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Polyphyllin Ⅰ enhances tumor necrosis factor-related apoptosis-inducing ligand-induced inhibition of human osteosarcoma cell growth via downregulating the Wnt/β-catenin pathway

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Journal of Traditional Chinese Medicine 2024年第2期44卷 251-259页

作者： CHANG Junli ZHAO Fulai SUN Xingyuan MA Xiaoping ZHAO Peng ZHOU Chujie SHI Binhao GU Wenchao WANG Yongjun YANG Yanping spine Disease institute Longhua Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 200032China Department of Diagnostic and Interventional Radiology University of TsukubaIbaraki 315-0114Japan

OBJECTIVE:To investigate the synergistic effects of polyphyllin Ⅰ(PPⅠ)combined with tumor necrosis factorrelated apoptosis-inducing ligand(TRAIL)on the growth of osteosarcoma cells through downregulating the Wnt/β-catenin signaling ***:Cell viability,apoptosis and cell cycle distribution were examined using cell counting kit-8 and flow cytometry *** morphology of cancer cells was observed with inverted phase contrast *** migration and invasion abilities were examined by xCELLigence real time cell analysis DP system and transwell *** expressions of poly(adenosine diphosphate-ribose)polymerase,C-Myc,Cyclin B1,cyclin-dependent kinases 1,N-cadherin,Vimentin,Active-β-catenin,β-catenin,p-glycogen synthase kinase 3β(GSK-3β)and GSK-3βwere determined by Western blotting ***:PPⅠ sensitized TRAIL-induced decrease of viability,migration and invasion,as well as increase of apoptosis and cell cycle arrest of MG-63 and U-2 OS osteosarcoma *** synergistic effect of PPⅠwith TRAIL in inhibiting the growth of osteosarcoma cells was at least partially realized through the inactivation of Wnt/β-catenin signaling ***:The combination of PPⅠ and TRAIL is potentially a novel treatment strategy of osteosarcoma.

关键词： osteosarcoma tumor necrosis factor-related apoptosis-inducing ligand Wnt signaling pathway beta-catenin polyphyllinⅠ

Pharmacological interventions targeting the microcirculation following traumatic spinal cord injury

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Neural Regeneration research 2024年第1期19卷 35-42页

作者： Rongrong Wang Jinzhu Bai Department of spine and Spinal Cord Surgery Beijing Bo’ai HospitalChina Rehabilitation Research CenterBeijingChina School of Rehabilitation Medicine Capital Medical UniversityBeijingChina

Traumatic spinal cord injury is a devastating disorder chara cterized by sensory,motor,and autonomic dysfunction that seve rely compromises an individual's ability to perform activities of daily *** adve rse outcomes are closely related to the complex mechanism of spinal cord injury,the limited regenerative capacity of central neurons,and the inhibitory environment fo rmed by traumatic *** to the microcirculation is an important pathophysiological mechanism of spinal cord injury.A number of therapeutic agents have been shown to improve the injury environment,mitigate secondary damage,and/or promote regeneration and *** them,the spinal cord microcirculation has become an important target for the treatment of spinal cord *** inte rventions targeting the microcirculation can improve the microenvironment and promote recovery following spinal cord *** drugs target the structure and function of the spinal cord microcirculation and are essential for maintaining the normal function of spinal neuro ns,axons,and glial *** review discusses the pathophysiological role of spinal cord microcirculation in spinal cord injury,including its structure and histopathological ***,it summarizes the progress of drug therapies targeting the spinal cord mic rocirc ulation after spinal cord injury.

关键词： blood-spinal cord barrier drug therapy microcirculation microvascular blood flow neuroprotection pharmacological intervention pharmacotherapy spinal cord injury trauma

Loss of Tet hydroxymethylase activity causes mouse embryonic stem cell differentiation bias and developmental defects

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Science China Life Sciences 2024年第10期67卷 2132-2148页

作者： Mengting Wang Liping Wang Yanxin Huang Zhibin Qiao Shanru Yi Weina Zhang Jing Wang Guang Yang Xinyu Cui Xiaochen Kou Yanhong Zhao Hong Wang Cizhong Jiang Shaorong Gao Jiayu Chen Clinical and Translational research Center of Shanghai First Maternity and Infant Hospital Shanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji University Frontier Science Center for Stem Cell research Tongji University Shanghai Tenth People's Hospital School of MedicineTongji University Key Laboratory of spine and Spinal Cord Injury Repair and Regeneration of the Ministry of Education Orthopaedic Department of Tongji HospitalTongji University Shanghai institute of Stem Cell research and Clinical Translation

