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Emodin improves alveolar hypercoagulation and inhibits pulmonary inflammation in LPS-provoked ARDS in mice via NF-κB inactivation

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INTERNATIONAL IMMUNOPHARMACOLOGY 2020年 88卷 107020-107020页

作者： Liu, Bo Cheng, Yumei Wu, Yanqi Zheng, Xinghao Li, Xiang Yang, Guixia he, Tianhui Li, shuwen Shen, Feng Guizhou Med Univ Dept Intens Care Unit Affiliated Hosp Guiyang 550001 Peoples R China Guizhou Med Univ Guiyang 550001 Peoples R China

Background: Alveolar hypercoagulation and pulmonary inflammation are important characteristics and they regulate each other in acute respiratory distress syndrome (ARDS). NF-kappa B pathway has been confirmed to be involved in regulation of this crosstalk. Emodin, a traditional Chinese herb, shows potent inhibitory effect on NF-kappa B pathway, but whether it is effective in alveolar hypercoagulation and pulmonary inflammation in ARDS remains to be elucidated. Purpose: The aim of this experiment was to evaluate the efficacy of emodin on LPS-provoked alveolar hypercoagulation and excessive pulmonary inflammation in ARDS, and its potential mechanism. Methods: Mice ARDS was set up through LPS (40 mu l, 4 mg/ml) inhalation. Male mice were randomly received with BPS, LPS only, LPS + emodin (5 mg/kg, 10 mg/kg, 20 mg/kg, respectively) and BAY65-1942, an inhibitor of IKK beta. After 48 h of LPS stimulation, pulmonary pathological injury, expressions of Tissue factor (TF), plasminogen activator inhibitor (PAI)-1, activated protein C (APC), collagen I, collagen III, interleukin (IL) 8, IL-1 beta and tumor necrosis factor (TNF)-alpha in lung tissues, as well as concentrations of antithrombin III (AT III), procollagen peptide type III (PIIIP), soluble thrombomodulin (sTM), thrombin antithrombin complex (TAT), myeloperoxidase (MPO) and the percentage of inflammatory cells in bronchoalveolar lavage fluid (BALF) were all determined. NF-kappa B pathway activation as well as NF-kappa B DNA binding activity in pulmonary tissue were simultaneously checked. Results: LPS stimulation resulted in obvious lung injury, excessive inflammatory cells infiltration, which all were dose-dependently ameliorated by emodin. Expressions of TF, PAI-1, collagen I and collagen III as well as IL-8, IL-1 beta and TNF-alpha in pulmonary tissue were all elevated while APC decreased under LPS provocation, which were all reversed by emodin treatment in dose-dependent manner. LPS promoted the secretions of PII

关键词： Emodin Acute respiratory distress syndrome NF-kappa B pathway Alvolar hypercoagulation and fibrinolytic inhibition Pulmonary inflammation

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Single amino acid variations drive functional divergence of cytochrome P450s in helicoverpa species

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INSECT BIOCheMISTRY AND MOLECULAR BIOLOGY 2022年第0期146卷 000-000页

作者： Shi, Yu Sun, Shuo Zhang, Yujun he, Yingshi Du, Minghong OReilly, Andrias O. Wu, shuwen Yang, Yihua Wu, Yidong Nanjing Agr Univ Coll Plant Protect Nanjing 210095 Peoples R China Liverpool John Moores Univ Sch Biol & Environm Sci Liverpool England

