Publications by authors named "Zhen Zhou"

730 Publications

MOF-Derived Co and Fe Species Loaded on N-Doped Carbon Networks as Efficient Oxygen Electrocatalysts for Zn-Air Batteries.

Nanomicro Lett 2022 Aug 11;14(1):162. Epub 2022 Aug 11.

School of Chemical Engineering, Zhengzhou University, Zhengzhou, 450001, People's Republic of China.

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http://dx.doi.org/10.1007/s40820-022-00890-wDOI Listing
August 2022

Incremental prognostic value of left atrial strain in patients with heart failure.

ESC Heart Fail 2022 Aug 11. Epub 2022 Aug 11.

Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.

Aims: The present study aimed to evaluate the prognostic value of atrial strain and strain rate (SR) parameters derived from cardiac magnetic resonance (CMR) feature tracking (FT) in patients with ischaemic and non-ischaemic dilated cardiomyopathy with heart failure with reduced ejection fraction (HFrEF) but without atrial fibrillation.

Methods And Results: A total of 300 patients who underwent CMR with left ventricular ejection fraction (LVEF) ≤ 40% and ischaemic or non-ischaemic dilated cardiomyopathy were analysed in this retrospective study. Major adverse cardiac events (MACEs) include cardiovascular death, heart transplantation, and rehospitalization for worsening HF. Ninety-four patients had MACEs during median follow-up of 3.84 years. Multivariate Cox regression models adjusted for common clinical and CMR risk factors detected a significant association between LA-εs and MACE in ischaemic (HR = 0.94/%; P = 0.002), non-ischaemic dilated cardiomyopathy (HR = 0.88/%; P = 0.001), or all included patients (HR = 0.87; P < 0.001). LA-εs provided incremental prognostic value over conventional outcome predictors (Uno C statistical comparison model: from 0.776 to 0.801, P < 0.0001; net reclassification improvement: 0.075, 95% CI: 0.0262-0.1301). Kaplan-Meier analysis revealed that the risk of MACE occurrence increased significantly with lower tertiles of left atrial reservoir strain (LA-εs) (log-rank P < 0.0001). Patients in the worst LA-εs tertile faced a significantly increased risk of MACEs irrespective of late gadolinium enhancement (LGE) (log-rank P < 0.0001).

Conclusions: LA-εs derived from CMR FT has a significant prognostic impact on patients with ischaemic or non-ischaemic dilated cardiomyopathy, incremental to common clinical and CMR risk-factors.
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http://dx.doi.org/10.1002/ehf2.14106DOI Listing
August 2022

Renshen Baidu Powder Attenuated Intestinal Inflammation and Apoptosis in Ulcerative Colitis Rats through the Inhibition of PI3K/AKT/NF-B Signaling Pathway.

Evid Based Complement Alternat Med 2022 30;2022:5234025. Epub 2022 Jul 30.

School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.

Objective: Renshen Baidu Powder (RBP) is a famous classic compound of traditional Chinese medicine (TCM) and is commonly used for treating ulcerative colitis (UC). However, the pharmacological mechanism of RBP in treating UC remains unclear. This study investigates the possible mechanism of RBP for UC treatment by network pharmacological analysis and rat validation.

Methods: First, the main chemical constituents of RBP were identified using ultrahigh-performance liquid chromatography quadrupole Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap-HRMS). Then, we obtained targets of identified compounds from the SwissTargetPrediction database and targets associated with UC from GeneCards database. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyze the metabolism-related signaling pathways affected by RBP. Hematoxylin-eosin (HE) staining was used to observe the pathological change of colon in UC rats after treating RBP, and terminal deoxynucleotidyl-transferase (TdT)-mediated dUTP Nick end labeling (TUNEL) staining was used to detect apoptosis after RBP treatment. The enzyme-linked immunosorbent assay (ELISA) was employed to evaluate cytokine levels of TNF-, IL-1, and IL-6. The protein expressions of Bax, Bcl-2, PI3K, AKT, and NF-B in colonic tissue were detected using immunohistochemistry (IHC). Real-time quantitative polymerase chain reaction (RT-QPCR) was employed to evaluate mRNA expression of PI3K, AKT, and NF-B.

Results: We found a total of 24 main compounds and 329 potential targets related to UC. According to KEGG results, 3 main pathways were identified as responsible for UC, including PI3K-AKT, HIF-1, and VEGF signaling pathway. Animal experiments showed that RBP treatment significantly attenuated colon damage in rats with UC. Mechanistically, RBP could inhibit PI3K/AKT/NF-B pathway; decrease cell apoptosis; and downregulate the expression of TNF-, IL-1, and IL-6.

Conclusions: This study demonstrated that RBP may exert anti-inflammatory and antiapoptotic therapeutic benefits in UC by regulating the PI3K/AKT/NF-B signaling pathways, providing a scientific basis for understanding the mechanism of RBP against UC.
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http://dx.doi.org/10.1155/2022/5234025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356782PMC
July 2022

The Cost-Effectiveness of Tislelizumab Plus Chemotherapy for Locally Advanced or Metastatic Nonsquamous Non-Small Cell Lung Cancer.

Front Pharmacol 2022 22;13:935581. Epub 2022 Jul 22.

Department of Pharmacy, The Second Xiangya Hospital of Central South University, Changsha, China.

To investigate the cost-effectiveness of adding Chinese-developed anti-PD-1 antibody tislelizumab to first-line pemetrexed-platinum chemotherapy in (1) a study population of patients with locally advanced or metastatic nonsquamous non-small cell lung cancer (nsqNSCLC) and without known sensitizing EGFR mutations or ALK rearrangements and (2) its subgroups from the perspective of Chinese healthcare system. Separate Markov models were constructed for the entire study population and its subgroups; 10,000 patients with locally advanced or metastatic nsqNSCLC and without driver gene mutations were simulated in the first-line tislelizumab plus pemetrexed-platinum (TPP) arm and first-line pemetrexed-platinum (PP) arm, respectively. Transition probabilities were extracted from the RATIONALE 304 trial. Public health state utilities and costs were obtained from published literature, public national databases, and local general hospitals. The main outputs were incremental cost-effectiveness ratios (ICERs). The ICERs were compared to a willingness-to-pay threshold of $35,663 per quality-adjusted life-years (QALYs) to determine the cost-effective treatment. Sensitivity analyses were employed to assess the uncertainty in the model. For the entire patient population, first-line TPP versus PP use increased the effectiveness by 0.99 QALYs and healthcare costs by $28,749, resulting in an ICER of $28,749/QALY that was lower than the prespecified WTP threshold. For patient subgroups, first-line TPP conferred the greatest survival benefit in patients with PD-L1 expression ≥50%, followed by patients with liver metastasis and those who are current or former smokers. Overall, the ICERs for the first-line TPP versus PP ranged from $27,018/QALYs to $33,074/QALYs, which were consistently below the WTP threshold. For Chinese patients with locally advanced or metastatic nsqNSCLC who had no known sensitizing EGFR mutations or ALK rearrangements, adding the Chinese-developed anti-PD-1 antibody tislelizumab to the first-line pemetrexed-platinum chemotherapy was cost-effective regardless of their baseline characteristics.
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http://dx.doi.org/10.3389/fphar.2022.935581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9354466PMC
July 2022

Association of Apatinib and Breast Cancer: A systematic review and meta-analysis.

