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Xiang Li,1,2 Jun Zhang,3 Zhongxue Fu1 1Department of General Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of General Surgery, Chongqing University FuLing Hospital, Chongqing, People’s Republic of China; 3Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Zhongxue Fu, Department of General Surgery, The Third Affiliated Hospital of Chongqing Medical University, No. 1 Shuanghu Branch Road, Huixing Street, Yubei District, Chongqing, People’s Republic of China, Email fzx19990521@126.comPurpose: This study aims to investigate the correlation between a novel integrated inflammatory marker: The inflammation-combined prognostic index (ICPI), combining NLR, PLR, and MLR, with the clinicopathological characteristics and overall survival (OS) of gastric cancer (GC).Patients and Methods: Data from 876 patients with GC were retrospectively analyzed from January 1, 2017, to April 30, 2023. PSM was employed to mitigate confounding factors between groups. Receiver operating characteristic (ROC) curves were utilized to determine the optimal cutoff value. Univariate, LASSO, and multivariate regression analyses were executed. Subsequently, a nomogram for predicting OS was developed and validated.Results: The cohort with a poor prognosis exhibited significantly elevated levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and ICPI (P< 0.001). Similarly, higher levels of NLR, PLR, MLR, and ICPI were associated with a poorer prognosis (P< 0.001). Following regression analysis, ICPI, T-stage, lymph node ratio (LNR), and primary site were identified as independent risk factors affecting OS. A nomogram was constructed based on these factors to predict 1-, 3-, and 5-year OS, yielding C-indexes of 0.8 and 0.743 for the training and validation sets, respectively. The calibration curves demonstrated close alignment between predicted and actual results, indicating high predictive accuracy. Moreover, the decision curve underscored the practical utility of the model.Conclusion: The new inflammatory parameter ICPI integrates NLR, PLR and MLR. The ICPI-based nomogram and web calculator accurately predict OS in patients with GC.Keywords: gastric cancer, ICPI, PSM, nomogram, OS

Xinyao Shui,1,&ast; Jingsong Chen,2– 4,&ast; Ziyue Fu,1 Haoyue Zhu,1 Hualin Tao,2– 4 Zhaoyinqian Li2– 4 1Clinical Medical College, Southwest Medical University, Luzhou, People’s Republic of China; 2Department of Laboratory Medicine, the Affiliated Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 3Sichuan Province Engineering Technology Research Center of Molecular Diagnosis of Clinical Diseases, Luzhou, People’s Republic of China; 4Molecular Diagnosis of Clinical Diseases Key Laboratory of Luzhou, Luzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhaoyinqian Li, Department of Laboratory Medicine, the Affiliated Hospital of Southwest Medical University, No. 25, Taiping Street, Jiangyang District, Luzhou, Sichuan, 646000, People’s Republic of China, Email lizhaoyinqian@swmu.edu.cnAbstract: Ischemic stroke is the most common type of stroke, which is the main cause of death and disability on a global scale. As the primary immune cells in the brain that are crucial for preserving homeostasis of the central nervous system microenvironment, microglia have been found to exhibit dual or even multiple effects at different stages of ischemic stroke. The anti-inflammatory polarization of microglia and release of neurotrophic factors may provide benefits by promoting neurological recovery at the lesion in the early phase after ischemic stroke. However, the pro-inflammatory polarization of microglia and secretion of inflammatory factors in the later phase of injury may exacerbate the ischemic lesion, suggesting the therapeutic potential of modulating the balance of microglial polarization to predispose them to anti-inflammatory transformation in ischemic stroke. Microglia-mediated signaling crosstalk with other cells may also be key to improving functional outcomes following ischemic stroke. Thus, this review provides an overview of microglial functions and responses under physiological and ischemic stroke conditions, including microglial activation, polarization, and interactions with other cells. We focus on approaches that promote anti-inflammatory polarization of microglia, inhibit microglial activation, and enhance beneficial cell-to-cell interactions. These targets may hold promise for the creation of innovative therapeutic strategies.Keywords: microglia, ischemic stroke, phagocytosis, polarization, crosstalk, anti-inflammatory, therapeutic targets

Nan Jiang,1,&ast; Wei Jin,2,&ast; Zhenghui Fu,3,&ast; He Cao,1 Hong Zheng,3 Quqing Wang,1 Qiongting Zhang,3 Kang Ju,3 Jiwei Wang1 1Key Laboratory of Health Technology Assessment of Ministry of Health, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 2Department of Patriotic Public Health and Health Promotion instruction, Shanghai Municipal Center for Health Promotion, Shanghai, People’s Republic of China; 3Shanghai Changning Mental Health Center (Affiliated to East China Normal University), Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiwei Wang, Key Laboratory of Health Technology Assessment of Ministry of Health, School of Public Health, Fudan University, Shanghai, People’s Republic of China, Email jiweiwang@fudan.edu.cn Kang Ju, Shanghai Changning Mental Health Center (Affiliated to East China Normal University), Shanghai, People’s Republic of China, Email jukang2009@163.comPurpose: This study aims to explore the serial mediating effect of stigma and depression on the association between social support and medication adherence.Patients and Methods: A cross-sectional survey was undertaken in the Changning District of Shanghai using a five-part questionnaire from August to December 2023. A convenient sampling method was employed, and 35 patients with schizophrenia were invited from each of the 9 streets in Changning District to participate in the survey, resulting in a total of 305 valid questionnaires collected. The questionnaire measured social support, stigma, depression, medication adherence, and demographic characteristics. Data analysis involved descriptive statistics, independent samples t-tests, ANOVA, Pearson correlation analysis, and the bootstrap method.Results: There was a direct and significantly positive association between social support and medication adherence (β = 0.69, p < 0.001). Moreover, increased levels of stigma (β = - 0.45, p = 0.013) and depression (β = - 0.09, p = 0.017) were both associated with a decline in medication adherence. Bootstrapping analysis revealed that the association between social support and medication adherence operated indirectly through stigma (β = 0.11, 95% CI: 0.03, 0.18). Additionally, social support was indirectly associated with medication adherence through depression (β = 0.15, 95% CI: 0.04, 0.30). Further analysis indicated that social support had an indirect association with medication adherence through both stigma and depression (β = 0.04, 95% CI: 0.01, 0.07).Conclusion: Stigma and depression serially mediate the association between social support and medication adherence among patients with schizophrenia. This serial multiple mediation model underscores the importance of integrating social support interventions with psychological interventions aimed at reducing stigma and depression, thereby effectively enhancing medication adherence in patients with schizophrenia.Keywords: social support, stigma, depression, medication adherence, schizophrenia

