in one step, we synthesized fine antimony nanoparticles with a size of ∼20 nm on reduced graphene oxide (Sb@rGO) sheets using a hydrothermal route with facile and cost-effective processes. It is proposed as a new anode material and coupled with the AgCl cathode in an aqueous CIB. The specific capacity is maintained constantly at 51.6 mA h g-1 at a current density of 400 mA g-1 even after 200 cycles. In addition, characterization methods such as electrochemical analysis, X-ray diffraction, etc. were used to confirm the reaction mechanism. The chloride ion capture material developed in this research work will be significant for CIBs as an energy storage technology or battery desalination system.

Structure-Based Design and Pharmacokinetic Optimization of Covalent Allosteric Inhibitors of the Mutant GTPase KRASG12C.

Attempts to directly drug the important oncogene KRAS have met with limited success despite numerous efforts across industry and academia. The KRASG12C mutant represents an "Achilles heel" and has recently yielded to covalent targeting with small molecules that bind the mutant cysteine and create an allosteric pocket on GDP-bound RAS, locking it in an inactive state. A weak inhibitor at this site was optimized through conformational locking of a piperazine-quinazoline motif and linker modification. Subsequent introduction of a key methyl group to the piperazine resulted in enhancements in potency, permeability, clearance, and reactivity, leading to identification of a potent KRASG12C inhibitor with high selectivity and excellent cross-species pharmacokinetic parameters and in vivo efficacy.