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意大利地震:科学依随政治

国际地震动态 2011年第12期32卷 4-4页

作者： benedetto de vivo 李平恩（译）左玉玲（校） University of Naples Federico Ⅱ Naples Italy 中国地震局地球物理研究所

John E Vidale的报道中指出（见本期第3页译文：“意大利地震：批评者的逻辑值得商榷”——编者注），有关2009年4月袭击拉奎拉的6．3级地震的过失杀人案是不公正的。

关键词：意大利地震政治科学逻辑值杀人案

In vivo real-time monitoring delayed administration of M2 macrophages to enhance healing of tendon by NIR-II fluorescence imaging

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Nano Research 2024年第5期17卷 4379-4390页

作者： Yuzhou Chen Mo Chen Chengxuan Yu Huizhu Li Liman Sai Nguyen T.K.Thanh Yueming Wang Yan Wo Jian Zhang Xing Yang Evgenii L.Guryev Andrei V.Zvyagin Hao de Min Tang Shiyi Chen Yunxia Li Yuefeng Hao Sijia Feng Jun Chen Sports Medicine Institute of Fudan University Department of Sports MedicineHuashan HospitalFudan UniversityShanghai 200040China department of Orthopedic Surgery Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200092China department of Bone and Joint Surgery Department of OrthopedicsRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200001China department of Physics Shanghai Normal UniversityShanghai 200234China Biophysics Group Department of Physics and AstronomyUniversity College LondonLondon WC1E 6BTUK UCL Healthcare Biomagnetic and Nanomaterials Laboratories London W1S 4BSUK department of Anatomy and Physiology School of MedicineShanghai Jiao Tong UniversityShanghai 200025China department of Orthopedics Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou 215500China Institute of Biology and Biomedicine Lobachevsky State University of Nizhny NovgorodNizhny Novgorod 603950Russia Mathematical Institute University of OxfordOxford OX26GGUK Institute of Natural Sciences School of MathematicsShanghai Jiao Tong UniversityShanghai 200240China

The administration time is a critical but long-neglected point in cell therapy based on macrophages because the incorrect time of macrophage administration could result in diverse outcomes regarding the same macrophage *** this work,the second near-infrared(NIR-II)fluorescence imaging in vivo tracking of M2 macrophages during a pro-healing therapy in the mice model of rotator cuff injury revealed that the behavior of administrated macrophages was influenced by the timing of their *** delayed cell therapy(DCT)group had a longer retention time of injected M2 macrophages in the repairing tissue than that in the immediate cell therapy(ICT)*** Keller-Segel model and histological analysis further demonstrated that DCT altered the chemotaxis of M2 macrophages and improved the healing outcome of the repaired structure in comparison with *** results offer a possible explanation of previous conflicting results on reparative cell therapy and provoke reconsideration of the timing of these therapies.

关键词： macrophage cell therapy NIR-II in vivo imaging delayed therapy tendon healing

METTL5 promotes gastric cancer progression via sphingomyelin metabolism

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1925-1946页

作者： Ya-Qiong Zhang Jian Li Zhe Qin de-Ming Li Fang-Zhou Ye Song-Hua Bei Xiao-Hong Zhang Li Feng Endoscopy Center Minhang Hospital Affiliated to Fudan UniversityShanghai 201100China

BACKGROUND The treatment of gastric cancer(GC)has caused an enormous social burden *** studies have reported that N6-methyladenosine(m6A)is closely related to tumor ***5 is a m6A methyltransferase that plays a pivotal role in maintaining the metabolic stability of ***,its aberrant regulation in GC has not been fully *** To excavate the role of METTL5 in the development of *** METTL5 expression and clinicopathological characteristics were analyzed via The Cancer Genome Atlas dataset and further verified via immunohistochemistry,western blotting and real-time quantitative polymerase chain reaction in tissue microarrays and clinical *** tumor-promoting effect of METTL5 on HGC-27 and AGS cells was explored in vitro by Cell Counting Kit-8 assays,colony formation assays,scratch healing assays,transwell assays and flow *** tumor-promoting role of METTL5 in vivo was evaluated in a xenograft tumor *** EpiQuik m6A RNA Methylation Quantification Kit was used for m6A ***,liquid chromatography-mass spectrometry was used to evaluate the association between METTL5 and sphingomyelin metabolism,which was confirmed by Enzyme-linked immunosorbent assay and rescue *** addition,we investigated whether METTL5 affects the sensitivity of GC cells to cisplatin via colony formation and transwell *** Our research revealed substantial upregulation of METTL5,which suggested a poor prognosis of GC *** METTL5 expression indicated distant lymph node metastasis,advanced cancer stage and pathological *** increased level of METTL5 correlated with a high degree of m6A ***5 markedly promotes the proliferation,migration,and invasion of GC cells in ***5 also promotes the growth of GC in animal ***5 knockdown resulted in significant changes in sphingomyelin metabolism,which implies that METTL5 may impact the development of GC via sphin