Surg Oncol 2022 Jul 19;44:101818. Epub 2022 Jul 19.

AMITA Health Saint Joseph Hospital Chicago, 2900 N. Lake Shore Drive, Chicago, IL, 60657, USA. Electronic address:

Background: Breast cancer (BC) is a common malignant tumor. Apatinib in combination with other treatments has been used for BC; however, its safety and efficacy are not well-known. Therefore, this meta-analysis was performed to assess the efficacy and safety of apatinib in the treatment of BC.

Methods: Studies comparing the effects of apatinib-based therapy versus control among BC patients were included. On January 21, 2022, a systematic search was performed in 9 databases. The risk ratio (RR) with 95% confidence interval (CI) was used to estimate efficacy and safety. The I square value (I) was used to assess heterogeneity. A leave-one-out sensitivity analysis was also conducted. Publication bias was assessed by funnel plots and Egger's and Begg's tests.

Results: A total of 31 studies including 2,258 BC patients were included. The results showed that apatinib group had a significant improvement in disease control rate (DCR, RR = 1.43, 95% CI = 1.35-1.52, I = 43.8%) and objective response rate (ORR, RR = 1.79, 95% CI = 1.51-2.13, I = 61.8%) compared to the control group. Except for hemorrhage, hypertension, and hand-foot syndrome, the adverse events were similar between apatinib group and control group. Subgroup analyses found statistically significant differences in DCR in all subgroups except for apatinib combined with radiation therapy and with paclitaxel liposome plus S1. For ORR, there were statistically significant differences in all subgroups except for the radiation therapy, and apatinib monotherapy subgroups.

Conclusions: Our study shown apatinib showed good efficacy and acceptable safety in the treatment of BC patients. More high-quality randomized controlled trials from different regions and countries are needed to confirm our findings.
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http://dx.doi.org/10.1016/j.suronc.2022.101818DOI Listing
July 2022

Li(110) lattice plane evolution induced by a 3D MXene skeleton for stable lithium metal anodes.

Chem Commun (Camb) 2022 Aug 3. Epub 2022 Aug 3.

School of Chemical Engineering, Zhengzhou University, Zhengzhou 450001, Henan, China.

The non-uniform plating-stripping behaviours of Li metal anodes hinder the application of Li metal batteries. Here, a stable 3D matrix is designed by coating a carbon skeleton with MXene, and the significant influence of the crystallographic texture of Li metal on electrochemical behaviour is investigated. The results demonstrate that the 3D MXene/carbon skeleton can effectively induce the evolution of advantageous Li(110) facets with a dendrite-free anode interface. Consequently, the modified Li metal anodes deliver stable plating-stripping behaviours.
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http://dx.doi.org/10.1039/d2cc03288kDOI Listing
August 2022

Association of urinary or blood heavy metals and mortality from all causes, cardiovascular disease, and cancer in the general population: a systematic review and meta-analysis of cohort studies.

Environ Sci Pollut Res Int 2022 Aug 2. Epub 2022 Aug 2.

AMITA Health Saint Joseph Hospital Chicago, 2900 N. Lake Shore Drive, Chicago, IL, 60657, USA.

Amounting epidemiological evidence has shown detrimental effects of heavy metals on a wide range of diseases. However, the effect of heavy metal exposure on mortality in the general population remains unclear. The primary objective of this study was to clarify the associations between heavy metals and mortality from all causes, cardiovascular disease (CVD), and cancer based on prospective studies. We comprehensively searched Pubmed, Embase, and Web of Science electronic databases to identify studies published from their inception until 1 March 2022. Investigators identified inclusion criteria, extracted study characteristics, and assessed the methodological quality of included studies according to standardized guidelines. Meta-analysis was conducted if the effect estimates of the same outcome were reported in at least three studies. Finally, 42 original studies were identified. The results of meta-analysis showed that cadmium and lead exposure was significantly associated with mortality from all causes, CVD, and cancer in the general population. Moderate evidence suggested there was a link between arsenic exposure and mortality. The adverse effects of mercury and other heavy metals on mortality were inconclusive. Epidemiological evidence for the joint effect of heavy metal exposure on mortality was still indeterminate. In summary, our study provided compelling evidence that exposure to cadmium, lead, and arsenic were associated with mortality from all causes, CVD, and cancer, while the evidence on other heavy metals, for example mercury, was insignificant or indeterminate. Nevertheless, further prospective studies are warranted to explore the joint effects of multiple metal exposure on mortality.
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http://dx.doi.org/10.1007/s11356-022-22353-wDOI Listing
August 2022

Identification and Verification of Potential Biomarkers in Gastric Cancer By Integrated Bioinformatic Analysis.

Front Genet 2022 15;13:911740. Epub 2022 Jul 15.

Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Gastric cancer (GC) is a common cancer with high mortality. This study aimed to identify its differentially expressed genes (DEGs) using bioinformatics methods. DEGs were screened from four GEO (Gene Expression Omnibus) gene expression profiles. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. A protein-protein interaction (PPI) network was constructed. Expression and prognosis were assessed. Meta-analysis was conducted to further validate prognosis. The receiver operating characteristic curve (ROC) was analyzed to identify diagnostic markers, and a nomogram was developed. Exploration of drugs and immune cell infiltration analysis were conducted. Nine up-regulated and three down-regulated hub genes were identified, with close relations to gastric functions, extracellular activities, and structures. Overexpressed Collagen Type VIII Alpha 1 Chain (COL8A1), Collagen Type X Alpha 1 Chain (COL10A1), Collagen Triple Helix Repeat Containing 1 (CTHRC1), and Fibroblast Activation Protein (FAP) correlated with poor prognosis. The area under the curve (AUC) of ADAM Metallopeptidase With Thrombospondin Type 1 Motif 2 (ADAMTS2), COL10A1, Collagen Type XI Alpha 1 Chain (COL11A1), and CTHRC1 was >0.9. A nomogram model based on CTHRC1 was developed. Infiltration of macrophages, neutrophils, and dendritic cells positively correlated with COL8A1, COL10A1, CTHRC1, and FAP. Meta-analysis confirmed poor prognosis of overexpressed CTHRC1. ADAMTS2, COL10A1, COL11A1, and CTHRC1 have diagnostic values in GC. COL8A1, COL10A1, CTHRC1, and FAP correlated with worse prognosis, showing prognostic and therapeutic values. The immune cell infiltration needs further investigations.
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http://dx.doi.org/10.3389/fgene.2022.911740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9337873PMC
July 2022

Critical Factors Affecting the Catalytic Activity of Redox Mediators on Li-O Battery Discharge.