The TET family is well known for active DNA demethylation and plays important roles in regulating transcription, the epigenome and development. Nevertheless, previous studies using knockdown（KD） or knockout（KO） models to investigate the function of TET have faced challenges in distinguishing its enzymatic and nonenzymatic roles, as well as compensatory effects among TET family members, which has made the understanding of the enzymatic role of TET not accurate enough. To solve this problem, we successfully generated mice catalytically inactive for specific Tet members(Tetm/m). We observed that, compared with the reported KO mice, mutant mice exhibited distinct developmental defects, including growth retardation, sex imbalance, infertility, and perinatal lethality. Notably, Tetm/mmouse embryonic stem cells（mESCs） were successfully established but entered an impaired developmental program, demonstrating extended pluripotency and defects in ectodermal differentiation caused by abnormal DNA methylation. Intriguingly, Tet3, traditionally considered less critical for m ESCs due to its lower expression level, had a significant impact on the global hydroxymethylation, gene expression, and differentiation potential of mESCs. Notably, there were common regulatory regions between Tet1 and Tet3 in pluripotency regulation. In summary, our study provides a more accurate reference for the functional mechanism of Tet hydroxymethylase activity in mouse development and ESC pluripotency regulation.

关键词： Tet hydroxymethylase activity mESCs DNA demethylation 5hmC

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Human umbilical cord mesenchymal stem cell-derived exosomes loaded into a composite conduit promote functional recovery after peripheral nerve injury in rats

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Neural Regeneration research 2024年第4期19卷 900-907页

作者： Haoshuai Tang Junjin Li Hongda Wang Jie Ren Han Ding Jun Shang Min Wang Zhijian Wei Shiqing Feng Department of Othopaedics Tianjin Medical University General Hospital International Science and Technology Cooperation Base of Spinal Cord Injury Tianjin Key Laboratory of Spine and Spinal Cord InjuryDepartment of OrthopedicsTianjin Medical University General Hospital Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment Tianjin Lung Cancer InstituteTianjin Medical University General Hospital Department of Othopaedics Qilu Hospital of Shandong UniversityShandong University Centre for OthopedicsAdvanced Medical Research InstituteShandong University Orthopedic research Center of Shandong University&Advanced Medical research institute Cheeloo College of MedicineShandong University

Complete transverse injury of peripheral nerves is challenging to *** secreted by human umbilical cord mesenchymal stem cells are considered to play an important role in intercellular communication and regulate tissue *** previous studies,a collagen/hyaluronic acid sponge was shown to provide a suitable regeneration environment for Schwann cell proliferation and to promote axonal *** three-dimensional(3D)composite conduit contains a collagen/hyaluronic acid inner sponge enclosed in an electrospun hollow poly(lactic-co-glycolic acid)***,whether there is a synergy between the 3D composite conduit and exosomes in the repair of peripheral nerve injury remains *** this study,we tested a comprehensive strategy for repairing long-gap(10 mm)peripheral nerve injury that combined the 3D composite conduit with human umbilical cord mesenchymal stem cell-derived *** effectiveness was evaluated by sciatic functional index,sciatic nerve compound muscle action potential recording,recovery of muscle mass,measuring the cross-sectional area of the muscle fiber,Masson trichrome staining,and transmission electron microscopy of the regenerated nerve in *** results showed that transplantation of the 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes promoted peripheral nerve regeneration and restoration of motor function,similar to autograft *** CD31-positive endothelial cells were observed in the regenerated nerve after transplantation of the loaded conduit than after transplantation of the conduit without exosomes,which may have contributed to the observed increase in axon regeneration and distal nerve ***,the use of a 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes represents a promising cell-free therapeutic option for the treatment of peripheral nerve injury.

