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Yang Zhao,1,* Yi-Han Wang,2,* Wei-Chao Tu,1 Da-Wei Wang,1 Mu-Jun Lu,3,4 Yuan Shao1 1Department of Urology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, Shanghai, 201800, People’s Republic of China; 2Department of Urology, Sixth People’s Hospital South Campus Affiliated to Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 3Department of Urology and Andrology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 4Shanghai Institute of Andrology, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mu-Jun Lu; Yuan Shao, Email lumujun@163.com; shaoyuan10772@163.comBackground: Chronic kidney disease (CKD) is a significant worldwide health concern that leads to high mortality rates. The bioactive substance costunolide (CTD) has demonstrated several pharmacological effects and holds promise as a CKD treatment. This study aims to investigate the impact of CTD on CKD and delve into its mechanisms of action.Methods: Unilateral ureteral obstruction (UUO) methods and renal fibrosis mice models were created. Various concentrations of CTD were injected into UUO mice models to investigate the therapeutic effects of CTD on renal fibrosis of mice. Then, renal morphology, pathological changes, and the expression of genes related to fibrosis, inflammation and ferroptosis were analysed. RNA sequencing was utilized to identify the main biological processes and pathways involved in renal injury. Finally, both overexpression and inhibition of IKKβ were studied to examine their respective effects on fibrosis and inflammation in both in vitro and in vivo models.Results: CTD treatment was found to significantly alleviate fibrosis, inflammation and ferroptosis in UUO-induced renal fibrosis mice models. The results of RNA sequencing suggested that the IKKβ acted as key regulatory factor in renal injury and the expression of IKKβ was increased in vitro and in vivo renal fibrosis model. Functionally, down-regulated IKKβ expression inhibits ferroptosis, inflammatory cytokine production and collagen deposition. Conversely, IKKβ overexpression exacerbates progressive renal fibrosis. Mechanistically, CTD alleviated renal fibrosis and inflammation by inhibiting the expression of IKKβ and attenuating IKKβ/NF-κB pathway.Conclusion: This study demonstrates that CTD could mitigate renal fibrosis, ferroptosis and inflammation in CKD by modulating the IKKβ/NF-κB pathway, which indicates targeting IKKβ has an enormous potential for treating CKD. Keywords: chronic kidney disease, costunolide, renal fibrosis, IKKβ/NF-κB pathway

Sisi Zhang,1 Miao Yu,2 Yu Zhang,2 Conying Liang,2 Dayi Hu,1 Dao Wen Wang,1 Xiaoping Meng2 1Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Department of Cardiology and Cardiac Rehabilitation, Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, 130000, People’s Republic of ChinaCorrespondence: Xiaoping Meng, Department of Cardiology and Cardiac Rehabilitation, Affiliated Hospital of Changchun University of Chinese Medicine, #1473 Gongnong Road, Chaoyang District, Changchun, 130000, People’s Republic of China, Email xiopingmeng@126.comPurpose: This study aimed to translate and cross-culturally adapt the cardiac rehabilitation barriers scale to the Chinese, and examine its reliability and validity among the older population.Methods: An approach comprising translation, cultural adaptation, reliability, and validity examination in the Chinese version was conducted in two hospitals in Jilin, China. The t-tests were used to compare the sex differences between each item. Participants included Chinese individuals > 60 who were eligible for the cardiac rehabilitation program.Results: In total, 325 participants completed the questionnaire with an average age of 61.23 ± 9.68 years. The item-total correlations were 0.432 to 0.678. Factor analysis of CRBS-C (Kaiser Meyer Olkin = 0.867, Bartlett’s test p = 0.000) revealed four factors: logistical factors, comorbidities/functional status, perceived need/healthcare factors, and work/time conflict. The confirmatory factor analysis (CFA) indicated a good model fit (χ 2/df = 1.84, RMSEA = 0.051, CFI = 0.953, TLI = 0.945, SRMR=0.046). Cronbach’s alpha was 0.88 for the scale, ranging from 0.801 to 0.88 for each item, which indicates the internal reliability was acceptable.Conclusion: The Chinese version of the CRRS has acceptable reliability and validity in the Chinese elderly population.Keywords: cardiac rehabilitation, internal reliability, cross-cultural adaptation, exploratory factor analysis, confirmatory factor analysis

Cao MD, Song YC, Yang ZM, Wang DW, Lin YM, Lu HD. Onco Targets Ther. 2020;13:8095-8107. We, the Editors and Publisher of OncoTargets and Therapy, have retracted the following article. Concerns were raised about the integrity of the data in the article after it was found images from Figure 6 had been duplicated with those from other unrelated articles. Specifically, The image for Figure 6D, MG63, WT, has been duplicated with the images for Figure 3A, SW620, miR-1236-3p mimics and Figure 2b, MDA-MB-231, Con, from Zhao Y, Zhou H, Shen J, et al. MiR1236-3p Inhibits the Proliferation, Invasion, and Migration of Colon Cancer Cells and Hinders Epithelial Mesenchymal Transition by Targeting DCLK3. Front Oncol. 2021;11:688882. https://doi.org/10.3389/fonc.2021.688882 and Wang S, Zhang Y, Ren T, et al. A novel 4-aminoquinazoline derivative, DHW-208, suppresses the growth of human breast cancer cells by targeting the PI3K/AKT/mTOR pathway. Cell Death Dis. 2020;11:491. https://doi.org/10.1038/s41419-020-2690-y, respectively. The image for Figure 6D, MG63, shTLR7, has been duplicated with the image for Figure 3A, SW620, Mimics control, from Zhao Y, et al. Front Oncol. 2021;11:688882. The image for Figure 6E, MG63, WT, has been duplicated with the image for Figure 2b, MDA-MB-231, 400 and Figure 6E, Si-SLC26A4-AS1, from Wang S, et al, Cell Death Dis. 2020;11:491 and Li Z, Lin W, Zheng J, et al. Identification of immune-related lncRNAs to improve the prognosis prediction for patients with papillary thyroid cancer. Biosci Rep. 2021;41(2): BSR20204086. doi: https://doi.org/10.1042/BSR20204086, respectively. The image for Figure 6E, MG63, shTLR7, has been duplicated with the images for Figure 3B, SW620, miR-1236-3p mimics; Figure 2b, MDA-MB-231, 200; Figure 6E, NC; Figure 10H, scCD200R1 and Figure 2E, sh-KIF4A, from Zhao Y, et al. Front Oncol. 2021;11:688882; Wang S, et al. Cell Death Dis. 2020;11:491; Li Z, et al. Biosci Rep. 2021;26:41(2):BSR20204086; Ling B, Ye G, Zhao Q, Jiang Y, Liang L, Tang Q. Identification of an Immunologic Signature of Lung Adenocarcinomas Based on Genome-Wide Immune Expression Profiles. Front Mol Biosci. 2021;7:603701: https://doi.org/10.3389/fmolb.2020.603701 and Feng S, Luo S, Ji C, et al. miR-29c-3p regulates proliferation and migration in ovarian cancer by targeting KIF4A. World J Surg Onc. 2020;18:315. https://doi.org/10.1186/s12957-020-02088-z, respectively. When approached for an explanation, the authors were cooperative and provided some data for their study. However, the author’s explanation and the provided data did not satisfactorily explain how the duplication of these images occurred and was unable to alleviate the journal’s concerns regarding the validity of the findings. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article and the authors were notified of this. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

