Background:A One Health approach has been increasingly mainstreamed by the international community, as it provides for holistic thinking in recognizing the close links and inter-dependence of the health of humans, ani...Background:A One Health approach has been increasingly mainstreamed by the international community, as it provides for holistic thinking in recognizing the close links and inter-dependence of the health of humans, animals and the environment. However, the dearth of real-world evidence has hampered application of a One Health approach in shaping policies and practice. This study proposes the development of a potential evaluation tool for One Health performance, in order to contribute to the scientific measurement of One Health approach and the identification of gaps where One Health capacity building is most urgently needed.Methods:We describe five steps towards a global One Health index (GOHI), including (i) framework formulation;(ii) indicator selection;(iii) database building;(iv) weight determination;and (v) GOHI scores calculation. A cell-like framework for GOHI is proposed, which comprises an external drivers index (EDI), an intrinsic drivers index (IDI) and a core drivers index (CDI). We construct the indicator scheme for GOHI based on this framework after multiple rounds of panel discussions with our expert advisory committee. A fuzzy analytical hierarchy process is adopted to determine the weights for each of the indicators.Results:The weighted indicator scheme of GOHI comprises three first-level indicators, 13 second-level indicators, and 57 third-level indicators. According to the pilot analysis based on the data from more than 200 countries/territories the GOHI scores overall are far from ideal (the highest score of 65.0 out of a maximum score of 100), and we found considerable variations among different countries/territories (31.8–65.0). The results from the pilot analysis are consistent with the results from a literature review, which suggests that a GOHI as a potential tool for the assessment of One Health performance might be feasible.Conclusions:GOHI—subject to rigorous validation—would represent the world’s first evaluation tool that constructs the conceptual framework from a holistic per展开更多
Background:Schwann cell-like cells(SCLCs),differentiated from mesenchymal stem cells,have shown promising outcomes in the treatment of peripheral nerve injuries in preclinical studies.However,certain clinical obstacle...Background:Schwann cell-like cells(SCLCs),differentiated from mesenchymal stem cells,have shown promising outcomes in the treatment of peripheral nerve injuries in preclinical studies.However,certain clinical obstacles limit their application.Hence,the primary aim of this study was to investigate the role of exosomes derived from SCLCs(SCLCs-exo)in peripheral nerve regeneration.Methods:SCLCs were differentiated from human amniotic mesenchymal stem cells(hAMSCs)in vitro and validated by immunofluorescence,real-time quantitative PCR and western blot analysis.Exosomes derived from hAMSCs(hAMSCs-exo)and SCLCs were isolated by ultracentrifugation and validated by nanoparticle tracking analysis,WB analysis and electron microscopy.A prefab-ricated nerve graft was used to deliver hAMSCs-exo or SCLCs-exo in an injured sciatic nerve rat model.The effects of hAMSCs-exo or SCLCs-exo on rat peripheral nerve injury(PNI)regeneration were determined based on the recovery of neurological function and histomorphometric variation.The effects of hAMSCs-exo or SCLCs-exo on Schwann cells were also determined via cell prolifer-ation and migration assessment.Results:SCLCs significantly expressed the Schwann cell markers glial fibrillary acidic protein and S100.Compared to hAMSCs-exo,SCLCs-exo significantly enhanced motor function recov-ery,attenuated gastrocnemius muscle atrophy and facilitated axonal regrowth,myelin forma-tion and angiogenesis in the rat model.Furthermore,hAMSCs-exo and SCLCs-exo were effi-ciently absorbed by Schwann cells.However,compared to hAMSCs-exo,SCLCs-exo signifi-cantly promoted the proliferation and migration of Schwann cells.SCLCs-exo also significantly upregulated the expression of a glial cell-derived neurotrophic factor,myelin positive regulators(SRY-box transcription factor 10,early growth response protein 2 and organic cation/carnitine transporter 6)and myelin proteins(myelin basic protein and myelin protein zero)in Schwann cells.Conclusions:These findings suggest that SCLCs-exo can more efficiently prom展开更多
The differentiation status of neuroblastoma (NB) strongly correlates with its clinical outcomes; however, the molecular mechanisms driving maintenance of sternness and differentiation remain poorly understood. Here,...The differentiation status of neuroblastoma (NB) strongly correlates with its clinical outcomes; however, the molecular mechanisms driving maintenance of sternness and differentiation remain poorly understood. Here, we show that plant homeodomain finger-containing protein 20 (PHF20) functions as a critical epigenetic regulator in sustaining stem cell-like phenotype of NB by using CRISPR/Casg-based targeted knockout (KO) for high-throughput screening of gene function in NB cell differentiation. The expression of PHF20 in NB was significantly associated with high aggressiveness of the tumor and poor outcomes for NB patients. Deletion of PHF20 inhibited NB cell proliferation, invasive migration, and stem ceU-Uke traits. Mechanistically, PHF20 interacts with poly(ADP-ribose) polymerase 1 (PARP1) and directly binds to promoter regions of octamer-binding transcription factor 4 (OCT4) and sex determining region Y-box 2 (SOX2) to modulate a histone mark associated with active transcription, trimethylation of lysine 4 on histone H3 protein subunit (H3K4me3). Overexpression of OCT4 and SOX2 restored growth and progression of PHF20 KO tumor cells. Consistently, OCT4 and SOX2 protein levels in clinical NB specimens were positively correlated with PHF20 expression. Our results establish PHF20 as a key driver of NB stem cell-like properties and aggressive behaviors, with implications for prognosis and therapy.展开更多
