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In-situ construction of Co(OH)_(2. nanoparticles decorated biochar for highly efficient degradation of tetracycline hydrochloride via peracetic acid activation

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中国化学快报:英文版 2023年第9期34卷 264-269页

作者： Fengbin sun Xudong Yang Feng Shao fan Li Zhicheng Pan Lin Qiao Ziniu Xiao Wen Liu institute of Urban Meteorology China Meteorological AdministrationBeijing 100089China State Key Laboratory of Numerical Modeling for Atmospheric Sciences and Geophysical Fluid Dynamics Institute of Atmospheric PhysicsChinese Academy of SciencesBeijing 100029China The Key Laboratory of Water and Sediment Sciences Ministry of EducationCollege of Environmental Sciences and EngineeringPeking UniversityBeijing 100871China College of Landscape Architecture Zhejiang Agriculture and Forestry UniversityHangzhou 311300China Water Safety and Water Pollution Control Engineering Technology Research Center in sichuan Province Haitian Water GroupChengdu 610299China

Peracetic acid(CH_(3)C(O)OOH,PAA)-based heterogeneous advanced oxidation process(AOP)has attacked intensive interests due to production of various reactive ***,Co(OH)_(2.nanoparticles decorated biochar(Co(OH)_(2./BC)was fabricated by a simple and controllable method,which was used to degrade tetracycline hydrochloride(TTCH)in water through PAA *** results indicated that 100%TTCH(C_(0)=10μmol/L)degradation efficiency was realized within 7 min at pH 7,with a high kinetic rate constant(k_(1))of 0.64 min^(-1)by the optimized Co(OH)_(2./*** characterizations suggested that Co(OH)_(2.nanoparticle was successfully decorated on biochar,leading to more active sites and electronic structure alteration of biochar,thus greatly promoting the catalytic cleavage of PAA for radicals ***,the reactive oxygen species(ROS)quenching experiments and electron paramagnetic resonance(EPR)analysis demonstrated the key species were alkoxyl radicals(R–O^(·),mainly CH_(3)CO_(2.^(·)and CH_(3)CO_(3)^(·)),HO^(·)and^(1)O_(2.in this ***,density functional theory(DFT)calculation on Fukui index further revealed that the vulnerable sites of TTCH and three possible degradation pathways were *** study can provide a new strategy for synthesis functional materials in PAA activation AOPs for removal of antibiotics in water.

关键词： Biochar Peracetic acid(PAA) Tetracycline hydrochloride Intermediates DFT calculation

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芦山6.1级地震山区典型震害调查与分析

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土木工程学报 2023年第12期56卷 35-48页

作者：潘毅范元青任宇杨兵侯江荣熊耀清西南交通大学土木工程学院四川成都610031 西南交通大学抗震工程技术四川省重点实验室四川成都610031 中国建筑西南设计研究院有限公司四川成都610042

2.2.年6月1日,四川省雅安市芦山县发生6.1级地震及多次余震,引发了地质灾害,并造成了建筑物的破坏。为掌握此次地震中地质灾害和建筑物震害的情况,对芦山县、宝兴县等地区进行震害调查,分析滑坡、崩塌等地质灾害和建筑物震害的特征和成... 详细信息

2.2.年6月1日,四川省雅安市芦山县发生6.1级地震及多次余震,引发了地质灾害,并造成了建筑物的破坏。为掌握此次地震中地质灾害和建筑物震害的情况,对芦山县、宝兴县等地区进行震害调查,分析滑坡、崩塌等地质灾害和建筑物震害的特征和成因,并对地质灾害隐患点数量、地质灾害防治设施的破坏数量和不同结构类型的建筑震害进行统计和分析。调查和分析结果表明:地震诱发滑坡、崩塌,导致道路中断、河道阻塞和被动柔性防护网损坏,地质灾害隐患点数量为143处。各结构类型的建筑震害中,木结构和隔震结构表现良好,无明显震害;砖木结构和砖混结构的震害主要表现为墙体破坏、屋盖破坏、楼面破坏和楼梯间破坏;混凝土结构震害主要表现为填充墙、门窗和吊顶等非结构构件破坏;其中,砖木结构、砖混结构和混凝土结构的严重破坏数量分别占14.2.、2..9%、0%。相比2.13年芦山7.0级地震,此次地质灾害隐患点数量仅为2.13年的2.78%,房屋破坏数量显著下降,严重破坏占比仅2..7%,且无房屋倒塌。根据山区震害特征及原因,对地质灾害防治、非结构构件的抗震设计、隔震结构的构造措施及管理维护提出建议,以期为山区地质灾害防治和建筑抗震防灾提供参考。