Xin Xu,1,2,&ast; James Jiqi Wang,1,2,&ast; Hu Zhao,1,2 Kun Miao,1,2 Guanglin Cui,1,2 Yuxuan Zhang,1,2 Xiaoyun Yang,1,2 Luyun Wang,1,2 Junfang Wu,2 Dao Wen Wang1,2 1Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiological Disorders, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dao Wen Wang; Junfang Wu, Division of Cardiology, Department of Internal Medicine Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095# Jiefang Ave, Wuhan, 430030, People’s Republic of China, Tel/Fax +86-278366-3280, Email dwwang@tjh.tjmu.edu.cn; junfang.wu@tjh.tjmu.edu.cnBackground: Vasospastic angina (VSA) is caused by severe diffuse or segmental coronary artery spasms. Patients with variant angina have poor clinical outcomes, although nitrates and calcium blockers help improve patient symptoms because there is no understanding of the etiology and causal treatment. The present study investigated whether VSA is associated with inflammation of the heart.Patients and Methods: A total of 109 patients with VSA diagnosed by the presence of recurrent angina pectoris, typical electrocardiography, and coronary angiography were recruited, and 61 normal participants and 61 patients with acute myocardial infarction (AMI) and coronary artery stenosis were recruited as controls. The plasma levels of 24 cytokines were measured using a magnetic Luminex assay, and endothelin-1 and histamine levels tested using enzyme-linked immunosorbent assay and mass-spectrometry, respectively, for all participants. Furthermore, four patients with VSA underwent 18-fluorine fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT).Results: The plasma levels of interleukin (IL)-12p70, IL-13, PDL-1, IL-10, IL-6, IL-15, macrophage inflammatory protein (MIP)-1α, and MIP-1β in patients with VSA were significantly higher than those in both normal controls and patients with AMI (p< 0.001) but did not differ between normal controls and patients with AMI. 18F-FDG PET/CT showed that the left ventricle, coronary perivascular tissue volume, and coronary perivascular FDG uptake were significantly increased in all four patients.Conclusion: Our findings demonstrate that VSA patients have significantly elevated plasma cytokine levels and myocardial and pericoronary inflammation, suggesting that VSA is associated with myocarditis. This study provides novel insights into the etiology and treatment of VSA.Keywords: variant angina, myocarditis, cytokines, inflammation

Xiao Ran,1 Dao Wen Wang,2 Zhen Yu,1 Rongxue Wu,3 Qin Zhang4 1Department of Emergency, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, People’s Republic of China; 2The Institute of Hypertension and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, People’s Republic of China; 3Department of Biological Sciences Division/ Cardiology, University of Chicago, Chicago, IL, 60637, USA; 4Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, People’s Republic of ChinaCorrespondence: Qin Zhang Email qzhang8@tjh.tjmu.cnAim: Tissue kallikrein (TK) exerts protective effects on cardiac cerebrovascular diseases (CCVDs). Changes in TK level in plasma are associated with ischemic stroke and coronary artery disease (CAD); however, a causal correlation could not be established. Therefore, we investigated the association between TK levels and CCVDs in a community-based cross-sectional study in China.Methods: A total of 6043 subjects (4242 men and 1801 women) were enrolled in this community-based cross-sectional study. Then, TK levels were measured using an enzyme-linked immunosorbent assay kit. Multivariate linear regression model and logistic regression were used to assess the correlations between TK levels and CCVDs. Subsequently, the receiver operating characteristic (ROC) curve was drawn to assess the value of TK level in evaluating the risk of ischemic stroke. Finally, the influence of various medications was evaluated on TK levels.Results: The TK level was significantly lower in subjects with ischemic stroke (P < 0.001) and hypertension (P < 0.001) and negatively associated with ischemic stroke (P < 0.001) but not associated with hypertension, coronary heart disease, and diabetes compared to the traditional risk factors. The diagnostic accuracy for ischemic stroke, as quantified by the area under the curve, was 0.892 (95% CI, 0.884– 0.900) for TK level, deeming it as a promising assessment tool. Moreover, no appreciable influence of various drugs therapy was found in TK levels (P = 0.222) except for those taking antilipemic agents.Conclusion: TK is a strong and independent endogenous protective factor against ischemic stroke in the Chinese population and could be a promising biomarker for the risk of ischemic stroke.Keywords: tissue kallikrein, ischemic stroke, cardiac cerebral vascular disease, risk factor