Bio-mimicking graphene films,deposited on textured nickel substrates,were synthesized by the following method:replicating the surface textures of the lotus leaf by polymer duplication,fabricating textured nickel subst...Bio-mimicking graphene films,deposited on textured nickel substrates,were synthesized by the following method:replicating the surface textures of the lotus leaf by polymer duplication,fabricating textured nickel substrates by electroplating on the polymer coated with a Au film,preparing bio-mimicking graphene oxide films on the nickel substrates by vacuum filtration,and electrochemical reduction.By controlling the vacuum filtration,this replica method can not only replicate the lotus leaf structure by a graphene film,but also can achieve a novel cell-like graphene film.展开更多
The cancer stem cell hypothesis provides a basis for prediction of the recurrence and risk of metastasis in breast cancer.However,the unique expression pattern of stemness markers and the presence of nonstem-like canc...The cancer stem cell hypothesis provides a basis for prediction of the recurrence and risk of metastasis in breast cancer.However,the unique expression pattern of stemness markers and the presence of nonstem-like cancer cells with varied phenotypes have brought great challenges to the characterization of breast cancer stem cells.To address these challenges,a phenotype-directed DNA nanomachine has been designed for high-accuracy labeling and in situ analysis of the stem cell-like subpopulation in breast cancer.The key for the design is to use cell surfaceanchored inputs to activate the nanomachine,which undergoes different branch migration pathways such that the signal strand can only be brought onto the cancer cells having the stem cell-like phenotype.Highly sensitive determination and single-step isolation of the stem cell-like subpopulation were achieved by incorporating functional groups into the signal strand such that the nanomachine was successfully applied in a tumor-bearing mouse model.Overall,the approach provides for a substantial improvement in capability for the analysis of the breast cancer stem cell-like subpopulation,and it is expected that the new approach will advance the use of DNA nanomachines in cancer-related studies.展开更多
Basic magnesium carbonate microspheres with a red blood cell (RBC)-like appearance and diameters of ~3μm were synthesized by amphiphilic molecule-participated self-assembly under hydrothermal conditions, In the sel...Basic magnesium carbonate microspheres with a red blood cell (RBC)-like appearance and diameters of ~3μm were synthesized by amphiphilic molecule-participated self-assembly under hydrothermal conditions, In the self-assembly, sodium dodecyl benzene sulfonate served as a template for the formation of Mg(OH)2 spherical micelles and also as a reactant precursor that releases CO2 to react with Mg(OH)2. The growth of the microspheres is driven by the continuous generation of new hydrophobic centers because of the consumption of hydrophilic poles (--SO3-). The surfactant-directed self-assembly can be applied to the synthesis of other carbonate or metallic oxide self-assemblies, indicating that it is a universal self-assembly method for amphiphilic molecules.展开更多
BACKGROUND: S100 protein can promote axonal growth. Therefore, transplantation of induced bone marrow-derived mesenchymal stem cells (MSCs) that can secrete S100 may provide a beneficial microenvironment for neural...BACKGROUND: S100 protein can promote axonal growth. Therefore, transplantation of induced bone marrow-derived mesenchymal stem cells (MSCs) that can secrete S100 may provide a beneficial microenvironment for neural regeneration. OBJECTIVE: To explore the changes in S100 expression during rat MSCs differentiation into Schwann ceils in vitro. DESIGN, TIME AND SETTING: This cytology experiment was performed at the Jiangsu Key Laboratory of Neuroregeneration, Nantong University in China, from January 2006 to May 2007. MATERIALS: The rabbit anti-S100 polyclonal antibody was purchased from Dako, Denmark; the mouse anti-rat S100 monoclonal antibody was purchased from Sigma, USA. METHODS: MSCs were cultured from adult Sprague-Dawley rat femur and tibia. Cell proliferation was determined by the MTT method and CD markers, and cell cycle was measured by flow cytometry. MSCs were induced to differentiate into SC cells. SC cells were stained for S100 protein, glial fibrillary acidic protein, and low-affinity nerve growth factor receptor. S100 protein and mRNA levels were evaluated by flow cytometry, Western blot, and reverse transcription-polymerase chain reaction. MAIN OUTCOME MEASURES: S100 protein and mRNA expression. RESULTS: MSCs exhibited high amplification potential over eight passages. Prior to induction, the majority of MSCs were at the G0/G1 phase of the cell cycle. After induction, MSCs displayed morphology changes similar to Schwann cells. Moreover, induction increased S100 mRNA levels. Immunofluorescence showed that MSCs expressed S100 protein, glial fibrillary acidic protein, and low-affinity nerve growth factor receptor at 7 days of induction. Induction also increased S100 protein levels compared with untreated MSCs. CONCLUSION: MSCs are capable of differentiating into Schwann cells-like cells under conditional induction in vitro, with increasing S100 mRNA and protein expression.展开更多
