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| 1 | Hydrogen peroxide primes heart regeneration with a derepression mechanism显示文摘当成年的人的心很限制了再生潜力时,成年 zebrafish 心能充分在 20% 室的切除术以后再生。尽管以前的报告建议象 FGF 和 PDGF 那样的发展发信号小径在成年的心新生被再使用,内在的细胞内部的机制仍然保持大部分未知。这里,我们显示出那 H 2 O 2 充当新奇 epicardial 和心肌的信号在成年 zebrafish 为新生告知心。未经触动的心的实时成像揭示了高度局部性的 H 2 O 2(~ 30 μ M ) 在在切除术地点的心外膜和邻近的紧缩的心肌层的生产。减少的 H 2有 Duox 禁止者 diphenyleneiodonium (点每英寸)或 apocynin 的 O 2形成,或清除 H 2当时,由过氧化氢酶 overexpression 的 O 2显著地损害了心脏的新生外长的 H 2 O 2在心脏的新生上救了点每英寸的禁止的效果,显示那 H 2 O 2是在这个过程的一个必要、足够的信号。机械学地,提高了 H 2 O 2 使动摇氧化还原作用敏感的磷酸酶 Dusp6 并且因此增加了 Erk1/2 的 phosphorylation。当 dusp6 的转基因的 overexpression 损害了心脏的新生时, Dusp6 禁止者 BCI 完成了类似的支持 regenerative 效果。H 2 O 2 在招募起一个双作用通过二条相对独立的小径的有免疫力的房间和支持的心新生。我们结束那 H 2 潜在地从 Duox/Nox2 产生的 O 2 由解开通过包含 Dusp6 的 derepression 机制发信号的地图 kinase 在 zebrafish 支持心新生。 | Peidong Han Xiao-Hai Zhou Nannan Chang Cheng-Lu Xiao Shouyu Yah He Ren Xin-Zhuang Yang Mei-Ling Zhang Qing Wu Boyang Tang Ju-Peng Diao Xiaojun Zhu Chuanmao Zhang Chuan-Yun Li Heping Cheng Jing-Wei Xiong | 2014 | Cell Research2014，24，9： | 10 |
| 2 | Prognostic value of programmed death.1, programmed death-ligand 1, programmed death-ligand 2 expression, and CD8(+) T cell density in primary tumors and metastatic lymph nodes from patients with stage T1.4N+M0 gastric adenocarcinoma显示文摘Background: Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1) immunotherapy has been proved to be effective on gastric cancer in ongoing clinical trials. However, the value of PD-L1 in predicting responses of patients with gastric cancer to anti-PD-1/PD-L1 immunotherapy is controversial. Some studies suggested that intra-and inter-tumoral heterogeneity of PD-L1 expression might explain the controversy.This study aimed to analyze the expression of PD-L1, PD-L2, and PD-1 as well as CD8(+) T-cell density in primary tumors and lymph nodes from patients with stage T1-4 N+M0 gastric adenocarcinoma to explore the heterogeneity of PD-1 signaling pathway molecules.Methods: In primary tumors and metastatic as well as non-metastatic lymph nodes from patients with stage T1-4 N+M0 gastric adenocarcinoma, we detected PD-L1 and PD-L2 expression with immunohistochemistry. CD8(+)T-cell density in primary tumors and PD-1 expression on CD8(+)T cells were detected with immunofluorescence. Univariate analysis was used to determine the prognostic values of them. Cox proportional hazard regression model was used to identify independent risk factors that affect patients' overall survival and disease-free survival.Results: Among 119 eligible patients who had undergone surgical resection, the positive rate of PD-L1 was higher in metastatic lymph nodes than in primary tumors(45.4% vs. 38.7%, P = 0.005); the positive rate of PD-1 on CD8(+)T cells was significantly higher in primary tumors and metastatic lymph nodes than in tumor-free lymph nodes(both P < 0.001). The intensity of PD-1 expression on CD8(+) T cells in primary tumors and in metastatic lymph nodes were stronger than that in tumor-free lymph nodes from the same patient. Beside, the positive rate of PD-L2 did not show any differences between primary tumors and metastatic lymph nodes. In multivariate analysis, PD-L1 expression,PD-L2 expression, a low density of CD8(+) T cells in primary tumors, and PD-1 expression on CD8(+) T cells in primary tumors were associated with poor prognosis.Conclusion: The expression of PD-L1 is heterogeneous in primary tumors and in metastatic lymph nodes from patients with stageT1-4 N+M0 gastric adenocarcinoma, which might explain the inconsistent results in assessing the prognostic value of PD-L1 expression in previous studies. | Yuan Gao Su Li Dazhi Xu Shangxiang Chen Yuchen Cai Wenqi Jiang Xinke Zhang Jin Sun Kefeng Wang Boyang Chang Fenghua Wang Minghuang Hong | 2017 | Chinese Journal of Cancer2017，36，11： | 8 |
| 3 | Deregulation of Bmi-1 is associated with enhanced migration, invasion and poor prognosis in salivary adenoid cystic carcinoma显示文摘 | Boyang Chang Su Li Qianting He Zhonghua Liu Luodan Zhao Tingting Zhao Anxun Wang | 2014 | BBA - General Subjects2014，，12： | 1 |
| 4 | Identification and determination of the major constituents in Traditional Chinese Medicinal formula Danggui-Shaoyao-San by HPLC–DAD–ESI-MS/MS显示文摘 | Linlin Chen Jin Qi Yan-xu Chang Danni Zhu Boyang Yu | 2009 | Journal of Pharmaceutical and Biomedical Analysis2009，，2： | 1 |