Divergence of gene function is a hallmark of evolution, but assessing such divergence in one species or between species requires information on functional alterations of the alleles and homologs. here, we explore the functional divergence of two paralogs, CYP6AE19 and CYP6AE20, from helicoverpa armigera, and two close orthologs, CYP6B8 and CYP6B7, from two related species (helicoverpa zea and H. armigera);although there is high sequence identity within each pair of enzymes, the latter P450 of each pair has lost metabolic competence towards the plant allelochemical xanthotoxin. Multiple chimeric and single/double site mutants were created by exchanging the diverse substrate recognition sites (SRSs) and amino acids within each pair of P450s. heterologous expression in Sf9 cells and in vitro metabolism studies showed that the exchange of SRS4 swapped the activity of CYP6AE19 and CYP6AE20, and subsequent site-directed mutagenesis demonstrated that the CYP6AE20 V318M substitution causes a gain-of-function towards xanthotoxin. Meanwhile, a single amino acid substitution (L489P) in SRS6 was found to swap activity between the CYP6B orthologs. Sequence alignments of CYP6AE paralogs and all reported insect xanthotoxin-metabolizing P450s suggest M318 and P489 are essential for the catalytic activities of CYP6AE paralogs and CYP6B orthologs, respectively, but P450s in different subfamilies may have different mechanisms towards the same substrate. Our findings demonstrate that a single amino acid substitution can suffice to alter substrate metabolism and this functional divergence resulting from natural mutations will help to further our understanding of the process of natural selection of P450 genes and their role in insect-host plant interactions.

关键词： Cytochrome P450 Functional divergence Detoxification Xanthotoxin Molecular modelling

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Metabonomics analysis of flavonoids in seeds and sprouts of two Chinese soybean cultivars

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SCIENTIFIC REPORTS 2022年第1期12卷 1-13页

作者： Bi, Weiwei Zhao, Guixing Zhou, Yutong Xia, Xiaoyu Wang, Jinsheng Wang, Guangjin Lu, shuwen he, Wenjin Bi, Taifei Li, Jinrong Heilongjiang Acad Agr Sci Postdoctoral Stn Harbin 150086 Peoples R China Heilongjiang Acad Agr Sci Soybean Res Inst Harbin 150086 Peoples R China Yulin Univ Coll Life Sci Yulin 719000 Peoples R China Heilongjiang Univ Sch Hydraul & Elect Power Harbin 150086 Peoples R China Heilongjiang Acad Agr Sci Food Proc Res Inst Harbin 150086 Peoples R China

A popular food in China, soybean seeds and sprouts contained many biologically active substances which are beneficial to the human body, such as flavonoids. Northeast of China is the main producing area of soybean. The experimental materials came from the main soybean producing areas in Northeast China, this study compared flavonoids of two China cultivars of soybeans, heinong52(HN52) and heinong71(HN71). here, we also considered the effects of germination on the chemical profile of flavonoids. Using a LC-ESI-MS/MS system, 114 differential flavonoid metabolites were identified. A total of 18 metabolites were significantly different between the two soybean varieties before germination, of which 14 were up-regulated and 4 were down-regulated. After germination, 33 significantly different metabolites were found in the two soybean sprouts, of which 19 were up-regulated and 14 were down-regulated. These experimental results revealed significant up-regulation of metabolites in soybean sprouts compared with soybean seeds, thus suggesting that soybean germination may increase content of flavonoid metabolites. There are six main pathways for the synthesis of flavonoids: isoflavonoid biosynthesis, flavonoid biosynthesis, flavone and flavonol biosynthesis, biosynthesis of secondary metabolites, and biosynthesis of phenylpropanoids. Soybean seeds lack flavone and flavanol biosynthesis and develop the capacity for this biosynthetic pathway after germination as sprouts. Isoflavonoid biosynthesis is the most abundantly utilized pathway.

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CuET overcomes regorafenib resistance by inhibiting epithelial-mesenchymal transition through suppression of the ERK pathway in hepatocellular carcinoma

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Translational Oncology 2024年 47卷 102040-102040页

作者： Ma, Ding Liu, shuwen Liu, Kua he, Qinyu Hu, Lili Shi, Weiwei Cao, Yin Zhang, Guang Xin, Qilei Wang, Zhongxia Wu, Junhua Jiang, Chunping Jinan Microecological Biomedicine Shandong Laboratory Shandong Jinan 250117 China Department of Hepatobiliary Surgery the Affiliated Drum Tower Hospital of Nanjing University Medical School Nanjing 210008 China Department of Gastroenterology Third Xiangya Hospital Central South University Hunan Changsha China State Key Laboratory of Pharmaceutical Biotechnology National Institute of Healthcare Data Science at Nanjing University Jiangsu Key Laboratory of Molecular Medicine Medical School Nanjing University 22 Hankou Road Jiangsu Nanjing 210093 China

