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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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Stem cell therapy for chronic skin wounds in the era of personalized medicine:From bench to bedside

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Genes & Diseases 2019年第4期6卷 342-358页

作者： Elam Coalson Elliot Bishop Wei Liu Yixiao Feng Mia Spezia Bo Liu Yi Shen Di Wu Scott Du Alexander J.Li Zhenyu Ye Ling Zhao Daigui Cao Alissa Li Ofir Hagag Alison Deng Winny Liu Mingyang Li rex C.Haydon Lewis Shi Aravind Athiviraham Michael J.Lee Jennifer Moriatis Wolf Guillermo A.Ameer Tong-Chuan He russell r.reid The University of Chicago Pritzker School of Medicine ChicagoIL 60637USA Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Key Laboratory of Diagnostic Medicine(Ministry of Education) College of Laboratory MedicineChongqing Medical UniversityChongqingChina Department of Orthopaedic Surgery Xiangya Second Hospital of Central South UniversityChangsha 410011China Student Inquiry research Program Illinois Mathematics and Science Academy(IMSA)AuroraIL60506USA Department of General Surgery The Second Affiliated Hospital of Soochow UniversitySuzhou 215004China Department of Orthopaedic Surgery Chongqing General HospitalChongqing 400013China Department of Biomedical Engineering Northwestern UniversityEvanstonIL 60208USA Department of Surgery Northwestern University Feinberg School of MedicineChicagoIL 60616USA Center for Advanced regenerative Engineering(CArE) EvanstonIL 60208USA

With the significant financial burden of chronic cutaneous wounds on the healthcare system,not to the personal burden mention on those individuals afflicted,it has become increasingly essential to improve our clinical *** requires the translation of the most recent benchtop approaches to clinical wound repair as our current treatment modalities have proven *** most promising potential treatment options rely on stem cellbased *** cell proliferation and signaling play crucial roles in every phase of the wound healing process and chronic wounds are often associated with impaired stem cell *** approaches involving stem cells could thus be utilized in some cases to improve a body’s inhibited healing *** aim to present the laboratory research behind the mechanisms and effects of this technology as well as current clinical trials which showcase their therapeutic *** the current problems and complications presented by chronic wounds,we hope to show that developing the clinical applications of stem cell therapies is the rational next step in improving wound care.

关键词： Chronic inflammation Chronic wounds Growth factors Personalized medicine Skin Stem cells Wound healing

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Characterization of the essential role of bone morphogenetic protein 9 (BMP9) in osteogenic differentiation of mesenchymal stem cells (MSCs) through rNA interference

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Genes & Diseases 2018年第2期5卷 172-184页