Zhen-Zhen Wang,1– 3,&ast; Hang Li,4,&ast; Anish R Maskey,2,&ast; Kamal Srivastava,2,5,&ast; Changda Liu,6,&ast; Nan Yang,2,5 Taoyun Xie,7 Ziyi Fu,8 Junxiong Li,9 Xiaohong Liu,10 Hugh A Sampson,6 Xiu-Min Li2,11 1Academy of Chinese Medical Science, Henan University of Chinese Medicine, Zhengzhou, Henan, People’s Republic of China; 2Department of Pathology, Microbiology & Immunology, New York Medical College, Valhalla, NY, USA; 3Collaborative Innovation Center of Research and Development on the Whole Industry Chain of Yu-Yao, Zhengzhou, Henan, People’s Republic of China; 4Central Lab, Shenzhen Bao’an Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, People’s Republic of China; 5General Nutraceutical Technology, Elmsford, NY, USA; 6Department of Pediatrics, Division of Allergy and Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; 7The Affiliated TCM Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People’s Republic of China; 8The First Clinical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 9Guangdong Province Hospital of Integrated Chinese and Western Medicine, Foshan, Guangdong, People’s Republic of China; 10Department of Respiratory Medicine, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 11Department of Otolaryngology, Westchester Medical Center New York Medical College, Valhalla, NY, USA&ast;These authors contributed equally to this workCorrespondence: Xiu-Min Li, Tel +1 914-594-4197, Email XiuMin_Li@NYMC.eduIntroduction: Neutrophil predominant airway inflammation is associated with severe and steroid-resistant asthma clusters. Previously, we reported efficacy of ASHMI, a three-herb TCM asthma formula in a steroid-resistant neutrophil-dominant murine asthma model and further identified Ganoderic Acid C1 (GAC1) as a key ASHMI active compound in vitro. The objective of this study is to investigate GAC1 effect on neutrophil-dominant, steroid-resistant asthma in a murine model.Methods: In this study, Balb/c mice were systematically sensitized with ragweed (RW) and alum and intranasally challenged with ragweed. Unsensitized/PBS challenged mice served as normal controls. Post sensitization, mice were given 4 weeks of oral treatment with GAC1 or acute dexamethasone (Dex) treatment at 48 hours prior to challenge. Pulmonary cytokines were measured by ELISA, and lung sections were processed for histology by H&E staining. Furthermore, GAC1 effect on MUC5AC expression and on reactive oxygen species (ROS) production in human lung epithelial cell line (NCI-H292) was determined by qRT-PCR and ROS assay kit, respectively. Computational analysis was applied to select potential targets of GAC1 in steroid-resistant neutrophil-dominant asthma. Molecular docking was performed to predict binding modes between GAC1 and Dex with TNF-α.Results: The result of the study showed that chronic GAC1 treatment, significantly reduced pulmonary inflammation (P < 0.01– 0.001 vs Sham) and airway neutrophilia (P < 0.01 vs Sham), inhibited TNF-α, IL-4 and IL-5 levels (P < 0.05– 0.001 vs Sham). Acute Dex treatment reduced eosinophilic inflammation and IL-4, IL-5 levels, but had no effect on neutrophilia and TNF-α production. GAC1 treated H292 cells showed decreased MUC5AC gene expression and production of ROS (P < 0.001 vs stimulated/untreated cells). Molecular docking results showed binding energy of complex GAC1-TNF was − 10.8 kcal/mol.Discussion: GAC1 may be a promising anti-asthma botanical drug for treatment of steroid-resistant asthma.Keywords: asthma, mouse model, neutrophilic inflammation, Ganoderma, ganoderic acid

Qingsong Liu,1,2,&ast; Lunyu Li,2,&ast; Dan Zheng,1 Songlin Jin,2 Xiaotian Guan,2 Zeting Fu,2 Zhigang Xiong,1 Haili Ding3 1Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2School of Sports Medicine and Health, Chengdu Sport University, Chengdu, People’s Republic of China; 3Insititute of Sports Medicine and Health, Chengdu Sport University, Chengdu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haili Ding, No. 2, Gymnasium Road, Chengdu, Sichuan, People’s Republic of China, Tel +86 13688467479, Email dingdingtang111@163.comPurpose: This study examined the underlying mechanisms of SJD’s anti-inflammatory and analgesic effects on acute GA flares.Methods: This study used pharmacology network and molecular docking methods. The active ingredients of ShuiJingDan (SJD) were obtained from the Traditional Chinese Medicine Systems Pharmacology Analysis Platform (TCMSP), and the relevant targets of GA were obtained from the Online Mendelian Inheritance in Man (OMIM) database and Therapeutic Target Database (TTD). The core drug group–target–disease Venn diagram was formed by crossing the active ingredients of SJD and the relevant targets. Gene Ontology (GO) analysis was conducted for functional annotation, DAVID was used for Kyoto Encyclopedia of Genes, and Genomes pathway enrichment analysis, and R was used to find the core targets. The accuracy of SJD network pharmacology analysis in GA treatment was verified by molecular docking simulations. Finally, a rat GA model was used to further verify the anti-inflammatory mechanism of SJD in the treatment of GA.Results: SJD mainly acted on target genes including IL1B, PTGS2, CXCL8, EGF, and JUN, as well as signal pathways including NF-κB, Toll-like receptor (TLR), IL-17, and MAPK. The rat experiments showed that SJD could significantly relieve ankle swelling, reduce the local skin temperature, and increased the paw withdrawal threshold. SJD could also reduce synovial inflammation, reduced the concentrations of interleukin-1β (IL-1β), IL-8, and COX-2 in the synovial fluid, and suppressed the expression of IL1B, CXCL8, and PTGS2 mRNA in the synovial tissue.Conclusion: SJD has a good anti-inflammatory effect to treat GA attacks, by acting on target genes such as IL-1β, PTGS2, and CXCL8.Keywords: ShuiJingDan, gouty arthritis, network pharmacology, molecular docking, IL-1β, COX-2