J Phys Chem Lett 2022 Aug 28;13(30):7081-7086. Epub 2022 Jul 28.

School of Chemical Engineering, Zhengzhou University, Zhengzhou, Henan 450001, China.

Redox mediators (RMs) have a substantial ability to govern oxygen reduction reaction (ORR) in Li-O batteries, which can realize large capacity and high-rate capability. However, studies on understanding RM-assisted ORR mechanisms are still in their infancy. Herein, a quinone-based molecule, vitamin K1 (VK1), is first used as the ORR RM for Li-O batteries, together with 2,5-di--butyl-1,4-benzoquinone (DBBQ), to elucidate key factors on the catalytic activity of RMs. By combining experiments and first-principle computations, we demonstrate that the reduced VK1 has strong oxygen affinity and can effectively retard the deposition of LiO films on the electrode surface, thereby guaranteeing enough active sites for electron transfer. Besides, the low reaction free energy of disproportionation of the Li(VK1)O intermediate into LiO also significantly accelerates the ORR process. Consequently, the catalytic activity of VK1 is significantly boosted, and the discharge capacity of VK1-assisted batteries is 3.2-4.5 times that of DBBQ-assisted batteries. This study provides new insight for better understanding the working roles of RMs in Li-O batteries.
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http://dx.doi.org/10.1021/acs.jpclett.2c01818DOI Listing
August 2022

Evaluation of potentially inappropriate medications in older patients admitted to the cardiac intensive care unit according to the 2019 Beers criteria, STOPP criteria version 2 and Chinese criteria.

J Clin Pharm Ther 2022 Jul 27. Epub 2022 Jul 27.

Department of Pharmacy, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

What Is Known And Objectives: Potential inappropriate medications (PIMs) can increase the risk of medication-induced harm. However, there are no studies regarding PIMs in older and critically ill patients with cardiovascular diseases in China. Therefore, studies evaluating PIMs in these patients can help in the implementation of more effective interventions to reduce the risk of drug use. Our objective was to analyse the prevalence of PIMs in elderly patients admitted to the cardiac intensive care unit (CICU) comparing the 2019 Beers criteria (Beers criteria), Screening Tool of Older People's Potentially Inappropriate Prescriptions (STOPP) criteria version 2 (STOPP criteria) and criteria of potentially inappropriate medications for older adults in China (Chinese criteria); and analyse the factors influencing the PIMs.

Methods: This cross-sectional and retrospective study was performed with elderly patients (≥65 years) admitted to the CICU of the Beijing Tongren Hospital in China from January 2019 to June 2020. The PIMs were identified based on the Chinese, STOPP and Beers criteria at admission and discharge. The three criteria were compared using the Kappa statistic. Multiple regression analysis was used to investigate the influencing factors associated with PIMs.

Results And Discussion: A total of 369 patients who met the inclusion/exclusion criteria were included in this study. According to the three criteria used to evaluate the PIMs, the prevalence was 78.3% and 72.6% at admission and discharge, respectively. The prevalence rate of PIMs determined by the Chinese criteria was 62.1% at admission versus 56.6% at discharge (p = 0.134); the Beers criteria was 53.9% at admission versus 46.9% at discharge (p = 0.056); by the STOPP criteria was 20.6% at admission versus 13.8% at discharge (p = 0.015). Moreover, 28.9% (STOPP criteria), 56.8% (Beers criteria) and 73.4% (Chinese criteria) of patients taking PIMs on admission still had the same problem at discharge. The most common PIMs screened by the Beers, STOPP and Chinese criteria were diuretics, benzodiazepines and clopidogrel, respectively. Besides, the three criteria showed poor agreement. Finally, the stronger predictor of PIMs was the increased number of medications (p < 0.05).

What Is New And Conclusion: The prevalence of PIMs in elderly patients admitted to the CICU was high. The Chinese, STOPP and Beers criteria are effective screening tools to detect PIMs, but the consistency between them was poor. The increased number of medications was a significant predictor of PIMs.
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http://dx.doi.org/10.1111/jcpt.13736DOI Listing
July 2022

CCNB2 expression correlates with worse outcomes in breast cancer patients: a pooled analysis.

Women Health 2022 Aug 26;62(7):655-663. Epub 2022 Jul 26.

Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA.

Cyclin B2 (CCNB2) is upregulated in Breast Cancer (BC) and associated with worse relapse-free survival (RFS). However, its correlation with other clinical outcomes in BC was yet to be clarified. Therefore, this study aimed to explore the clinical significance of CCNB2 in BC. A comprehensive search was performed in PrognoScan and Gene Expression Omnibus (GEO) databases by searching the keywords of CCNB2 and breast cancer. Pooled hazard ratios (HRs) of overall survival (OS), relapse-free survival (RFS), distant metastasis-free survival (DMFS), disease-specific survival (DSS), and disease-free survival (DFS), and their corresponding 95 percent confidence intervals (CI) were calculated. Sensitivity analysis by omitting one study at a time and publication bias assessment by Egger's test and Begg's test were conducted. The clinical outcomes were externally verified via Kaplan-Meier Plotter. All of the statistical analyses were performed through STATA 17.0, and values of less than 0.05 were taken to be statistically significant. Seven records with 1,074 participants were included for OS, with HR of 1.71 (95 percent CI = 1.24-2.35). Verification through Kaplan-Meier Plotter online tool based on 1,897 patients showed an HR of 1.75 (95 percent CI = 1.45-2.12,  < .01). For RFS, 11 records with 1,253 participants were included with the pooled HR of 1.37 (95 percent CI: 1.10-1.71). Verification based on 4,929 patients found and HR of 1.97 (95 percent CI = 1.78-2.19,  < .01). Regarding DMFS, the pooled HR of 10 records with 1,395 participants was 1.60 (95 percent CI: 1.24-2.05) and verification based on 2,765 patients revealed an HR of 1.97 (95 percent CI = 1.68-2.31,  < .01). For DSS, four records with 689 participants were included for DSS, with HR of 1.38 (95 percent CI = 0.59-3.24). The HR of DFS was 1.60 (95 percent CI: 0.46-5.51) after pooling 3 records with 379 participants. High expression of CCNB2 in BC is associated with worse OS, RFS, and DMFS, but not with DSS and DFS. More well-designed studies from different populations and different BC types are still needed.
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http://dx.doi.org/10.1080/03630242.2022.2106530DOI Listing
August 2022

Mosaicism for the smooth muscle cell (SMC)-specific knock-in of the Acta2 R179C pathogenic variant: Implications for gene editing therapies.

J Mol Cell Cardiol 2022 Jul 22;171:102-104. Epub 2022 Jul 22.

Division of Medical Genetics, Department of Internal Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, TX 77030, USA. Electronic address:

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http://dx.doi.org/10.1016/j.yjmcc.2022.07.004DOI Listing
July 2022

Insights into the different mixing states and formation processes of amine-containing single particles in Guangzhou, China.