During the last decade,increasing evidence suggested that bone marrow stromal cells(MSCs) have the potential to differentiate into neural lineages.Many studies have reported that MSCs showed morphological changes and ...During the last decade,increasing evidence suggested that bone marrow stromal cells(MSCs) have the potential to differentiate into neural lineages.Many studies have reported that MSCs showed morphological changes and expressed a limited number of neural proteins under experimental conditions.However,no proteomic studies on MSCs differentiated into Schwann cell-like cells have been reported.In this study,we isolated MSCs from adult Sprague-Dawley rat femur and tibia bone marrows and induced the cells in vitro under specific conditions.By using two-dimensional gel electrophoresis(2-DE),we compared the protein profiles of MSCs before and after induced differentiation.We obtained 792 protein spots in the protein profile by 2-DE,and found that 74 spots changed significantly before and after the differentiation using PDQuest software,with 43 up-regulated and 31 down-regulated.We analyzed these 74 spots by a matrix assisted laser desorption ionization-time of flight mass spectrometry(MALDI-TOF-MS) and by database searching,and found that they could be grouped into various classes,including cytoskeleton and structure proteins,growth factors,metabolic proteins,chaperone proteins,receptor proteins,cell cycle proteins,calcium binding proteins,and other proteins.These proteins also include neural and glial proteins,such as BDNF,CNTF and GFAP.The results may provide valuable proteomic information about the differentiation of MSCs into Schwann cell-like cells.展开更多
Parthenogenetic embryos,created by activation and diploidization of oocytes,arrest at mid-gestation for defective paternal imprints,which impair placental development.Also,viable offspring has not been obtained withou...Parthenogenetic embryos,created by activation and diploidization of oocytes,arrest at mid-gestation for defective paternal imprints,which impair placental development.Also,viable offspring has not been obtained without genetic manipulation from parthenogenetic embryonic stem cells(pESCs)derived from parthenogenetic embryos,presumably attributable to their aberrant imprinting.We show that an unlimited number of oocytes can be derived from pESCs and produce healthy offspring.Moreover,normal expression of imprinted genes is found in the germ cells and the mice.pESCs exhibited imprinting consistent with exclusively maternal lineage,and higher X-chromosome activation compared to female ESCs derived from the same mouse genetic background.pESCs differentiated into primordial germ cell-like cells(PGCLCs)and formed oocytes following in vivo transplantation into kidney capsule that produced fertile pups and reconstituted ovarian endocrine function.The transcriptome and methylation of imprinted and X-linked genes in pESC-PGCLCs closely resembled those of in vivo produced PGCs,consistent with efficient reprogramming of methylation and genomic imprinting.These results demonstrate that amplification of germ cells through parthenogenesis faithfully maintains maternal imprinting,offering a promising route for deriving functional oocytes and having potential in rebuilding ovarian endocrine function.展开更多
In vitro gametogenesis(IVG)has been a topic of great interest in recent years not only because it allows for further exploration of mechanisms of germ cell development,but also because of its prospect for innovative m...In vitro gametogenesis(IVG)has been a topic of great interest in recent years not only because it allows for further exploration of mechanisms of germ cell development,but also because of its prospect for innovative medical applications especially for the treatment of infertility.Elucidation of the mechanisms underlying gamete development in vivo has inspired scientists to attempt to recapitulate the entire process of gametogenesis in vitro.While earlier studies have established IVG methods largely using pluripotent stem cells of embryonic origin,the scarcity of sources for these cells and the ethical issues involved in their use are serious limitations to the progress of IVG research especially in humans.However,with the emergence of induced pluripotent stem cells(iPSCs)due to the revolutionary discovery of dedifferentiation and reprogramming factors,IVG research has progressed remarkably in the last decade.This paper extensively reviews developments in IVG using iPSCs.First,the paper presents key concepts from groundwork studies on IVG including earlier researches demonstrating that IVG methods using embryonic stem cells(ESCs)also apply when using iPSCs.Techniques for the derivation of iPSCs are briefly discussed,highlighting the importance of generating transgene-free iPSCs with a high capacity for germline transmission to improve efficacy when used for IVG.The main part of the paper discusses recent advances in IVG research using iPSCs in various stages of gametogenesis.In addition,current clinical applications of IVG are presented,and potential future applications are discussed.Although IVG is still faced with many challenges in terms of technical issues,as well as efficacy and safety,novel IVG methodologies are emerging,and IVG using iPSCs may usher in the next era of reproductive medicine sooner than expected.This raises both ethical and social concerns and calls for the scientific community to cautiously develop IVG technology to ensure it is not only efficacious but also safe and adheres to social and et展开更多
We prove that a locally compact ANR-space X is a Q-manifold if and only if it has the Disjoint Disk Property (DDP), all points of X are homological Z∞-points and X has the countable-dimensional approximation property...We prove that a locally compact ANR-space X is a Q-manifold if and only if it has the Disjoint Disk Property (DDP), all points of X are homological Z∞-points and X has the countable-dimensional approximation property (cd-AP), which means that each map f:K→X of a compact polyhedron can be approximated by a map with the countable-dimensional image. As an application we prove that a space X with DDP and cd-AP is a Q-manifold if some finite power of X is a Q-manifold. If some finite power of a space X with cd-AP is a Q-manifold, then X2 and X×[0,1] are Q-manifolds as well. We construct a countable familyχof spaces with DDP and cd-AP such that no space X∈χis homeomorphic to the Hilbert cube Q whereas the product X×Y of any different spaces X, Y∈χis homeomorphic to Q. We also show that no uncountable familyχwith such properties exists.展开更多