关键词： axon growth collagen exosome human umbilical cord mesenchymal stem cells hyaluronic acid muscular atrophy nerve guidance conduits peripheral nerve regeneration

6DOF pose estimation of a 3D rigid object based on edge-enhanced point pair features

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Computational Visual Media 2024年第1期10卷 61-77页

作者： Chenyi Liu Fei Chen Lu Deng Renjiao Yi Lintao Zheng Chenyang Zhu Jia Wang Kai Xu College of Computing National University of Defense TechnologyChangsha410073China Department of spine Surgery the Second Xiangya HospitalCentral South UniversityChangsha410011China Clinical Nursing Teaching and research Section the Second Xiangya HospitalChangsha410011China College of Meteorology and Oceanography National University of Defense TechnologyChangsha410073China Beijing institute of Tracking and Communication Technology Beijing100094China

The point pair feature(PPF)is widely used for 6D pose *** this paper,we propose an efficient 6D pose estimation method based on the PPF *** introduce a well-targeted down-sampling strategy that focuses on edge areas for efficient feature extraction for complex geometry.A pose hypothesis validation approach is proposed to resolve ambiguity due to symmetry by calculating the edge matching *** perform evaluations on two challenging datasets and one real-world collected dataset,demonstrating the superiority of our method for pose estimation for geometrically complex,occluded,symmetrical *** further validate our method by applying it to simulated punctures.

关键词： point pair feature(PPF) pose estimation object recognition 3D point cloud

Unresolved Excess Accumulation of Myelin-Derived Cholesterol Contributes to Scar Formation after Spinal Cord Injury

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research 2024年第1期2023卷 17-32页

作者： Bolin Zheng Yijing He Shuai Yin Xu Zhu Qing Zhao Huiyi Yang Zhaojie wang Rongrong Zhu Liming Cheng Key Laboratory of spine and Spinal Cord Injury Repair and Regeneration Ministry of EducationDepartment of OrthopedicsTongji HospitalSchool of MedicineTongji UniversityShanghai 200092China Frontier Science Center for Stem Cell research School of Life Science and TechnologyTongji UniversityShanghai 200092China Clinical Center for Brain and Spinal Cord research Tongji UniversityShanghai 200092China

Spinal cord injury triggers complex pathological cascades,resulting in destructive tissue damage and incomplete tissue *** formation is generally considered a barrier for regeneration in the central nervous ***,the intrinsic mechanism of scar formation after spinal cord injury has not been fully ***,we report that excess cholesterol accumulates in phagocytes and is inefficiently removed from spinal cord lesions in young adult ***,we observed that excessive cholesterol also accumulates in injured peripheral nerves but is subsequently removed by reverse ***,preventing reverse cholesterol transport leads to macrophage accumulation and fibrosis in injured peripheral ***,the neonatal mouse spinal cord lesions are devoid of myelin-derived lipids and can heal without excess cholesterol *** found that transplantation of myelin into neonatal lesions disrupts healing with excessive cholesterol accumulation,persistent macrophage activation,and *** internalization suppresses macrophage apoptosis mediated by CD5L expression,indicating that myelin-derived cholesterol plays a critical role in impaired wound *** together,our data suggest that the central nervous system lacks an efficient approach for cholesterol clearance,resulting in excessive accumulation of myelin-derived cholesterol,thereby inducing scar formation after injury.

关键词： healing Spinal impaired

Prognositic value of anoikis and tumor immune microenvironment-related gene in the treatment of osteosarcoma

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中南大学学报（医学版） 2024年第5期49卷 758-774页

作者： WANG Dong DENG Qing PENG Yi TONG Zhaochen LI Zixin HUANG Liping ZENG Jin LI Jinsong MIAO Jinglei CHEN Shijie Department of spine Surgery Third Xiangya HospitalCentral South UniversityChangsha 410013 Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical SciencesSchool of Life SciencesEast China Normal UniversityShanghai 200241China

Objective:Osteosarcoma is a highly aggressive primary malignant bone tumor commonly seen in children and adolescents,with a poor ***-dependent cell death(anoikis)has been proven to be indispensable in tumor metastasis,regulating the migration and adhesion of tumor cells at the primary ***,as a type of programmed cell death,anoikis is rarely studied in osteosarcoma,especially in the tumor immune *** study aims to clarify prognostic value of anoikis and tumor immune microenvironment-related gene in the treatment of ***:Anoikis-related genes(ANRGs)were obtained from *** information and ANRGs expression profiles of osteosarcoma patients were sourced from the therapeutically applicable research to generate effective therapies and Gene Expression Omnibus(GEO)*** highly associated with tumor immune microenvironment were identified by the estimate package and the weighted gene coexpression network analysis(WGCNA)*** learning algorithms were performed to construct long-term survival predictive strategy,each sample was divided into high-risk and low-risk subgroups,which was further verified in the GEO ***,based on single-cell RNA-seq from the GEO database,analysis was done on the function of signature genes in the osteosarcoma tumor ***:A total of 51 hub ANRGs closely associated with the tumor microenvironment were identified,from which 3 genes(MERTK,BNIP3,S100A8)were selected to construct the prognostic *** differences in immune cell activation and immune-related signaling pathways were observed between the high-risk and low-risk groups based on tumor microenvironment analysis(all P<0.05).Additionally,characteristic genes within the osteosarcoma microenvironment were identified in regulation of intercellular crosstalk through the GAS6-MERTK signaling ***:The prognostic model based on ANRGs and tumor microenvironment