关键词：芦山地震震害调查山区地质灾害建筑震害

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Multiplexed imaging of tumor immune microenvironmental markers in locally advanced or metastatic non-small-cell lung cancer characterizes the features of response to PD-1 blockade plus chemotherapy

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Cancer Communications 2022年第12期42卷 1331-1346页

作者： Fengying Wu Tao Jiang Gongyan Chen Yunchao Huang Jianying Zhou Lizhu Lin Jifeng Feng Zhehai Wang Yongqian Shu Jianhua Shi Yi Hu Qiming Wang Ying Cheng Jianhua Chen Xiaoyan Lin Yongsheng Wang Jianan Huang Jiuwei Cui Lejie Cao Yunpeng Liu Yiping Zhang Yueyin Pan Jun Zhao LiPing Wang Jianhua Chang Qun Chen Xiubao ren Wei Zhang Yun fan Zhiyong He Jian fang Kangsheng Gu Xiaorong Dong Tao Zhang Wei Shi Jianjun Zou Xuejuan Bai Shengxiang ren Caicun Zhou Department of Thoracic Medical Oncology Shanghai Pulmonary HospitalTongji University School of MedicineShanghai 200433P.R.China Department of Respiratory Medicine Harbin Medical University Cancer HospitalHarbinHeilongjiang 150000P.R.China Department of Thoracic Surgery Oncology Yunnan Cancer Hospital&The Third Affiliated Hospital of Kunming Medical University&Yunnan Cancer CenterKunmingYunnan 650118P.R.China Department of Respiratory Medicine The First Affiliated Hospital of Zhejiang UniversityHangzhouZhejiang 310009P.R.China Department of Oncology Center The First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhouGuangdong 510405P.R.China Department of Thoracic Medical Oncology Jiangsu Cancer Hospital&Jiangsu Institute of Cancer Research&The Affiliated Cancer Hospital of Nanjing Medical UniversityNanjingJiangsu 210009P.R.China Department of Respiratory Shandong Cancer Hospital&InstituteJinanShandong 250117P.R.China Department of Oncology Jiangsu Province HospitalNanjingJiangsu 210000P.R.China Department of Medical Oncology Linyi Cancer HospitalLinyiShandong 276000P.R.China Department of Oncology Chinese PLA General HospitalBeijing 100853P.R.China Department of Respiratory Medicine Henan Cancer HospitalZhengzhouHenan 450000P.R.China Department of Thoracic Oncology Jilin Cancer HospitalChangchunJilin 130012P.R.China Department of Medical Oncology-Chest Hunan Cancer HospitalChangshaHunan 410006P.R.China Department of Oncology Fujian Medical University Union HospitalFuzhouFujian 350001P.R.China Department of Thoracic Medical Oncology West China HospitalSichuan UniversityChengduSichuan 610000P.R.China Department of Respiration First Affiliated Hospital of Suzhou UniversitySuzhouJiangsu 215002P.R.China Department of Medical Oncology The First Bethune Hospital of Jilin UniversityChangchunJilin 130021P.R.China Pulmonary and Critical Care Medicine The First Affiliated Hospital University of Science Technology of ChinaHefeiAnhui 230036P.R.China De

Background:Although programmed cell death 1(PD-1)blockade plus chemotherapy can significantly prolong the progression-free survival(PFS)and overall survival(OS)in first-line settings in patients with driver-negative advanced non-small-cell lung cancer(NSCLC),the predictive biomarkers remain ***,we investigated the predictive value of tumor immune microenvironmental marker expression to characterize the response features to PD-1 blockade plus ***:Tumor tissue samples at baseline were prospectively collected from 144 locally advanced or metastatic NSCLC patients without driver gene alterations who received camrelizumab plus chemotherapy or chemotherapy *** immune microenvironmental markers,including PD-1 ligand(PDL1),CD8,CD68,CD4 and forkhead box P3,were assessed using multiplex immunofluorescence(mIF)***-Meier curveswere used to determine treatment outcome differences according to their expression *** profiles were compared between tumors with distinct expression levels of these markers and their ***:Responders had significantly higher CD8/PD-L1(P=0.015)or CD68/PD-L1 co-expression levels(P=0.02.)than non-responders in the camrelizumab plus chemotherapy group,while no difference was observed in the chemotherapy *** with high CD8/PD-L1 or CD68/PD-L1 co-expression level was associated with significantly longer PFS(P=0.002.P=0.02.;respectively)and OS(P=0.006,P=0.02.;respectively)than those with low co-expression in camrelizumab plus chemotherapy *** comparing survival in the camrelizumab plus chemotherapy with chemotherapy by CD8/PD-L1 co-expression stratification,significantly better PFS(P=0.003)and OS(P=0.032.were observed in high co-expression *** predictive value of CD8/PD-L1 and CD68/PD-L1 co-expression remained statistically significant for PFS and OS when adjusting clinicopathological *** the prevalence of TP53 or KRAS mutations was similar bet