Yicheng Guo,1 Huiqun Gan,1 Shigui Xu,1 Guosheng Zeng,2 Lili Xiao,2 Zhijun Ding,2 Jie Zhu,3 Xinglong Xiong,3 Zhiyuan Fu1 1Department of Pharmacy, Dermatology Hospital of Jiangxi Province, Nanchang, People’s Republic of China; 2Jiangxi Provincial Clinical Research Center for Skin Diseases, Nanchang, People’s Republic of China; 3Candidate Branch of National Clinical Research Center for Skin Diseases, Nanchang, People’s Republic of ChinaCorrespondence: Zhiyuan Fu, Department of Pharmacy, Dermatology Hospital of Jiangxi Province, 388, Yinbing Road, Nanchang, Jiangxi, People’s Republic of China, Tel +86 13970827820, Email fuzhiyuan0774@yeah.netPurpose: This study aims to confirm the efficacy of Xijiao Dihuang decoction (XJDHT), a classic prescription, in treating psoriasis and to explore the potential therapeutic mechanism.Methods: For pharmacodynamic analysis, a mouse model of imiquimod cream (IMQ)-induced psoriasis was constructed. Active ingredients and genes of XJDHT, as well as psoriasis-related targets, were obtained from public databases. Intersecting genes (IGEs) of XJDHT and psoriasis were collected by Venn Diagram. A protein–protein interaction (PPI) network of IGEs is constructed through the STRING database. The Molecular Complex Detection (MCODE) and Cytohubba plug-ins of Cytoscape software were used to identified hub genes. In addition, we conducted enrichment analysis of IGEs using the R package clusterProfiler. Hub genes were validated via external GEO databases. The influence of XJDHT on Hub gene expression was examined by qPCR and ELISA, and molecular docking was used to evaluate the binding efficacy between active ingredients and hub genes.Results: The results revealed that XJDHT possesses 92 potential genes for psoriasis, and 8 Hub genes were screened. Enrichment analysis suggested that XJDHT ameliorate psoriasis through multiple pathways, including AGE-RAGE, HIF-1, IL-17 and TNF signaling pathway. Validation data confirmed the differential expression of IL6, VEGFA, TNF, MMP9, STAT3, and TLR4. Molecular docking revealed a strong affinity between active ingredients and Hub genes. The efficacy of XJDHT in improving psoriatic lesions in model mice was demonstrated by PASI score and HE staining, potentially attributed to the down-regulation of VEGFA, MMP9, STAT3, TNF, and IL-17A, as evidenced by ELISA and qPCR.Conclusion: This study employed network pharmacology and in vitro experiments to identify the potential mechanisms underlying the therapeutic effects of XJDHT on psoriasis, providing a new theoretical basis for its clinical application in the treatment of psoriasis.Keywords: psoriasis, Xijiao Dihuang decoction, network pharmacology, molecular docking, angiogenesis

Bo Liu,1,2 Yan Li,2,3 Jinying Xiang,2,3 Yuehan Li,2,3 Mi Zhou,2,3 Yinying Ren,2,3 Zhou Fu,2,3 Fengxia Ding2,3 1Department of Cardiothoracic Surgery, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Pediatrics, Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Respiratory Medicine, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Fengxia Ding, Department of Respiratory Medicine, Ministry of Education Key Laboratory of Child Development and Disorder, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Children’s Hospital of Chongqing Medical University, No. 136, Zhongshan 2nd Road, Yuzhong Dis, Chongqing, 400014, People’s Republic of China, Tel +86-15178712548, Email 482613@hospital.cqmu.edu.cnObjective: This study aimed to investigate the role of pyroptosis in alveolar macrophages regarding the immune microenvironment of acute respiratory distress syndrome (ARDS) and its prognosis.Methods: ARDS Microarray data were downloaded from Gene Expression Omnibus (GEO). Support vector machine (SVM) and random forest (RF) models were applied to identify hub pyroptosis-related genes (PRGs) with prognostic significance in ARDS. RT-PCR was used to detect the relative expression of PRGs mRNA in alveolar macrophages of ARDS mice. Consensus clustering analysis was conducted based on the expression of the PRGs to identify pyroptosis modification patterns. Bioinformatic algorithms were used to study the immune traits and biological functions of the pyroptosis patterns. Finally, protein-protein interaction (PPI) networks were established to identify hub regulatory proteins with implications for the pyroptosis patterns.Results: In our study, a total of 12 PRGs with differential expression were obtained. Four hub PRGs, including GPX4, IL6, IL18 and NLRP3, were identified and proven to be predictive of ventilator-free days (VFDS) in ARDS patients. The AUC values of the 4 PRGs were 0.911 (GPX4), 0.879 (IL18), 0.851 (IL6) and 0.841 (NLRP3), respectively. In ARDS mice, GPX4 mRNA decreased significantly, while IL6, IL18, and NLRP3 mRNA increased. Functional analysis revealed that IL6 had the strongest positive correlation with the CCR pathway, while GPX4 exhibited the strongest negative correlation with the T co-inhibition pathway. Based on the expression of the 4 PRGs, three pyroptosis modification patterns representing different immune states were obtained, and pattern C might represent immune storm.Conclusion: The results showed that pyroptosis plays an important regulatory role in the immune microenvironment of ARDS. This finding provides new insights into the pathogenesis, diagnosis, and treatment of ARDS.Keywords: ARDS, macrophage, pyroptosis, immune, prognosis

Chenrui Zhang,1 Jinping Li,2 Rong Lu,2 Song Wang,2 Zheng Fu,2 Zhi Yao1 1Department of Immunology, Key Laboratory of Immune Microenvironment and Disease of the Educational Ministry of China, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, People’s Republic of China; 2Kangzhe Pharmaceutical Technology Development Company, Ltd., Tianjin, People’s Republic of ChinaCorrespondence: Zhi Yao, Tianjin Medical University, Tianjin, 300070, People’s Republic of China, Tel/Fax +8622-83336817, Email yaozhi@tmu.edu.cn Zheng Fu, Kangzhe Pharmaceutical Technology Development Company, Tianjin, 300110, People’s Republic of China, Tel/Fax +86 13821232027, Email fuzhengcn@vip.sina.comBackground: The number of incidences of antimicrobial resistance is rising continually, necessitating new and effective antibacterial drugs. The present study aimed to assess the in vitro and in vivo activity of XF-73 against antibiotic-resistant Staphylococcus aureus (S. aureus) isolates and to investigate the potential mechanism of action of XF-73.Methods: The in vitro antibacterial activity of XF-73 and comparator antibacterial drugs, (mupirocin, fusidine, retapamulin, vancomycin, erythromycin, linezolid and daptomycin), against S. aureus (both antibiotic sensitive and resistant strains) was assessed using a broth microdilution method. Two different superficial Staphylococcal skin infection murine models were established to study the in vivo efficacy of XF-73 against antibiotic-resistant strains. The effect of XF-73 on the ultrastructure and cellular morphology of S. aureus was studied using transmission electron microscopy (TEM) and scanning electron microscopy (SEM).Results: The MICs (minimum inhibitory concentration) determined by the broth microdilution method for XF-73 demonstrated that the compound had a high potency against S. aureus isolates with varying susceptibility to the study drugs. Also, the antibacterial activity of XF-73 was superior or similar to most of the tested antibacterial drugs. We also found that the XF-73 dermal formulation significantly inhibited S. aureus survival in both the murine skin tape-stripping and suture superficial skin infection models, maintained a consistently high inhibitory capacity against the antibiotic-resistant strains tested and was significantly more effective than mupirocin ointment, a commonly used antibiotic for the treatment of skin infections. The morphological studies using TEM suggest that XF-73 had a rapid (2 minute) bacterial cell wall disruption activity, with longer incubation (10 minute) subsequently causing membrane damage. SEM analysis demonstrated that this cell wall and cell membrane disruption did not lead to disintegration of the plasma membrane, and did not cause bacterial cell lysis.Conclusion: Therefore, XF-73 may be an effective drug alternative to combat multi-drug-resistant skin infections in the clinical setting.Keywords: antibiotic resistance, mupirocin-resistant strains, skin infections, bacterial cell membrane, in vivo, S. aureus