Stem cell-like memory T(TSCM)cells possess stem cell properties including multipotency and self-renewal and are being recognized as emerging players in various human diseases.Advanced technologies such as multiparamet...Stem cell-like memory T(TSCM)cells possess stem cell properties including multipotency and self-renewal and are being recognized as emerging players in various human diseases.Advanced technologies such as multiparametric flowcytometry and single cell sequencing have enabled their identification and molecular characterization.In case of chronic viral diseases such as human immunodeficiency virus-1,CD4+T_(SCM) cells,serve as major reservoirs of the latent virus.However,during immune activation and functional exhaustion of effector T cells,these cells also possess the potential to replenish the pool of functional effector cells to curtail the infection.More recently,these cells are speculated to play important role in protective immunity following acute viral infections such as coronavirus disease 2019 and might be amenable for therapeutics by ex vivo expansion.Similarly,studies are also investigating their pathological role in driving autoimmune responses.However,there are several gaps in the understanding of the role of T_(SCM) cells in viral and autoimmune diseases to make them potential therapeutic targets.In this minireview,we have attempted an updated compilation of the dyadic role of these complex T_(SCM) cells during such human diseases along with their biology and transcriptional programs.展开更多
Prostate cancers(PCa)have been reported to actively suppress antitumor immune responses by creating an immune-suppressive microenvironment.There is mounting evidence that PCas may undergo an‘‘Epithelial Immune Cell-...Prostate cancers(PCa)have been reported to actively suppress antitumor immune responses by creating an immune-suppressive microenvironment.There is mounting evidence that PCas may undergo an‘‘Epithelial Immune Cell-like Transition’’(EIT)by expressing molecules conventionally associated with immune cells(e.g.,a variety of cytokines/receptors,immune transcription factors,Ig motifs,and immune checkpoint molecules),which subsequently results in the suppression of anti-cancer immune activity within the tumor microenvironment.Recent progress within the field of immune therapy has underscored the importance of immune checkpoint molecules in cancer development,thus leading to the development of novel immunotherapeutic approaches.Here,we review the expression of select immune checkpoint molecules in PCa epithelial and associated immune cells,with particular emphasis on clinical data supporting the concept of an EIT-mediated phenotype in PCa.Furthermore,we summarize current advances in anti-immune checkpoint therapies,and provide perspectives on their potential applicability.展开更多
Micron/nano scale topographic modification has been a significant focus of interest in current titanium(Ti)surface design.However,the influence of micron/nano structured surface on cell or bacterium behavior on the Ti...Micron/nano scale topographic modification has been a significant focus of interest in current titanium(Ti)surface design.However,the influence of micron/nano structured surface on cell or bacterium behavior on the Ti implant has rarely been systematically evaluated.Moreover,except for popular microgrooves,little work has been carried out on the reaction of cells to the bionic structure.In this study,several micro-pillars mimicking cell morphology were prepared on Ti surfaces by lithography and contact printing(ICP)method,and they were further decorated with nanotube arrays by anodization technology.These surface modifications remarkablly increased the surface roughness of pristine Ti surface from 91.17 nm±5.57 nm to be more than 1000 nm,and reduced their water contact angles from 68.3°±0.7°to be 16.9°±2.4°.Then,the effects of these hierarchical micron/nano scale patterns on the behaviors of MG63 osteoblasts,L929 fibroblasts,SCC epithelial cells and P.gingivalis were studied,aiming to evaluate their performance in osseointegration,gingival epithelial sealing and antibacterial ability.Through an innovative scoring strategy,our findings showed that square micro-pillars with 6μm width and 2μm height combined with 85 nm diameter nanotubes was suitable for implant neck design,while square micro-pillars with 3μm width and 3.6μm height combined with 55 nm diameter nanotubes was the best for implant body design.Our study reveals the synergistic effect of the hierarchical micron/nano scale patterns on MG63 osteoblasts,L929 fibroblasts,SCC epithelial cells and P.gingivalis functions.It provides insight into the design of biomedical implant surfaces.展开更多
目的探讨胃肠道透明细胞肉瘤(clear cell sarcoma of the gastrointestinal tract,CCS-GI)的临床病理特征及遗传学特点。方法对1例CCS-GI进行组织学观察、免疫组化染色、荧光原位杂交(fluorescence in situ hybridization,FISH)检测,并...目的探讨胃肠道透明细胞肉瘤(clear cell sarcoma of the gastrointestinal tract,CCS-GI)的临床病理特征及遗传学特点。方法对1例CCS-GI进行组织学观察、免疫组化染色、荧光原位杂交(fluorescence in situ hybridization,FISH)检测,并复习相关文献。结果患者女性,因"腹痛1周"入院,CT检查示右半结肠肿瘤,肉眼观察结肠黏膜面可见一溃疡型肿块,切面灰白、实性、质嫩,侵及全层。镜下见中等大小的圆形或卵圆形肿瘤细胞呈片状排列,肿瘤细胞间可见散在分布的破骨细胞样多核巨细胞。肿瘤细胞S-100蛋白弥漫阳性,HMB-45、Melan-A、CD117、CD1a及PCK均阴性。FISH检测结果示74%的肿瘤细胞存在EWSR1基因易位。结论 CCS-GI是一种特殊类型的胃肠道肿瘤,具有独特的组织学、免疫表型、超微结构及遗传学特征,该类肿瘤中的胃肠道透明细胞肉瘤样肿瘤亚型是否为一个独立的病变实体,尚需增加病例量进一步研究,包括细胞遗传学和分子生物学的相关研究。展开更多
基金The project was supported by China Medical Board(no.20-365)Shanghai Jiao Tong University Integrated Innovation Fund(no.2020-01).
