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Niclosamide(NA)overcomes cisplatin resistance in human ovarian cancer

Genes & Diseases 2023年第4期10卷 1687-1701页

作者： Linjuan Huang Jing Zhang Youling Deng Hao Wang Piao Zhao Guozhi Zhao Wei Zeng Yonghui Wang connie chen William Wagstaff Rex C.Haydon Russell R.Reid Tong-Chuan He Le Shen Hue H.Luu Ling Zhao Departments of Obstetrics and Gynecology Orthopaedic Surgery and UrologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqing 400046China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Department of Neurology The Second Affiliated Hospital of Jianghan UniversityWuhanHubei 430050China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Department of Surgery The University of Chicago Medical CenterChicagoIL 60637USA

Ovarian cancer(OC)is one of the most lethal malignancies of the female reproduc-tive *** patients are usually diagnosed at advanced stages due to the lack of early *** standard treatment for OC includes a combination of debulking surgery and platinum-taxane chemotherapy,while several targeted therapies have recently been approved for maintenance *** vast majority of OC patients relapse with chemoresistant tu-mors after an initial ***,there is an unmet clinical need to develop new therapeu-tic agents to overcome the chemoresistance of *** anti-parasite agent niclosamide(NA)has been repurposed as an anti-cancer agent and exerts potent anti-cancer activities in human cancers including ***,we investigated whether NA could be repurposed as a therapeutic agent to overcome cisplatin-resistant(CR)in human OC *** this end,we first established two CR lines SKOV3CR and OVCAR8CR that exhibit the essential biological characteristics of cisplatin resistance in human *** showed that NA inhibited cell proliferation,sup-pressed cell migration,and induced cell apoptosis in both CR lines at a low micromole ***,NA inhibited multiple cancer-related pathways including AP1,ELK/SRF,HIF1,and TCF/LEF,in SKOV3CR and OVCAR8CR *** was further shown to effectively inhibit xenograft tumor growth of SKOV3CR ***,our findings strongly suggest that NA may be repurposed as an efficacious agent to combat cisplatin resistance in chemoresistant hu-man OC,and further clinical trials are highly warranted.

关键词： Chemotherapy resistance Cisplatin Drug repurposing Niclosamide Ovarian cancer

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基于“棕色土方”视角解读德国北杜伊斯堡景观公园

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景观设计学（中英文） 2015年第6期3卷 20-29页

作者：郑晓笛清华大学建筑学院

"棕色土方"是棕地的本体核心要素,是对场地污染的空间性诠释,与棕地再生过程中景观系统的构建密切相关。德国鲁尔区的北杜伊斯堡公园是国际风景园林领域内具有里程碑意义的开端性棕地再生项目,本文主要从"棕色土方"的角度对其进行解读,... 详细信息

"棕色土方"是棕地的本体核心要素,是对场地污染的空间性诠释,与棕地再生过程中景观系统的构建密切相关。德国鲁尔区的北杜伊斯堡公园是国际风景园林领域内具有里程碑意义的开端性棕地再生项目,本文主要从"棕色土方"的角度对其进行解读,用一种全新的视角来探讨该项目是如何通过风景园林学途径应对棕地再生过程中的多重挑战与困境,探讨"棕色土方"治理与其核心设计理念及策略的关系。

关键词：景观设计棕地再生棕色土方北杜伊斯堡公园彼得·拉茨

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SV40 large T antigen-induced immortalization reprograms mouse cardiomyocyte progenitors with mesenchymal stem cell characteristics and osteogenic potential

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Genes & Diseases 2023年第4期10卷 1161-1164页

作者： Yichun Yu Jiamin Zhong connie chen Yannian Gou Guozhi Zhao Piao Zhao Yonghui Wang Wei Zeng Annie Wang William D.Wagstaff Jr Rex C.Haydon Tong-Chuan He Russell R.Reid Michael J.Lee Hue H.Luu Jiaming Fan Emergency Department Beijing Hospitaland The National Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100051China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and the School of Laboratory Diagnostic MedicineChongqing Medical UniversityChongqing 400016China Departments of Orthopaedic Surgery and Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200025China Department of Neurology The Second Affiliated Hospital of Jianghan UniversityWuhanHubei 430050China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

While progenitor cell-based cardiomyocyte regeneration holds great promise of repairing an injured heart,primary cardiomyogenic progenitors(CPs)have a limited life span in culture,hampering the use of CPs for in vitro and in vivo *** previously isolated primary CPs from mouse E15.5 fetal heart,and reversibly immortalized them with SV40 large T antigen(SV40 LTA),resulting in immortalized CPs(iCPs),which maintain long-term proliferation and ex-press cardiomyogenic markers and retain differentiation potential under appropriate differentiation conditions.

