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| 1 | Bispecific prodrug nanoparticles circumventing multiple immune resistance mechanisms for promoting cancer immunotherapy显示文摘Cancer immunotherapy is impaired by the intrinsic and adaptive immune resistance.Herein,a bispecific prodrug nanoparticle was engineered for circumventing immune evasion of the tumor cells by targeting multiple immune resistance mechanisms.A disulfide bond-linked bispecific prodrug of NLG919 and JQ1(namely NJ) was synthesized and self-assembled into a prodrug nanoparticle,which was subsequently coated with a photosensitizer-modified and tumor acidity-activatable diblock copolymer PHP for tumor-specific delivery of NJ.Upon tumor accumulation via passive tumor targeting,the polymeric shell was detached for facilitating intracellular uptake of the bispecific prodrug.NJ was then activated inside the tumor cells for releasing JQ1 and NLG919 via glutathione-mediated cleavage of the disulfide bond.JQ1 is a bromodomain-containing protein 4 inhibitor for abolishing interferon gamma-triggered expression of programmed death ligand 1.In contrast,NLG919 suppresses indoleamine-2,3-dioxygenase 1-mediated tryptophan consumption in the tumor microenvironment,which thus restores robust antitumor immune responses.Photodynamic therapy(PDT) was performed to elicit antitumor immunogenicity by triggering immunogenic cell death of the tumor cells.The combination of PDT and the bispecific prodrug nanoparticle might represent a novel strategy for blockading multiple immune evasion pathways and improving cancer immunotherapy. | Jiayi Ye Bo Hou Fangmin Chen Shunan Zhang Muya Xiong Tianliang Li Yechun Xu Zhiai Xu Haijun Yu | 2022 | Acta Pharmaceutica Sinica B2022,12,6: | 4 |
| 2 | RTN1-C mediates cerebral ischemia/reperfusion injury via modulating autophagy显示文摘It has been widely accepted that autophagic cell death exacerbates the progression of cerebral ischemia/reperfusion (I/R). Our previous study revealed that overexpression of reticulon protein 1-C (RTN1-C) is involved in cerebral I/R injury. However, the underlying mechanisms have not been studied intensively. This study was designed to evaluate the effect of RTN1-C on autophagy under cerebral I/R. Using an in vitro oxygen-glucose deprivation followed by reoxygenation and a transient middle cerebral artery occlusion model in rats, we found that the expression of RTN1-C protein was significantly upregulated. We also revealed that RTN1-C knockdown suppressed overactivated autophagy both in vivo and in vitro, as indicated by decreased expressions of autophagic proteins. The number of Beclin-1/propidium iodide-positive cells was significantly less in the LV-shRTN1-C group than in the LV-shNC group. In addition, rapamycin, an activator of autophagy, aggravated cerebral I/R injury. RTN1-C knockdown reduced brain infarct volume, improved neurological deficits, and attenuated cell vulnerability to cerebral I/R injury after rapamycin treatment. Taken together, our findings demonstrated that the modulation of autophagy from RTN1-C may play vital roles in cerebral I/R injury, providing a potential therapeutic treatment for ischemic brain injury. | Jun Ling Haijian Cai Muya Lin Shunli Qi Jian Du Lijian Chen | 2021 | Acta Biochimica et Biophysica Sinica2021,53,2: | 2 |
| 3 | Single-cell RNA sequencing reveals Nestin+active neural stem cells outside the central canal after spinal cord injury显示文摘Neural stem cells(NSCs)in the spinal cord hold great potential for repair after spinal cord injury(SCI).The ependyma in the central canal(CC)region has been considered as the NSCs source in the spinal cord.However,the ependyma function as NSCs after SCI is still under debate.We used Nestin as a marker to isolate potential NSCs and their immediate progeny,and characterized the cells before and after SCI by single-cell RNA-sequencing(scRNA-seq).We identified two subgroups of NSCs:the subgroup located within the CC cannot prime to active NSCs after SCI,while the subgroup located outside the CC were activated and exhibited the active NSCs properties after SCI.We demonstrated the comprehensive dynamic transcriptome of NSCs from quiescent to active NSCs after SCI.This study reveals that Nestin+cells outside CC were NSCs that activated upon SCI and may thus serve as endogenous NSCs for regenerative treatment of SCI in the future. | Muya Shu Xiaoyu Xue Hu Nie Xianming Wu Minghan Sun Lianyong Qiao Xing Li Bai Xu Zhifeng Xiao Yannan Zhao Yongheng Fan Bing Chen Jixiang Zhang Ya Shi Yaming Yang Falong Lu Jianwu Dai | 2022 | Science China(Life Sciences)2022,65,2: | 2 |
| 4 | Lineage tracing reveals the origin of Nestin-positive cells are heterogeneous and rarely from ependymal cells after spinal cord injury显示文摘Nestin is expressed extensively in neural stem/progenitor cells during neural development, but its expression is mainly restricted to the ependymal cells in the adult spinal cord. After spinal cord injury(SCI), Nestin expression is reactivated and Nestinpositive(Nestin;) cells aggregate at the injury site. However, the derivation of Nestin;cells is not clearly defined. Here, we found that Nestin expression was substantially increased in the lesion edge and lesion core after SCI. Using a tamoxifen inducible CreER(T2)-loxP system, we verified that ependymal cells contribute few Nestin;cells either to the lesion core or the lesion edge after SCI. In the lesion edge, GFAP+astrocytes were the main cell type that expressed Nestin;they then formed an astrocyte scar.In the lesion core, Nestin;cells expressed αSMA or Desmin, indicating that they might be derived from pericytes. Our results reveal that Nestin;cells in the lesion core and edge came from various cell types and rarely from ependymal cells after complete transected SCI, which may provide new insights into SCI repair. | Xiaoyu Xue Muya Shu Zhifeng Xiao Yannan Zhao Xing Li Haipeng Zhang Yongheng Fan Xianming Wu Bing Chen Bai Xu Yaming Yang Weiyuan Liu Sumei Liu Jianwu Dai | 2022 | Science China(Life Sciences)2022,65,4: | 2 |