关键词： Non-small-cell lung cancer PD-1 CD8 CD68 tumor immune microenvironment

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2.06~2.19年珠三角地区臭氧污染趋势

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环境科学 2021年第1期42卷 97-105页

作者：赵伟高博卢清钟志强梁小明刘明马社霞孙家仁陈来国范绍佳生态环境部华南环境科学研究所国家环境保护城市生态环境模拟与保护重点实验室广州510535 中山大学大气科学学院广州510275

研究基于2.06~2.19年粤港澳珠江三角洲区域空气监测网络数据,利用Mann-Kendall检验法和Sen斜率法等统计方法计算了珠三角不同区域臭氧年际变化情况,并分析了变化的原因.结果表明:①2.06~2.19年珠三角平均臭氧浓度上升趋势显著(P<0.05),... 详细信息

研究基于2.06~2.19年粤港澳珠江三角洲区域空气监测网络数据,利用Mann-Kendall检验法和Sen斜率法等统计方法计算了珠三角不同区域臭氧年际变化情况,并分析了变化的原因.结果表明:①2.06~2.19年珠三角平均臭氧浓度上升趋势显著(P2.16年之后,臭氧平均增长速率为2.08μg·(m^(3)·a)^(-1),臭氧浓度增速加快.②珠三角臭氧浓度变化趋势有明显的空间差异和季节差异.中部地区臭氧年均浓度增加趋势显著,外围区域臭氧增加趋势不显著;臭氧增加趋势主要集中在夏季,其他季节变化趋势不显著.③珠三角臭氧变化趋势是由前体物和气象条件共同造成的,特别与NOx的浓度变化密切相关.2.06~2.19年珠三角中部区域NO2.度明显下降,滴定效应减弱导致臭氧浓度增加;边缘地区NO2.度变化较小,臭氧浓度未发生明显的改变.④随着前体物浓度的变化,珠三角臭氧生成敏感区的特征正在发生改变,VOCs控制区面积不断减少,协同控制区和NOx控制区面积逐渐增加,区域臭氧污染防治需要加强对前体物的协同控制.

关键词：臭氧污染珠三角趋势变化臭氧生成敏感性气象条件

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Impact of thymosinα1 as an immunomodulatory therapy on long-term survival of non-small cell lung cancer patients after R0 resection:a propensity score-matched analysis

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Chinese Medical Journal 2021年第6期134卷 2700-2709页

作者： Cheng-Lin Guo Jian-Dong Mei Yu-Long Jia fan-Yi Gan Yu-Dong Tang Cheng-Wu Liu Zhen Zeng Zhen-Yu Yang Sen-Yi Deng Xing sun Lun-Xu Liu Department of Thoracic Surgery and institute of Thoracic Oncology West China HospitalSichuan UniversityChengduSichuan 610041China Western china Collaborative Innovation Center for Early Diagnosis and Multidisciplinary Therapy of Lung Cancer ChengduSichuan 610041China Chinese Evidence-Based Medicine Centre West China HospitalSichuan UniversityChengduSichuan 610041China.

Background:There is limited information about thymosinα1(Tα1)as adjuvant immunomodulatory therapy,either used alone or combined with other treatments,in patients with non-small cell lung cancer(NSCLC).This study aimed to evaluate the effect of adjuvant Tα1 treatment on long-term survival in margin-free(R0)-resected stage IA–IIIA NSCLC ***:A total of 5746 patients with pathologic stage IA-IIIA NSCLC who underwent R0 resection were *** patients were divided into the Tα1 group and the control group according to whether they received Tα1 or not.A propensity score matching(PSM)analysis was performed to reduce bias,resulting in 102. pairs of ***:After PSM,the baseline clinicopathological characteristics were similar between the two *** 5-year disease-free survival(DFS)and overall survival(OS)rates were significantly higher in the Tα1 group compared with the control *** multivariable analysis showed that Tα1 treatment was independently associated with an improved prognosis.A longer duration of Tα1 treatment was associated with improved OS and *** subgroup analyses showed that Tα1 therapy could improve the DFS and/or OS in all subgroups of age,sex,Charlson Comorbidity Index(CCI),smoking status,and pathological tumor-node-metastasis(TNM)stage,especially for patients with non-squamous cell NSCLC and without targeted ***:Tα1 as adjuvant immunomodulatory therapy can significantly improve DFS and OS in patients with NSCLC after R0 resection,except for patients with squamous cell carcinoma and those receiving targeted *** duration of Tα1 treatment is recommended to be>2. months.