作者： Shujuan Yan ruyi Zhang Ke Wu Jing Cui Shifeng Huang Xiaojuan Ji Liping An Chengfu Yuan Cheng Gong Linghuan Zhang Wei Liu Yixiao Feng Bo Zhang Zhengyu Dai Yi Shen Xi Wang Wenping Luo Bo Liu rex C.Haydon Michael J.Lee russell r.reid Jennifer Moriatis Wolf Qiong Shi Hue H.Luu Tong-Chuan He Yaguang Weng Ministry of Education Key Laboratory of Diagnostic Medicine and School of Laboratory Medicine Chongqing Medical UniversityChongqing 400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA The School of Pharmacy and the Affiliated Hospitals of Chongqing Medical University Chongqing 400016China Key Laboratory of Orthopaedic Surgery of Gansu Province and the Department of Orthopaedic Surgery The Second Hospital of Lanzhou UniversityLanzhou730030China Department of Biochemistry and Molecular Biology China Three Gorges University School of MedicineYichang 443002China Department of Surgery The Affiliated Zhongnan Hospital of Wuhan UniversityWuhan 430071China Department of Orthopaedic Surgery Chongqing Hospital of Traditional Chinese MedicineChongqing 400021China Department of Orthopaedic Surgery Xiangya Second Hospital of Central South UniversityChangsha 410011China Department of Surgery Laboratory of Craniofacial Biology and DevelopmentSection of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Mesenchymal stem cells(MSCs)are multipotent stem cells and capable of differentiating into multiple cell types including osteoblastic,chondrogenic and adipogenic *** previously identified BMP9 as one of the most potent BMPs that induce osteoblastic differentiation of MSCs although exact molecular mechanism through which BMP9 regulates osteogenic differentiation remains to be fully ***,we seek to develop a recombinant adenovirus system to optimally silence mouse BMP9 and then characterize the important role of BMP9 in osteogenic differentiation of *** two different sirNA bioinformatic prediction programs,we design five sirNAs targeting mouse BMP9(or simB9),which are expressed under the control of the converging H1 and U6 promoters in recombinant adenovirus *** demonstrate that two of the five sirNAs,simB9-4 and simB9-7,exhibit the highest efficiency on silencing exogenous mouse BMP9 in ***,simB9-4 and simB9-7 act synergistically in inhibiting BMP9-induced expression of osteogenic markers,matrix mineralization and ectopic bone formation from ***,our findings demonstrate the important role of BMP9 in osteogenic differentiation of *** characterized simB9 sirNAs may be used as an important tool to investigate the molecular mechanism behind BMP9 osteogenic *** results also indicate that recombinant adenovirus-mediated expression of sirNAs is efficient and sustained,and thus may be used as an effective delivery vehicle of sirNA therapeutics.

关键词： BMP9 Bone formation Mesenchymal stem cells Osteogenic differentiation rNA interference recombinant adenovirus sirNA

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Modeling colorectal tumorigenesis using the organoids derived from conditionally immortalized mouse intestinal crypt cells (ciMICs)

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Genes & Diseases 2021年第6期8卷 814-826页

作者： Xiaoxing Wu Zhaoxia Li Hongyu Zhang Fang He Min Qiao Huaxiu Luo Jing Zhang Meng Zhang Yukun Mao William Wagstaff Yongtao Zhang Changchun Niu Xia Zhao Hao Wang Linjuan Huang Deyao Shi Qing Liu Na Ni Kai Fu rex C.Haydon russell r.reid Hue H.Luu Tong-Chuan He Ziwei Wang Houjie Liang Bing-Qiang Zhang Ning Wang Departments of Gastrointestinal Surgery Medicine/Gastroenterologyand Obstetrics and GynecologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqing400016PR China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 606037USA Department of Oncology The PLA Rocket Force Characteristic Medical CenterBeijing100088PR China Departments of Burn&Plastic Surgery West China Hospital of Sichuan UniversityChengduSichuan Province610041PR China Department of Orthopaedic Surgery The First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhouGuangdong Province510405PR China Departments of Orthopaedic Surgery The Affiliated Zhongnan Hospital of Wuhan UniversityWuhanHubei Province430071PR China Department of Orthopaedic Surgery The Affiliated Hospital of Qingdao UniversityQingdaoShandong Province266000PR China Department of Clinical Laboratory Medicine Chongqing General Hospital Affiliated with the University of Chinese Academy of SciencesChongqing400013PR China Ministry of Education Key Laboratory of Diagnostic Medicine and the School of Laboratory Diagnostic MedicineChongqing Medical UniversityChongqing400016PR China Department of Orthopaedics Union Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei Province430022PR China Department of Spine Surgery Second Xiangya HospitalCentral South UniversityChangshaHunan Province410008PR China Department of Oncology and Southwest Cancer Center Southwest HospitalArmy Medical UniversityChongqing400038PR China