Jian Gong,1,2,&ast; Weiwei Wu,3,&ast; Liguo Qiu,1,2 Xi Wang,1,2 Jianwei Bao,1,2 Jinjing Wang,4 Lifang Cheng,1,2 Zhiyuan Fu,1,5 Fengming Hu1,2 1Department of Integrated Traditional Chinese and Western Medicine of Dermatology, Dermatology Hospital of Jiangxi Province, Nanchang, Jiangxi, People’s Republic of China; 2Jiangxi Provincial Clinical Research Center for Skin Diseases, Nanchang, Jiangxi, People’s Republic of China; 3Department of Plastic and Dermatological Surgery, The Fifth People’s Hospital of Hainan Province, Haikou, Hainan, People’s Republic of China; 4Clinical School of Medicine, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, People’s Republic of China; 5Department of Pharmacy, Dermatology Hospital of Jiangxi Province, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiyuan Fu, Department of Pharmacy, Dermatology Hospital of Jiangxi Province, Nanchang, Jiangxi, People’s Republic of China, Tel +86 13970827820, Fax +86-0791-85207512, Email 1074586168@qq.com Fengming Hu, Department of Integrated Traditional Chinese and Western Medicine of Dermatology, Dermatology Hospital of Jiangxi Province, Nanchang, Jiangxi, People’s Republic of China, Tel +86 13970935828, Fax +86-0791-85207512, Email 18970802429@163.comAbstract: Psoriasis is an immune-mediated chronic inflammatory dermatosis influenced by hereditary and environmental factors. Human immunodeficiency virus (HIV) infection affects the immune system and exacerbates psoriatic lesions. We report the case of a 33-year-old male patient diagnosed with psoriasis vulgaris, psoriatic arthritis and HIV infection. Acitretin capsules, etanercept and high-active antiretroviral therapy (HAART) were effective. Two months after etanercept was discontinued, his condition worsened. After switching to secukinumab combined with HAART, the symptoms of psoriatic arthritis resolved rapidly after four weeks, with a Disease Activity Index for Psoriatic Arthritis score of 0. The time to achieve psoriasis area and severity index 40, 75, 90, and 100 were 2, 4, 8, and 29 weeks. The treatment was maintained for 1 year with no adverse reactions. Regarding the stable CD4+ T lymphocyte count and the viral load, administering anti-IL-17 monoclonal antibodies is an effective treatment option for psoriasis patients.Keywords: psoriasis, HIV, etanercept, secukinumab, biologics

Chen Tian,1,&ast; XiaoLei Xue,2,&ast; Ye Chen,3,&ast; Ruiyuan Liu,4 Yutong Wang,5 Sheng Ye,4 Zeyu Fu,5 Yingrui Luo,5 Shengmiao Wang,5 Xiaofeng He,1 Huajin Pang1 1Division of Vascular and Interventional Radiology, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 2Department Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 3Laboratory of Interventional Radiology, Department of Minimally Invasive Interventional Radiology and Department of Radiology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, 510260, People’s Republic of China; 4Guangdong Provincial Key Laboratory of Medical Image Processing, School of BioMedical Engineering, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 5Cancer Research Institute, Experimental Education/Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaofeng He; Huajin Pang, Tel +86 13760661610, Email ozonetherapy@126.com; nfyyphj@163.comIntroduction: Second near-infrared photothermal therapy (NIR-II PTT) has become a promising strategy for treating cancer in terms of safety and potency. However, the application of NIR-II PTT was limited in the treatment of deep-buried solid tumors due to the low dose of NIR-II absorption nanomaterials and the inadequate laser energy in the deep tumor.Methods: Herein, the authors report the engineering of NIR-II absorbing polyaniline nanorods, termed HPW@PANI Nanorods, for in situ NIR-II PTT based on optical fibers transmission of laser power and transarterial infusion for the treatment of orthotopic hepatocellular carcinoma in the rabbit. HPW@PANI Nanorods were prepared via chemical oxidant polymerization of aniline under phosphotungstic acid, which exhibited effective NIR-II absorption for hyperthermia ablation cells.Results: HPW@PANI Nanorods were fast and efficiently deposited into primary orthotopic transplantation VX2 tumor in rabbits via transarterial infusion. Furthermore, an optical fiber was interventionally inserted into the primary VX2 tumor to transmit 1064nm laser energy for in situ NIR-II PTT, which could ablate primary tumor, inhibit distant tumor, and suppress peritoneal metastasis.Conclusion: This study provides new insights into the application of in situ NIR-II PTT based on optical fibers transmission of laser power and transarterial injection of NIR-II absorption nanomaterials to treat deep-buried tumors.Graphical Abstract: Keywords: NIR-II absorption nanomaterials, orthotopic animal model, transarterial infusion, optical fiber transmission of laser power, deep-buried tumors

Qi Zhou, Kezhu Hou, Zhiqiang Fu Department of Thoracic Surgery, Shanghai Shidong Hospital, Shanghai, 200438, People’s Republic of ChinaCorrespondence: Kezhu Hou; Zhiqiang Fu, Department of Thoracic Surgery, Shanghai Shidong Hospital, Yangpu District, Shanghai, 200438, People’s Republic of China, Email phuang718@163.com; fuzhiqiang1311@163.comIntroduction: Mangiferin is a plant antitumor compound with poor water solubility and low bioavailability. In this study, transferrin-modified mangiferin-loaded solid lipid nanoparticles (Tf-modified MGF-SLNs) were prepared to overcome the above defects.Methods: Tf-modified MGF-SLNs were prepared by the emulsification-solvent evaporation method. The physicochemical properties of Tf-MGF-SLNs such as particle size, zeta potential and in vitro drug release were investigated. We also demonstrated the effect of Tf-MGF-SLNs in lung cancer.Results: The mean hydrodynamic diameter of the Tf-MGF-SLNs was 121.8± 2.9 nm with a polydispersity index of 0.134± 0.03. According to TEM micrographs, Tf-MGF-SLNs are spherical and uniform, and the EE% was found to be 72.5± 2.4%. In vitro release, we identified an initial burst effect release, followed by controlled release, in SLNs at both pHs and the Tf-MGF-SLNs drug accumulation release percentages reached over 68% at pH 4.0 and 72% at pH 7.4 in 6 hours, respectively. In vivo studies showed that depending on surface modification, Tf-MGF-SLNs, which suggested that cell internalization was changed and more drugs entered the cells successfully.Discussion: Tf-MGF-SLNs were highly efficient in suppressing the tumor growth in xenograft tumor model. Sustained release of the drug delivery system and Tf-modified MGF-SLNs played a major role. Tf-MGF-SLNs would be a promising formulation for the treatment of lung cancer.Keywords: transferrin, mangiferin, SLNs, A549 lung cancer cell