关键词： progenitor cardio potential

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The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

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Genes & Diseases 2024年第3期11卷 155-187页

作者： Michael Yu Kevin Qin Jiaming Fan Guozhi Zhao Piao Zhao Wei Zeng connie chen Annie Wang Yonghui Wang jiamin Zhong Yi Zhu William Wagstaff Rex C.Haydon Hue H.Luu Sherwin Ho Michael J.Lee Jason Strelzow Russell R.Reid Tong-Chuan He School of Medicine Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Department of Orthopedic Surgery The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Department of Orthopaedic Surgery Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Department of Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China

The evolutionarily conserved Wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across *** proteins are secreted,lipid-modified signaling molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)Wnt signaling *** behaviors such as proliferation,differ-entiation,maturation,and proper body-axis specification are carried out by the canonical pathway,which is the best characterized of the known Wnt signaling *** signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various *** includes but is not limited to embryonic,hematopoietic,mesenchymal,gut,neural,and epidermal stem *** signaling has also been implicated in tumor cells that exhibit stem cell-like *** signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone *** surprisingly,aberrant Wnt signaling is also associated with a wide variety of diseases,including *** of Wnt pathway members in cancer can lead to unchecked cell proliferation,epithelial-mesenchymal transition,and ***,advances in the understand-ing of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt *** with a brief overview of the mechanisms of canonical and non-canonical Wnt,this review aims to summarize the cur-rent knowledge of Wnt signaling in stem cells,aberrations to the Wnt pathway associated with diseases,and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies.

关键词： β-Catenin Cancer Canonical Wnt Disease Non-canonical Wnt Stem cells Targeted therapy Wnt signaling

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Ferroptosis as a novel form of regulated cell death:Implications in the pathogenesis,oncometabolism and treatment of human cancer

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Genes & Diseases 2022年第2期9卷 347-357页

作者： Feifei Pu Fengxia chen Zhicai Zhang Deyao Shi Binlong Zhong Xiao Lv Andrew Blake Tucker Jiaming Fan Alexander J.Li Kevin Qin Daniel Hu connie chen Hao Wang Fang He Na Ni Linjuan Huang Qing Liu William Wagstaff Hue H.Luu Rex C.Haydon Le Shen Tong-Chuan He Jianxiang Liu Zengwu Shao Department of Orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022PR China Department of Radiation and Medical Oncology Zhongnan HospitalWuhan UniversityWuhanHubei 430071PR China Hubei Cancer Clinical Study Center Zhongnan HospitalWuhan UniversityWuhanHubei 430071PR China Department of Orthopaedic Surgery Johns Hopkins UniversityBaltimoreMD 21205USA Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine Department of Clinical BiochemistrySchool of Laboratory MedicineChongqing Medical UniversityChongqing 400016PR China Departments of Nephrology and Obstetrics and GynecologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016PR China Department of Spine Surgery Second Xiangya HospitalCentral South UniversityChangshaHunan 410011PR China Department of Surgery The University of Chicago Medical CenterChicagoIL 60637USA

The treatment of cancer mainly involves surgical excision supplemented by radiotherapy and *** drugs act by interfering with tumor growth and inducing the death of cancer ***-tumor drugs were developed to induce apoptosis,but some patient’s show apoptosis escape and chemotherapy ***,other forms of cell death that can overcome the resistance of tumor cells are important in the context of cancer *** is a newly discovered iron-dependent,non-apoptotic type of cell death that is highly negatively correlated with cancer *** is mainly caused by the abnormal increase in iron-dependent lipid reactive oxygen species and the imbalance of redox *** review summarizes the progression and regulatory mechanism of ferroptosis in cancer and discusses its possible clinical applications in cancer diagnosis and treatment.

关键词： Cancer Cancer therapy Clinical application Ferroptosis Lipid peroxidation Pathogenesis

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Canonical and noncanonical Wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk

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Genes & Diseases 2024年第1期11卷 103-134页