Ming-Chao Wei,1 Yu-Min Wang,2 Da-Wei Wang3 1Department of Thoracic Surgery, Yantai Affiliated Hospital of Binzhou Medical University, Shandong, People’s Republic of China; 2Binzhou Medical University, Shandong, People’s Republic of China; 3Department of Thoracic Surgery, Yantai Mountain Hospital, Shandong, People’s Republic of ChinaCorrespondence: Da-Wei WangDepartment of Thoracic Surgery, Yantai Mountain Hospital, Yantai, Shandong, 264001, People’s Republic of ChinaTel +86-0535-6602183Email gebizhizhang44557@163.comBackground: The role of microRNA (miR) in tumors has been reported in numerous articles. Previous studies have found that miR-130a is low expressed in lung cancer, but the related mechanism has not been fully elucidated. This study mainly explores the mechanism of miR-130a in lung cancer, so as to provide potential therapeutic targets for clinical applications.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-130a and KLF3 in the tissues of lung cancer patients. The miR-130a-mimics and miR-130a-inhibit were constructed. Cell proliferation, invasion, migration and apoptosis were determined by CCK-8, transwell, scratch test and flow cytometry. Western Blot was used to determine the expression of KLF3 protein in cells, and the dual-luciferase reporter to determine the relationship between KLF3 and miR-130a.Results: miR-130a shows low expression in NSCLC patients, while KLF3 shows high expression, exhibiting a negative correlation. The 5-year survival rate of patients with low miR-130a expression and high KLF3 expression was reduced. Cox regression analysis showed that miR-130a was an independent prognostic factor for NSCLC patients. The dual-luciferase reporter revealed that miR-130a bound to KLF3 in a targeted manner, and cell experiments showed that miR-130a could inhibit the growth of lung cancer cells by regulating the expression of KLF3.Conclusion: miR-130a shows low expression in lung cancer and predicts a poor prognosis. In addition, up-regulation of miR-130a can down-regulate KLF3 and inhibit the growth of lung cancer.Keywords: miR-130a, KLF3, lung cancer, prognosis

Yu Liu,1 Wen-Li Zhang,1 Ji-Qiang Bu,1 Jian-Jun Gu,1 Yong-Quan Sun,1 Hong-Zhan Cui,1 Da-Wei Wang,2 Zi-Ying Chen1 1Department of Cardiac Surgery, Second Hospital of Hebei Medical University, Shi Jiazhuang, 050000, People’s Republic of China; 2Department of Cardiac Surgery, The First Affiliated Hospital of Hebei North University, Zhangjiakou, 075000, People’s Republic of ChinaCorrespondence: Zi-Ying ChenDepartment of Cardiac Surgery, Second Hospital of Hebei Medical University, No. 215 of Heping West Road, XinHua District, Shijiazhuang, 050000, People’s Republic of ChinaTel +86 15803210520Fax +86 311 6600 2995Email chenziying258@163.comObjective: This study aims to investigate the value of thromboelastography (TEG) in predicting blood loss, and its relationship with blood transfusion demand, during the perioperative period in off-pump coronary artery bypass grafting (OPCABG).Methods: The data of 398 patients undergoing OPCABG were retrospectively analyzed. Blood was drawn before anesthesia induction (T1) and at 10 minutes after heparin neutralization (T2) for further TEG detection. The patients were divided into two groups based on the results at T2: a TEG normal group and a TEG abnormal group. Logistic regression analysis was used to predict the related factors contributing to the significant increase in perioperative blood loss (more than 20% of the estimated blood volume).Results: There were 277 (69.6%) patients in the TEG normal group and 121 (30.4%) in the TEG abnormal group. Compared with the TEG normal group, the volume of blood loss, red blood cell count, and volume of plasma transfusion in the TEG abnormal group significantly increased within 24 hours after surgery. The results of the logistic regression analysis identified the use of clopidogrel, platelet count at T2, fibrinogen level at T2, and abnormality in TEG value as independent predictors for the significant increase in perioperative blood loss (P < 0.001).Conclusion: The abnormality in TEG value after heparin neutralization is correlated with massive hemorrhage and blood transfusion during the perioperative period in OPCABG. TEG detection can assist in clinical treatment and reduce the volume of blood lost in a hemorrhage and the volume of blood required in a transfusion during OPCABG.Keywords: thromboelastography, off-pump coronary artery bypass grafting, perioperative period, blood loss, blood transfusion

Ming-De Cao,1 Yan-Cheng Song,2 Zhong-Meng Yang,1 Da-Wei Wang,1 Yi-Ming Lin,1 Hua-Ding Lu1 1Department of Orthopaedics, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai 519000, Guangdong, People’s Republic of China; 2Department of Orthopedics, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510000, Guangdong, People’s Republic of ChinaCorrespondence: Hua-Ding LuDepartment of Orthopaedics, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai 519000, Guangdong, People’s Republic of ChinaTel +86 13807918420Email johnniehuading@163.comBackground: Metastasis is the leading cause of death for patients with osteosarcoma (OS). In the present study, we explore the biomarkers for metastatic OS and provide potential therapeutic approaches.Materials and Methods: RNA-Seq data and clinical follow-up information were downloaded from TARGET and GEO databases. A Cox regression model was used to analyze metastatic events. L1000FWD, DGIdb, and CMap databases were used to identify potential drugs related to metastasis. Invasion and migration transwell assays and an adhesion assay were used to identify biological functions of genes.Results: A total of 15 metastasis-related signatures (MRSs) were associated with the prognosis based on the TARGET or GSE21257 cohorts, among which IL10RA and TLR7 genes were especially significant. In the DGIdb drug–gene interaction database, TLR7 and IFNGR1 were found to have potential interactions with drugs. After inhibiting the expression of TLR7, the migration, invasion, and adhesion ability of OS cells were significantly enhanced, which further promoted metastasis.Conclusion: We identified a set of MRS that may be related to OS metastases. Among them, TLR7 plays a vital role and may be a potential target for OS metastasis treatment.Keywords: osteosarcoma, metastatic-related signatures, drug–gene interaction, TLR7, migration, invasion

Ning Li,1 Tao Cui,2 Wenling Guo,1 Dianwei Wang,1 Li Mao31Obstetrical Department, Binzhou Central Hospital, Binzhou, Shandong 251700, People’s Republic of China; 2Anesthesiology Department, Huimin County Maternal and Child Health Hospital, Binzhou, Shandong, 251700, People’s Republic of China; 3Gynecology Department, Binzhou Central Hospital, Binzhou, Shandong 251700, People’s Republic of ChinaBackground: The dysregulation of microRNAs has been implicated in the progression of different malignancies. Herein, we sought to identify the precise roles of miR-155-5p in the progression of cervical cancer.Materials and methods: The expressions of miR-155-5p in cervical carcinoma cells and clinical tissues were assessed using qRT-PCR analysis. The functions of miR-155-5p on the growth of cervical cancer cell were investigated using MTT and colony formation. The Transwell and wound closure assays were selected to explore the influence of miR-155-5p on the invasion and migration of cervical cancer cell. The effect of miR-155-5p on cervical carcinoma cell growth and metastasis in vivo was investigated using xenograft model and experimental lung metastasis model. Bioinformatics analysis and luciferase reporter assay were applied to identify that tumor protein p53-inducible nuclear protein 1 (TP53INP1) was the target of miR-155-5p.Results: MiR-155-5p was significantly upregulated in cervical cancer tissue than that in control normal tissue. Downexpression of miR-155-5p decreased the growth, migration as well as invasiveness abilities of cervical cancer cell in vitro whereas overregulation of miR-155-5p caused the opposite outcomes. In addition, the in vivo mice xenograft model suggested that downexpression of miR-155-5p restrained the progression of cervical cancer cell whereas overexpression of miR-155-5p caused opposite outcomes. Furthermore, we revealed that TP53INP1 was the target of miR-155-5p and the level of TP53INP1 was inversely associated with miR-155-5p level in cervical carcinoma. Furthermore, TP53INP1 knockdown mimicked the influence of miR-155-5p on cervical cancer proliferation, migration and invasion phenotypes. Finally, overexpression of TP53INP1 impaired the promote effect of miR-155-5p on cervical cancer cell and downregulation of TP53INP1 counteracted the suppressive impact of miR-155-5p on the aggressiveness of cervical cancer cell.Conclusion: Our study indicated that miR-155-5p regulated the development of cervical cancer cell by regulating the expression of TP53INP1.Keywords: miR-155-5p, cervical cancer, TP53INP1, metastasis