ScN in the rock salt structure is a well-investigated material due to its desirable properties like the high hardness or large thermal conductivity. Recent computations by Adamski et al. [Appl. Phys. Lett. 115, 232103 (2019)] showed that ScN/GaN heterostructures exhibit an outstanding polarization gradient which would be beneficial for polarization induced electron gases. The pseudobinary semiconductor Sc x Al 1 − x N, when maintaining the cubic rock salt structure, could be beneficial for tailoring the polarization gradient using the Sc dependency of material properties. The structural properties of rs-Sc x Al 1 − x N are not fully discovered yet, thus in this work, DC-magnetron sputtered cubic rock salt Sc x Al 1 − x N thin films with 0.55 < x < 1.00 were grown and analyzed on ScN(111)/Si(111). The epitaxial relation of ScN(111) thin films on the Si(111) substrate is determined to be ScN[110] ∥ Si[100]. Furthermore, concentration dependent properties like the lattice parameter of Sc x Al 1 − x N were measured [a(ScN) = 4.50 Å, a(Sc0.55Al0.45N) = 4.30 Å] and the stress σ within the layers was determined. The crystal quality was evaluated using ω -scans, revealing FWHM = 1.14 ° for Sc0.95Al0.05N. The diameters of the columns were determined by atomic force microscopy and scanning electron microscopy and they are range from 34 to 59 nm for 0.55 < x < 1.00. At x = 0.55 , Sc x Al 1 − x N columns in the hexagonal wurtzite as well as cubic rock salt structure were detected. This information about the structural specifications of Sc x Al 1 − x N in the rock salt structure forms the basis for further investigations and experimental confirmation of the electric properties of ScN/GaN heterostructures or even a Sc x Al 1 − x N/GaN based approach for improved structures for high-electron-mobility transistors. [ABSTRACT FROM AUTHOR]

Bingwei Hu,1,2 Liang Li,2 Hongwei Wang,2 Tingting Ma,2 Zhimei Fu,2 Xianhui Kang,3 Zhiying Feng1 1Department of Pain, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Anesthesiology, Tongde Hospital of Zhejiang Province, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Anesthesiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Zhiying Feng; Xianhui KangThe First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou, 310003, Zhejiang, People’s Republic of China, Email fzy1972@zju.edu.cn; kxhui66@zju.edu.cnPurpose: Epidural anesthesia (EA) is the main anesthesia method for transforaminal percutaneous endoscopic lumbar discectomy (PELD). Reducing the concentration of ropivacaine can help preserve tactile sensation, allowing patients to provide timely feedback to the surgeons when a nerve root is contacted to avoid nerve injury. Therefore, a 90% effective concentration (EC90) that allows for mild pain [visual analog scale (VAS) score ≤ 3] while maximizing tactile sensation must be identified.Methods: The concentration of ropivacaine for EA was varied for consecutive patients in this study using a two-stage biased-coin design (BCD) according to the response of the previous patient; the concentration used for the first patient was 0.2%. When the previous patient had a negative response (VAS score > 3), the concentration used for the next one was increased by 0.015%. When the previous patient had a positive response (VAS score ≤ 3), the concentration used for the next one had an 89% probability of remaining the same and an 11% probability of being reduced by 0.015%. The EC90 of ropivacaine was estimated using isotonic regression, and the 95% confidence interval (CI) was estimated using the bootstrapping method in R.Results: A total of 58 patients were included in the study. The calculated EC90 was 0.294% [95% CI (0.271%, 0.303%)]. Among 13 patients who reported unintended nerve root contact during the operation, none were found to have irreversible nerve injury after the operation.Conclusion: To preserve maximum tactile sensation, the EC90 of ropivacaine was 0.294% for patients with allowed mild pain. This concentration could allow for timely feedback when the nerve root is contacted, to avoid nerve injury.Keywords: minimum effective concentration, epidural anesthesia, ropivacaine, transforaminal percutaneous endoscopic lumbar discectomy, biased-coin design, isotonic regression

Wen Hu,1,2,&ast; Panpan Yang,3,&ast; Zhenzhen Fu,1 Yongqing Wang,4 Ying Zhou,1 Zhengqin Ye,1 Yingyun Gong,1 Aijie Huang,1 Luning Sun,4 Yang Zhao,5 Tao Yang,1 Zhong Li,6,7 Xian-Cheng Jiang,8 Weinan Yu,2 Hongwen Zhou1,6 1Department of Endocrinology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Endocrinology and Metabolism, The Affiliated Huai’an Hospital of Xuzhou Medical College, Huai’an, Jiangsu, People’s Republic of China; 3Department of Respiratory Diseases, The Affiliated Huai’an Hospital of Xuzhou Medical College, Huai’an, Jiangsu, People’s Republic of China; 4Research Division of Clinical Pharmacology, First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 5School of Public Health Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 6Key Laboratory of Rare Metabolic Diseases, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 7Jiangsu Province Key Laboratory of Human Functional Genomics, Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 8Department of Anatomy and Cell Biology, State University of New York Downstate Medical Center, Brooklyn, NY, USA&ast;These authors contributed equally to this workCorrespondence: Hongwen Zhou, Department of endocrinology, The First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, People’s Republic of China, Tel +862583718836-6893, Fax +862583781781, Email drhongwenzhou@njmu.edu.cn Weinan Yu, Department of Endocrinology and Metabolism, Huai’an Hospital Affiliated to Xuzhou Medical University and Huai’an Second People’s Hospital, Huai’an, 223001, People’s Republic of China, Email hayuweinan@163.comObjective: Branched-chain amino acids (BCAAs) are essential AAs which are widely used as antioxidants in patients with liver and kidney dysfunction. However, BCAAs are strongly correlated with insulin resistance (IR) and diabetes. This study aimed to evaluate the relationship among BCAAs, oxidative stress, and type 2 diabetes mellitus (T2DM) in a Chinese population.Methods: Anthropometric and biochemical examinations were performed in 816 individuals who participated in the Huai’an Diabetes Prevention Program. Serum BCAAs concentrations were measured by hydrophilic interaction chromatography-tandem mass spectrometric method. Oxidative stress was evaluated by malondialdehyde (MDA) as an index of lipid peroxidation and the superoxide dismutase (SOD) activity.Results: A total of 816 participants were divided into three groups: normal glucose metabolism (NGM), prediabetes, and newly-diagnosed diabetes mellitus (NDM). Subjects in NDM group show higher MDA and lower SOD levels than subjects in other groups. L-Val levels positively correlated with MDA levels and negatively with SOD in NDM groups. After adjusting for T2DM risk factors, high L-Val levels were significantly associated with higher BMI, WC, FPG, increased LnTG and decreased HDL-C. L-Val was also independently associated with NDM (OR 1.06, 95% CI 1.02– 1.10; P = 0.005). Furthermore, the odds ratios for NDM among participants with high L-Val (≥ 35.25μg/mL) levels showed a 2.25-fold (95% CI 1.11– 4.57; P = 0.024) increase compared to participants with low L-Val (< 27.26 μg/mL) levels after adjusting for MDA and confounding factors.Conclusion: High serum L-Val levels are independently associated with oxidative stress, thus promoting IR and NDM. Further study should be done to clarify the mechanism.Keywords: branched chain amino acids, oxidative stress, new diagnosed type 2 diabetes mellitus, hydrophilic interaction chromatography-tandem mass spectrometric method