Sci Total Environ 2022 Jul 19;846:157440. Epub 2022 Jul 19.

Institute of Mass Spectrometry and Atmospheric Environment, Guangdong Provincial Engineering Research Center for Online Source Apportionment System of Air Pollution, Jinan University, Guangzhou 510632, China; Guangdong-Hongkong-Macau Joint Laboratory of Collaborative Innovation for Environmental Quality, Guangzhou 510632, China.

The formation processes of particulate amines are closely related to their emission sources and secondary reactions, which can be revealed through the investigation of their real-time mixing states in individual particles. The mixing states of methylamine (MA)-, trimethylamine (TMA)-, and diethylamine (DEA)-containing particles were studied using a high-performance single particle aerosol mass spectrometer (HP-SPAMS) in Guangzhou, China, in January 2020. The sharp increase in TMA particles was found to be closely associated with the increase in the ambient relative humidity (RH), while the MA- and DEA-containing particles were not similarly influenced by the changes in the RH. The prominent enrichment of secondary oxygenated organics in DEA particles during the daytime was consistent with the active period of photochemistry, implying that the sharp decrease in DEA particles in the afternoon was likely due to photo-oxidation of the DEA. The number fraction (N) of DEA particles, the N of the nitrate in the DEA particles, and the abundance of nitrate increased as the NO content all increased during the nighttime, suggesting that the formation of DEA·HNO salt was the dominant pathway of particulate DEA production. These results are consistent with our previous measurements in Nanjing, confirming the general and distinct mixing states of TMA and DEA particles. Positive matrix factorization analysis revealed that the total fraction of the more oxidized organics factor and the less oxidized organics factor were much higher in the DEA particles (26.9 %) than in the TMA particles (9 %), confirming the significant enrichment of oxygenated species in the DEA particles. The different mixing states of the amines revealed the unique response of each type of amine to the same atmospheric environment, and the prominent mixing states of the DEA with secondary oxygenated species suggest the potential role of DEA in tracing the evolution of organic aerosols.
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http://dx.doi.org/10.1016/j.scitotenv.2022.157440DOI Listing
July 2022

Metabolism regulator adiponectin prevents cardiac remodeling and ventricular arrhythmias via sympathetic modulation in a myocardial infarction model.

Basic Res Cardiol 2022 07 11;117(1):34. Epub 2022 Jul 11.

Department of Cardiology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuchang District, Wuhan, 430060, Hubei Province, People's Republic of China.

The stellate ganglia play an important role in cardiac remodeling after myocardial infarction (MI). This study aimed to investigate whether adiponectin (APN), an adipokine mainly secreted by adipose tissue, could modulate the left stellate ganglion (LSG) and exert cardioprotective effects through the sympathetic nervous system (SNS) in a canine model of MI. APN microinjection and APN overexpression with recombinant adeno-associated virus vector in the LSG were performed in acute and chronic MI models, respectively. The results showed that acute APN microinjection decreased LSG function and neural activity, and suppressed ischemia-induced ventricular arrhythmia. Chronic MI led to a decrease in the effective refractory period and action potential duration at 90% and deterioration in echocardiography performance, all of which was blunted by APN overexpression. Moreover, APN gene transfer resulted in favorable heart rate variability alteration, and decreased cardiac SNS activity, serum noradrenaline and neuropeptide Y, which were augmented after MI. APN overexpression also decreased the expression of nerve growth factor and growth associated protein 43 in the LSG and peri-infarct myocardium, respectively. Furthermore, RNA sequencing of LSG indicated that 4-week MI up-regulated the mRNA levels of macrophage/microglia activation marker Iba1, chemokine ligands (CXCL10, CCL20), chemokine receptor CCR5 and pro-inflammatory cytokine IL6, and downregulated IL1RN and IL10 mRNA, which were reversed by APN overexpression. Our results reveal that APN inhibits cardiac sympathetic remodeling and mitigates cardiac remodeling after MI. APN-mediated gene therapy may provide a potential therapeutic strategy for the treatment of MI.
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http://dx.doi.org/10.1007/s00395-022-00939-2DOI Listing
July 2022

Pharmacological Mechanism of Ganlu Powder in the Treatment of NASH Based on Network Pharmacology and Molecular Docking.

Dis Markers 2022 29;2022:7251450. Epub 2022 Jun 29.

School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Nonalcoholic steatohepatitis (NASH), a progression of nonalcoholic fatty liver disease (NAFLD), is a clinical syndrome characterized by liver steatosis, inflammation, and hepatocellular damage. Ganlu powder (GLP) is a classic traditional Chinese medicine prescription that has shown favorable treatment effects on NASH. However, the underlying therapeutic mechanisms are still poorly understood. This study is aimed at exploring the potential mechanism of GLP in the treatment of NASH via network pharmacology and molecular docking. PubMed and CNKI databases were used to identify the components of GLP. Swiss and STITCH databases were employed to obtain corresponding drug targets. NASH targets were adopted from the Therapeutic Target Database (TTD), DisGeNET, DrugBank, GeneCards, and MalaCards databases. Cytoscape software was utilized to construct "drug-ingredient-target-disease" networks and the protein-protein interaction (PPI) network of GLP in NASH. AKT1 was identified as the key target. The GO functional enrichment analysis revealed that GLP might treat NASH by modulating the inflammatory response and regulating phosphatidylinositol 3-kinase signaling. The KEGG analysis showed that GLP might treat NASH by regulating the tumor necrosis factor (TNF) signal pathway by affecting the role of AKT1. According to the network pharmacology results, a virtual docking of active compounds with AKT1 was carried out, and the results indicated that the 7 components, berberine, epiberberine, jatrorrhizine, coptisine, palmatine, evodiamine, and rutecarpine, can bind stably with AKT1 and have higher binding energy than AKT1 inhibitors. The overall study findings suggest that GLP may treat NASH by regulating AKT1.
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http://dx.doi.org/10.1155/2022/7251450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9259220PMC
July 2022

Coal-based ultrathin N-doped carbon nanosheets synthesized by molten-salt method for high-performance lithium-ion batteries.

Nanotechnology 2022 Jul 26;33(42). Epub 2022 Jul 26.

School of Chemical Engineering, Zhengzhou University, Zhengzhou, 450001, People's Republic of China.