Xiao-Ming Zhu1, Yi-Xiang J Wang1, Ken Cham-Fai Leung2,3, Siu-Fung Lee2, Feng Zhao1, Da-Wei Wang2, Josie MY Lai4, Chao Wan4, Christopher HK Cheng4, Anil T Ahuja11Department of Imaging and Interventional Radiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR; 2Institute of Molecular Functional Materials and Department of Chemistry, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR; 3Institute of Creativity and Department of Chemistry, The Hong Kong Baptist University, Kowloon Tong, Kowloon, Hong Kong SAR; 4School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong KongPurpose: To compare the cellular uptake efficiency and cytotoxicity of aminosilane (SiO2-NH2)-coated superparamagnetic iron oxide (SPIO@SiO2-NH2) nanoparticles with three other types of SPIO nanoparticles coated with SiO2 (SPIO@SiO2), dextran (SPIO@dextran), or bare SPIO in mammalian cell lines.Materials and methods: Four types of monodispersed SPIO nanoparticles with a SPIO core size of 7 nm and an overall size in a range of 7–15 nm were synthesized. The mammalian cell lines of MCF-7, MDA-MB-231, HT-29, RAW264.7, L929, HepG2, PC-3, U-87 MG, and mouse mesenchymal stem cells (MSCs) were incubated with four types of SPIO nanoparticles for 24 hours in the serum-free culture medium Dulbecco’s modified Eagle’s medium (DMEM) with 4.5 µg/mL iron concentration. The cellular uptake efficiencies of SPIO nanoparticles were compared by Prussian blue staining and intracellular iron quantification. In vitro magnetic resonance imaging of MSC pellets after SPIO labeling was performed at 3 T. The effect of each SPIO nanoparticle on the cell viability of RAW 264.7 (mouse monocyte/macrophage) cells was also evaluated.Results: Transmission electron microscopy demonstrated surface coating with SiO2-NH2, SiO2, and dextran prevented SPIO nanoparticle aggregation in DMEM culture medium. MCF-7, MDA-MB-231, and HT-29 cells failed to show notable iron uptake. For all the remaining six cell lines, Prussian blue staining and intracellular iron quantification demonstrated that SPIO@SiO2-NH2 nanoparticles had the highest cellular uptake efficiency. SPIO@SiO2-NH2, bare SPIO, and SPIO@dextran nanoparticles did not affect RAW 264.7 cell viability up to 200 µg Fe/mL, while SPIO@SiO2 reduced RAW 264.7 cell viability from 10 to 200 µg Fe/mL in a dose-dependent manner.Conclusion: Cellular uptake efficiency of SPIO nanoparticles depends on both the cell type and SPIO surface characteristics. Aminosilane surface coating enhanced the cellular uptake efficiency without inducing cytotoxicity in a number of cell lines.Keywords: magnetic nanoparticles, SPIO, iron oxide, surface coating, cellular uptake

BackgroundThe Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry.Methods and resultsA total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P

Intensive field measurements were carried out at a mountain site and an urban site at the foot of the mountain from September to November 2010 in Hong Kong. Acetone was monitored using both canister air samples and 2,4-dinitrophenylhydrazine cartridges. The spatiotemporal patterns of acetone showed no difference between the two sites (p > 0.05), and the mean acetone mixing ratios on O3 episode days were higher than those on non-O3 episode days at both sites (p < 0.05). The source contributions to ambient acetone at both sites were estimated using a receptor model i.e. Positive Matrix Factorization (PMF). The PMF results showed that vehicular emission and secondary formation made the most important contribution to ambient acetone, followed by the solvent use at both sites. However, the contribution of biogenic emission at the mountain site was significantly higher than that at the urban site, whereas biomass burning made more remarkable contribution at the urban site than that at the mountain site. The mechanism of oxidation formation of acetone was investigated using a photochemical box model. The results indicated that i-butene was the main precursor of secondary acetone at the mountain site, while the oxidation of i-butane was the major source of secondary acetone at the urban site. © 2012 Elsevier Ltd.

A field campaign was carried out in September-November 2010 near the summit of Mt. Tai Mo Shan in Hong Kong. Isoprene, methyl vinyl ketone (MVK) and methacrolein (MAC) were measured. The average isoprene mixing ratio was 109 pptv, and the average MAC and MVK levels were 68 pptv and 164 pptv, respectively. The average daytime levels of isoprene (14920 pptv, average95% confidence interval, p

Background and the purpose of the study: Epoxyeicosatrienoic acids (EETs), which are cytochrome P450 epoxygenase metabolites of arachidonic acid, have anti-inflammatory effects, modulate smooth muscle proliferation, and inhibit smooth muscle migration. This study was designed to determine whether exogenous EETs have any effect on the cell proliferation and apoptosis of carcinoma cell as well as the possible signaling pathways of EETs in this regulation. Methods: The effects of EETs on the proliferation and anti-apoptosis of human carcinoma cells were measured by MTT assay and flowcytometric analysis, and the regulation of PPARγ, epithelial growth factor receptor (EGFR), extracellular signal-regulated kinase (ERK), phosphatidylinositol 3 (PI3)-Kinase/AKT pathways was investigated by reverse transcriptase polymerase chain reaction (RT-PCR) and western blot analysis. Results: Results of this study suggested that 14, 15-EET may activate the expression of PPARγ in Tca-8113 cells. 14,15-EET may stimulate cell proliferation, and increase the percentage of cells during S-G2-M phase in Tca-8113 cells significantly. The levels of EGFR, ERK, and PI3 kinase/AKT proteins were significantly induced by treatment of 14, 15-EET and 14,15-EET/ AUDA, but no significant changes were observed by addition of GW9662. Conclusion: These findings suggest that exogenous 14,15-EET has potent inhibitory effect on proliferation, and could induce apoptosis in Tca-8113 cell, and these changes are related to the expression of PPARγ, the activation of EGFR, ERK, and PI3 kinase/AKT proteins. [ABSTRACT FROM AUTHOR]