文摘Background:A One Health approach has been increasingly mainstreamed by the international community, as it provides for holistic thinking in recognizing the close links and inter-dependence of the health of humans, animals and the environment. However, the dearth of real-world evidence has hampered application of a One Health approach in shaping policies and practice. This study proposes the development of a potential evaluation tool for One Health performance, in order to contribute to the scientific measurement of One Health approach and the identification of gaps where One Health capacity building is most urgently needed.Methods:We describe five steps towards a global One Health index (GOHI), including (i) framework formulation;(ii) indicator selection;(iii) database building;(iv) weight determination;and (v) GOHI scores calculation. A cell-like framework for GOHI is proposed, which comprises an external drivers index (EDI), an intrinsic drivers index (IDI) and a core drivers index (CDI). We construct the indicator scheme for GOHI based on this framework after multiple rounds of panel discussions with our expert advisory committee. A fuzzy analytical hierarchy process is adopted to determine the weights for each of the indicators.Results:The weighted indicator scheme of GOHI comprises three first-level indicators, 13 second-level indicators, and 57 third-level indicators. According to the pilot analysis based on the data from more than 200 countries/territories the GOHI scores overall are far from ideal (the highest score of 65.0 out of a maximum score of 100), and we found considerable variations among different countries/territories (31.8–65.0). The results from the pilot analysis are consistent with the results from a literature review, which suggests that a GOHI as a potential tool for the assessment of One Health performance might be feasible.Conclusions:GOHI—subject to rigorous validation—would represent the world’s first evaluation tool that constructs the conceptual framework from a holistic per
基金supported by the InnovationGroup Major Research Project of Guizhou Province Education Department(No.Qianjiaohe KY[2017]043)the Science and Technology Support Project of Guizhou Province(2020-5012)+3 种基金the PhD Fund of Scientific Research Foundation of the Affiliated Hospital of ZunyiMedical University(2020-03)the National Nature Science Foundation of China(81660325)the Collaborative Innovation Center of the Chinese Ministry of Education(2020-39)the Master Fund of Scientific Research Foundation of the Affiliated Hospital of Zunyi Medical University(2016-35).
文摘Background:Schwann cell-like cells(SCLCs),differentiated from mesenchymal stem cells,have shown promising outcomes in the treatment of peripheral nerve injuries in preclinical studies.However,certain clinical obstacles limit their application.Hence,the primary aim of this study was to investigate the role of exosomes derived from SCLCs(SCLCs-exo)in peripheral nerve regeneration.Methods:SCLCs were differentiated from human amniotic mesenchymal stem cells(hAMSCs)in vitro and validated by immunofluorescence,real-time quantitative PCR and western blot analysis.Exosomes derived from hAMSCs(hAMSCs-exo)and SCLCs were isolated by ultracentrifugation and validated by nanoparticle tracking analysis,WB analysis and electron microscopy.A prefab-ricated nerve graft was used to deliver hAMSCs-exo or SCLCs-exo in an injured sciatic nerve rat model.The effects of hAMSCs-exo or SCLCs-exo on rat peripheral nerve injury(PNI)regeneration were determined based on the recovery of neurological function and histomorphometric variation.The effects of hAMSCs-exo or SCLCs-exo on Schwann cells were also determined via cell prolifer-ation and migration assessment.Results:SCLCs significantly expressed the Schwann cell markers glial fibrillary acidic protein and S100.Compared to hAMSCs-exo,SCLCs-exo significantly enhanced motor function recov-ery,attenuated gastrocnemius muscle atrophy and facilitated axonal regrowth,myelin forma-tion and angiogenesis in the rat model.Furthermore,hAMSCs-exo and SCLCs-exo were effi-ciently absorbed by Schwann cells.However,compared to hAMSCs-exo,SCLCs-exo signifi-cantly promoted the proliferation and migration of Schwann cells.SCLCs-exo also significantly upregulated the expression of a glial cell-derived neurotrophic factor,myelin positive regulators(SRY-box transcription factor 10,early growth response protein 2 and organic cation/carnitine transporter 6)and myelin proteins(myelin basic protein and myelin protein zero)in Schwann cells.Conclusions:These findings suggest that SCLCs-exo can more efficiently prom
基金This work was supported by grants from the National Natural Science Foundation of China (81572766 and 31771630), the National Key Research and Development Program of China (2017YFA0103800), Guangdong Innovative and Entrepreneurial Research Team Program (2016ZT06S029), Guangdong Natural Science Foundation (2016A030313215 and 2016A030313238), SYSU Young Teachers Training Program (16YKZD14) and grants (CA101795 and IU54CA210181) from U.S. National Cancer Institute, National Institutes of Health (NIH), DOD (W81XWH-16- 1-0417), and CPRIT (DP150099, RP170537, and RP150611).