Li He,1,&ast; Zhi Fu,2,&ast; Menglong Wang,2 Xin Wang,1 Lu Wang,1 Guangming Li,2 Dongdong Lin2 1Department of Intensive Care Unit, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China; 2Department of General Surgery Center, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangming Li; Dongdong LinDepartment of General Surgery Center, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of ChinaTel +86 10 83997733; Tel/Fax +86 10 83997733Email gm_drli@163.com; dongdlin01@163.comObjective: To evaluate and explore the effectiveness of the new prevention and control measures for the donor-derived infection (DDI) associated with CRO after liver transplantation.Methods: The data of 120 organ donors and recipients from January 2018 to May 2020 were retrospectively analyzed at The Liver Transplantation Center of Beijing Youan Hospital, Capital Medical University, to investigate the epidemiological status of CRO in donors. The cases were divided into two groups. The implemented group was treated according to the execution of a clustered CRO prevention and control measure based on active screening combined with early initiation of prophylactic/therapeutic administration of antibiotics. The effectiveness of the prevention and control measures was evaluated by comparing the length of postoperative ICU stay, total postoperative length of hospital stay, duration of ventilator use, duration of restricted antibiotics use, the incidence of DDI, incidence and composition distribution of DDI-related CRO, and incidence of severe DDI-relevant adverse events between the two groups.Results: There was a high detection rate of 39.32% (105 strains) of drug-resistant bacteria in the donors. Fifty-six strains of CRO were detected. Participants in group B, which implemented the new prevention and control measures, were transferred out of the ICU sooner (P = 0.023), used fewer restrictive antibiotics (P = 0.003), and were discharged more quickly (P = 0.013) than those in group A. Postoperative DDI incidences (P = 0.113) and severe DDI-related adverse events were not statistically different between the two groups (P = 0.062). CR-Kp-related DDI was less common in group B (P = 0.021).Conclusion: The situation of donor-derived drug-resistant bacterial infections remains critical. The clustered prevention and control measures for CRO based on active screening combined with early initiation of prophylactic/therapeutic application of antibiotics would be beneficial.Keywords: organ donation, liver transplantation, drug-resistant bacteria, epidemiology, carbapenem-resistant Enterobacteriaceae, active screening, novel β-lactamase inhibitors

Xujie Xi,&ast; Zhaoli Fu,&ast; Tianwen Liu,&ast; Yanfeng Lin, Wenbin Wu, Jianmin Li, Ming Luo, Beiping Zhang Department of Spleen and Stomach Diseases, The Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Beiping ZhangDepartment of Spleen and Stomach Diseases, The Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, No. 111 Dade Road, Yuexiu District, Guangzhou, 510120, Guangdong Province, People’s Republic of ChinaTel +86-13602762766Email beipingzhang@21cn.comObjective: The purpose of this study was to establish and verify a risk-scoring system for colorectal adenoma recurrence.Methods: A total of 359 patients with colorectal adenoma who underwent polypectomy from October 2017 to December 2018 were included in this retrospective study. Information including taking traditional Chinese medicine, demographic characteristics, adenoma characteristics were collected. The patients will review the colonoscopy one year after surgery. The patients were divided into a modeling cohort (216 cases) and a model validation cohort (143 cases) according to the ratio of 6:4. Modeling and model verification were performed by logistic regression, ROC curve, nomogram (calibration chart) and other methods.Results: After adjusting for confounding factors by logistic regression, it was found that taking Chinese medicine, the number, size, site, pathological type and morphology of adenoma were independent influencing factors for the recurrence of colorectal adenoma. The area under the ROC curve (AUC) in the model validation cohort of established risk scoring system was 0.771 (95% CI: 0.694– 0.847), indicating that there was good consistency.Conclusion: The established risk prediction model of colorectal adenoma recurrence and its risk scoring system performed well and had high predictive value.Keywords: colorectal adenoma, recurrence, prediction model, risk scoring system

Che X, Lu R, Fu Z, et al. Drug Des Devel Ther. 2018;12:3357–3368. At the authors request, the Editor and Publisher of Drug Design, Development and Therapy wish to retract the published article. The authors became aware of concerns relating to the alleged duplication of images in Figure 7. Specifically, Figure 7B, Medium (100x), appears to have been duplicated with the same image for Figure 7E, YSL 0.4 mg/ml (100x), which has been flipped. While some original data was still available, the authors were unable to retrieve all of it in a satisfactory manner. In addition, some to the key cellular extraction material had not been well preserved. While the authors were still confident in the overall findings described in the article, to maintain the integrity of the scientific publication record, they decided it appropriate to request a retraction rather than pursue a corrigendum. The editor agreed with decision and approved the authors retraction request. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

Po-En Chiu,1,2,&ast; Zhonghua Fu,3,&ast; Guan-Wei Jian,4,5 Ching-Hsuan Huang,2,6 Te-Mao Li,2 Li-Wei Chou7– 9 1Department of Chinese Medicine, Chang Bing Show Chwan Memorial Hospital, Changhua, Taiwan; 2School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan; 3Institute of Fu’s Subcutaneous Needling, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan; 5Department of Chinese Medicine, Sinying Hospital, Ministry of Health and Welfare, Tainan, Taiwan; 6Department of Chinese Traumatology Medicine, China Medical University Hospital, Taichung, Taiwan; 7Department of Physical Medicine and Rehabilitation, China Medical University Hospital, Taichung, Taiwan; 8Department of Physical Therapy and Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan; 9Department of Physical Medicine and Rehabilitation, Asia University Hospital, Asia University, Taichung, Taiwan&ast;These authors contributed equally to this workCorrespondence: Li-Wei ChouDepartment of Physical Medicine and Rehabilitation, China Medical University Hospital, No. 2 Yuh-Der Road, Taichung, 40447, TaiwanTel +886-4-22052121-2381Fax +886-4-22026041Email chouliwe@gmail.comBackground: Knee osteoarthritis (OA) is a common clinical disease. Knee pain is the major symptom of knee OA and the primary reason why patients seek treatment. Fu’s subcutaneous needling (FSN) has been used to treat knee OA for more than 20 years. However, the establishment of treatment methods and rigorous evaluation of FSN’s efficacy are still lacking. A randomized single-blind clinical trial will be conducted to evaluate whether FSN treatment can immediately alleviate pain due to knee OA surrounding the patella and the curative effective of 1-week and 2-week treatments. In addition, the feasibility and initial effect of FSN treatment for patients with knee OA will be discussed.Materials and Methods: Patients with confirmed knee OA, as diagnosed by doctors using X-ray films or from clinical symptoms, who are over 50 years old will be participants recruited. They will be randomly assigned either FSN treatment or transcutaneous electrical nerve stimulation treatment. In addition, their pressure pain threshold, muscle tone of lower leg muscle, and physical ability will be measured. Participants will be asked to complete the questionnaires of Western Ontario and McMaster Universities Osteoarthritis Index and Lequesne’ index as the measurements for quality of life.Results: The findings of this study will reveal whether FSN or transcutaneous electrical nerve stimulation is clinically efficacious for treating pain due to knee OA, with respect to muscle stiffness, gait, dynamic balance, the pressure pain threshold, and quality of life before and after treatment.Study Registration: This study is approved by the Research Ethics Committee of China Medical University & Hospital, Taichung, Taiwan (CMUH107-REC3-027) and registered at the ClinicalTrials.gov Protocol Registration and Results System (registration number NCT04356651).Keywords: dry needling, Fu’s subcutaneous needling, knee osteoarthritis, myofascial trigger point, tightened muscle