The cholinergic anti-inflammatory pathway (CAP) is a neurophysiological mechanism that regulates the immune system. The CAP inhibits inflammation by suppressing cytokine synthesis via release of acetylcholine in organs of the reticuloendothelial system, including the lungs, spleen, liver, kidneys and gastrointestinal tract. Acetylcholine can interact with alpha7 nicotinic acetylcholine receptors (alpha7 nAchR) expressed by macrophages and other cytokine producing cells, down-regulate pro-inflammatory cytokine synthesis and prevent tissue damage. Herein is a review of the neurophysiological mechanism in which the CAP regulates inflammatory response, as well as its potential interventional strategy for inflammatory diseases. [ABSTRACT FROM AUTHOR]

BACKGROUND: Subtalar bone-block distraction arthrodesis using structural autograft carries the risk of donor site morbidity. Recent reports suggest that structural allograft may be an attractive alternative to structural autograft in subtalar arthrodesis. This prospective study analyzes subtalar distraction arthrodesis using interpositional structural allograft. MATERIALS AND METHODS: Between 2000 and 2006, 22 patients (24 feet; mean age, 45.6 years) underwent subtalar arthrodesis with interpositional fresh-frozen femoral head structural allograft. Indications included subtalar arthrosis, loss of heel height, and anterior ankle impingement. Clinical outcome was assessed using the AOFAS ankle-hindfoot scoring system. Time to union was determined by previously reported clinical findings and radiographic evidence for bridging trabeculation between host bone and structural allograft. RESULTS: Mean followup was 35.8 months for 20 patients (21 feet) available for followup evaluation. Union was achieved in 19 of 21 patients (90%) at a mean of 15.5 (range, 11 to 19) weeks. Mean AOFAS hindfoot score improved from 21 to 71 points (p < 0.05). Radiographic analysis suggested significant (p < 0.05) improvement in all measurements. Complications included nonunion (2), varus malalignment (1), persistent subfibular impingement (1), sural neuralgia (1), and prominent hardware (2). Both patients with nonunions had avascular bone at the arthrodesis site and used tobacco products. CONCLUSION: This study supports recent publications that subtalar arthrodesis using interpositional structural allograft can have a favorable outcome. Our clinical and radiographic results suggest that restoration of hindfoot function and dimensions with structural allograft are comparable to results reported for the same procedure using structural autograft. LEVEL OF EVIDENCE: Level IV, prospective case series. [ABSTRACT FROM AUTHOR]

BACKGROUND: Exposure of the posterolateral talar dome for osteochondral autograft transfer can be challenging. The purpose of this study is to compare surgical exposures for perpendicular access to the posterolateral talar dome using osteochondral transfer instrumentation. MATERIALS AND METHODS: Five surgical approaches were performed on each of eight cadaveric ankles. The sequence was: (1) Anterolateral arthrotomy with ATFL release, (2) Anterolateral tibial osteotomy, (3) Fibular osteotomy with ATFL intact, (4) Fibular osteotomy with ATFL release, and (5) Fibular osteotomy with ATFL/CFL release. (ATFL repaired between 1 and 2). While maintaining the orientation of the harvester perpendicular to the talar dome articular surface, osteochondral plugs were harvested as far posteriorly as possible using a 6-mm harvester. Distances from the anterior talar articular surface to the posterior aspect of the recipient site were measured. Statistical analysis used ANOVA and Fisher post hoc tests. RESULTS: Average AP exposure (mm) and percentage of AP talar dome dimensions exposed: (1) Anterolateral arthrotomy with ATFL release: 21.2 mm (43.3%), (2) Anterolateral tibial osteotomy: 33.7 mm (68.5%), (3) Fibular osteotomy(ATFL intact): 43.2 mm (87.8%), (4) Fibular osteotomy with ATFL release: 44.9 mm (91.2%), and (5) Fibular osteotomy with ATFL/CFL release: 46.6 mm (94.6%). All osteotomies provided greater exposure than anterolateral arthrotomy with ATFL release (p < 0.0001). A significant difference was obtained between each of the fibular osteotomies and tibial osteotomy (p < 0.0001). Differences between the fibular osteotomy approaches (3 to 5) were not significant. CONCLUSION: Fibular osteotomy provides the greatest perpendicular exposure to the posterolateral talar dome. Anterolateral tibial osteotomy provides greater exposure than arthrotomy alone. CLINICAL RELEVANCE: This study provides a guide for surgical exposures to the posterolateral talar dome for osteochondral autograft transfer. [ABSTRACT FROM AUTHOR]