Intestinal cancers are developed from intestinal epithelial stem cells(ISCs)in intestinal crypts through a multi-step process involved in genetic mutations of oncogenes and tumor suppressor *** play a key role in maintaining the homeostasis of gut *** 2009,Sato et al established a three-dimensional culture system,which mimicked the niche microenvironment by employing the niche factors,and successfully grew crypt ISCs into organoids or Mini-guts in *** then,the intestinal organoid technology has been used to delineate cellular signaling in ISC ***,the cultured organoids consist of heterogeneous cell populations,and it was technically challenging to introduce genomic changes into three-dimensional ***,there was a technical necessity to develop a twodimensional ISC culture system for effective genomic *** this study,we established a conditionally immortalized mouse intestinal crypt(ciMIC)cell line by using a piggyBac transposon-based SV40 T antigen expression *** showed that the ciMICs maintained long-term proliferative activity under two-dimensional niche factor-containing culture condition,retained the biological characteristics of intestinal epithelial stem cells,and could form intestinal organoids in three-dimensional *** in vivo cell implantation tests indicated that the ciMICs were non-tumorigenic,the ciMICs overexpressing oncogenic b-catenin and/or KrAS exhibited high proliferative activity and developed intestinal adenoma-like pathological features in ***,these findings strongly suggested that the engineered ciMICs should be used as a valuable tool cell line to dissect the genetic and/or epigenetic underpinnings of intestinal tumorigenesis.

关键词： Cancer modeling Conditional immortalization Mini-gut organoids Mouse intestinal crypt(MIC)cells Tumorigenesis

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The wonders of BMP9:From mesenchymal stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism to regenerative medicine

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Genes & Diseases 2019年第3期6卷 201-223页

作者： Sami Mostafa Mikhail Pakvasa Elam Coalson Allen Zhu Alex Alverdy Hector Castillo Jiaming Fan Alex Li Yixiao Feng Di Wu Elliott Bishop Scott Du Mia Spezia Alissa Li Ofir Hagag Alison Deng Winny Liu Mingyang Li Sherwin S·Ho Aravind Athiviraham Michael J·Lee Jennifer Moriatis Wolf Guillermo A·Ameer Hue H·Luu rex C·Haydon Jason Strelzow Kelly Hynes Tong-Chuan He russell r.reid The University of Chicago Pritzker School of Medicine ChicagoIL 60637USA Laboratory of Craniofacial Biology and Development Section of Plastic and Reconstructive SurgeryDepartment of SurgeryThe University of Chicago MedicineChicagoIL 60637USA Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA rosalind Franklin University Chicago Medical SchoolNorth ChicagoIL 60064USA SIr Program Illinois Math and Science Academy(IMSA)AuroraIL 60506USA Department of Biomedical Engineering Northwestern UniversityEvanstonIL60208USA The Department of Surgery Feinberg School of MedicineNorthwestern UniversityChicagoIL60616USA

Although bone morphogenetic proteins(BMPs)initially showed effective induction of ectopic bone growth in muscle,it has since been determined that these proteins,as members of the TGF-b superfamily,play a diverse and critical array of biological *** roles include regulating skeletal and bone formation,angiogenesis,and development and homeostasis of multiple organ *** of the members of the TGF-b/BMP superfamily result in severe skeletal and extra-skeletal irregularities,suggesting high therapeutic potential from understanding this family of BMP *** it was once one of the least characterized BMPs,BMP9 has revealed itself to have the highest osteogenic potential across numerous experiments both in vitro and in vivo,with recent studies suggesting that the exceptional potency of BMP9 may result from unique signaling pathways that differentiate it from other *** effectiveness of BMP9 in inducing bone formation was recently revealed in promising experiments that demonstrated efficacy in the repair of critical sized cranial defects as well as compatibility with bone-inducing bio-implants,revealing the great translational promise of ***,emerging evidence indicates that,besides its osteogenic activity,BMP9 exerts a broad range of biological functions,including stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and *** review aims to summarize our current understanding of BMP9 across biology and the body.