Background and Purpose: Regorafenib was approved by the US Food and Drug Administration (FDA) for hepatocellular carcinoma (HCC) patients showing progress on sorafenib treatment. However, there is an inevitably high rate of drug resistance associated with regorafenib, which reduces its effectiveness in clinical treatment. Thus, there is an urgent need to find a potential way to solve the problem of regorafenib resistance. The metabolite of disulfiram complexed with copper, the Diethyldithiocarbamate-copper complex (CuET), has been found to be an effective anticancer drug candidate. In the present study, we aimed to evaluate the effect of CuET on regorafenib resistance in HCC and uncover the associated mechanism. Experimental Approach: Regorafenib-resistant HCC strains were constructed by applying an increasing concentration gradient. This study employed a comprehensive range of methodologies, including the cell counting kit-8 (CCK-8) assay, colony formation assay, cell cycle analysis, wound healing assay, Transwell assay, tumor xenograft model, and immunohistochemical analysis. These methods were utilized to investigate the antitumor activity of CuET, assess the combined effect of regorafenib and CuET, and elucidate the molecular mechanism underlying CuET-mediated regorafenib resistance. Key Results: The inhibitory effect of regorafenib on cell survival, proliferation and migration was decreased in regorafenib-resistant MHCC-97H (MHCC-97H/REGO) cells compared with parental cells. CuET demonstrated significant inhibitory effects on cell survival, proliferation, and migration of various HCC cell lines. CuET restored the sensitivity of MHCC-97H/REGO HCC cells to regorafenib in vitro and in vivo. Mechanistically, CuET reverses regorafenib resistance in HCC by suppressing epithelial-mesenchymal transition (EMT) through inhibition of the ERK signaling pathway. Conclusion and Implications: Taken together, the results of this study demonstrated that CuET inhibited the activ

关键词： CuET HCC Regorafenib Regorafenib-resistant MHCC-97H Reversal of regorafenib resistance

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老年神经重症患者并发肺部感染的影响因素及预测价值——一项连续4年的数据分析

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中华危重病急救医学 2023年第1期35卷 66-70页

作者：袁佳刘颖刘頔王迪芬沈锋刘旭李书文何德华贵州医科大学附属医院重症医学科贵阳550004 北京师范大学新闻传播学院北京师范大学中国教育与社会发展研究院国家数字健康研究中心北京100875

目的:分析重症监护病房(ICU)内老年神经重症患者并发肺部感染的影响因素,并探讨危险因素对肺部感染的预测价值。方法:回顾性分析2016年1月1日至2019年12月31日在贵州医科大学附属医院重症医学科住院的713例老年神经重症患者〔年龄≥65... 详细信息