Telmisartan, an angiotensin II type 1 receptor (AT1R) blocker, exhibits broad anti-tumor activity. However, in vitro, anti-proliferative effects are shown at doses far beyond the therapeutic plasma concentration. Considering the role of tumor microenvironment in glioma progression, glioma-astrocyte co-cultures were employed to test the anti-tumor potential of low-dose telmisartan. When a high dose was required for a direct anti-proliferative effect on glioma cell lines, a low dose significantly inhibited glioma cell proliferation and migration in the co-culture system. Under co-culture conditions, upregulated IL-6 expression in astrocytes played a critical role in glioma progression. Silencing IL-6 in astrocytes or IL-6R in glioma cells reduced proliferation and migration. Telmisartan (5 μM) inhibited astrocytic IL-6 expression, and its anti-tumor effects were reversed by silencing IL-6 or IL-6R and inhibiting signal transducer and activator of transcription 3 (STAT3) activity in glioma cells. Moreover, the telmisartan-driven IL-6 downregulation was not imitated by losartan, an AT1R blocker with little capacity of peroxisome proliferator-activated receptor-gamma (PPARγ) activation, but was eliminated by a PPARγ antagonist, indicating that the anti-glioma effects of telmisartan rely on its PPARγ agonistic activity rather than AT1R blockade. This study highlights the importance of astrocytic IL-6-mediated paracrine signaling in glioma growth and the potential of telmisartan as an adjuvant therapy for patients with glioma, especially those with hypertension., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Moshen Fuyuan Formula (MSFY) is one of the representative Chinese medicine compound for Idiopathic membranous nephropathy (IMN), that originate from Fang Ji Huang Qi decoction in the Han dynasty. IMN is usually accompanied by different tongue coatings in traditional Chinese medicine (TCM), and tongue microorganisms are important factors affecting the formation of the tongue coating. Recently, oral microbiomes, including bacteria and fungi, have been identified as pivotal factors that contribute to disease development. However, the regulation of oral microbiomes by MSFY has not been defined., Aim of the Study: In this work, we explore the characteristics of oral bacteria and fungi in IMN patients with different tongue coatings, and clarify the therapeutic effect of MSFY based on oral microbiome., Materials and Methods: We enrolled 24 patients with IMN, including 11 with white tongue (IMN-W) and 13 with yellow tongue (IMN-Y), and recruited an additional 10 healthy individuals. Patients with IMN were treated with the MSFY. The oral bacteriome and fungi before and after treatment were detected using full-length 16S rRNA and internal transcribed spacer gene sequencing., Results: The therapeutic effect of MSFY on patients with yellow tongue coating was more significant than that on patients with white tongue coating. In terms of oral bacteriome, Campylobacter bacteria were enriched in patients with yellow tongue and could be a promising biomarker for yellow coating. Enrichment of Veillonella parvula&#95;A may partially account for the therapeutic effect of MSFY. As for oral fungi, Malassezia globosa was enhanced in patients with IMN-W and reduced in patients with IMN-Y. Notably, it was reduced by MSFY. We also found that mycobiome-bacteriome interactions were highly complex and dynamic in patients with IMN., Conclusion: The regulation of the dynamic balance between oral fungi and bacteria by MSFY contributes to the treatment of IMN. This study determined the oral bacteriome and mycobiome of patients with IMN with different tongue coatings before and after MSFY treatment, which aids in promoting personalized treatment in clinical TCM and provides direction for investigating the mechanism of Chinese herbal medicines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Arrhythmogenic cardiomyopathy (ACM) is an inherited cardiomyopathy characterized with progressive cardiac fibrosis and heart failure. However, the exact mechanism driving the progression of cardiac fibrosis and heart failure in ACM remains elusive. This study aims to investigate the underlying mechanisms of progressive cardiac fibrosis in ACM caused by newly identified Desmoglein-2 (DSG2) variation., Methods: We identified homozygous DSG2 F531C variant in a family with 8 ACM patients using whole-exome sequencing and generated Dsg2 F536C knock-in mice. Neonatal and adult mouse ventricular myocytes isolated from Dsg2 F536C knock-in mice were used. We performed functional, transcriptomic and mass spectrometry analyses to evaluate the mechanisms of ACM caused by DSG2 F531C variant., Results: All eight patients with ACM were homozygous for DSG2 F531C variant. Dsg2 F536C/F536C mice displayed cardiac enlargement, dysfunction, and progressive cardiac fibrosis in both ventricles. Mechanistic investigations revealed that the variant DSG2-F536C protein underwent misfolding, leading to its recognition by BiP within the endoplasmic reticulum, which triggered endoplasmic reticulum stress, activated the PERK-ATF4 signaling pathway and increased ATF4 levels in cardiomyocytes. Increased ATF4 facilitated the expression of TGF-β1 in cardiomyocytes, thereby activating cardiac fibroblasts through paracrine signaling and ultimately promoting cardiac fibrosis in Dsg2 F536C/F536C mice. Notably, inhibition of the PERK-ATF4 signaling attenuated progressive cardiac fibrosis and cardiac systolic dysfunction in Dsg2 F536C/F536C mice., Conclusions: Hyperactivation of the ATF4/TGF-β1 signaling in cardiomyocytes emerges as a novel mechanism underlying progressive cardiac fibrosis in ACM. Targeting the ATF4/TGF-β1 signaling may be a novel therapeutic target for managing ACM., (© 2024. The Author(s).)

The Rosa cymosa Tratt, an herbal plant from the Rosaceae family, has historically been valued in China for its medicinal and edible properties. In this study, a novel polysaccharide from R. cymosa fruit, termed PRCP (purified R. cymosa polysaccharide), was isolated using water extraction, decolorization, deproteinization, and ion-exchange chromatography. The structural characteristics of PRCP were investigated using monosaccharide composition analysis, methylation, GPC, FTIR, CD, and NMR spectroscopy. The immunomodulatory effect and potential mechanism of PRCP were evaluated in vitro using a macrophage cell model. Results indicated that PRCP (37.28 kDa) is a highly branched polysaccharide (72.61 %) primarily composed of arabinogalactan, rhamnogalacturonan, and galactoglucan domains with 13 types of glycosidic linkage fragments. Furthermore, PRCP appears to modulate immunomodulatory effects by influencing the phosphorylation of P38 and JNK proteins in the MAPK pathway. Collectively, these findings highlight the potential of PRCP as a promising natural functional food ingredient for immunostimulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

A cascade reaction of cyclopropyl alcohols, DABSO (1,4-diazoniabicyclo[2.2.2]octane-1,4-disulfinate), and N -(sulfonyl)acrylamides has been developed. This tandem process went through a cyclopropanol ring opening and Michael addition sequence. The γ-keto sulfinate generated from the reaction between cyclopropanol and DABSO serves as the nucleophilic reagent, and N -(sulfonyl)acrylamide is used as the Michael addition acceptor. By utilizing this strategy, multitudinous sulfone-bridged 1,7-dicarbonyl compounds that contain both a β-sulfonyl amide unit and γ-keto sulfone skeleton were conveniently synthesized.