作者： Kevin Qin Michael Yu Jiaming Fan Hongwei Wang Piao Zhao Guozhi Zhaoo Wei Zeng connie chen Yonghui Wang Annie Wang Zander Schwartz Jeffrey Hong Lily Song William Wagstaff Rex C.Haydon Hue H.Luu Sherwin H.Ho Jason Strelzow Russell R.Reid Tong-Chuan He Lewis L.Shi Chicago Medical School Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Departments of Orthopaedic Surgery and Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China School of Biomedical Engineering Vanderbilt UniversityNashvilleTN 37235USA Laboratory of Craniofacial Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Wnt signaling plays a major role in regulating cell proliferation and *** Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and LRP5/6 coreceptors and transducing the signal either throughβ-catenin in the canonical pathway or through a series of other proteins in the nonca-nonical *** of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body,establishing the complex interplay between Wnt signaling and other signaling *** crosstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many cellular and organ ***-regulation of this system has been implicated in many diseases affecting a wide array of organ systems,including cancer and embryological defects,and can even cause embryonic *** complexity of this system and its interacting proteins have made Wnt signaling a target for many therapeutic ***,both stimulatory and inhibitory treatments come with potential risks that need to be *** review synthesized much of the current knowl-edge on the Wnt signaling pathway,beginning with the history of Wnt *** thoroughly described the different variants of Wnt signaling,including canonical,noncanonical Wnt/PCP,and the noncanonical Wnt/Ca2+*** description involved each of its components and their involvement in other cellular ***,this review explained the various other pathways and processes that crosstalk with Wnt signaling.

关键词： β-catenin Canonical Wnt Noncanonical Wnt Signal transduction Signaling crosstalk

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Reversibly immortalized keratinocytes(iKera)facilitate re-epithelization and skin wound healing:Potential applications in cell-based skin tissue engineering

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Bioactive Materials 2022年第3期7卷 523-540页

作者： Jiamin Zhong Hao Wang Ke Yang Huifeng Wang Chongwen Duan Na Ni Liqin An Yetao Luo Piao Zhao Yannian Gou Shiyan Sheng Deyao Shi connie chen William Wagstaff b Bryce Hendren-Santiago b Rex C.Haydon b Hue H.Luu b Russell R.Reid Sherwin HHo Guillermo A.Ameer Le Shen Tong-Chuan He Jiaming Fan Ministry of Education Key Laboratory of Diagnostic Medicine And Department of Clinical BiochemistrySchool of Laboratory MedicineChongqing Medical UniversityChongqing400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL60637USA The Pediatric Research Institute The Children’s Hospital of Chongqing Medical UniversityChongqing400014China Biomedical Engineering Department Northwestern UniversityEvanstonIL60208USA Department of Orthopaedics Union Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of Surgery The University of Chicago Medical CenterChicagoIL60637USA Center for Advanced Regenerative Engineering(CARE) EvanstonIL60208USA Department of Surgery Northwestern University Feinberg School of MedicineChicagoIL60616USA

Skin injury is repaired through a multi-phase wound healing process of tissue granulation and *** failure in the healing process may lead to chronic non-healing wounds or abnormal scar *** significant progress has been made in developing novel scaffolds and/or cell-based therapeutic strategies to promote wound healing,effective management of large chronic skin wounds remains a clinical *** are critical to re-epithelialization and wound ***,we investigated whether exogenous keratinocytes,in combination with a citrate-based scaffold,enhanced skin wound *** first established reversibly immortalized mouse keratinocytes(iKera),and confirmed that the iKera cells expressed keratinocyte markers,and were responsive to UVB treatment,and were *** a proof-of-principle experiment,we demonstrated that iKera cells embedded in citrate-based scaffold PPCN provided more effective re-epithelialization and cutaneous wound healing than that of either PPCN or iKera cells alone,in a mouse skin wound ***,these results demonstrate that iKera cells may serve as a valuable skin epithelial source when,combining with appropriate biocompatible scaffolds,to investigate cutaneous wound healing and skin regeneration.

关键词： Keratinocytes Skin tissue engineering Reversible immortalization SV40 large T antigen PPCN Skin wound healing

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Argonaute(AGO)proteins play an essential role in mediating BMP9-induced osteogenic signaling in mesenchymal stem cells(MSCs)

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Genes & Diseases 2021年第6期8卷 918-930页

作者： Yukun Mao Na Ni Linjuan Huang Jiaming Fan Hao Wang Fang He Qing Liu Deyao Shi Kai Fu Mikhail Pakvasa William Wagstaff Andrew Blake Tucker connie chen Russell R.Reid Rex C.Haydon Sherwin H.Ho Michael J.Lee Tong-Chuan He Jian Yang Le Shen Lin Cai Hue H.Luu Departments of Spine Surgery and Musculoskeletal Tumor and NeurosurgeryZhongnan Hospital of Wuhan UniversityWuhanHubei Province430072PR China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and the School of Laboratory MedicineChongqing Medical UniversityChongqing400016PR China Departments of Nephrology and Obstetrics and GynecologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqing400016PR China Department of Spine Surgery Second Xiangya HospitalCentral South UniversityChangshaHunan Province410011PR China Department of Orthopaedic Surgery Union Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei Province430022PR China Section of Plastic Surgery and Laboratory of Craniofacial Biology and Development and Section of Surgical ResearchDepartment of SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Department of Biomedical Engineering Materials Research InstituteThe Huck Institutes of the Life SciencesThe Pennsylvania State UniversityUniversity ParkPA 16802USA