Coal is a typical fossil fuel and it is also a natural carbon material, therefore, converting it to functional carbon materials is an effective way to enhance the economic advantages of coal. Here, ultrathin N-doped carbon nanosheets were prepared from low-cost coal via a handy and green molten-salt method, which shown excellent performance for lithium-ion batteries (LIBs). The formation mechanism of ultrathin nanosheets was studied in detail. The eutectic molten salts possess low melting points and become a strong polar solvent at the calcined temperature, making the acidified coal miscible with them in very homogeneously state. Therefore, they can play a gigantic role inpore-forming during the carbonization and induce the formation of ultrathin nanosheets due to the salt ions. Simultaneously, the ultrathin N-doped carbon nanosheets with rich defects and controllable surface area was smoothly prepared without any more complex process while revealing brilliant electrochemical performance due to rich ion diffusion pathways. It delivers reversible capacity of 727.0 mAh gat 0.2 A gafter 150 cycles. Thus, the molten-salt method broadens the avenue to construct porous carbon materials with tailor-made morphologies. Equally important, this approach provides a step toward the sustainable materials design and chemical science in the future.
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http://dx.doi.org/10.1088/1361-6528/ac7fa5DOI Listing
July 2022

Artificial intelligence-based full aortic CT angiography imaging with ultra-low-dose contrast medium: a preliminary study.

Eur Radiol 2022 Jul 5. Epub 2022 Jul 5.

Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, No. 2, Anzhen Road, Chaoyang District, Beijing, 100029, China.

Objectives: To further reduce the contrast medium (CM) dose of full aortic CT angiography (ACTA) imaging using the augmented cycle-consistent adversarial framework (Au-CycleGAN) algorithm.

Methods: We prospectively enrolled 150 consecutive patients with suspected aortic disease. All received ACTA scans of ultra-low-dose CM (ULDCM) protocol and low-dose CM (LDCM) protocol. These data were randomly assigned to the training datasets (n = 100) and the validation datasets (n = 50). The ULDCM images were reconstructed by the Au-CycleGAN algorithm. Then, the AI-based ULDCM images were compared with LDCM images in terms of image quality and diagnostic accuracy.

Results: The mean image quality score of each location in the AI-based ULDCM group was higher than that in the ULDCM group but a little lower than that in the LDCM group (all p < 0.05). All AI-based ULDCM images met the diagnostic requirements (score ≥ 3). Except for the image noise, the AI-based ULDCM images had higher attenuation value than the ULDCM and LDCM images as well as higher SNR and CNR in all locations of the aorta analyzed (all p < 0.05). Similar results were also seen in obese patients (BMI > 25, all p < 0.05). Using the findings of LDCM images as the reference, the AI-based ULDCM images showed good diagnostic parameters and no significant differences in any of the analyzed aortic disease diagnoses (all K-values > 0.80, p < 0.05).

Conclusions: The required dose of CM for full ACTA imaging can be reduced to one-third of the CM dose of the LDCM protocol while maintaining image quality and diagnostic accuracy using the Au-CycleGAN algorithm.

Key Points: • The required dose of contrast medium (CM) for full ACTA imaging can be reduced to one-third of the CM dose of the low-dose contrast medium (LDCM) protocol using the Au-CycleGAN algorithm. • Except for the image noise, the AI-based ultra-low-dose contrast medium (ULDCM) images had better quantitative image quality parameters than the ULDCM and LDCM images. • No significant diagnostic differences were noted between the AI-based ULDCM and LDCM images regarding all the analyzed aortic disease diagnoses.
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http://dx.doi.org/10.1007/s00330-022-08975-1DOI Listing
July 2022

Seasonal variations of imidazoles in urban areas of Beijing and Guangzhou, China by single particle mass spectrometry.

Sci Total Environ 2022 Jun 28;844:156995. Epub 2022 Jun 28.

Institute of Mass Spectrometry and Atmospheric Environment, Guangdong Provincial Engineering Research Center for On-line Source Apportionment System of Air Pollution, Jinan University, Guangzhou 510632, China; Guangdong-Hongkong-Macau Joint Laboratory of Collaborative Innovation for Environmental Quality, Guangzhou 510632, China.

Imidazoles (IMs) are potential contributors to brown carbon; they may notably contribute to climate radiative forcing. However, only a few studies have assessed the mixing state, seasonal and spatial distributions of IMs, and influencing factors for IM formation in urban aerosols. In this study, two single-particle aerosol mass spectrometers were employed to investigate the IM-containing particles in the urban areas of Beijing and Guangzhou, China. IM-containing particles were identified in the size range (d) of 0.2-2.0 μm, accounting for 0.7-21.7 % of all the detected particles. The number fractions of IM-containing particles in both cities were the lowest in winter and the highest in spring, probably owing to the difference in the abundance of precursors and the particle acidity. Majority of (60-80 % by number) the IM-containing particles were mixed with organic carbon (OC), with the lowest fractions found in summer. Although the number fractions of IM-containing particles in Beijing were generally higher (~1.5-3 times) than those in Guangzhou, the mixing states of the IM-containing particles at these two sites were only slightly different. Potassium-rich (K-rich) and potassium-sodium (KNa) particles were rarely found in Guangzhou; they accounted for ~15 % of the IM-containing particles in Beijing. Additionally, our results indicate that particles with higher acidity are favorable for IM formation. These findings help improving our knowledge of the mixing state, seasonal variation, and spatial distribution of IMs in urban aerosols, and the insights in influencing factors into IM formation provide valuable information for future studies of the atmospheric chemical processes associated with IMs.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156995DOI Listing
June 2022

Impact of Blood Lipids on 10-Year Cardiovascular Risk in Individuals Without Dyslipidemia and With Low Risk Factor Burden.

Mayo Clin Proc 2022 06 24. Epub 2022 Jun 24.

Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.

Objective: To determine the association of plasma lipids with the prevalence of subclinical atherosclerosis and 10-year risk of incident cardiovascular (CV) events among healthy individuals without dyslipidemia and with low risk factor burden.

Patients And Methods: The analysis (June 24, 2020, through June 12, 2021) included 1204 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) study who were current nonsmokers and did not have CV disease, hypertension (blood pressure ≥130/80 mm Hg or antihypertensive use), diabetes (fasting glucose ≥126 mg/dL or glucose-lowering medication use), and dyslipidemia (low-density-lipoprotein-cholesterol [LDL-C] ≥160 mg/dL, high-density-lipoprotein-cholesterol [HDL-C] <40 mg/dL, total cholesterol [TC] ≥240 mg/dL, triglycerides [TGs] ≥150 mg/dL, or lipid-lowering medication use) at baseline. Associations of lipids with baseline atherosclerosis (presence of carotid plaque and/or coronary calcification) and incident CV events over 10 years were examined using multivariable relative risk regression and Cox regression, respectively.

Results: At baseline, participants' median age was 54 (IQR, 49 to 62) years, and 10-year CV risk was 2.7% (IQR, 1.0% to 6.6%); 43.4% had subclinical atherosclerosis. A 1-SD higher LDL-C (23.4 mg/dL), TC (24.7 mg/dL), non-HDL-C (25.3 mg/dL), TC/HDL-C (0.75), and LDL-C/HDL-C (0.66) was associated with a higher prevalence of atherosclerosis of between 6% and 9% (P<.05). For every 1-SD higher LDL-C, non-HDL-C, TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C (0.49), the 10-year incidence of CV events was significantly increased by 40%, 44%, 51%, 49%, and 39%, respectively. For every 1-SD lower HDL-C (13.5 mg/dL), CV risk was increased by 37%. Triglycerides had no association with either outcome.