关键词： Non-small cell lung cancer Resection Adjuvant therapy Thymosinα1

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酸樱桃酒澄清剂的筛选

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食品工业科技 2018年第10期39卷 133-137页

作者：吴澎贾朝爽郗良卿周涛李向阳张倩范苏仪任琪孙玉刚山东农业大学食品学院山东省高校食品加工技术与质量控制重点实验室山东泰安271018 山东省果树研究所山东泰安271018

酸樱桃酒的澄清工艺十分重要,以自制酸樱桃酒为原料,研究了明胶、单宁、硅藻土、壳聚糖、果胶酶、鸡蛋清6种澄清剂对酸樱桃酒澄清度和色度的影响。在单因素实验基础上,采用正交实验设计,确定复合澄清剂在酸樱桃酒中的最佳组合为:单宁1.6... 详细信息

酸樱桃酒的澄清工艺十分重要,以自制酸樱桃酒为原料,研究了明胶、单宁、硅藻土、壳聚糖、果胶酶、鸡蛋清6种澄清剂对酸樱桃酒澄清度和色度的影响。在单因素实验基础上,采用正交实验设计,确定复合澄清剂在酸樱桃酒中的最佳组合为:单宁1.6 g/L、明胶1.0 g/L、鸡蛋清6.0 g/L,酒体澄清度为92.6%,并对澄清前后的酸樱桃酒进行透光率、色度、总酚、总糖、总酸、酒精度、p H的测定,进一步验证了澄清剂对酸樱桃酒的主要成分和感官品质无明显影响,成品酒果香怡人、口感醇厚、酒体澄清丰满。

关键词：酸樱桃酒澄清剂澄清度色度

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Combining methylated SEPTIN9 and RNF180 plasma markers for diagnosis and early detection of gastric cancer

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Cancer Communications 2023年第11期43卷 1275-1279页

作者： Yongzhan Nie Xianchun Gao Xiqiang Cai Zhen Wu Qiaoyi Liang Guobing Xu Na Liu Peng Gao Jingyu Deng Hongzhi Xu Zhanlong Shen Changqi Cao Fenrong Chen Nannan Zhang Yongxi Song Mingjun sun Chengyin Liu Guangpeng Zhou Weili Han Jianhua Dou Huahong Xie Liping Yao Zhiguo Liu Gang Ji Xin Wang Qingchuan Zhao Lei Shang Daiming fan Xiaoliang Han Jianlin {2. Han Liang Zhenning Wang Jinhai Wang Qi Wu Jun Yu Kaichun Wu the MAGIS Study Group State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers and National Clinical Research Center for Digestive Diseases Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi'anShaanxiP. R. China Department of Gastroenterology Tangdu HospitalFourth Military Medical UniversityXi'anShaanxiP. R. China BioChain (Beijing) Science & Technology Inc. BeijingP. R. China Department of Medicine and Therapeutics Institute of Digestive DiseasePrince of Wales HospitalThe Chinese University of Hong KongHong KongP. R. China Department of Endoscopy Center Peking University Cancer Hospital & InstituteKey Laboratory of Carcinogenesis and Translational ResearchMinistry of EducationBeijingP. R. China Department of Gastroenterology the Second Affiliated HospitalXi'an Jiaotong UniversityXi'anShaanxiP. R. China Department of Surgical Oncology and General Surgery Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal TumorsThe First Affiliated Hospital of China Medical UniversityShenyangLiaoningP. R. China Department of Gastric Surgery Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin's Clinical Research Center for CancerTianjinP. R. China Department of Gastroenterology Zhongshan HospitalXiamen UniversityXiamenFujianP. R. China Department of Gastrointestinal Surgery Peking University People's HospitalBeijingP. R. China Department of Endoscope The First Hospital Affiliated to China Medical UniversityShenyangLiaoningP. R. China Department of Health Statistics School of Preventive MedicineFourth Military Medical UniversityXi'anShaanxiP. R. China 不详