As multipotent progenitor cells,mesenchymal stem cells(MSCs)can renew themselves and give rise to multiple lineages including osteoblastic,chondrogenic and adipogenic ***’s previously shown that BMP9 is the most potent BMP and induces osteogenic and adipogenic differentiation of ***,the molecular mechanism through which BMP9 regulates MSC differentiation remains poorly *** evidence indicates that noncoding RNAs,especially microRNAs,may play important roles in regulating MSC differentiation and bone *** highly conserved RNA binding proteins,Argonaute(AGO)proteins are essential components of the multi-protein RNA-induced silencing complexes(RISCs),which are critical for small RNA ***,we investigate possible roles of AGO proteins in BMP9-induced lineage-specific differentiation of *** first found that BMP9 upregulated the expression of Ago1,Ago2 and Ago3 in *** engineering multiplex siRNA vectors that express multiple siRNAs targeting individual Ago genes or all four Ago genes,we found that silencing individual Ago expression led to a decrease in BMP9-induced early osteogenic marker alkaline phosphatase(ALP)activity in ***,we demonstrated that simultaneously silencing all four Ago genes significantly diminished BMP9-induced osteogenic and adipogenic differentiation of MSCs and matrix mineralization,and ectopic bone ***,our findings strongly indicate that AGO proteins and associated small RNA biogenesis pathway play an essential role in mediating BMP9-induced osteogenic differentiation of MSCs.

关键词： Argonaute(AGO)proteins BMP9 Bone formation Lineage-specific differentiation Mesenchymal stem cells miRNA biogenesis Osteogenic signaling

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北京城区公园景观格局对夏季鸟类群落的影响

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景观设计学（中英文） 2016年第3期4卷 10-21页

作者：谢世林逯非曹垒周伟奇欧阳志云中国科学技术大学中国科学院生态环境研究中心中国科学院生态环境研究中心城市与区域生态国家重点实验室

城市公园是最重要的城市绿地类型,也是当前城市生物多样性研究的热点。公园面积及其景观格局特征对鸟类的影响规律对公园的设计和管理具有重要指导意义。本研究以城区29个公园为对象,利用高分辨率(1m)的卫星数据,研究了公园面积、景观... 详细信息

城市公园是最重要的城市绿地类型,也是当前城市生物多样性研究的热点。公园面积及其景观格局特征对鸟类的影响规律对公园的设计和管理具有重要指导意义。本研究以城区29个公园为对象,利用高分辨率(1m)的卫星数据,研究了公园面积、景观破碎度、林地和人工表面比例、林地最大斑块指数、景观聚集度指数、景观多样性及均匀度指数等公园景观格局特征,探讨了公园景观格局特征对夏季鸟类群落的影响。结果表明,北京城区公园面积平均值较小(约为13.9hm^2),公园中林地比例较高(平均约为74.7%),林地景观是公园的优势景观类型,但景观破碎化程度很高(平均约为8.63个/hm^2),且景观聚集度指数偏低(平均约为63.0)。公园中平均鸟类物种数为13.2种,鸟类物种数与公园面积、景观聚集度、林地面积比例呈显著正相关,而与景观均匀度、斑块密度、景观多样性呈显著负相关,本研究表明,由于平均斑块面积小,公园景观多样性和均匀度指数对鸟类物种丰富度有明显的不利影响,研究结果可以为城市公园的设计提供参考。

关键词：城市公园景观格局鸟类群落生物多样性景观设计北京

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Urban recreational water – potential breeding ground for antibiotic resistant bacteria?

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Journal of Environmental Sciences 2019年第7期31卷 1-3页

作者： Jing Yang Xu connie Le Baowei chen Hongquan Zhang Division of Analytical and Environmental Toxicology Department of Laboratory Medicine and Pathology Faculty of Medicine & DentistryUniversity of Alberta Li Ka Shing Institute of Virology Department of Medical Microbiology and Immunology University of Alberta Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering School of Marine Sciences Sun Yat-Sen University

The emergence of multidrug-resistant bacteria, or'superbugs,' has become an urgent and worldwide ***-resistant bacteria (ARB) cause significant morbidity and mortality (O’Neill, 2016). It has been estimated that ARB cause at least 23,000 deaths annually in the United States alone and hundreds of thousands of deaths in developing countries (Bougnom and Piddock, 2017).

关键词： Antibiotic resistance genes (ARGs) Multidrug resistance in bacteria Microbial pathogens Lake water and sediment

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