关键词： Adipogenesis Bone morphogenetic proteins(BMPs) BMP9/GDF2 Mesenchymal stem cells(MSCs) Metabolism Osteogenesis regenerative medicine Tumorigenesis

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Notch signaling:Its essential roles in bone and craniofacial development

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Genes & Diseases 2021年第1期8卷 8-24页

作者： Mikhail Pakvasa Pranav Haravu Michael Boachie-Mensah Alonzo Jones Elam Coalson Junyi Liao Zongyue Zeng Di Wu Kevin Qin Xiaoxing Wu Huaxiu Luo Jing Zhang Meng Zhang Fang He Yukun Mao Yongtao Zhang Changchun Niu Meng Wu Xia Zhao Hao Wang Linjuan Huang Deyao Shi Qing Liu Na Ni Kai Fu Michael J.Lee Jennifer Moriatis Wolf Aravind Athiviraham Sherwin S.Ho Tong-Chuan He Kelly Hynes Jason Strelzow Mostafa El Dafrawy russell r.reid Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Pritzker School of Medicine University of ChicagoChicagoIL 60637USA Section of Plastic and reconstructive Surgery Department of SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Departments of Orthopaedic Surgery Gastrointestinal SurgeryObstetrics and Gynecologyand NephrologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqing400016PR China Ministry of Education Key Laboratory of Diagnostic Medicine and School of Laboratory and Diagnostic MedicineChongqing Medical UniversityChongqing400016PR China Department of Burn and Plastic Surgery West China Hospital of Sichuan UniversityChengduSichuan610041PR China Department of Orthopaedic Surgery The First Affiliated HospitalGuangzhou University of Chinese MedicineGuangzhouGuangdong510405PR China Departments of Orthopaedic Surgery and Neurosurgery The Affiliated Zhongnan Hospital of Wuhan UniversityWuhanHubei430072PR China Department of Orthopaedic Surgery The Affiliated Hospital of Qingdao UniversityQingdaoShandong266061PR China Department of Laboratory Diagnostic Medicine Chongqing General HospitalChongqing400021PR China Institute of Bone and Joint research and the Department of Orthopaedic SurgeryThe Second Hospitals of Lanzhou UniversityGansuLanzhou730030PR China Department of Orthopaedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei430072PR China Department of Spine Surgery Second Xiangya HospitalCentral South UniversityChangshaHunan410011PR China

Notch is a cellecell signaling pathway that is involved in a host of activities including development,oncogenesis,skeletal homeostasis,and much *** specifically,recent research has demonstrated the importance of Notch signaling in osteogenic differentiation,bone healing,and in the development of the *** craniofacial skeleton is complex and understanding its development has remained an important focus in *** this review we briefly summarize what recent research has revealed about Notch signaling and the current understanding of how the skeleton,skull,and face *** then discuss the crucial role that Notch plays in both craniofacial development and the skeletal system,and what importance it may play in the future.

关键词： Alagille syndrome Bone Craniofacial development Craniosynostosis Notch Oncogenesis Osteogenesis Spondylocostal dysosotosis

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The development of a sensitive fluorescent protein-based transcript reporter for high throughput screening of negative modulators of lncrNAs

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Genes & Diseases 2018年第1期5卷 62-74页

作者： Zongyue Zeng Bo Huang Shifeng Huang ruyi Zhang Shujuan Yan Xinyi Yu Yi Shu Chen Zhao Jiayan Lei Wenwen Zhang Chao Yang Ke Wu Ying Wu Liping An Xiaojuan Ji Cheng Gong Chengfu Yuan Linghuan Zhang Wei Liu Yixiao Feng Bo Zhang Zhengyu Dai Yi Shen Xi Wang Wenping Luo rex C.Haydon Hue H.Luu Lan Zhou russell r.reid Tong-Chuan He Xingye Wu Ministry of Education Key Laboratory of Diagnostic Medicine and School of Laboratory Medicine Chongqing Medical UniversityChongqing400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL60637USA Department of Clinical Laboratory Medicine The Second Affiliated Hospital of Nanchang UniversityNanchang330006China Departments of Clinical Laboratory Medicine General SurgeryOrthopedic SurgeryNephrologyand CardiologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqing400016China The Children’s Hospital Chongqing Medical UniversityChongqing400014China Department of Laboratory Medicine and Clinical Diagnostics The Affiliated Yantai HospitalBinzhou Medical UniversityYantai264100China Department of Immunology and Microbiology Beijing University of Chinese MedicineBeijing100029China Key Laboratory of Orthopaedic Surgery of Gansu Province and the Department of Orthopaedic Surgery The Second Hospital of Lanzhou UniversityLanzhou730030China Department of Surgery The Affiliated Zhongnan Hospital of Wuhan UniversityWuhan430071China Department of Biochemistry and Molecular Biology China Three Gorges University School of MedicineYichang443002China Department of Orthopaedic Surgery Chongqing Hospital of Traditional Chinese MedicineChongqing400021China Department of Orthopaedic Surgery Xiangya Second Hospital of Central South UniversityChangsha410011China Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences Chongqing401147China The Affiliated Hospital of Stomatology of Chongqing Medical University Chongqing401147China Department of Surgery Laboratory of Craniofacial Biology and DevelopmentSection of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL60637USA