Dear Editor,Early diagnosis is critical for successful treatment of gastric adenocarcinoma(GA).However,the sensitivities of tumor markers carcinoembryonic antigen(CEA),cancer antigen 19-9(CA19-9)and CA72.4 for GA detection are approximately 2.%[1],and the sensitivities of all markers combined for early gastric cancer detection is still very low[2..DNA methylation plays a major role in tumorigenesis and therefore has obvious potential as a non-invasive biomarker for cancer detection[3].Through genome-wide methylation analysis and histological verification,we previously identified ring finger protein 180(RNF180)as a novel preferentially methylated gene in GA[4,5].

关键词： RNF180 diagnosis gastric

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Klotho in Osx+-mesenchymal progenitors exerts pro-osteogenic and anti-inflammatory effects during mandibular alveolar bone formation and repair

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Signal Transduction and Targeted Therapy 2022年第6期7卷 2053-2065页

作者： Yi fan Chen Cui Clifford JRosen Tadatoshi Sato Ruoshi Xu Peiran Li Xi Wei Ruiye Bi Quan Yuan Chenchen Zhou State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesDepartment of Cariology and EndodonticsWest China Hospital of StomatologySichuan University610041 ChengduSichuanChina Hospital of Stomatology Guanghua School of StomatologySun Yat-Sen UniversityGuangdong Provincial Key Laboratory of Stomatology510055 GuangzhouGuangdongChina Maine Medical Center Research institute ScarboroughME 04074USA Endocrine Unit Massachusetts General HospitalHarvard Medical SchoolBostonMA 02215USA State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesDepartment of Orthognathic and TMJ SurgeryWest China Hospital of StomatologySichuan University610041 ChengduSichuanChina State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesDepartment of Oral ImplantologyWest China Hospital of StomatologySichuan University610041 ChengduSichuanChina State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesDepartment of OrthodonticsWest China Hospital of StomatologySichuan University610041 ChengduSichuanChina

Maxillofacial bone defects are commonly seen in clinical practice.A clearer understanding of the regulatory network directing maxillofacial bone formation will promote the development of novel therapeutic approaches for bone *** fibroblast growth factor(FGF)signalling pathway is critical for the development of maxillofacial ***,a type I transmembrane protein,is an important components of FGF receptor *** studies have reported the presence of Klotho expression in ***,the role of Klotho in cranioskeletal development and repair remains ***,we use a genetic strategy to report that deletion of Klotho in Osx-positive mesenchymal progenitors leads to a significant reduction in osteogenesis under physiological and pathological ***-deficient mensenchymal progenitors also suppress osteoclastogenesis in vitro and in *** conditions of inflammation and trauma-induced bone loss,we find that Klotho exerts an inhibitory function on inflammation-induced TNFR signaling by attenuating Rankl *** importantly,we show for the first time that Klotho is present in human alveolar bone,with a distinct expression pattern under both normal and pathological *** summary,our results identify the mechanism whereby Klotho expressed in Osx+-mensenchymal progenitors controls osteoblast differentiation and osteoclastogenesis during mandibular alveolar bone formation and ***-mediated signaling is an important component of alveolar bone remodeling and *** may also be a target for future therapeutics.

关键词： Klotho progenitor alveolar

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巴中水宁寺摩岩石刻的彩绘颜料分析

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光谱学与光谱分析 2022年第2期42卷 505-511页

作者：孙凤王若苏梁雅鑫刘伽如姚雪赵凡文化遗产研究与保护技术教育部重点实验室陕西西安710069 西北大学文化遗产学院陕西西安710069 西南民族大学旅游与历史文化学院四川成都610041 四川省文物考古研究院四川成都610041

巴中水宁寺摩崖造像以题材广泛、形式多样、雕刻精致著称于世,但潮湿的环境,不稳定的崖体,半露天的保存环境使水宁寺石刻遭到了严重的破坏,影响了石刻的艺术性,因此水宁寺摩崖造像保护修复工作迫在眉睫。通过对水宁寺石刻颜料的分析,获... 详细信息