文摘The differentiation status of neuroblastoma (NB) strongly correlates with its clinical outcomes; however, the molecular mechanisms driving maintenance of sternness and differentiation remain poorly understood. Here, we show that plant homeodomain finger-containing protein 20 (PHF20) functions as a critical epigenetic regulator in sustaining stem cell-like phenotype of NB by using CRISPR/Casg-based targeted knockout (KO) for high-throughput screening of gene function in NB cell differentiation. The expression of PHF20 in NB was significantly associated with high aggressiveness of the tumor and poor outcomes for NB patients. Deletion of PHF20 inhibited NB cell proliferation, invasive migration, and stem ceU-Uke traits. Mechanistically, PHF20 interacts with poly(ADP-ribose) polymerase 1 (PARP1) and directly binds to promoter regions of octamer-binding transcription factor 4 (OCT4) and sex determining region Y-box 2 (SOX2) to modulate a histone mark associated with active transcription, trimethylation of lysine 4 on histone H3 protein subunit (H3K4me3). Overexpression of OCT4 and SOX2 restored growth and progression of PHF20 KO tumor cells. Consistently, OCT4 and SOX2 protein levels in clinical NB specimens were positively correlated with PHF20 expression. Our results establish PHF20 as a key driver of NB stem cell-like properties and aggressive behaviors, with implications for prognosis and therapy.
基金supported by the"Hundred Talants Program"of the Chinese Academy of Sciences and the National Natural Science Foundation of China(51005225and51002161)
文摘Bio-mimicking graphene films,deposited on textured nickel substrates,were synthesized by the following method:replicating the surface textures of the lotus leaf by polymer duplication,fabricating textured nickel substrates by electroplating on the polymer coated with a Au film,preparing bio-mimicking graphene oxide films on the nickel substrates by vacuum filtration,and electrochemical reduction.By controlling the vacuum filtration,this replica method can not only replicate the lotus leaf structure by a graphene film,but also can achieve a novel cell-like graphene film.
基金the National Natural Science Foundation of China(grant nos.81972799 and 81871449)the Natural Science Foundation of Shanghai(grant no.23ZR1421400).
文摘The cancer stem cell hypothesis provides a basis for prediction of the recurrence and risk of metastasis in breast cancer.However,the unique expression pattern of stemness markers and the presence of nonstem-like cancer cells with varied phenotypes have brought great challenges to the characterization of breast cancer stem cells.To address these challenges,a phenotype-directed DNA nanomachine has been designed for high-accuracy labeling and in situ analysis of the stem cell-like subpopulation in breast cancer.The key for the design is to use cell surfaceanchored inputs to activate the nanomachine,which undergoes different branch migration pathways such that the signal strand can only be brought onto the cancer cells having the stem cell-like phenotype.Highly sensitive determination and single-step isolation of the stem cell-like subpopulation were achieved by incorporating functional groups into the signal strand such that the nanomachine was successfully applied in a tumor-bearing mouse model.Overall,the approach provides for a substantial improvement in capability for the analysis of the breast cancer stem cell-like subpopulation,and it is expected that the new approach will advance the use of DNA nanomachines in cancer-related studies.
基金supported by the National Natural Science Foundation of China(No.21206191)the Science Foundation of China University of Petroleum,Beijing(No.2462013YXBS007)
文摘Basic magnesium carbonate microspheres with a red blood cell (RBC)-like appearance and diameters of ~3μm were synthesized by amphiphilic molecule-participated self-assembly under hydrothermal conditions, In the self-assembly, sodium dodecyl benzene sulfonate served as a template for the formation of Mg(OH)2 spherical micelles and also as a reactant precursor that releases CO2 to react with Mg(OH)2. The growth of the microspheres is driven by the continuous generation of new hydrophobic centers because of the consumption of hydrophilic poles (--SO3-). The surfactant-directed self-assembly can be applied to the synthesis of other carbonate or metallic oxide self-assemblies, indicating that it is a universal self-assembly method for amphiphilic molecules.
基金the National High-Tech Research & Development Program of China, No. 2006AA02A128the National Natural Science Foundation of China, No. 30670667
文摘BACKGROUND: S100 protein can promote axonal growth. Therefore, transplantation of induced bone marrow-derived mesenchymal stem cells (MSCs) that can secrete S100 may provide a beneficial microenvironment for neural regeneration. OBJECTIVE: To explore the changes in S100 expression during rat MSCs differentiation into Schwann ceils in vitro. DESIGN, TIME AND SETTING: This cytology experiment was performed at the Jiangsu Key Laboratory of Neuroregeneration, Nantong University in China, from January 2006 to May 2007. MATERIALS: The rabbit anti-S100 polyclonal antibody was purchased from Dako, Denmark; the mouse anti-rat S100 monoclonal antibody was purchased from Sigma, USA. METHODS: MSCs were cultured from adult Sprague-Dawley rat femur and tibia. Cell proliferation was determined by the MTT method and CD markers, and cell cycle was measured by flow cytometry. MSCs were induced to differentiate into SC cells. SC cells were stained for S100 protein, glial fibrillary acidic protein, and low-affinity nerve growth factor receptor. S100 protein and mRNA levels were evaluated by flow cytometry, Western blot, and reverse transcription-polymerase chain reaction. MAIN OUTCOME MEASURES: S100 protein and mRNA expression. RESULTS: MSCs exhibited high amplification potential over eight passages. Prior to induction, the majority of MSCs were at the G0/G1 phase of the cell cycle. After induction, MSCs displayed morphology changes similar to Schwann cells. Moreover, induction increased S100 mRNA levels. Immunofluorescence showed that MSCs expressed S100 protein, glial fibrillary acidic protein, and low-affinity nerve growth factor receptor at 7 days of induction. Induction also increased S100 protein levels compared with untreated MSCs. CONCLUSION: MSCs are capable of differentiating into Schwann cells-like cells under conditional induction in vitro, with increasing S100 mRNA and protein expression.