关键词： Gastric cancer METTL5 Sphingomyelin metabolism Cisplatin

Sinomenine increases osteogenesis in mice with ovariectomyinduced bone loss by modulating autophagy

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World Journal of Stem Cells 2024年第5期16卷 486-498页

作者： Hai-Xiang Xiao Lei Yu Yu Xia Kai Chen Wen-Ming Li Gao-Ran Ge Wei Zhang Qing Zhang Hong-Tao Zhang de-Chun Geng department of Orthopedics The Fourth Affiliated Hospital of Soochow UniversitySuzhou Dushu Lake HospitalMedical Centre of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina department of Orthopedics Jingjiang People’s Hospital Affiliated to Yangzhou UniversityJingjiang 214500Jiangsu ProvinceChina department of Orthopedics The First Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina department of Orthopedics Hai’an People’s HospitalHai’an 226600Jiangsu ProvinceChina department of Orthopedics The Affiliated Huai’an Hospital of Xuzhou Medical UniversityHuai’an Second People’s HospitalXuzhou 223002Jiangsu ProvinceChina department of Orthopaedics The First Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina

BACKGROUND A decreased autophagic capacity of bone marrow mesenchymal stromal cells(BMSCs)has been suggested to be an important cause of decreased osteogenic differentiation.A pharmacological increase in autophagy of BMSCs is a potential therapeutic option to increase osteoblast viability and ameliorate *** To explore the effects of sinomenine(SIN)on the osteogenic differentiation of BMSCs and the underlying *** For in vitro experiments,BMSCs were extracted from sham-treated mice and ovariectomized mice,and the levels of autophagy markers and osteogenic differentiation were examined after treatment with the appropriate concen-trations of SIN and the autophagy inhibitor *** vivo,the therapeutic effect of SIN was verified by establishing an ovariectomy-induced mouse model and by morphological and histological assays of the mouse *** SIN reduced the levels of AKT and mammalian target of the rapamycin(mTOR)phosphorylation in the phosphatidylinositol 3-kinase(PI3K)/AKT/mTOR signaling pathway,inhibited mTOR activity,and increased autophagy ability of BMSCs,thereby promoting the osteogenic differentiation of BMSCs and effectively alleviating bone loss in ovariectomized mice in *** The Chinese medicine SIN has potential for the treatment of various types of osteoporosis,bone homeostasis disorders,and autophagy-related diseases.

关键词： Sinomenine Osteogenesis Autophagy Ovariectomy Osteoporosis

Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

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World Journal of Gastrointestinal Oncology 2024年第8期16卷 3585-3599页

作者： de-Gang Li Jia-Peng Jiang Fan-Ye Chen Wei Wu Jun Fu Gong-He Wang Yu-Bo Li department of Gastrointestinal and Anorectal Surgery The First Affiliated Hospital of Guangxi University of Chinese MedicineNanning 530023Guangxi Zhuang Autonomous RegionChina

BACKGROUND Gastrointestinal stromal tumors(GISTs)are typical gastrointestinal tract *** is the first-line therapy for GIST *** resistance limits the long-term effectiveness of *** regulatory effect of insulin-like growth factor 2(IGF2)has been confirmed in various cancers and is related to resistance to chemotherapy and a worse *** To further investigate the mechanism of IGF2 specific to *** IGF2 was screened and analyzed using Gene Expression Omnibus(GEO:GSE225819)*** IGF2 knockdown or overexpression by transfection,the phenotypes(proliferation,migration,invasion,apoptosis)of GIST cells were characterized by cell counting kit 8,Transwell,and flow cytometry *** used western blotting to evaluate pathway-associated and epithelial-mesenchymal transition(EMT)-associated *** injected transfected cells into nude mice to establish a tumor xenograft model and observed the occurrence and metastasis of *** Data from the GEO indicated that IGF2 expression is high in GISTs,associated with liver metastasis,and closely related to drug *** cells with high expression of IGF2 had increased proliferation and migration,invasiveness and *** of IGF2 significantly inhibited those *** addition,OEIGF2 promoted GIST metastasis in vivo in nude ***2 activated IGF1R signaling in GIST cells,and IGF2/IGF1R-mediated glycolysis was required for GIST with liver *** cells with IGF2 knockdown were sensitive to imatinib treatment when IGF2 overexpression significantly raised imatinib ***,2-deoxy-D-glucose(a glycolysis inhibitor)treatment reversed IGF2 overexpressionmediated imatinib resistance in *** IGF2 targeting of IGF1R signaling inhibited metastasis and decreased imatinib resistance by driving glycolysis in GISTs.

