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Genes & Diseases 2024年第3期11卷 26-29页

作者： Xiangyu Dong Yannian Gou Meichun Guo Jiamin Zhong Aohua Li Ailing hao Wei Zeng Rex C.haydon hue h.luu Russell R.Reid Tongchuan he Yan Xu Jiaming Fan Ministry of Education Key Laboratory of Diagnostic Medicine And Department of Clinical BiochemistryCollege of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Institute of Sports Medicine Beijing Key Laboratory of Sports InjuriesPeking University Third HospitalBejing 100191China

With the rapid advances in stem cell research and po-tential cell-based therapies,there is an urgent need to develop safe and reliable cell transport *** for autologous stem cell-based therapies,allogeneic stem cell therapies and ex vivo genetically engineered cell therapies would require safe,efficient,and reliable cell preservation and transport methods.

关键词： transport methods simplified

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

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

Transient response of doubly-curved bio-inspired composite shells resting on viscoelastic foundation subject to blast load using improved first-order shear theory and isogeometric approach

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Defence Technology（防务技术） 2024年第8期38卷 171-193页

作者： Thuy Tran Thi Thu Tu Nguyen Anh hue Nguyen Thi hong Nguyen Thi School of Mechanical and Automotive Engineering Hanoi University of IndustryHanoiViet Nam Faculty of Technical Fundamental University of Transport TechnologyHanoiViet Nam Faculty of Mechanical Engineering Thuyloi University175 Tay SonDong DaHanoiViet Nam

Investigating natural-inspired applications is a perennially appealing subject for scientists. The current increase in the speed of natural-origin structure growth may be linked to their superior mechanical properties and environmental resilience. Biological composite structures with helicoidal schemes and designs have remarkable capacities to absorb impact energy and withstand damage. however, there is a dearth of extensive study on the influence of fiber redirection and reorientation inside the matrix of a helicoid structure on its mechanical performance and reactivity. The present study aimed to explore the static and transient responses of a bio-inspired helicoid laminated composite(B-ihLC) shell under the influence of an explosive load using an isomorphic method. The structural integrity of the shell is maintained by a viscoelastic basis known as the Pasternak foundation, which encompasses two coefficients of stiffness and one coefficient of damping. The equilibrium equations governing shell dynamics are obtained by using hamilton's principle and including the modified first-order shear theory,therefore obviating the need to employ a shear correction factor. The paper's model and approach are validated by doing numerical comparisons with respected publications. The findings of this study may be used in the construction of military and civilian infrastructure in situations when the structure is subjected to severe stresses that might potentially result in catastrophic collapse. The findings of this paper serve as the foundation for several other issues, including geometric optimization and the dynamic response of similar mechanical structures.

关键词： Blast load Modified first-order shear theory Biological composite structures

Engineered nucleus-free mesenchymal stem cells (MSCs) for the targeted delivery of therapeutics to disease site

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Genes & Diseases 2023年第2期10卷 310-312,I0001页

作者： Zander Schwartz Piao Zhao Annie Wang Guozhi Zhao Wei Zeng Yonghui Wang hue h. luu Rex C. haydon Tong-Chuan he Russell R. Reid Jason Strelzow School of Biomedical Engineering Vanderbilt UniversityNashvilleTN 37235USA Molecular Oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA 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 200000China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Specialized therapeutic delivery, or use of pharmaceuticals and other biomaterials to target specific parts of the body or diseased tissue, has long been sought as an ideal way of treating human diseases. A recent article published in Nature Biomedical Engineering revealed an innovative strategy to engineer nucleus-free human mesenchymal stem cells (MSCs) for targeted delivery of therapeutics to disease site.1 MSCs have emerged as promising vehicles of therapeutic delivery.2,3 MSCs are undifferentiated pluripotent stem cells derived from areas such as bone marrow and adipose tissue.4,5 MSCs are sought after for their chemotaxis, or ability to home towards a chemical stimulus, and capacity for modification with elements such as chemoattractant receptors and adhesion molecules.1 These properties allow for site-specific and minimally-invasive therapeutic administration and treatment.

关键词： targeted delivery sought

3-D bioprinting technologies in tissue engineering and regenerative medicine:Current and future trends

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Genes & Diseases 2017年第4期4卷 185-195页

作者： Elliot S.Bishop Sami Mostafa Mikhail Pakvasa hue h.luu Michael J.Lee Jennifer Moriatis Wolf Guillermo A.Ameer Tong-Chuan he Russell R.Reid Laboratory of Craniofacial Biology and Development Section of Plastic and Reconstructive SurgeryDepartment of SurgeryThe University of Chicago MedicineChicagoIL 60637USA Molecular Oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA The University of Chicago Pritzker School of Medicine ChicagoIL 60637USA Biomedical Engineering Department Northwestern UniversityEvanstonIL 60208USA Department of Surgery Feinberg School of MedicineNorthwestern UniversityChicagoIL 60616USA

Advances in three-dimensional(3D)printing have increased feasibility towards the synthesis of living *** as 3D bioprinting,this technology involves the precise layering of cells,biologic scaffolds,and growth factors with the goal of creating bioidentical tissue for a variety of *** successes have demonstrated distinct advantages over conventional tissue engineering *** surprisingly,there are current challenges to address before 3D bioprinting becomes clinically *** we provide an overview of 3D bioprinting technology and discuss key advances,clinical applications,and current *** 3D bioprinting is a relatively novel tissue engineering strategy,it holds great potential to play a key role in personalized medicine.