基金Supported by National High-Tech Research and Development Program of China(Grant No.2006AA02A128)National Natural Science Foundation of China(Grant No.30670667)
文摘During the last decade,increasing evidence suggested that bone marrow stromal cells(MSCs) have the potential to differentiate into neural lineages.Many studies have reported that MSCs showed morphological changes and expressed a limited number of neural proteins under experimental conditions.However,no proteomic studies on MSCs differentiated into Schwann cell-like cells have been reported.In this study,we isolated MSCs from adult Sprague-Dawley rat femur and tibia bone marrows and induced the cells in vitro under specific conditions.By using two-dimensional gel electrophoresis(2-DE),we compared the protein profiles of MSCs before and after induced differentiation.We obtained 792 protein spots in the protein profile by 2-DE,and found that 74 spots changed significantly before and after the differentiation using PDQuest software,with 43 up-regulated and 31 down-regulated.We analyzed these 74 spots by a matrix assisted laser desorption ionization-time of flight mass spectrometry(MALDI-TOF-MS) and by database searching,and found that they could be grouped into various classes,including cytoskeleton and structure proteins,growth factors,metabolic proteins,chaperone proteins,receptor proteins,cell cycle proteins,calcium binding proteins,and other proteins.These proteins also include neural and glial proteins,such as BDNF,CNTF and GFAP.The results may provide valuable proteomic information about the differentiation of MSCs into Schwann cell-like cells.
基金This work was supported by China National Key R&D Program(2018YFC1003004,2018YFA0107002)the National Natural Science Foundation of China(31430052,91749129)as well as the Stanley H.Kaplan Research Fund at NYU School of Medicine.
文摘Parthenogenetic embryos,created by activation and diploidization of oocytes,arrest at mid-gestation for defective paternal imprints,which impair placental development.Also,viable offspring has not been obtained without genetic manipulation from parthenogenetic embryonic stem cells(pESCs)derived from parthenogenetic embryos,presumably attributable to their aberrant imprinting.We show that an unlimited number of oocytes can be derived from pESCs and produce healthy offspring.Moreover,normal expression of imprinted genes is found in the germ cells and the mice.pESCs exhibited imprinting consistent with exclusively maternal lineage,and higher X-chromosome activation compared to female ESCs derived from the same mouse genetic background.pESCs differentiated into primordial germ cell-like cells(PGCLCs)and formed oocytes following in vivo transplantation into kidney capsule that produced fertile pups and reconstituted ovarian endocrine function.The transcriptome and methylation of imprinted and X-linked genes in pESC-PGCLCs closely resembled those of in vivo produced PGCs,consistent with efficient reprogramming of methylation and genomic imprinting.These results demonstrate that amplification of germ cells through parthenogenesis faithfully maintains maternal imprinting,offering a promising route for deriving functional oocytes and having potential in rebuilding ovarian endocrine function.
基金supported by an academic grant from Repro Optima Center for Reproductive Health,Inc.
文摘In vitro gametogenesis(IVG)has been a topic of great interest in recent years not only because it allows for further exploration of mechanisms of germ cell development,but also because of its prospect for innovative medical applications especially for the treatment of infertility.Elucidation of the mechanisms underlying gamete development in vivo has inspired scientists to attempt to recapitulate the entire process of gametogenesis in vitro.While earlier studies have established IVG methods largely using pluripotent stem cells of embryonic origin,the scarcity of sources for these cells and the ethical issues involved in their use are serious limitations to the progress of IVG research especially in humans.However,with the emergence of induced pluripotent stem cells(iPSCs)due to the revolutionary discovery of dedifferentiation and reprogramming factors,IVG research has progressed remarkably in the last decade.This paper extensively reviews developments in IVG using iPSCs.First,the paper presents key concepts from groundwork studies on IVG including earlier researches demonstrating that IVG methods using embryonic stem cells(ESCs)also apply when using iPSCs.Techniques for the derivation of iPSCs are briefly discussed,highlighting the importance of generating transgene-free iPSCs with a high capacity for germline transmission to improve efficacy when used for IVG.The main part of the paper discusses recent advances in IVG research using iPSCs in various stages of gametogenesis.In addition,current clinical applications of IVG are presented,and potential future applications are discussed.Although IVG is still faced with many challenges in terms of technical issues,as well as efficacy and safety,novel IVG methodologies are emerging,and IVG using iPSCs may usher in the next era of reproductive medicine sooner than expected.This raises both ethical and social concerns and calls for the scientific community to cautiously develop IVG technology to ensure it is not only efficacious but also safe and adheres to social and et
基金This work was supported by the Slovenian-Ukrainian(Grant No.SLO-UKR 04-06/07)
文摘We prove that a locally compact ANR-space X is a Q-manifold if and only if it has the Disjoint Disk Property (DDP), all points of X are homological Z∞-points and X has the countable-dimensional approximation property (cd-AP), which means that each map f:K→X of a compact polyhedron can be approximated by a map with the countable-dimensional image. As an application we prove that a space X with DDP and cd-AP is a Q-manifold if some finite power of X is a Q-manifold. If some finite power of a space X with cd-AP is a Q-manifold, then X2 and X×[0,1] are Q-manifolds as well. We construct a countable familyχof spaces with DDP and cd-AP such that no space X∈χis homeomorphic to the Hilbert cube Q whereas the product X×Y of any different spaces X, Y∈χis homeomorphic to Q. We also show that no uncountable familyχwith such properties exists.