While the human genome is pervasively transcribed,<2%of the human genome is transcribed into protein-coding mrNAs,leaving most of the transcripts as noncoding rNAs,such as microrNAs and long-noncoding rNAs(lncrNAs),wh... 详细信息

While the human genome is pervasively transcribed,ranscribed into protein-coding mrNAs,leaving most of the transcripts as noncoding rNAs,such as microrNAs and long-noncoding rNAs(lncrNAs),which are critical components of epigenetic *** are emerging as critical regulators of gene expression and genomic ***,it remains largely unknown about how lncrNAs are ***,we develop a highly sensitive and dynamic reporter that allows us to identify and/or monitor negative modulators of lncrNA transcript levels in a high throughput ***,we engineer a fluorescent fusion protein by fusing three copies of the PEST destruction domain of mouse ornithine decarboxylase(MODC)to the C-terminal end of the codon-optimized bilirubin-inducible fluorescent protein,designated as dBiFP,and show that the dBiFP protein is highly destabilized,compared with the commonly-used eGFP *** further demonstrate that the dBiFP signal is effectively down-regulated when the dBiFP and mouse lncrNA H19 chimeric transcript is silenced by mouse H19-specific ***,our results strongly suggest that the dBiFP fusion protein may serve as a sensitive and dynamic transcript reporter to monitor the inhibition of lncrNAs by microrNAs,synthetic regulatory rNA molecules,rNA binding proteins,and/or small molecule inhibitors so that novel and efficacious inhibitors targeting the epigenetic circuit can be discovered to treat human diseases such as cancer and other chronic disorders.

关键词： BiFP Green fluorescent protein High throughput screening lncrNA Noncoding rNA Transcript reporter assay

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Long noncoding rNA(lncrNA)H19:An essential developmental regulator with expanding roles in cancer,stem cell differentiation,and metabolic diseases

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Genes & Diseases 2023年第4期10卷 1351-1366页

作者： Junyi Liao Bowen Chen Zhenglin Zhu Chengcheng Du Shengqiang Gao Guozhi Zhao Piao Zhao Yonghui Wang Annie Wang Zander Schwartz Lily Song Jeffrey Hong William Wagstaff rex CHaydon Hue HLuu Jiaming Fan russell rreid Tong-Chuan He Lewis Shi Ning Hu Wei Huang Departments of Orthopedic Surgery and Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Orthopedic research Center Chongqing Medical UniversityChongqing 400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China School of Biomedical Engineering Vanderbilt UniversityNashvilleTN 37235USA The Medical Scientist Training Program The University of Chicago Pritzker School of MedicineChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