Background: Immune response and inflammation play important roles in the physiological and pathophysiological processes of heart failure (HF). In our previous study, myeloid-derived suppressor cells (MDSCs), a heterogeneous group of immature myeloid cells with anti-inflammatory and immunosuppressive functions, were shown to exert cardioprotective effects in HF. The pharmacological targeting of MDSCs using rapamycin may emerge as a promising strategy for the prevention and treatment of HF. However, the specific mechanisms underlying rapamycin-induced MDSC accumulation remain unclear. Our study aimed to clarify the effects of rapamycin on the recruitment and function of MDSCs in HF, exploring new therapeutic options for the prevention and treatment of HF., Methods: We used transverse aortic constriction surgery and isoproterenol injection to establish HF models. Flow cytometry, reverse transcription polymerase chain reaction, transcriptomics and western blot were used to explore the regulation of rapamycin on recruitment and function of MDSCs in HF. Furthermore, rapamycin and granulocyte-macrophage colony-stimulating factor (GM-CSF) were combined to induce exogenous MDSCs from bone marrow cells., Results: Rapamycin promotes the recruitment of MDSCs by inhibiting their maturation and differentiation via suppression of the Wnt signaling in HF mice and enhanced the immunosuppressive function of MDSCs via the NF-κB signaling. Furthermore, exogenous MDSCs induced by rapamycin and GM-CSF can significantly alleviate transverse aortic constriction-induced cardiac dysfunction., Conclusions: The pharmacological targeting of MDSCs using rapamycin is a promising strategy for the prevention and treatment of HF., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Heart failure (HF), as the terminal manifestation of multiple cardiovascular diseases, causes a huge socioeconomic burden worldwide. Despite the advances in drugs and medical-assisted devices, the prognosis of HF remains poor. HF is well-accepted as a myriad of subcellular dys-synchrony related to detrimental structural and functional remodelling of cardiac components, including cardiomyocytes, fibroblasts, endothelial cells and macrophages. Through the covalent chemical process, post-translational modifications (PTMs) can coordinate protein functions, such as re-localizing cellular proteins, marking proteins for degradation, inducing interactions with other proteins and tuning enzyme activities, to participate in the progress of HF. Phosphorylation, acetylation, and ubiquitination predominate in the currently reported PTMs. In addition, advanced HF is commonly accompanied by metabolic remodelling including enhanced glycolysis. Thus, glycosylation induced by disturbed energy supply is also important. In this review, firstly, we addressed the main types of HF. Then, considering that PTMs are associated with subcellular locations, we summarized the leading regulation mechanisms in organelles of distinctive cell types of different types of HF, respectively. Subsequently, we outlined the aforementioned four PTMs of key proteins and signaling sites in HF. Finally, we discussed the perspectives of PTMs for potential therapeutic targets in HF., Competing Interests: Declaration of Competing Interest Nothing to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To investugate the unique electrocardiogram (ECG) characteristics of fulminant myocarditis (FM) patients and provide important clues for the diagnosis of FM. Methods: This was a retrospective study. Patients diagnosed with acute myocarditis at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from February 2017 to April 2022 were enrolled and divided into fulminant myocarditis group (FM) and non-fulminant myocarditis group (NFM) according to clinical diagnosis. A total of 246 healthy people who underwent physical examination in the Health examination Center of Tongji Hospital at the same period were selected as the control group. The clinical data and ECG characteristics of the above 3 groups were analyzed and compared. Logistic regression model was used to analyze the influence of ECG parameters on left ventricular ejection fraction in FM patients. Receiver operating curves were constructed to evaluate the predictive value of different ECG parameters for FM. Results: A total of 180 patients were included in this study (FM group: n =123; NFM group: n =57), with an age of (35.0±16.2) years and 106 males (58.89%). Compared with NFM group, ECG was significantly abnormal in FM group, with a higher incidence of sinus tachycardia, ventricular tachycardia or ventricular fibrillation, escape rhythm, right bundle branch block, third degree atrioventricular block, ST-segment elevation, low voltage, prolonged QTc interval, and widened QRS wave in the FM group (all P <0.05). The ECG parameters showed that the amplitude of the full lead QRS wave in FM group was lower than that in NFM group ( P <0.01). The average heart rate and QTc interval of FM group were significantly higher than those of NFM and control groups (all P <0.05). Although ST-segment elevation had a higher incidence in the FM group, ECG parameters showed that except for leads Ⅲ and aVF, the ST segment levels in all leads in the FM group were lower than those in the control group (all P <0.05). There was a statistically significant difference in some ST segment changes between FM and NFM groups, while there was no statistical difference between the NFM and control groups. Multivariate regression analysis showed that widened QRS wave and increased heart rate were the influencing factors for left ventricular systolic dysfunction in FM patients ( OR =16.914, 95% CI : 1.367-209.224, P =0.028; OR =1.026, 95% CI : 1.010-1.042, P =0.001). Receiver operating curve analysis showed that heart rate>86.90 beat/min, QTc>431.50 ms, and RV5+SV1<1.72 mV had certain predictive value for FM diagnosis. Conclusions: FM patients displayed marked and severe ECG abnormalities, and characteristic changes in ECG can provide important first clues for the diagnosis of FM.

Objective: Emerging evidence highlights the pivotal roles of long non-coding RNAs (lncRNAs) in lipid metabolism. Apoprotein C3 (ApoC3) is a well-established therapeutic target for hypertriglyceridemia and exhibits a strong association with cardiovascular disease. However, the exact mechanisms via which the lncRNAs control ApoC3 expression remain unclear., Methods: We identified a novel long noncoding RNA (lncRNA), GM47544, within the ApoA1/C3/A4/A5 gene cluster. Subsequently, the effect of GM47544 on intracellular triglyceride metabolism was analyzed. The diet-induced mouse models of hyperlipidemia and atherosclerosis were established to explore the effect of GM47544 on dyslipidemia and plaque formation in vivo. The molecular mechanism was explored through RNA sequencing, immunoprecipitation, RNA pull-down assay, and RNA immunoprecipitation., Results: GM47544 was overexpressed under high-fat stimulation. GM47544 effectively improved hepatic steatosis, reduced blood lipid levels, and alleviated atherosclerosis in vitro and in vivo. Mechanistically, GM47544 directly bound to ApoC3 and facilitated the ubiquitination at lysine 79 in ApoC3, thereby facilitating ApoC3 degradation via the ubiquitin-proteasome pathway. Moreover, we identified AP006216.5 as the human GM47544 transcript, which fulfills a comparable function in human hepatocytes., Conclusions: The identification of GM47544 as a lncRNA modulator of ApoC3 reveals a novel mechanism of post-translational modification, with significant clinical implications for the treatment of hypertriglyceridemia and atherosclerosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Discovering and engineering herbicide-resistant genes is a crucial challenge in crop breeding. This study focuses on the 4-hydroxyphenylpyruvate dioxygenase Inhibitor Sensitive 1-Like (HSL) protein, prevalent in higher plants and exhibiting weak catalytic activity against many β-triketone herbicides (β-THs). The crystal structures of maize HSL1A complexed with β-THs were elucidated, identifying four essential herbicide-binding residues and explaining the weak activity of HSL1A against the herbicides. Utilizing an artificial evolution approach, we developed a series of rice HSL1 mutants targeting the four residues. Then, these mutants were systematically evaluated, identifying the M10 variant as the most effective in modifying β-THs. The initial active conformation of substrate binding in HSL1 was also revealed from these mutants. Furthermore, overexpression of M10 in rice significantly enhanced resistance to β-THs, resulting in a notable 32-fold increase in resistance to methyl-benquitrione. In conclusion, the artificially evolved M10 gene shows great potential for the development of herbicide-resistant crops., Competing Interests: Competing interests statement:The authors declare no competing interest.