Conclusion: Except for TGs, all lipid variables were associated with atherosclerosis and future risk of CV disease among persons without dyslipidemia and with low risk factor burden.
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http://dx.doi.org/10.1016/j.mayocp.2022.03.025DOI Listing
June 2022

Impact of Amarogentin on Gastric Carcinoma Cell Multiplication, Apoptosis and Migration via circKIF4A/miR-152-3p.

J Immunol Res 2022 14;2022:2156204. Epub 2022 Jun 14.

Department of Health Care, First Hospital of Changsha, Changsha, 410005 Hunan, China.

Objective: The active ingredients extracted from natural plants have anti-GC actions and can slow down gastric carcinoma (GC) progression. To investigate the impact of Amarogentin (AG) on GC cell multiplication, apoptosis and migration and the possible mechanisms.

Methods: qRT-PCR quantification of circKIF4A and miR-152-3p in GC tissues and normal counterparts as well as HGC-27 (human GC cell strain) and GES-1 (human gastric mucosal epithelial cell strain) was performed. HGC-27 cells were intervened by AG of various concentrations. si-NC, si-circKIF4A were further transfected into HGC-27 cells. Besides, pcDNA and pcDNA-circKIF4A were transfected into HGC-27 cells, after which 60 mmol/L AG was added for intervention. Cell multiplication, clone formation, as well as apoptosis and migration measurements were made by MTT, plate clone formation, flow cytometry and Transwell assays, respectively; Double luciferase reporter assay was performed for targeting relationship identification between circKIF4A and miR-152-3p; Western blots were carried out to measure Bax and Bcl-2 protein levels.

Results: circKIF4A increased (P <0.05) and miR-152-3p decreased (P <0.05) in GC tissues and cell strains. Concentration-dependently, AG intervention contributed to enhanced cell multiplication inhibitory rate, apoptosis rate, miR-152-3p expression and Bax protein level (P <0.05), together with declined number of cell clones formed, migrating cells, circKIF4A expression and Bcl-2 protein level (P <0.05). After transfection of si-circKIF4A, cell multiplication inhibition rate, apoptosis rate and Bax protein level enhanced (P <0.05), while cell clones formed and migrating cells as well as Bcl-2 protein level reduced (P <0.05). miR-152-3p can be controlled by circKIF4A; pcDNA-circKIF4A transfection antagonized AG's effects on HGC-27 cell multiplication, clone formation, apoptosis and migration.

Conclusion: AG can decrease GC multiplication, clone formation and migration and induce apoptosis via modulating circKIF4A/miR-152-3p expression.
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http://dx.doi.org/10.1155/2022/2156204DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213178PMC
June 2022

Myogenic Determination and Differentiation of Chicken Bone Marrow-Derived Mesenchymal Stem Cells under Different Inductive Agents.

Animals (Basel) 2022 Jun 13;12(12). Epub 2022 Jun 13.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Lingnan Guangdong Laboratory of Agriculture, College of Animal Science, South China Agricultural University, Guangzhou 510642, China.

Poultry plays an important role in the meat consumer market and is significant to further understanding the potential mechanism of muscle development in the broiler. Bone marrow-derived mesenchymal stem cells (BM-MSCs) can provide critical insight into muscle development due to their multi-lineage differentiation potential. To our knowledge, chicken BM-MSCs demonstrate limited myogenic differentiation potential under the treatment with dexamethasone (DXMS) and hydrocortisone (HC). 5-azacytidine (5-Aza), a DNA demethylating agent, which has been widely used in the myogenic differentiation of BM-MSCs in other species. There is no previous report that applies 5-Aza to myogenic-induced differentiation of chicken BM-MSCs. In this study, we evaluated the myogenic determination and differentiation effect of BM-MSCs under different inductive agents. BM-MSCs showed better differentiation potential under the 5-Aza-treatment. Transcriptome sequence analysis identified 2402 differentially expressed DEGs including 28 muscle-related genes after 5-Aza-treatment. The DEGs were significantly enriched in Gene Ontology database terms, including in the cell plasma membrane, molecular binding, and cell cycle and differentiation. KEGG pathway analysis revealed that DEGs were enriched in myogenic differentiation-associated pathways containing the PI3K-Akt signaling pathway, the TGF-β signaling pathway, Arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, and hypertrophic cardiomyopathy, which suggested that BM-MSCs differentiated into a muscle-like phenotype under 5-Aza-treatment. Although BM-MSCs have not formed myotubes in our study, it is worthy of further study. In summary, our study lays the foundation for constructing a myogenic determination and differentiation model in chicken BM-MSCs.
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http://dx.doi.org/10.3390/ani12121531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219535PMC
June 2022

Gene Expression Microarray Data Identify Hub Genes Involved in Osteoarthritis.

Front Genet 2022 6;13:870590. Epub 2022 Jun 6.

Department of Orthopedics, The Second Xiangya Hospital of Central South University, Changsha, China.

The present study was performed to explore the underlying molecular mechanisms and screen hub genes of osteoarthritis (OA) bioinformatics analysis. In total, twenty-five OA synovial tissue samples and 25 normal synovial tissue samples were derived from three datasets, namely, GSE55457, GSE55235, and GSE1919, and were used to identify the differentially expressed genes (DEGs) of OA by R language. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of DEGs were conducted using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). A Venn diagram was built to show the potential hub genes identified in all three datasets. The STRING database was used for constructing the protein-protein interaction (PPI) networks and submodules of DEGs. We identified 507 upregulated and 620 downregulated genes. Upregulated DEGs were significantly involved in immune response, MHC class II receptor activity, and presented in the extracellular region, while downregulated DEGs were mainly enriched in response to organic substances, extracellular region parts, and cadmium ion binding. Results of KEGG analysis indicated that the upregulated DEGs mainly existed in cell adhesion molecules (CAMs), while downregulated DEGs were significantly involved in the MAPK signaling pathway. A total of eighteen intersection genes were identified across the three datasets. These include Nell-1, ATF3, RhoB, STC1, and VEGFA. In addition, 10 hub genes including CXCL12, CXCL8, CCL20, and CCL4 were found in the PPI network and module construction. Identification of DEGs and hub genes associated with OA may be helpful for revealing the molecular mechanisms of OA and further promotes the development of relevant biomarkers and drug targets.
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http://dx.doi.org/10.3389/fgene.2022.870590DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207392PMC
June 2022

Does aspirin have an effect on risk of death in patients with COVID-19? A meta-analysis.

Eur J Clin Pharmacol 2022 Sep 22;78(9):1403-1420. Epub 2022 Jun 22.

Department of Epidemiology and Health Statistics, School of Public, Health Anhui Medical University, No. 81 Meishan Road, 230032, Anhui, People's Republic of China.

