Bone marrow mesenchymal stem cell-induced autophagy ameliorates TNBS-induced experimental colitis by downregulating the NLRP3 inflammasome

This study aimed to elucidate the potential mechanisms through which bone marrow-derived mesenchymal stem cells(BM-MSCs)may be effective in alleviating experimental colitis induced by treatment with 2,4,6-trinitrobenzene-sulfonate acid(TNBS),specifically through autophagy modulation.Methods:BM-MSCs were collected from BALB/c mice for subsequent experiments.The study employed cell counting kits(CCK-8)to investigate the impact of the MSC-conditioned medium(M medium)on the proliferation of RAW264.7 macrophages.The GFP-mRFP-LC3 adenovirus was transfected into RAW264.7 to detect autophagic flux.The gene expression of cytokines was assessed through quantitative reverse transcription polymerase chain reaction(qRT-PCR).Western blot analysis was employed to determine the presence of a binding interaction between NOD-like receptor protein 3(NLRP3)and autophagy.Furthermore,a colitis mouse model was established by TNBS induction.Clinical disease activity score was assessed regularly,and histological and morphometric analyses were performed on colonic tissues.Inflammatory serum cytokines were identified using an enzyme-linked immunosorbent assay.Results:BM-MSCs significantly promoted the proliferation of RAW264.7.In vitro lipopolysaccharide(LPS)-stimulated RAW264.7 cells,treated with BM-MSCs,triggered autophagy and inhibited cytokine mRNA expression.Additionally,in LPS-induced RAW264.7,BM-MSCs enhanced the Beclin1 protein expression and the microtubule-associated protein 1 light chain 3(LC3)-II to LC3-I ratio while suppressing the protein levels of NLRP3 and apoptosis-associated speck-like protein(ASC).Nevertheless,3-methyladenine(3-MA),an inhibitor of autophagy,prevented the impact of BM-MSCs by reducing the levels of NLRP3 and ASC proteins,suggesting that autophagy triggered the inhibition of the NLRP3 inflammasome.In comparison to the mice in the TNBS group,the mice in the TNBS+MSC group displayed a more acute form of colitis,and the IL1βand IL18 cytokines in their serum were lowered as well.In the meantime,3-MA raised IL1βand IL18 cytokine levels and worsened TNBS-induced experimental colitis.Conclusions:BM-MSCs can suppress inflammation in TNBS-induced experimental mice by inhibiting the NLRP3 inflammasome,thereby enhancing autophagy.

Resolving the lineage relationship between malignant cells and vascular cells in glioblastomas

Glioblastoma multiforme(GBM),a highly malignant and heterogeneous brain tumor,contains various types of tumor and non-tumor cells.Whether GBM cells can trans-differentiate into non-neural cell types,including mural cells or endothelial cells(ECs),to support tumor growth and invasion remains controversial.Here we generated two genetic GBM models de novo in immunocompetent mouse brains,mimicking essential pathological and molecular features of human GBMs.Lineage-tracing and transplantation studies demonstrated that,although blood vessels in GBM brains underwent drastic remodeling,evidence of trans-differentiation of GBM cells into vascular cells was barely detected.Intriguingly,GBM cells could promiscuously express markers for mural cells during gliomagenesis.Furthermore,single-cell RNA sequencing showed that patterns of copy number variations(CNVs)of mural cells and ECs were distinct from those of GBM cells,indicating discrete origins of GBM cells and vascular components.Importantly,single-cell CNV analysis of human GBM specimens also suggested that GBM cells and vascular cells are likely separate lineages.Rather than expansion owing to trans-differentiation,vascular cell expanded by proliferation during tumorigenesis.Therefore,cross-lineage trans-differentiation of GBM cells is very unlikely to occur during gliomagenesis.Our findings advance understanding of cell lineage dynamics during gliomagenesis,and have implications for targeted treatment of GBMs.