Cardiovascular diseases (CVDs) continue to pose a significant burden on global health, prominently contributing to morbidity and mortality rates worldwide. Recent years have witnessed an increasing recognition of the intricate involvement of neutrophil extracellular traps (NETs) in the pathology of diverse cardiovascular conditions. This review provides a comprehensive analysis of the multifaceted functions of NETs in cardiovascular diseases, shedding light on the impact on atherosclerosis, myocardial infarction, heart failure, myocarditis, atrial fibrillation, aortic stenosis, and the potential therapeutic avenues targeting NETs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Succinate dehydrogenase (SDH) has been considered an ideal target for discovering fungicides. To develop novel SDH inhibitors, in this work, 31 novel benzothiazol-2-ylthiophenylpyrazole-4-carboxamides were designed and synthesized using active fragment exchange and a link approach as promising SDH inhibitors. The findings from the tests on antifungal activity indicated that most of the synthesized compounds displayed remarkable inhibition against the fungi tested. Compound Ig N -(2-(((5-chlorobenzo[ d ]thiazol-2-yl)thio)methyl)phenyl)-3-(difluoromethyl)-1-methyl-1 H -yrazole-4-carboxamide, with EC 50 values against four kinds of fungi tested below 10 μg/mL and against Cercospora arachidicola even below 2 μg/mL, showed superior antifungal activity than that of commercial fungicide thifluzamide, and specifically compounds Ig and Im were found to show preventative potency of 90.6% and 81.3% against Rhizoctonia solani Kühn , respectively, similar to the positive fungicide thifluzamide. The molecular simulation studies suggested that hydrophobic interactions were the main driving forces between ligands and SDH. Encouragingly, we found that compound Ig can effectively promote the wheat seedlings and the growth of Arabidopsis thaliana . Our further studies indicated that compound Ig could stimulate nitrate reductase activity in planta and increase the biomass of plants.

Solid-state electrochemical energy systems have attracted numerous attentions for their excellent performance, high safety, and low cost. Recently, ice of aqueous electrolytes is reported as a new kind solid-state electrolyte for low-temperature solid-state devices. However, the lack of kinetically favorable electrodes hampers the performance of this new class of icy electrolyte-based solid-state devices at sub-zero temperatures. In this work, a hydrated layered polyaniline cathode active material (h-LPANi) with nanoconfined supercooled water by metatungstate clusters is utilized to improve the performance of sub-zero solid-state zinc ion hybrid capacitors (ZIHCs). The interlayer confined hydrated network of h-LPANi improves kinetics, surpassing pristine polyaniline and conventional porous carbon-based active materials. At -15 °C, the solid-state iced ZIHCs with h-LPANi cathode demonstrate an areal energy density of 580.0 µWh cm -2 at 1.1 mW cm -2 and 155.7 µWh cm -2 at 43.3 mW cm -2 , surpassing other low-temperature solid-state ZIHCs with conventional cathodes., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Objective: Tangbi capsule (TBC) is a traditional Chinese medicine prescription, which has the potential to improve the vascular insufficiency of lower extremities and limb numbness in diabetes. However, the potential mechanism remains unknown. This study aims to investigate the pharmacological effects and mechanism of TBC on rats with diabetic lower extremities arterial disease (LEAD)., Methods: The mechanism of TBC on diabetic LEAD was investigated through metabolomics and transcriptomics analysis, and the main components of TBC were determined by mass spectrometry. The efficacy and mechanism of TBC on diabetic LEAD rats were investigated through in vitro experiments, histopathology, blood flow monitoring, western blot, and real-time polymerase chain reaction., Results: Mass spectrometry analysis identified 31 active chemical components in TBC including (2R)-2,3-Dihydroxypropanoic acid, catechin, citric acid, miquelianin, carminic acid, salicylic acid, formononetin, etc. In vitro analysis showed that TBC could reduce endothelial cell apoptosis and promote angiogenesis. Histopathological analysis showed that TBC led to an obvious improvement in diabetic LEAD as it improved fibrous tissue proliferation and reduced arterial wall thickening. In addition, TBC could significantly increase the expression levels of HIF-1α, eNOS, and VEGFA proteins and genes while reducing that of calpain-1 and TGF-β, suggesting that TBC can repair vascular injury. Compared with the model group, there were 47 differentially expressed genes in the whole blood of TBC groups, with 25 genes upregulated and 22 downregulated. Eighty-seven altered metabolites were identified from the serum samples. Combining the changes in differentially expressed genes and metabolites, we found that TBC could regulate arginine biosynthesis, phenylalanine metabolism, pyrimidine metabolism, arachidonic acid metabolism, pyrimidine metabolism, arachidonic acid metabolism, nucleotide metabolism, vitamin B6 metabolism and other metabolic pathways related to angiogenesis, immune-inflammatory response, and cell growth to improve diabetic LEAD., Conclusion: TBC improved vascular endothelial injury, apoptosis, lipid accumulation, liver and kidney function, and restored blood flow in the lower extremities of diabetic LEAD rats. The mechanism of TBC in the treatment of diabetic LEAD may be related to the modulation of inflammatory immunity, lipid metabolism, and amino acid metabolism. This study presented preliminary evidence to guide the use of TBC as a therapy option for diabetic LEAD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Luo, Wang, Yao, Hu, Zhao, Wen, Zhang, Wu, Fan and Song.)