关键词： Insulin-like growth factor 2 Gastrointestinal stromal tumors IGF1R Glycolysis Imatinib resistance

First total synthesis,antitumor evaluation and target identification of mornaphthoate E:A new tubulin inhibitor template acting on PI3K/Akt signaling pathway

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2177-2193页

作者： Peipei Shan Tao Ye Ying-de Tang Hui Song Chao Wang Kongkai Zhu Feifei Yang Shi-Lei Zhang Pei-Wen Su Shuanhu Gao Hua Zhang Institute of Translational Medicine the Affiliated Hospital of Qingdao UniversityCollege of MedicineQingdao UniversityQingdao 266021China School of Biological Science and Technology University of JinanJinan 250022China Advanced Medical Research Institute Cheeloo College of MedicineShandong UniversityJinan 250012China College of Pharmaceutical Sciences Soochow UniversitySuzhou 215127China School of Chemistry and Molecular Engineering East China Normal UniversityShanghai 200062China

Mornaphthoate E(MPE)is a prenylated naphthoic acid methyl ester isolated from the roots of a famous Chinese medicinal plant Morinda officinalis and shows remarkable cytotoxicity against several human tumor cell *** the current project,the first total synthesis of(±)-MPE was achieved in seven steps and 5.6%overall *** the in vitro anti-tumor activity of MPE was first assessed for both enantiomers in two breast cancer cells,with the levoisomer exerting slightly better *** in vivo anti-tumor effect was further verified by applying the racemate in an orthotopic autograft mouse ***,MPE exerted promising anti-metastasis activity both in vitro and in vivo and showed no obvious toxicity on mice at the therapeutic *** investigations demonstrated that MPE acted as a tubulin polymerization stabilizer and disturbed the dynamic equilibrium of microtubules via regulating PI3K/Akt *** conclusion,our work has provided a new chemical template for the future design and development of next-generation tubulin-targeting chemotherapies.

关键词： Mornaphthoate E Tubulin inhibitor Antitumor Anti-metastasis Breast cancer PI3K/Akt

A novel alternative for pyrogen detection based on a transgenic cell line

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1221-1229页

作者： Qing He Chuan-Fei Yu Gang Wu Kai-Qin Wang Yong-Bo Ni Xiao Guo Zhi-Hao Fu Lan Wang de-Jiang Tan Hua Gao Can Wang Gang Chen Xu-Hong Chen Bo Chen Jun-Zhi Wang National Institutes for Food and Drug Control BeijingChina School of Life Science and Biopharmaceutics Shenyang Pharmaceutical UniversityShenyangChina Shanghai Institute for Food and Drug Control ShanghaiChina KeyMed Biosciences Inc. ChengduChina

Pyrogen,often as a contaminant,is a key indicator affecting the safety of almost all parenteral drugs(including biologicals,chemicals,traditional Chinese medicines and medical devices).It has become a goal to completely replace the in vivo rabbit pyrogen test by using the in vitro pyrogen test based on the promoted‘reduction,replacement and refinement’principle,which has been highly considered by regulatory agencies from different *** used NF-κB,a central signalling molecule mediating inflammatory responses,as a pyrogenic marker and the monocyte line THP-1 transfected with a luciferase reporter gene regulated by NF-κB as an in vitro model to detect pyrogens by measuring the intensity of a fluorescence ***,we show that this test can quantitatively and sensitively detect endotoxin(lipopolysaccharide from different strains)and nonendotoxin(lipoteichoic acid,zymosan,peptidoglycan,lectin and glucan),has good stability in terms of NF-κB activity and cell phenotypes at 39 cell passages and can be applied to detect pyrogens in biologicals(group A&C meningococcal polysaccharide vaccine;basiliximab;rabies vaccine(Vero cells)for human use,freeze-dried;Japanese encephalitis vaccine(Vero cells),inactivated;insulin aspart injection;human albumin;recombinant human erythropoietin injection(CHO Cell)).The within-laboratory reproducibility of the test in three independent laboratories was 85%,80%and 80%and the interlaboratory reproducibility among laboratories was 83.3%,95.6%and 86.7%.The sensitivity(true positive rate)and specificity(true negative rate)of the test were 89.9%and 90.9%,*** summary,the test provides a novel alternative for pyrogen detection.