目的:分析重症监护病房(ICU)内老年神经重症患者并发肺部感染的影响因素,并探讨危险因素对肺部感染的预测价值。方法:回顾性分析2016年1月1日至2019年12月31日在贵州医科大学附属医院重症医学科住院的713例老年神经重症患者〔年龄≥65岁、格拉斯哥昏迷评分(GCS)≤12分〕的临床资料。根据是否发生医院获得性肺炎(HAP)分为两组,比较两组基线资料、用药及治疗情况、结局指标。采用Logistic回归分析发生肺部感染的影响因素;针对危险因素,绘制受试者工作特征曲线(ROC曲线),并构建预测模型,评估其对肺部感染的预测价值。结果:最终纳入341例患者,其中非HAP组164例,HAP组177例,HAP发生率为51.91%。单因素分析显示,与非HAP组比较,HAP组机械通气时间、ICU住院时间、总住院时间明显延长〔机械通气时间(h):171.00(95.00,273.00)比60.17(24.50,120.75),ICU住院时间(h):263.50(160.00,409.00)比114.00(77.05,187.50),总住院时间(d):29.00(13.50,39.50)比27.00(11.00,29.50),均P<0.01〕;开放气道、合并糖尿病、使用质子泵抑制剂(PPI)、镇静剂、输血、糖皮质激素以及GCS≤8分的患者比例明显增加〔开放气道:95.5%比71.3%,糖尿病:42.9%比21.3%,PPI:76.3%比63.4%,镇静剂:93.8%比78.7%,输血:57.1%比29.9%,糖皮质激素:19.2%比4.3%,GCS≤8分:83.6%比57.9%,均P<0.05〕,前白蛋白(PA)、淋巴细胞计数(LYM)明显降低〔PA(g/L):125.28±47.46比158.57±54.12,LYM(×109/L):0.79(0.52,1.23)比1.05(0.66,1.57),均P<0.01〕。Logistic回归分析显示,开放气道、糖尿病、输血、糖皮质激素、GCS≤8分均是影响老年神经重症患者发生肺部感染的独立危险因素〔开放气道:优势比(OR)=6.522,95%可信区间(95%CI)为2.369~17.961;糖尿病:OR=3.917,95%CI为2.099~7.309;输血:OR=2.730,95%CI为1.526~4.883;糖皮质激素:OR=6.609,95%CI为2.273~19.215;GCS≤8分:OR=4.191,95%CI为2.198~7.991,均P<0.01〕;而LYM、PA是老年神经重症患者发生肺部感染的保护因素(LYM:OR=0.508,95%CI为0.345~0.748;PA:OR=0.988,95%CI为0.982~0.994,均P<0.01)。ROC曲线分析显示,以上述危险因素构建预测模型预测HAP的ROC曲线下面积(AUC)为0.812(95%CI为0.767~0.857,P<0.001),敏感度为72.3%,特异度为78.7%。结论:开放气道、糖尿病、糖皮质激素、输血、GCS≤8分均是影响老年神经重症患者发生肺部感染的独立危险因素;由上述危险因素构建的预测模型对老年神经重症患者发生肺部感染有一定预测价值。

关键词：老年神经重症肺部感染医院获得性肺炎危险因素预测模型

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Adsorption of heavy metals in water by modifying Fe₃O₄ nanoparticles with oxidized humic acid

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COLLOIDS AND SURFACES A-PHYSICOCheMICAL AND ENGINEERING ASPECTS 2021年 616卷 126333-126333页

作者： Xue, shuwen Xiao, Yawen Wang, Guoqiang Fan, Jinjin Wan, Keji he, Qiongqiong Gao, Mingqiang Miao, Zhenyong China Univ Min & Technol Sch Chem Engn & Technol Xuzhou 221116 Jiangsu Peoples R China China Univ Min & Technol Natl Engn Res Ctr Coal Preparat & Purificat Xuzhou 221116 Jiangsu Peoples R China

Magnetic nanoparticles require a protective coating to enable them to be used to adsorb heavy metals from wastewater, given their oxidation properties and instability in acidic media. Humic acid (HA) has an affinity for magnetic nanoparticles, but its adsorption capacity is low. To improve adsorption capacity, we synthesized a novel adsorbent (HA-O/Fe3O4) through chemical modification and examined its adsorption of Pb (II), Cu (II), Cd (II), and Ni (II) ions. The effects of pH competition, adsorption mechanism, isotherm, kinetics, regeneration, and stability were investigated. The HA-O/Fe3O4 exhibited faster kinetic performance (10 min), conforming to the pseudo-two kinetics equation, and the adsorption isotherm conforms to the Langmuir model with maximum adsorption capacities of 111.10, 76.92, 71.43, and 33.33 mg/g, respectively. The interaction between metal ions and functional groups of the adsorbent was further characterized by Fourier-transform infrared spectroscopy, and the results indicated that adsorption by cation exchange at low pH and complexation at high pH. Additionally, the adsorbent was recycled four times, and the removal rate was not significantly affected. A recycling efficiency of more than 90 % indicates good sustainability and reusability. The stability test shows that the amount of organic matter and heavy metals desorbed by the adsorbent were negligible. Most importantly, at low concentrations, all four metal ions meet the industrial emission standards, and Pb (II) and Cu (II) meet the drinking water standards.