recent advances in deep sequencing technologies have revealed that,while less than 2%of the human genome is transcribed into mrNA for protein synthesis,over 80%of the genome is transcribed,leading to the production of large amounts of noncoding rNAs(ncrNAs).It has been shown that ncrNAs,especially long non-coding rNAs(lncrNAs),may play crucial regulatory roles in gene *** one of the first isolated and reported lncrNAs,H19 has gained much attention due to its essential roles in regulating many physiological and/or pathological processes including embryogenesis,development,tumorigenesis,osteogen-esis,and ***,H19 mediates diverse regulatory functions by serving as competing endogenous rNAs(CerNAs),Igf2/H19 imprinted tandem gene,modular scaffold,cooperating with H19 antisense,and acting directly with other mrNAs or ***,we summarized the current understanding of H19 in embryogenesis and development,cancer development and progression,mesenchymal stem cell lineage-specific differentiation,and metabolic *** discussed the potential regulatory mechanisms underlying H19’s func-tions in those processes although more in-depth studies are warranted to delineate the exact molecular,cellular,epigenetic,and genomic regulatory mechanisms underlying the physiolog-ical and pathological roles of ***,these lines of investigation may lead to the development of novel therapeutics for human diseases by exploiting H19 functions.

关键词： Cancer Epigenetic regulation H19 LncrNA Long-noncoding rNA Metabolic diseases Stem cell differentiation

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Development of gradient boosting-assisted machine learning data-driven model for free chlorine residual prediction

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Frontiers of Environmental Science & Engineering 2024年第2期18卷 35-46页

作者： Wiley Helm Shifa Zhong Elliot reid Thomas Igou Yongsheng Chen School of Civil and Environmental Engineering Georgia Institute of TechnologyAtlantaGA 30332USA School of Ecological and Environmental Sciences East China Normal UniversityShanghai 200241China

Chlorine-based disinfection is ubiquitous in conventional drinking water treatment (DWT) and serves to mitigate threats of acute microbial disease caused by pathogens that may be present in source water. An important index of disinfection efficiency is the free chlorine residual (FCr), a regulated disinfection parameter in the US that indirectly measures disinfectant power for prevention of microbial recontamination during DWT and distribution. This work demonstrates how machine learning (ML) can be implemented to improve FCr forecasting when supplied with water quality data from a real, full-scale chlorine disinfection system in Georgia, USA. More precisely, a gradient-boosting ML method (CatBoost) was developed from a full year of DWT plant-generated chlorine disinfection data, including water quality parameters (e.g., temperature, turbidity, pH) and operational process data (e.g., flowrates), to predict FCr. Four gradient-boosting models were implemented, with the highest performance achieving a coefficient of determination, r2, of 0.937. Values that provide explanations using Shapley’s additive method were used to interpret the model’s results, uncovering that standard DWT operating parameters, although non-intuitive and theoretically non-causal, vastly improved prediction performance. These results provide a base case for data-driven DWT disinfection supervision and suggest process monitoring methods to provide better information to plant operators for implementation of safe chlorine dosing to maintain optimum FCr.

关键词： Machine learning Data-driven modeling Drinking water treatment Disinfection Chlorination

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APPrOXIMATE ESTIMATION OF HArDENING-SOFTENING BEHAVIOUr OF CIrCULAr PIPES SUBJECTED TO PUrE BENDING

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Acta Mechanica Sinica 1997年第3期13卷 227-240页

作者：杨嘉陵 S.r.reid The Solid Mechanics research Centre Beijing University of Aeronautics and AstronauticsBeijing 100083China Department of Mechanical Engineering UMISTP.O.Box 88Manchester M60 1QDUK

An approximate method for describing the plastic hardening-softening behaviour of circular pipes subjected to pure bending is presented. Theoretical estimation based on the uniform ovalization model and local collapse model proposed in the paper is incorporated to give several simple formulations with reasonable accuracy for determining the relationship between bending moment (M) and curvature (kappa) in the purely bended pipes. Attention is focused on the critical curvature associated with maximum resistant moment and the maximum change in the original diameter before the end of uniform ovalization stage as well as the local collapse behaviour. Some comparisons between analytical results and experimental results are made in order to examine the theory.

关键词： hardening-softening behaviour pure bended pipes circular pipes deformation characteristics of pipes

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