关键词： pyrogen rabbit replace

RANKL inhibition reduces lesional cellularity and Gαs variant expression and enables osteogenic maturation in fibrous dysplasia

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Bone Research 2024年第1期12卷 165-179页

作者： Luis F.de Castro Jarred M.Whitlock Zachary Michel Kristen Pan Jocelyn Taylor Vivian Szymczuk Brendan Boyce Daniel Martin Vardit Kram Rebeca Galisteo Kamran Melikov Leonid V.Chernomordik Michael T.Collins Alison M.Boyce Skeletal Disorders and Mineral Homeostasis Section National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA Section on Membrane Biology Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaMDUSA Metabolic Bone Disorders Unit National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA department of Plastic and Reconstructive Surgery The Johns Hopkins Medical InstitutionsBaltimoreMDUSA department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochesterNYUSA NIDCR Genomics and Computational Biology Core National Institute of Dental and Craniofacial ResearchNational Institutes of HealthBethesdaMDUSA

Fibrous dysplasia(FD)is a rare,disabling skeletal disease for which there are no established *** evidence supports inhibiting the osteoclastogenic factor receptor activator of nuclear kappa-B ligand(RANKL)as a potential treatment *** this study,we investigated the mechanisms underlying RANKL inhibition in FD tissue and its likely indirect effects on osteoprogenitors by evaluating human FD tissue pre-and post-treatment in a phase 2 clinical trial of denosumab(NCT03571191)and in murine in vivo and ex vivo preclinical *** analysis of human and mouse tissue demonstrated increased osteogenic maturation,reduced cellularity,and reduced expression of the pathogenic Gαs variant in FD lesions after RANKL *** sequencing of human and mouse tissue supported these *** interaction between osteoclasts and mutant osteoprogenitors was further assessed in an ex vivo lesion model,which indicated that the proliferation of abnormal FD osteoprogenitors was dependent on *** results from this study demonstrated that,in addition to its expected antiosteoclastic effect,denosumab reduces FD lesion activity by decreasing FD cell proliferation and increasing osteogenic maturation,leading to increased bone formation within *** findings highlight the unappreciated role of cellular crosstalk between osteoclasts and preosteoblasts/osteoblasts as a driver of FD pathology and demonstrate a novel mechanism of action of denosumab in the treatment of bone disease.

关键词： dysplasia treatment finding

In situ forming injectable MSC-loaded GelMA hydrogels combined with PD for vascularized sweat gland regeneration

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Military Medical Research 2024年第1期11卷 152-155页

作者： Enhe Jirigala Bin Yao Zhao Li Yi-Jie Zhang Chao Zhang Li-Ting Liang Fan-Liang Zhang Xing-Yu Yuan Xian-Lan Duan Wei Song Meng-de Zhang Yi Kong Xiao-Bing Fu Sha Huang Research Center for Tissue Repair and Regeneration Medical Innovation Research DepartmentChinese PLA General Hospital and PLA Medical CollegeBeijing 100048China Institute of Basic Medical Research Inner Mongolia Medical UniversityHohhot 010110China Academy of Medical Engineering and Translational Medicine Tianjin UniversityTianjin 300072China School of Medicine Nankai UniversityTianjin 300071China

dear Editor,Three dimensional(3D)bioprinted extracellular matrix(ECM)can be used to provide both biochemical and biophysical cues to direct mesenchymal stem cells(MSCs)differentiation,and then differentiated cells were isolated for implantation in vivo using surgical ***,the reduced cell activity after cell isolation from 3D constructs and low cell retention in injured sites limit its application[1].Methacrylated gelatin(GelMA)hydrogel has the advantage of fast crosslinking,which could resemble complex architectures of tissue construct in vivo[2].Here,we adopted a noninvasive bioprinting procedure to imitate the regenerative microenvironment that could simultaneously direct the sweat gland(SG)and vascular differentiation from MSCs and ultimately promote the replacement of glandular tissue in situ(Fig.1a).

关键词： Sweat gland GelMA In situ niche Cell differentiation Tissue incorporation Vascularization