关键词： Additive manufacturing Bioprinting CAD/CAM 3D printing Tissue engineering

Molecular pathogenesis and therapeutic strategies of human osteosarcoma

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The Journal of Biomedical Research 2016年第1期30卷 5-18页

作者： Sahitya K Denduluri Zhongliang Wang Zhengjian Yan Jing Wang Qiang Wei Maryam K Mohammed Rex C haydon hue h luu Tong-Chuan he The University of Chicago Pritzker School of Medicine and Molecular Oncology LaboratoryDepartment of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and the Affiliated Hospitals of Chongqing Medical UniversityChongqing 400016China

Osteosarcoma（OS）is a devastating illness with rapid rates of dissemination and a poor overall prognosis,despite aggressive standard-of-care surgical techniques and combination chemotherapy *** the molecular mechanisms involved in disease pathogenesis and progression may offer insight into new therapeutic *** in mesenchymal stem cell differentiation,abnormal expression of oncogenes and tumor suppressors,and dysregulation within various important signaling pathways have all been implicated in development of various disease *** such,a variety of basic science and translational studies have shown promise in identifying novel markers and modulators of these disease-specific *** out of these and similar investigations,a variety of emerging therapies are now undergoing various phases of OS clinical *** broadly include angiogenesis inhibitors,drugs that act on the bone microenvironment,receptor tyrosine kinase inhibitors,immune system modulators,and other radio-or chemo-sensitizing *** new forms of drug delivery are being developed simultaneously,the possibility of targeting tumors locally while minimizing systemic toxicityis is seemingly more achievable now than *** this review,we not only summarize our current understanding of OS disease processes,but also shed light on the multitude of potential therapeutic strategies the scientific community can use to make long-term improvements in patient prognosis.

关键词： osteosarcoma soft tissue tumors bone tumors cancer therapy osteogenic tumors osteogenic differentiation

Niclosamide(NA)overcomes cisplatin resistance in human ovarian cancer

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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

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 h*luu 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

Insulin-like growth factor(IGF)signaling in tumorigenesis and the development of cancer drug resistance

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Genes & Diseases 2015年第1期2卷 13-25页

作者： Sahitya K.Denduluri Olumuyiwa Idowu Zhongliang Wang Zhan Liao Zhengjian Yan Maryam K.Mohammed Jixing Ye Qiang Wei Jing Wang Lianggong Zhao hue h.luu The University of Chicago Pritzker School of Medicine ChicagoIL 60637USA Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation Medicine5841 South Maryland AvenueMC 3079ChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine The Affiliated Hospitals of Chongqing Medical UniversityChongqing 400016China Department of Orthopaedic Surgery Xiang-Ya Hospital of Central South UniversityChangsha 410008China School of Bioengineering Chongqing UniversityChongqingChina Department of Orthopaedic Surgery the Second Affiliated Hospital of Lanzhou UniversityLanzhouGansu 730000China

One of the greatest obstacles to current cancer treatment efforts is the development of drug resistance by *** recent advances in diagnostic practices and surgical interventions,many neoplasms demonstrate poor response to adjuvant or neoadjuvant radiation and *** a result,the prognosis for many patients afflicted with these aggressive cancers remains *** insulin-like growth factor(IGF)signaling axis has been shown to play critical role in the development and progression of various *** basic science and translational studies have shown that IGF pathway modulators can have promising effects when used to treat various *** also exists a substantial body of recent evidence implicating IGF signaling dysregulation in the dwindling response of tumors to current standard-of-care *** better understanding both the IGF-dependent and-independent mechanisms by which pathway members can influence drug sensitivity,we can eventually aim to use modulators of IGF signaling to augment the effects of current *** review summarizes and synthesizes numerous recent investigations looking at the role of the IGF pathway in drug *** offer a brief overview of IGF signaling and its general role in neoplasia,and then delve into detail about the many types of human cancer that have been shown to have IGF pathway involvement in resistance and/or sensitization to ***,our hope is that such a compilation of evidence will compel investigators to carry out much needed studies looking at combination treatment with IGF signaling modulators to overcome current therapy resistance.

关键词： Cancer Insulin-like growth factor Resistance Therapy Tumorigenesis