聚丙烯酸修饰的Fe3O4@C核壳型微球的制备及其在锂离子电池负极中的电化学性能

锂离子电池作为最有前途的储能技术之一,因具有循环寿命长、能量密度大、自放电率低、热稳定性能好、记忆效应不明显等优势,已成为新型能源领域的研究热点。本工作以聚丙烯酸(PAA)修饰的粒径约250 nm的Fe3O4微球为核,葡萄糖为碳源,通过水热法制备了Fe3O4@C核壳型微球,研究其作为锂离子电池负极材料的电化学特性。通过X射线衍射(XRD)、扫描电镜(SEM)、热重(TGA–DTA)和傅里叶红外光谱(FT-IR)等手段对其表征,并通过循环伏安特性曲线、循环性能曲线、倍率性能曲线,充放电平台曲线和阻抗及其拟合曲线等研究其电化学性能。结果表明,制备的聚丙烯酸(PAA)修饰的Fe3O4@C核壳型微球球状完整,粒径均一,平均尺寸约310 nm,碳层表面光滑,包覆均匀,平均厚度约30 nm。Fe3O4@C的核壳结构有效缓解了恒流充放电过程中的体积膨胀,避免了晶体结构的快速坍塌。PAA中大量的羧基基团对Fe3O4起到表面改性的作用,有效避免了颗粒团聚,保证了良好的分散性。碳的有效包覆可改善Fe3O4材料作为锂离子电池负极材料的离子和电子电导,增加其比容量、库伦效率和循环稳定性。Fe3O4@C核壳型微球在100 m A/g电流密度下,恒流充放电循环370圈后,仍能保持655 m Ah/g放电比容量,约为首次放电的50%,具有良好的容量保持率。

Paired related homeobox 1 transactivates dopamine D2 receptor to maintain propagation and tumorigenicity of glioma-initiating cells

Glioblastoma multiforme (GBM ) 是有有限治疗学的工具和差的预后的一个高度侵略的大脑肿瘤。最近的研究显示开始 glioma cells/glioma 干细胞(GICs/GSCs ) 可能为肿瘤开始，渗入，和复发负责。GIC 能异常地采用平衡胚胎的神经先锋的自强和区别的分子的机械。这里，我们发现那配对的相关 homeobox 1 (PRRX1 ) ，以前是的一个 homeodomain 抄写因素报导了控制骨胳的开发，在外皮的神经祖先被表示并且为他们的自强和合适的区别被要求。进一步， PRRX1 是在 glioma 样品和标签 GIC 的 overrepresented。Glioma 房间和 GIC 与 PRRX1 弄空不能在 vitro 宣传或在异种皮移植老鼠模型形成肿瘤。PRRX1 调整的 GIC 自强功能被多巴胺 D2 受体(DRD2 ) 调停。PRRX1 直接在 GIC 把它的表示绑在 DRD2 倡导者和 transactivates。发信号的 DRD2 的阻塞妨碍 GIC 自强，而它的 overexpression 恢复宣传和弄空 PRRX1 的 GIC 的 tumorigenic 潜力。最后， PRRX1 加强经由调停 DRD2 的细胞外的信号相关的 kinase (英皇家空军之阶级最低之兵) 和 AKT 的 GIC 激活。因此，我们的学习建议那治疗学的指向在 GIC 的 PRRX1DRD2ERK/AKT 轴是为对待 GBM 的有希望的策略。

Design and implementation of the galvanometer scanning system for reflectance confocal and stimulated Raman scattering microscopy

We report on two strategies to design and implement the galvanometer-based laser-scanning mechanisms for the realization of reflectance confocal microscopy(RCM) and stimulated Raman scattering(SRS) microscopy systems. The RCM system uses a resonant galvanometer scanner driven by a home-built field-programmable gate array circuit with a novel dual-trigger mode and a home-built high-speed data acquisition card. The SRS system uses linear galvanometers with commercially available modules. We demonstrate video-rate high-resolution imaging at 11 frames per second of in vivo human skin with the RCM system and label-free biomolecular imaging of cancer cells with the SRS system. A comparison of the two strategies for controlling galvanometer scanners provides scientific and technical reference for future design and commercialization of various laser-scanning microscopes using galvanometers.