| 5 | Oxidative exfoliation of spent cathode carbon:A two-in-one strategy for its decontamination and high-valued application显示文摘Spent cathode carbon(SCC)from aluminum electrolysis is a potential graphite resource.However,full use of the SCC remains a challenge,since it contains many hazardous substances(e.g.,fluoride salts,cyanides),encapsulated within the thick carbon layers and thus posing serious environmental concerns.This work presents a chemical oxidative exfoliation route to achieve the recycling of SCC and the decontaminated SCC with high-valued graphene oxide(GO)-like carbon structures(SCC-GO)is applied as an excellent adsorbent for organic pollutants.Specifically,after the oxidative exfoliation,the embedded hazardous constituents are fully exposed,facilitating their subsequent removal by aqueous leaching.Moreover,benefiting from the enhanced specific surface areas along with abundant O-containing functional groups,the as-produced SCC-GO,shows an adsorption capacity as high as 347 mg·g^(-1)when considering methylene blue as a pollutant model,which exceeds most of the recently reported carbon-based adsorbents.Our study provides a feasible solution for the efficient recycling of hazardous carbonaceous wastes. | Runze Chen Yuran Chen Xuemin Liang Yapeng Kong Yangyang Fan Quan Liu Zhenyu Yang Feiying Tang Johnny Muya Chabu Maru Dessie Walle Liqiang Wang | 2023 | Chinese Journal of Chemical Engineering2023,59,7: | 0 |
| 6 | Multi-omics for COVID-19:driving development of therapeutics and vaccines显示文摘The ongoing COVID-19 pandemic caused by SARS-CoV-2 has raised global concern for public health and economy.The development of therapeutics and vaccines to combat this virus is continuously progressing.Multi-omics approaches,including genomics,transcriptomics,proteomics,metabolomics,epigenomics and metallomics,have helped understand the structural and molecular features of the virus,thereby assisting in the design of potential therapeutics and accelerating vaccine development for COVID-19.Here,we provide an up-to-date overview of the latest applications of multi-omics technologies in strategies addressing COVID-19,in order to provide suggestions towards the development of highly effective knowledge-based therapeutics and vaccines. | Mengyu Guo Muya Xiong Jinying Peng Tong Guan Haixia Su Yanyi Huang Cai-Guang Yang Yang Li Diana Boraschi Thanigaimalai Pillaiyar Guanbo Wang Chengqi Yi Yechun Xu Chunying Chen | 2023 | National Science Review2023,10,9: | 0 |
| 7 | MiR-743a-5p regulates differentiation of myoblast by targeting Mob1b in skeletal muscle development and regeneration显示文摘The microRNAs (miRNAs) play an important role in regulating myogenesis by targeting mRNA. However, the understanding of miRNAs in skeletal muscle development and diseases is unclear. In this study, we firstly performed the transcriptome profiling in differentiating C2C12 myoblast cells. Totally, we identified 187 miRNAs and 4260 mRNAs significantly differentially expressed that were involved in myoblast differentiation. We carried out validation of microarray data based on 5 mRNAs and 5 miRNAs differentially expressed and got a consistent result. Then we constructed and validated the significantly up- and down-regulated mRNA-miRNA interaction networks. Four interaction pairs (miR-145a-5p-Fscn1, miR-200c-5p-Tmigd1, miR-27a-5p-Sln and miR-743a-5p-Mob1b) with targeted relationships in differentiated myoblast cells were demonstrated. They are all closely related to myoblast development. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated cell cycle signals important for exploring skeletal muscle development and disease. Functionally, we discovered that miR-743a targeting gene Mps One Binder Kinase Activator-Like 1B (Mob1b) gene in differentiated C2C12. The up-regulated miR-743a can promote the differentiation of C2C12 myoblast. While the down-regulated Mob1b plays a negative role in differentiation. In addition, the expression profile of miR-743a and Mob1b are consistent with skeletal muscle recovery after Cardiotoxin (CTX) injury. Our study revealed that miR-743a-5p regulates myoblast differentiation by targeting Mob1b involved in skeletal muscle development and regeneration. Our findings made a further exploration for mechanisms in myogenesis and might provide potential possible miRNA-based target therapies for skeletal muscle regeneration and disease in the near future. | YongSheng Zhang YiLong Yao ZiShuai Wang Dan Lu YuanYuan Zhang Adeyinka Abiola Adetula SiYuan Liu Min Zhu YaLan Yang XinHao Fan MuYa Chen YiJie Tang Yun Chen YuWen Liu GuoQiang Yi ZhongLin Tang | 2022 | Genes & Diseases2022,9,4: | 0 |