关键词： anoikis tumor immune microenvironment bioinformatics prognosis osteosarcoma

Pivotal role for long noncoding RNAs in zygotic genome activation in mice

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Science China(Life Sciences) 2024年第5期67卷 958-969页

作者： Kang Chen Wenju Liu Jiang Zhu Xiaochen Kou Yanhong Zhao Hong Wang Cizhong Jiang Shaorong Gao Lan Kang institute for Regenerative Medicine Shanghai East HospitalShanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200120China Key Laboratory of spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education Orthopaedic Department of Tongji HospitalShanghai Key Laboratory of Signaling and Disease ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Frontier Science Center for Stem Cell research Tongji UniversityShanghai 200092China Clinical and Translation research Center of Shanghai First Maternity&Infant Hospital School of Life Sciences and TechnologyTongji UniversityShanghai 200092China institute of Biophysics Chinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Vertebrate life begins with fertilization,and then the zygote genome is activated after transient silencing,a process termed zygotic genome activation(ZGA).Despite its fundamental role in totipotency and the initiation of life,the precise mechanism underlying ZGA initiation remains *** existence of minor ZGA implies the possible critical role of noncoding RNAs in the initiation of ***,we delineate the expression profile of long noncoding RNAs(lncRNAs)in early mouse embryonic development and elucidate their critical role in minor *** with protein-coding genes(PCGs),lncRNAs exhibit a stronger correlation with minor *** H3K9me3 profiles can be observed between lncRNA genes and PCGs,and the enrichment of H3K9me3 before ZGA might explain the suspended expression of major ZGA-related PCGs despite possessing PolII ***,we identified the presence of PolII-enriched MuERV-L around the transcriptional start site of minor ZGA-related lncRNAs,and these repeats are responsible for the activation of minor ZGA-related lncRNAs and subsequent embryo *** study suggests that MuERV-L mediates minor ZGA lncRNA activation as a critical driver between epigenetic reprogramming triggered by fertilization and the embryo developmental program,thus providing clues for understanding the regulatory mechanism of totipotency and establishing bona fide totipotent stem cells.

关键词： ZGA lncRNA MuERV-L

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Peripheral blood RNA biomarkers can predict lesion severity in degenerative cervical myelopathy

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Neural Regeneration research 2025年第6期20卷 1764-1775页

作者： Zhenzhong Zheng Jialin Chen Jinghong Xu Bin Jiang Lei Li Yawei Li Yuliang Dai Bing Wang Department of spine Surgery The Second Xiangya Hospital of Central South UniversityChangshaHunan ProvinceChina

Degenerative cervical myelopathy is a common cause of spinal cord injury,with longer symptom duration and higher myelopathy severity indicating a worse *** numerous studies have investigated serological biomarkers for acute spinal cord injury,few studies have explored such biomarkers for diagnosing degenerative cervical *** study involved 30 patients with degenerative cervical myelopathy(51.3±7.3 years old,12 women and 18 men),seven healthy controls(25.7±1.7 years old,one woman and six men),and nine patients with cervical spondylotic radiculopathy(51.9±8.6 years old,three women and six men).Analysis of blood samples from the three groups showed clear differences in transcriptomic *** analysis identified 128 differentially expressed genes that were enriched in patients with neurological *** least absolute shrinkage and selection operator analysis,we constructed a five-gene model(TBCD,TPM2,PNKD,EIF4G2,and AP5Z1)to diagnose degenerative cervical myelopathy with an accuracy of 93.5%.One-gene models(TCAP and SDHA)identified mild and severe degenerative cervical myelopathy with accuracies of 83.3%and 76.7%,*** of two immune cell types(memory B cells and memory-activated CD4^(+)T cells)predicted levels of lesions in degenerative cervical myelopathy with 80%*** results suggest that peripheral blood RNA biomarkers could be used to predict lesion severity in degenerative cervical myelopathy.

关键词： biomarkers candidate genes degenerative cervical myelopathy gene expression analysis immune cell types neurological disabilities peripheral blood RNA profiles spinal cord injury