Purpose: The coronavirus disease 2019 (COVID-19) pandemic has shown unprecedented impact world-wide since the eruption in late 2019. Importantly, emerging reports suggest an increased risk of thromboembolism development in patients with COVID-19. Meanwhile, it is found that aspirin reduced mortality in critically ill patients with non-COVID-19 acute respiratory distress syndrome. Therefore, a meta-analysis was performed to investigate the effects of aspirin on COVID-19 mortality.

Methods: A systematic literature search was conducted in 10 electronic databases and 4 registries. Random effects models were used to calculate pooled relative risks (RRs) with 95% confidence intervals (Cis) to estimate the effect of aspirin on COVID-19 mortality. Relevant subgroup analyses and sensitivity analyses were also performed.

Results: The results showed that aspirin use was associated with a reduction in COVID-19 mortality (adjusted RR 0.69; 95% CI 0.50-0.95; P < 0.001). Subgroup analysis found that the low-dose group was associated with a reduced COVID-19 mortality (adjusted RR 0.64; 95% CI 0.48-0.85; P < 0.01). Aspirin use was associated with reduced COVID-19 mortality in Europe and America (crude RR 0.71; 95% CI 0.52-0.98; P = 0.04), and results from cohort studies suggested that aspirin use was a protective factor for COVID-19 mortality (adjusted RR 0.73; 95% CI 0.52-0.99; P = 0.04). Meanwhile, aspirin use was not associated with bleeding risk (crude RR 1.22; 95% CI 0.80-1.87; P = 0.96).

Conclusions: This meta-analysis found that aspirin use was associated with a reduction in mortality in patients with COVID-19 and not with an increased risk of bleeding.
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http://dx.doi.org/10.1007/s00228-022-03356-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9217117PMC
September 2022

A home-made sampling system coupled to hectowatt-MPT mass spectrometry in positive ion mode to confirm target ions of copper and zinc from Poyang Lake, China.

Anal Bioanal Chem 2022 Aug 22;414(20):6115-6126. Epub 2022 Jun 22.

National and Provincial Union Engineering Research Center for the Veterinary Herbal Medicine Resources and Initiative, Hunan Agricultural University, Changsha, 410128, China.

A novel home-made HSO-Nafion (HN) tube sampling system coupled to a line ion trap mass spectrometer (LTQ-MS) with a versatile ambient ionization source, hectowatt microwave plasma torch (HMPT), has manifested unique advantages for picking directly metal elements in aqueous samples and acquiring the fully characteristic MPT mass spectra of copper and zinc composite ions. Here, we report the development of a novel HN-HMPT-LTQ-MS for metal elements assay based on environmental water to analyze samples of Poyang Lake, China. Detailed multi-stage tandem mass spectra show that the general structural form of target ions is [M(NO)(HO)(OH)] for the positive ion mode. Under the optimized conditions, the proposed method provided low limits of detection (LODs) of 0.23 μgL for Cu and 1.1 μgL for Zn, with relative standard deviations (RSDs) of less than 12.7% by MPT-LTQ-MS. This new result has met the requirements of national standards (GB 5750.6-2006) and is only about one magnitude order larger than the LOD of ICP-MS method. A wide linear response range of about 4 orders of magnitude for the method with linear coefficients (R) of 0.99709 - 0.99962 for copper and zinc tested was in accordance with that of ICP-MS. Except for the recovery of 79% for the third sample and 123.8% for the seventh sample, the present method also provided good recoveries (84 - 119.3%) in spiked 10 batches of drinking water samples. Furthermore, it is envisioned that the developed approach might build a powerful hectowatt-MPT-MS platform for food security detection, drug analysis, and origin traceability.
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http://dx.doi.org/10.1007/s00216-022-04172-7DOI Listing
August 2022

Does Aspirin Prevent Incident Heart Failure in Healthy Older Adults? Examining the Evidence From the ASPREE Trial.

Circ Heart Fail 2022 06 5;15(6):e009511. Epub 2022 Apr 5.

School of Public Health and Preventive Medicine, Monash University, Melbourne, VIC, Australia (J.M., A.T.).

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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.122.009511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9228581PMC
June 2022

Association Between Statin Use and Progression of Arterial Stiffness Among Adults With High Atherosclerotic Risk.

JAMA Netw Open 2022 06 1;5(6):e2218323. Epub 2022 Jun 1.

Department of Cardiology, Kailuan General Hospital, North China University of Science and Technology, Tangshan, China.

Importance: Limited studies have investigated the association between statin use and progression of arterial stiffness, a key player in the pathophysiology of cardiovascular disease.

Objective: To examine the association between statin use and progression of arterial stiffness in Chinese adults with high atherosclerotic risk measured by brachial-ankle pulse wave velocity (baPWV).

Design, Setting, And Participants: This retrospective cohort study enrolled 5105 adults with high atherosclerotic risk from the Kailuan General Hospital from 2010 to 2020. Data were analyzed from February 2021 to April 2022.

Exposures: Statin use information was retrieved from electronic medical records from 2010 to 2020, and statin users were those who have been prescribed any statin medications at least 6 months before baPWV measurements. Statin users were 1:1 matched with non-statin users by propensity score method.

Main Outcomes And Measures: Progression of baPWV was assessed using the absolute difference between baseline and follow-up baPWV, divided by the follow-up time in years. Multivariable linear regression models were used to estimate the association between statin use and arterial stiffness.

Results: Among 5105 adults with assessment of baPWV (mean [SD] age: 60.8 [9.7] years; 3842 [75.3%] men and 1263 [24.7%] women), 1310 statin users were matched with 1310 non-statin users (mean [SD] age, 63.2 [9.3] years). Compared with non-statin users, statin users were associated with significantly lower baPWV at baseline (difference: -33.6 cm/s; 95% CI, -62.1 to -5.1 cm/s). Among 1502 adults with repeated assessment of baPWV, 410 statin users were matched with 410 non-statin users (mean [SD] age, 62.9 [9.2] years). Compared with non-statin users, statin users had significantly slower progression of baPWV (difference, -23.3 cm/s per year; 95% CI, -40.6 to -6.0 cm/s per year) during a mean (SD) follow-up of 4.8 (2.7) years. A significantly slower progression of baPWV was observed in continuous statin users (difference, -24.2 cm/s per year; 95% CI, -42.2 to -6.3 cm/s per year) and high adherent users (difference, -39.7 cm/s per year; 95% CI, -66.9 to -12.4 cm/s per year), but not in discontinued users (difference, -17.3 cm/s per year; 95% CI, -52.4 to 17.8 cm/s per year) and low adherent users (difference, -17.9 cm/s per year; 95% CI, -36.5 to 0.7 cm/s per year), compared with non-statin users.

Conclusions And Relevance: In this cohort study, statin use was associated with slower progression of arterial stiffness in Chinese adults with high atherosclerotic risk.
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http://dx.doi.org/10.1001/jamanetworkopen.2022.18323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9206193PMC
June 2022

Preventing Cholesterol-Induced Perk (Protein Kinase RNA-Like Endoplasmic Reticulum Kinase) Signaling in Smooth Muscle Cells Blocks Atherosclerotic Plaque Formation.