关键词： Oxidation modified humic acid Magnetite nanoparticle Wastewater Adsorption mechanism pH-dependent competitive

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NOVEL SUBSTITUTED [1.1.1] BICYCLO COMPOUNDS AS INDOLEAMINE 2,3-DIOXYGENASE INHIBITORS

NOVEL SUBSTITUTED [1.1.1] BICYCLO COMPOUNDS AS INDOLEAMINE 2...

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作者： XIAO, Li ZHANG, Hongjun he, shuwen CLAUSEN, Dane GUO, Liangqin HAN, Yongxin HUANG, Xianhai PASTERNAK, Alexander PU, Qinglin XIAO, Dong

标准号: WO2019/231870(A1)

Disclosed herein are compounds of formula (I) which are inhibitors of an IDO enzyme: (I). Also disclosed herein are uses of the compounds in the potential treatment or prevention of an IDO-associated disease or disorder. Also disclosed herein are compositions comprising these compounds. Further disclosed herein are uses of the compositions in the potential treatment or prevention of an IDO-associated disease or disorder.

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Association between base excess and 28-day mortality in sepsis patients: A secondary analysis based on the MIMIC- IV database

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heLIYON 2023年第5期9卷 e15990页

作者： Yuan, Jia Liu, Xu Liu, Ying Li, Wei Chen, Xianjun Chen, Qiming Xiao, Chuan Wan, Ying Li, shuwen Li, Qing Li, Lu he, Juan Chen, Lu Shen, Feng Guizhou Med Univ Affiliated Hosp Dept Intens Care Unit Guiyang 550001 Guizhou Peoples R China Guizhou Med Univ Affiliated Hosp Dept Good Clin Practice Guiyang 550001 Guizhou Peoples R China

Objective: The relationship between base excess (BE) and 28-day death in sepsis patients remains to be elucidated. The aim of our clinical study is to explore the association of BE with 28-day mortality in patients with sepsis by using a large sample, multicenter Medical Information Mart for Intensive Care IV (MIMIC-IV) ***: We extracted the data of 35,010 patients with sepsis from the MIMIC-IV database, in which we used BE as an exposure variable and the 28-day mortality as an outcome variable, respectively, so as to explore the impact of BE on the 28-day mortality of patients with sepsis after adjusting for ***: BE and the 28-day mortality of patients with sepsis appeared to have a U-shaped relationship. The calculated inflection points were -2.5 mEq/L and 1.9 mEq/L, respectively. Our data demonstrated that BE was negatively associated with 28-day mortality in the range of -41.0 mEq/L to -2.5 mEq/L (odds ratio: 0.95;95% confidence intervals (95%CI): 0.93 to 0.96), p < 0.0001. When BE was in the range of 1.9 mEq/L to 55.5 mEq/L, however, a positive association existed between BE and 28-day mortality of patients with sepsis (odds ratio: 1.03;95% CI: 1.00 to 1.05;p < 0.05).Conclusion: The BE levels have a U-shaped relationship with the 28-day mortality in patients with sepsis, in which the mortality of patients will gradually decrease with a BE value from -41.0 mEq/L to -2.5 mEq/L, while the mortality will increase with a BE value from 1.9 mEq/L to 55.5 mEq/L.