This paper was attempted to investigate the microstructure degradation and low cycle fatigue (LCF) performance of a serviced K465 Ni‐based superalloy turbine blade. LCF tests were carried out with small‐scale plate specimens sampled from the blades. Relationship between residual LCF life and microstructure state was estimated. The results indicate that the coarsening of γ/γ′ phases was the most significant microstructure degradation mode for the serviced blades. Both the γ matrix width and the γ′ precipitate diameter increased with the increase of service duration, while the γ′ precipitate volume fraction slightly decreased. The most severe microstructure degradation occurred at the leading edge along the chord direction, particularly at 50–70 % airfoil spans. The residual LCF life exhibited an accelerated decrease characteristic as increases of microstructure degradation degree. The coarsened microstructure diminished shear resistance of the superalloy, which resulted in additional accumulated inelastic deformation and a corresponding reduction in LCF life. Highlights: Service induced microstructure evolution and LCF life decay of a blade were investigated.Coarsening was identified as the main degradation form of γ/γ' phases in serviced blade.Accelerated decrease of residual LCF life was identified as increases of coarsening.Reduced plastic deformation resistance owing to coarsening is crucial to decay LCF life. [ABSTRACT FROM AUTHOR]

The direct impact of structural quality on the ferroelectric properties of hexagonal Al1–xScxN with an Sc-content of x = 0.3 was investigated using dynamic hysteresis measurements, high-resolution x-ray diffraction (HRXRD), and atomic force microscopy. The films investigated were deposited on p-doped (001)-Si substrates by reactive pulsed DC magnetron sputtering under different gas mixtures to vary the structural quality and surface morphology between samples. Misoriented grains were identified as ferroelectrically inactive, as these grains resulted in an underestimation and distortion of the ferroelectric quantities. In fact, a high amount of misoriented volume was found to have a significant effect on the coercive electric field, as this is mainly determined by the crystal strain in the ferroelectric [0001]-oriented regions, independent of its origin. Furthermore, it was concluded that the crystal quality does not have a pronounced effect on the coercive field strength. Conversely, the polarization in the film is mainly determined by the crystal quality, as a difference of 1° in the HRXRD FWHM of the ω-scan resulted in a 60% loss of polarization. The amount of polarization was influenced to a lesser extent by the misoriented grains since the ferroelectric volume of the layers was only slightly overestimated. This reveals that optimizing reproducible and transferable properties, such as crystal quality and surface morphology, is more reasonable, as the film with the lowest misoriented volume and the highest degree of c-axis orientation showed the highest polarization. [ABSTRACT FROM AUTHOR]

Evaluating the ecological risks of metals and identifying their sources is useful for preventing and controlling heavy metal pollution in water bodies. Four sediment cores (S1~-S4) were collected from the Changhu Reservoir of South China to determine lead (Pb) concentrations and geochemical fractions, as well as the isotopic compositions of core S1. The results show that Pb concentrations increased from the upstream site (S1:173.2 mg kg-1) to the downstream site (S4:313.5 mg kg-1), resulting in a moderate to significant enrichment in the sediments. Sediment Pb in the geochemical fractions followed a decreasing order of residual (F4:54.7%) > reducible (F2: 23.1%) > oxidizable (F3: 16.6%) > acid-soluble fraction (F1: 5.8%). The geoaccumulation index (Igeo) and risk assessment code (RAC) showed that sediments were moderately polluted by Pb in S1 and S2 core, while sediments were moderately to heavily polluted in S3 and S4 core. The ecological risk of Pb in all sediment samples is generally at a low risk level, except for the sediments at a depth of 30-40 cm in the S4 core. Significant correlation between Pb concentration and 206Pb/207Pb ratios suggested possible binary mixing of Pb. In the present study, mining activities, which was the major anthropogenic Pb source base on its isotopic composition, contributed significantly (means: 45.3-77.5%) to sediment Pb. The anthropogenic Pb in sediments is most likely to come from Sphalerite and Galena. [ABSTRACT FROM AUTHOR]

Bistable transition is often applied in the design of microstructures in metamaterials. In this study, we introduce a series of strategically placed holes in the tilted struts, and observe, through numerical and experimental analysis, an effect of the perforation on the snap-through buckling behavior of the structure. By infilling the holes with thermal-sensitive polymer bars, we realize actively tuning the local stiffness of the holey struts, thereby enabling a means to switch the metamaterial between bistable and monostable states. Furthermore, we propose a multi-stable metamaterial by stacking bistable units with different arrange of infilled and empty holes. The designed metamaterial demonstrates a progressive restoration from the deformed shape to its original shape as the environment temperature reaches up to certain values. These findings highlight the potential of holey-type bistable metamaterials in the design of actuators, deployable structures, and reusable energy absorbers. [ABSTRACT FROM AUTHOR]

Despite the known benefits of data‐driven approaches, the lack of approaches for identifying functional neuroimaging patterns that capture both individual variations and inter‐subject correspondence limits the clinical utility of rsfMRI and its application to single‐subject analyses. Here, using rsfMRI data from over 100k individuals across private and public datasets, we identify replicable multi‐spatial‐scale canonical intrinsic connectivity network (ICN) templates via the use of multi‐model‐order independent component analysis (ICA). We also study the feasibility of estimating subject‐specific ICNs via spatially constrained ICA. The results show that the subject‐level ICN estimations vary as a function of the ICN itself, the data length, and the spatial resolution. In general, large‐scale ICNs require less data to achieve specific levels of (within‐ and between‐subject) spatial similarity with their templates. Importantly, increasing data length can reduce an ICN's subject‐level specificity, suggesting longer scans may not always be desirable. We also find a positive linear relationship between data length and spatial smoothness (possibly due to averaging over intrinsic dynamics), suggesting studies examining optimized data length should consider spatial smoothness. Finally, consistency in spatial similarity between ICNs estimated using the full data and subsets across different data lengths suggests lower within‐subject spatial similarity in shorter data is not wholly defined by lower reliability in ICN estimates, but may be an indication of meaningful brain dynamics which average out as data length increases. [ABSTRACT FROM AUTHOR]