Arterioscler Thromb Vasc Biol 2022 08 16;42(8):1005-1022. Epub 2022 Jun 16.

Division of Medical Genetics, Department of Internal Medicine, McGovern Medical School The University of Texas Health Science Center at Houston (A.C., P.G., S.M., K.K., Z.Z., S.K.P.' A.K., C.S.K., D.M.M.).

Background: Vascular smooth muscle cells (SMCs) undergo complex phenotypic modulation with atherosclerotic plaque formation in hyperlipidemic mice, which is characterized by de-differentiation and heterogeneous increases in the expression of macrophage, fibroblast, osteogenic, and stem cell markers. An increase of cellular cholesterol in SMCs triggers similar phenotypic changes in vitro with exposure to free cholesterol due to cholesterol entering the endoplasmic reticulum, triggering endoplasmic reticulum stress and activating Perk (protein kinase RNA-like endoplasmic reticulum kinase) signaling.

Methods: We generated an SMC-specific knockout mouse model, induced hyperlipidemia in the mice by AAV- injection, and subjected them to a high-fat diet. We then assessed atherosclerotic plaque formation and performed single-cell transcriptomic studies using aortic tissue from these mice.

Results: SMC-specific deletion of Perk reduces atherosclerotic plaque formation in male hyperlipidemic mice by 80%. Single-cell transcriptomic data identify 2 clusters of modulated SMCs in hyperlipidemic mice, one of which is absent when is deleted in SMCs. The 2 modulated SMC clusters have significant overlap of transcriptional changes, but the Perk-dependent cluster uniquely shows a global decrease in the number of transcripts. SMC-specific Perk deletion also prevents migration of both contractile and modulated SMCs from the medial layer of the aorta.

Conclusions: Our results indicate that hypercholesterolemia drives both Perk-dependent and Perk-independent SMC modulation and that deficiency of Perk significantly blocks atherosclerotic plaque formation.
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http://dx.doi.org/10.1161/ATVBAHA.121.317451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9311463PMC
August 2022

[Establishment of Drug-Resistant Cell Lines of Acute Myeloid Leukemia and Correlation of Sirt1 and PGC-1α Expression Levels with Drug Resistance].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2022 Jun;30(3):704-710

Department of Hematology, Baiyun Hospital Affiliated to Guizhou Medical University, Guiyang 550014, Guizhou Province, China,E-mail:

Objective: To construct cytarabine-resistant acute myeloid leukemia (AML) cell lines, and explore the correlation between Sirt1, PGC-1α expression levels and drug resistance.

Methods: Human acute promyelocytic leukemia Kasumi-1 cells were induced by the method of gradually increasing the concentration of Ara-C drug. The IC value of Kasumi-1 cells before and after drug addition was detected by CCK-8 method, so as to construct Ara-C resistant cell lines. The expression levels of Sirt1 and PGC-1α mRNA in Kasumi-1 drug-resistant cell lines and their parental cell lines were detected by real-time fluorescence quantitative PCR, and the expression levels of Sirt1 and PGC-1α protein in kasumi-1 drug-resistant cell lines and their parental cell lines were detected by Western blot.

Results: The constructed Kasumi-1 cell line had common morphological characteristics of drug-resistant cell lines under microscope, and the drug resistance index was greater than 5, indicating that Kasumi-1 drug-resistant cells had good drug resistance after the construction. The RT-qPCR and Western blot assays showed that the expression levels of Sirt1 and PGC-1α mRNA and protein in the drug-resistant cell lines were higher than those of the parental cell lines (P<0.001).

Conclusion: AML cell lines resistant to Ara-C can be successfully induced by the method of gradually increasing the concentration, and the co-high expression of Sirt1 and PGC-1α may mediate the drug resistance of AML cells.
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http://dx.doi.org/10.19746/j.cnki.issn.1009-2137.2022.03.007DOI Listing
June 2022

Light-Assisted Li-O Batteries with Lowered Bias Voltages by Redox Mediators.

Small 2022 Jul 9;18(27):e2200334. Epub 2022 Jun 9.

Engineering Research Center of Advanced Functional Material Manufacturing of Ministry of Education, School of Chemical Engineering, Zhengzhou University, Zhengzhou, Henan, 450001, China.

The enormous overpotential caused by sluggish kinetics of the oxygen reduction reaction and the oxygen evolution reaction prevents the practical application of Li-O batteries. The recently proposed light-assisted strategy is an effective way to improve round-trip efficiency; however, the high-potential photogenerated holes during the charge would degrade the electrolyte with side reactions and poor cycling performance. Herein, a synergistic interaction between a polyterthiophene photocatalyst and a redox mediator is employed in Li-O batteries. During the discharge, the voltage can be compensated by the photovoltage generated on the photoelectrode. Upon the charge with illumination, the photogenerated holes can be consumed by the oxidization of iodide ions, and thus the external circuit voltage is compensated by photogenerated electrons. Accordingly, a smaller bias voltage is needed for the semiconductor to decompose Li O , and the potential of photogenerated holes decreases. Finally, the round-trip efficiency of the battery reaches 97% with a discharge voltage of 3.10 V and a charge voltage of 3.19 V. The batteries show stable operation up to 150 cycles without increased polarization. This work provides new routes for light-assisted Li-O batteries with reduced overpotential and boosted efficiency.
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http://dx.doi.org/10.1002/smll.202200334DOI Listing
July 2022

White matter connectometry in patients with disorders of consciousness revealed by 7-Tesla magnetic resonance imaging.

Brain Imaging Behav 2022 Jun 6. Epub 2022 Jun 6.

College of Electrical Engineering, Zhejiang University, Hangzhou, China.

White matter disruption plays an important role in disorders of consciousness (DOC). The aim of this study was to analyze the connectometry between DOC patients and healthy controls and to explore the relationship between diffusion connectometry and levels of consciousness. Fourteen patients with DOC and 13 sex- and age-matched controls were included in this study. The participants underwent diffusion magnetic resonance imaging (MRI) and T1-weighted structural MRI at 7 Tesla. Diffusion MRI connectometry was performed to investigate the differences between groups, and to subsequently study the correlation between Coma Recovery Scale-Revised (CRS-R) indexes and white matter integrity. In DOC patients, the quantitative anisotropy (QA) was significantly reduced in deep white matter tracts, whereas significantly higher QA values were found in the bilateral cerebellum compared with healthy controls. Moreover, the QA values in many tracts within the right hemisphere were higher in patients in a minimally conscious state compared to those in vegetative state/unresponsive wakefulness syndrome, which was reflected by the correlation between diffusion connectometry and CRS-R indexes. These results indicate that the cerebellum may play an important role in DOC, and the lateralization of the cerebral hemisphere in affected patients may suggest neural compensation.
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http://dx.doi.org/10.1007/s11682-022-00668-zDOI Listing
June 2022
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