关键词： Base excess MIMIC -IV Retrospective study Sepsis 28-Day mortality

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Lyoprotective effect of soluble extracellular polymeric substances from Oenococcus oeni during its freeze-drying process

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PROCESS BIOCheMISTRY 2019年 84卷 205-212页

作者： Wang, Jifeng he, Ling An, Wei Yu, Dongliang Liu, shuwen Shi, Kan Northwest Agr & Forestry Univ Coll Enol Xianyang 712100 Shaanxi Peoples R China Chateau Kings Int Co Ltd Qinhuangdao 066600 Hebei Peoples R China Northwest Agr & Forestry Univ Coll Hort Yangling 712100 Shaanxi Peoples R China Shaanxi Engn Res Ctr Viti Viniculture Yangling 712100 Shaanxi Peoples R China Heyang Expt & Demonstrat Stn Grape Weinan 715300 Shaanxi Peoples R China

Development of a starter culture of Oenococcus oeni (O. oeni) to induce a predictable and successful malolactic fermentation (MLF) is of crucial importance for some winemaking processes. The key to obtaining a starter culture with high cell activity is to select an efficient lyoprotectant. In the present study, we first evaluated the lyoprotective effect of soluble extracellular polymeric substances (s-EPS) from O. oeni during its freeze-drying process. Our results showed that the better lyoprotective effect of s-EPS, over other those of common protectants on O. oeni was closely associated with its ability to maintain the fluidity and integrity of cytomembranes, and the integrity and activity of the cells. Additionally, we compounded an optimal lyoprotectant containing s-EPS for O. oeni that increased the cell survival rate up to 92.83% after the freeze-drying process. The results indicate that s-EPS from O oeni is a potential lyoprotectant for its freeze-drying process.

关键词： Oenococcus oeni Soluble extracellular polymeric substances Lyoprotectant Freeze drying

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第三类医疗器械经营许可检查结果预测模型的建立与验证

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中国药业 2024年第1期33卷 22-25页

作者：何羡霞侯珺胡树文姜志辉广东省广州市食品药品审评中心广东广州510140 中国人民解放军南部战区总医院广东广州510010

目的建立并验证第三类医疗器械经营许可检查结果预测模型,为科学、智慧监管提供参考。方法回顾性分析广州市2018年6月至2022年12月申报第三类医疗器械经营许可的企业提交的申报材料,确定纳入标准和排除标准,在内部系统中提取申报材料... 详细信息

目的建立并验证第三类医疗器械经营许可检查结果预测模型,为科学、智慧监管提供参考。方法回顾性分析广州市2018年6月至2022年12月申报第三类医疗器械经营许可的企业提交的申报材料,确定纳入标准和排除标准,在内部系统中提取申报材料中的相关信息及检查结果,对提取变量进行单因素分析、向前向后逐步回归分析和多因素Logistic回归分析,筛选与检查结果显著相关的变量,在此基础上构建预测模型,并应用受试者工作特征曲线(ROC)、校准曲线、Hosmer-Lemeshow拟合优度检验及决策曲线分析(DCA)评价预测模型。结果共纳入企业182家,单因素分析筛选出6个预测变量,包括专业技术人员数量(因素A)、质量管理人员数量(因素B)、质量负责人学历(因素C)、经营场所面积(因素D)、仓库面积(因素E)、冷库容积(因素F);向前向后逐步回归分析结果显示,可得到最小赤池信息准则(AIC)值为219,且此时模型兼具优良的预测性能和低复杂度。选取因素A、因素C、因素F作为最终预测变量进行Logistic多因素回归分析,绘制列线图,构建预测模型。ROC曲线下面积(AUC)为0.73,模型区分度较好;HosmerLemeshow拟合优度检验结果显示,模型校准度较好(P=0.387)。DCA结果显示,成本-收益比大于0.5时,根据模型的预测结果进行检查的净收益显著高于对所有企业进行检查和全部都不检查。结论因素A、因素C、因素F为企业现场检查通过与否的主要影响因素。所建立的列线图预测模型对第三类医疗器械经营许可检查结果有一定价值。

关键词：医疗器械企业经营许可检查预测模型列线图

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