文摘Stem cell-like memory T(TSCM)cells possess stem cell properties including multipotency and self-renewal and are being recognized as emerging players in various human diseases.Advanced technologies such as multiparametric flowcytometry and single cell sequencing have enabled their identification and molecular characterization.In case of chronic viral diseases such as human immunodeficiency virus-1,CD4+T_(SCM) cells,serve as major reservoirs of the latent virus.However,during immune activation and functional exhaustion of effector T cells,these cells also possess the potential to replenish the pool of functional effector cells to curtail the infection.More recently,these cells are speculated to play important role in protective immunity following acute viral infections such as coronavirus disease 2019 and might be amenable for therapeutics by ex vivo expansion.Similarly,studies are also investigating their pathological role in driving autoimmune responses.However,there are several gaps in the understanding of the role of T_(SCM) cells in viral and autoimmune diseases to make them potential therapeutic targets.In this minireview,we have attempted an updated compilation of the dyadic role of these complex T_(SCM) cells during such human diseases along with their biology and transcriptional programs.
文摘Prostate cancers(PCa)have been reported to actively suppress antitumor immune responses by creating an immune-suppressive microenvironment.There is mounting evidence that PCas may undergo an‘‘Epithelial Immune Cell-like Transition’’(EIT)by expressing molecules conventionally associated with immune cells(e.g.,a variety of cytokines/receptors,immune transcription factors,Ig motifs,and immune checkpoint molecules),which subsequently results in the suppression of anti-cancer immune activity within the tumor microenvironment.Recent progress within the field of immune therapy has underscored the importance of immune checkpoint molecules in cancer development,thus leading to the development of novel immunotherapeutic approaches.Here,we review the expression of select immune checkpoint molecules in PCa epithelial and associated immune cells,with particular emphasis on clinical data supporting the concept of an EIT-mediated phenotype in PCa.Furthermore,we summarize current advances in anti-immune checkpoint therapies,and provide perspectives on their potential applicability.
基金This work was funded by the National Natural Science Foundation of China(No.81801855)Young Elite Scientist Sponsorship Program by CSA(No.2018QNRC001)+1 种基金Fundamental Research Funds for the Central Universities,Chengguan District Science and Technology Project(No.2018-7-6)Lanzhou University Hospital of Stomatology Research Support Fund.
文摘Micron/nano scale topographic modification has been a significant focus of interest in current titanium(Ti)surface design.However,the influence of micron/nano structured surface on cell or bacterium behavior on the Ti implant has rarely been systematically evaluated.Moreover,except for popular microgrooves,little work has been carried out on the reaction of cells to the bionic structure.In this study,several micro-pillars mimicking cell morphology were prepared on Ti surfaces by lithography and contact printing(ICP)method,and they were further decorated with nanotube arrays by anodization technology.These surface modifications remarkablly increased the surface roughness of pristine Ti surface from 91.17 nm±5.57 nm to be more than 1000 nm,and reduced their water contact angles from 68.3°±0.7°to be 16.9°±2.4°.Then,the effects of these hierarchical micron/nano scale patterns on the behaviors of MG63 osteoblasts,L929 fibroblasts,SCC epithelial cells and P.gingivalis were studied,aiming to evaluate their performance in osseointegration,gingival epithelial sealing and antibacterial ability.Through an innovative scoring strategy,our findings showed that square micro-pillars with 6μm width and 2μm height combined with 85 nm diameter nanotubes was suitable for implant neck design,while square micro-pillars with 3μm width and 3.6μm height combined with 55 nm diameter nanotubes was the best for implant body design.Our study reveals the synergistic effect of the hierarchical micron/nano scale patterns on MG63 osteoblasts,L929 fibroblasts,SCC epithelial cells and P.gingivalis functions.It provides insight into the design of biomedical implant surfaces.
文摘目的探讨胃肠道透明细胞肉瘤(clear cell sarcoma of the gastrointestinal tract,CCS-GI)的临床病理特征及遗传学特点。方法对1例CCS-GI进行组织学观察、免疫组化染色、荧光原位杂交(fluorescence in situ hybridization,FISH)检测,并复习相关文献。结果患者女性,因"腹痛1周"入院,CT检查示右半结肠肿瘤,肉眼观察结肠黏膜面可见一溃疡型肿块,切面灰白、实性、质嫩,侵及全层。镜下见中等大小的圆形或卵圆形肿瘤细胞呈片状排列,肿瘤细胞间可见散在分布的破骨细胞样多核巨细胞。肿瘤细胞S-100蛋白弥漫阳性,HMB-45、Melan-A、CD117、CD1a及PCK均阴性。FISH检测结果示74%的肿瘤细胞存在EWSR1基因易位。结论 CCS-GI是一种特殊类型的胃肠道肿瘤,具有独特的组织学、免疫表型、超微结构及遗传学特征,该类肿瘤中的胃肠道透明细胞肉瘤样肿瘤亚型是否为一个独立的病变实体,尚需增加病例量进一步研究,包括细胞遗传学和分子生物学的相关研究。