巴中水宁寺摩崖造像以题材广泛、形式多样、雕刻精致著称于世,但潮湿的环境,不稳定的崖体,半露天的保存环境使水宁寺石刻遭到了严重的破坏,影响了石刻的艺术性,因此水宁寺摩崖造像保护修复工作迫在眉睫。通过对水宁寺石刻颜料的分析,获取彩绘颜料的信息,一方面为颜料复原提供科学依据,另一方面也有利于文物工作者展开针对性保护工作,具有重要的文物保护意义。采用超景深三维视频显微分析、X射线荧光光谱分析(XRF)、X射线衍射实验分析(XRD)以及激光拉曼光谱分析,从物质的外观、结构和成分综合分析水宁寺摩岩造像颜料的主要组成矿物。实验结果表明1号样品主要矿物为黄赭石,2.样品主要矿物为铅丹,3号样品主要矿物为石绿,4号样品主要矿物为硫酸铅,5号样品主要矿物为青金石,6号样品主要矿物为针铁矿,颜料下层的白粉层为二水石膏。因造像长期暴露在潮湿、半露天的的环境下,少数颜料不能直接检测出标准物质,需要根据相关资料进行二次分析,如黄赭石因长期风化导致最后测出的主要矿物是Fe_(2.O_(3);铅丹在潮湿及微生物存在的环境条件下发生分解变成K_(2.PbO_(2.与PbO_(2.;针铁矿是由赤铁矿或黄铁矿经化学反应而生成的。另外,通过对比人造群青的合成时间与造像的开凿年代,加之Fe元素的检出暗指天然青金石中金星的主要成分黄铁矿,可以判断本样品的颜料是由天然青金石制作的,丰富了天然青金石的使用案例。

关键词：水宁寺石窟彩绘颜料分析研究

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Berberine reverses multidrug resistance in Candida albicans by hijacking the drug efflux pump Mdr1p

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Science Bulletin 2021年第18期66卷 1895-1905,M0004页

作者： Yaojun Tong Jingyu Zhang Nuo sun Xiang-Ming Wang Qi Wei Yu Zhang ren Huang Yingying Pu Huanqin Dai Biao ren Gang Pei Fuhang Song Guoliang Zhu Xinye Wang Xuekui Xia Xiangyin Chen Lan Jiang Shenlin Wang Liming Ouyang Ning Xie Buchang Zhang Yuanying Jiang Xueting Liu Richard Calderone fan Bai Lixin Zhang Gil Alterovitzk State Key Laboratory of Bioreactor Engineering and School of Biotechnology East China University of Science and TechnologyShanghai 200237China Chinese Academy of Sciences Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100190China Biomedical Pioneering Innovation Center(BIOPIC) School of Life SciencesPeking UniversityBeijing J00871China Georgetown university Medical Center Department of Microbiology&Immunology.Washington DC 20057USA institute of Health Sciences School of Life SciencesAnhui UniversityHefei 230601China Guangdong Provincial Key Laboratory of Laboratory Animals Guangdong Laboratory Animals Monitoring InstituteGuangzhou 510663China Department of Pharmacology Second Military Medical UniversityShanghai 200433China State Key Laboratory of Mycology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China The Novo Nordisk Foundation Center for Biosustainability Technical University of Denmark2800 Kgs.LyngbyDenmark Key Biosensor Laboratory of Shandong Province Biology InstituteQilu University of Technology(Shandong Academy of Sciences)Jinan 250013China Brigham and Women's Hospital Boston MA 02115USA National Artificial Intelligence institute US.Department of Veterans AffairsWashington DC 20420USA

Clinical use of antimicrobials faces great challenges from the emergence of multidrug-resistant pathogens. The overexpression of drug efflux pumps is one of the major contributors to multidrug resistance(MDR). Reversing the function of drug efflux pumps is a promising approach to overcome MDR. In the life-threatening fungal pathogen Candida albicans, the major facilitator superfamily(MFS) transporter Mdr1p can excrete many structurally unrelated antifungals, leading to MDR. Here we report a counterintuitive case of reversing MDR in C. albicans by using a natural product berberine to hijack the overexpressed Mdr1p for its own importation. Moreover, we illustrate that the imported berberine accumulates in mitochondria and compromises the mitochondrial function by impairing mitochondrial membrane potential and mitochondrial Complex I. This results in the selective elimination of Mdr1 p overexpressed C. albicans cells. Furthermore, we show that berberine treatment can prolong the mean survival time of mice with blood-borne dissemination of Mdr1p overexpressed multidrug-resistant candidiasis. This study provides a potential direction of novel anti-MDR drug discovery by screening for multidrug efflux pump converters.

关键词： Candida albicans Berberine Multidrug-resistance Drug excretion transporter Mitochondria

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