In this paper, we propose a penalized weighted quantile estimating equations (PWQEEs) method to obtain sparse, robust and efficient estimators for the quantile regression with longitudinal data. The PWQEE incorporates the within correlations in the longitudinal data by Gaussian copulas and can also down-weight the high leverage points in covariates to achieve double-robustness to both the non-normal distributed errors and the contaminated covariates. To overcome the obstacles of discontinuity of the PWQEE and nonconvex optimization, a local distribution smoothing method and the minimization–maximization algorithm are proposed. The asymptotic properties of the proposed method are also proved. Furthermore, finite sample performance of the PWQEE is illustrated by simulation studies and a real-data example. [ABSTRACT FROM AUTHOR]

The state of burning plasma had been achieved in inertial confinement fusion (ICF), which was regarded as a great milestone for high-gain laser fusion energy. In the burning plasma, alpha particles incident on the cryogenic (warm dense) fuels cannot be simply regarded as single particles, and the new physics brought about by the density effects of alpha particles should be considered. In this work, the collective interaction between them has been considered, namely, the effect of the superposition of wake waves. The stopping power of alpha-particle clusters, i.e., the rate of energy loss per unit distance traveled has been calculated using both analytical and simulation approaches. In theory, we obtain the stopping power of alpha clusters in cryogenic (warm dense) fuel by the dielectric function method, which illustrates the importance of the effective interaction between particles. Simulation results using the LAPINS code show that the collective stopping power of the alpha cluster is indeed increased via coherent superposition of excitation fields (the excitation of high-amplitude wake waves). However, the comparison between simulation and theoretical results also illustrates a coherent–decoherent transition of the stopping power of the cluster. The initial conditions with various sizes and densities of the alpha clusters have been considered to verify the condition of decoherence transition. Our work provides a theoretical description of the transport properties of high-density alpha particles in warm dense cryogenic fuel and might give some theoretical guidance for the design of actual fusion processes. [ABSTRACT FROM AUTHOR]

In this paper, the flexible support mould is designed by using magnetorheological elastomer (MRE) to assist in the deep-drawing of magnesium alloys. Based on the magnesium alloy mechanical tensile test and magnetorheological elastomer regular force experiments, the deep-drawing process of AZ31 magnesium alloy supported by support mould was numerically simulated by finite-element analysis software ABAQUS. By varying the current input to the excitation coil to change the magnetic induction intensity and thus adjust the magnetic normal force of the magnetorheological elastomer, then using magnetic normal force to complete the auxiliary sheet metal deep-drawing. The results show that, compared with the unsupported mould, the supported mould can effectively reduce the maximum thinning rate of magnesium alloy on the original basis, thus effectively increasing the ultimate depth of magnesium alloy deep-drawing. It can replace the original buffer device, effectively solution the problem of pulling and cracking at the bottom of magnesium alloy caused by the original excessive damping force, and improve the yield rate of workpiece. [ABSTRACT FROM AUTHOR]

Background Clinical research associates (CRAs) play an important role in pharmaceutical research and development. Despite growing concern about occupational burnout among CRAs in China, little is known about this topic. Aims We evaluated the factors associated with occupational burnout among CRAs in China and assessed the extent and nature of this syndrome in order to develop effective countermeasures. Methods In October 2020, we collected data from a convenience sample of 438 CRAs from 26 major cities across China using a custom-designed questionnaire. We evaluated their psychopathological status and degree of occupational burnout based on the Maslach Burnout Inventory. Factors associated with burnout were identified using the Wilcoxon rank test, Kruskal–Wallis test, Spearman's rank correlation and multivariable ordinal logistic regression. Results Of the 438 CRAs analyzed, 82% showed signs of occupational burnout, with a large proportion experiencing moderate burnout (50%). Burnout in Chinese CRAs manifested as emotional exhaustion (77%), depersonalization (66%) and low sense of accomplishment (15%). The severity of burnout was significantly affected by mode of working (odds ratio [OR] 1.56, 95% confidence interval [CI] 1.04–2.34), average number of working hours per week (OR 1.68, 95% CI 1.14–2.46), support provided by the hospital (OR 3.13, 95% CI 1.40–6.99) and likelihood of receiving a promotion (OR 4.05, 95% CI 1.34–12.22) (all P < 0.05). Conclusions The incidence of occupational burnout among CRAs in China is high. Companies and hospitals must take effective measures to establish support systems for CRAs in order to alleviate this situation and thereby ensure the quality of clinical trials. [ABSTRACT FROM AUTHOR]

To study the effects of mannan oligosaccharides (MOS) on rumen fungal flora of dairy cows, four lactating Chinese Holstein dairy cows were randomly divided into two groups in the two-stage 2 × 2 cross-over design. The experimental group (MT) was fed with a basal ration and MOS were perfused orally 60 g/(d head). The control group (CK) was fed with a basal ration. The rumen fluid was collected through the oral cavity of dairy cows using a negative pressure suction device. 50ml rumen fluid of every cow was collected each time respectively before feeding (0 h) and 2h, 4h and 6h after feeding in a day. The rumen fungi were tested by ITS sequencing technology. The results showed that four phyla were identified in CK group and five in MT group. The dominant phyla in both groups were Ascomycota, Basidiomycota, Neocallimastigomycota, whose abundances were more than 90% of the total rumen fungi. At the level of genus, 74 genera were identified in CK group, while 91 genera in MT group. Several cellulolytic fungi genera showed a decreasing trend or decreased significantly, such as Neocallimastigaceae-NA. The previous experiments that shows the addition of mannan oligosaccharides promoted the proliferation of rumen bacteria, while the growth of rumen fungi was inhibited in this result, which may be due to the antagonism between rumen bacteria and fungi. The growth of cellulose-degrading fungi was inhibited to some extend after the addition of MOS in the diet. Candida and Zopfiella, closely related to mycotic mastitis and immunosuppression respectively, had decreasing trends in rumen with supplemental MOS in the diets of the dairy cows, indicating that MOS might play a positive role in inhibiting harmful fungi. The experimental result shows that mannan oligosaccharides in the diet of dairy cows inhibited the growth of cellulolytic fungi and the proliferation of harmful fungi. In addition, the results showed that there might be the antagonistic effect between rumen fungi and bacteria potentially, which should be focused on for further study. [ABSTRACT FROM AUTHOR]