| 5 | Intercellular transfer of activated STING triggered by RAB22A-mediated non-canonical autophagy promotes antitumor immunity显示文摘STING,an endoplasmic reticulum(ER)transmembrane protein,mediates innate immune activation upon cGAMP stimulation and is degraded through autophagy.Here,we report that activated STING could be transferred between cells to promote antitumor immunity,a process triggered by RAB22A-mediated non-canonical autophagy.Mechanistically,RAB22A engages PI4K2A to generate PI4P that recruits the Atg12–Atg5–Atg16L1 complex,inducing the formation of ER-derived RAB22A-mediated non-canonical autophagosome,in which STING activated by agonists or chemoradiotherapy is packaged.This RAB22A-induced autophagosome fuses with RAB22A-positive early endosome,generating a new organelle that we name Rafeesome(RAB22A-mediated non-canonical autophagosome fused with early endosome).Meanwhile,RAB22A inactivates RAB7 to suppress the fusion of Rafeesome with lysosome,thereby enabling the secretion of the inner vesicle of the autophagosome bearing activated STING as a new type of extracellular vesicle that we define as R-EV(RAB22A-induced extracellular vesicle).Activated STING-containing R-EVs induce IFNβrelease from recipient cells to the tumor microenvironment,promoting antitumor immunity.Consistently,RAB22A enhances the antitumor effect of the STING agonist diABZI in mice,and a high RAB22A level predicts good survival in nasopharyngeal cancer patients treated with chemoradiotherapy.Our findings reveal that Rafeesome regulates the intercellular transfer of activated STING to trigger and spread antitumor immunity,and that the inner vesicle of non-canonical autophagosome originated from ER is secreted as R-EV,providing a new perspective for understanding the intercellular communication of organelle membrane proteins. | Ying Gao Xueping Zheng Boyang Chang Yujie Lin Xiaodan Huang Wen Wang Shirong Ding Weixiang Zhan Shang Wang Beibei Xiao Lanqing Huo Youhui Yu Yilin Chen Run Gong Yuanzhong Wu Ruhua Zhang Li Zhong Xin Wang Qiuyan Chen Song Gao Zhengfan Jiang Denghui Wei Tiebang Kang | 2022 | Cell Research2022，32，12： | 1 |
| 6 | Bioinspired drug-delivery system emulating the natural bone healing cascade for diabetic periodontal bone regeneration显示文摘Diabetes mellitus(DM)aggravates periodontitis,resulting in accelerated periodontal bone resorption.Disordered glucose metabolism in DM causes reactive oxygen species(ROS)overproduction resulting in compromised bone healing,which makes diabetic periodontal bone regeneration a major challenge.Inspired by the natural bone healing cascade,a mesoporous silica nanoparticle(MSN)-incorporated PDLLA(poly(DL-lactide))-PEG-PDLLA(PPP)thermosensitive hydrogel with stepwise cargo release is designed to emulate the mesenchymal stem cell“recruitment-osteogenesis”cascade for diabetic periodontal bone regeneration.During therapy,SDF-1 quickly escapes from the hydrogel due to diffusion for early rat bone marrow stem cell(rBMSC)recruitment.Simulta-neously,slow degradation of the hydrogel starts to gradually expose the MSNs for sustained release of metformin,which can scavenge the overproduced ROS under high glucose conditions to reverse the inhibited osteogenesis of rBMSCs by reactivating the AMPK/β-catenin pathway,resulting in regulation of the diabetic microenvironment and facilitation of osteogenesis.In vitro experiments indicate that the hydrogel markedly restores the inhibited migration and osteogenic capacities of rBMSCs under high glucose conditions.In vivo results suggest that it can effectively recruit rBMSCs to the periodontal defect and significantly promote periodontal bone regeneration under type 2 DM.In conclusion,our work provides a novel therapeutic strategy of a bioinspired drug-delivery system emulating the natural bone healing cascade for diabetic periodontal bone regeneration. | He Wang Xiaowei Chang Qian Ma Boyang Sun Han Li Jinmin Zhou Yiyao Hu Xiaoyu Yang Jie Li Xin Chen Jinlin Song | 2023 | Bioactive Materials2023，，3： | 1 |
| 7 | METTL14 is a chromatin regulator independent of its RNA N^(6)-methyladenosine methyltransferase activity显示文摘METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m^(6)A methyltransferase complex(MTC)that installs m^(6)A.Surprisingly,depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell(mESC).While comparable global hypo-methylation in RNA m^(6)A was observed in Mettl3 or Mettl14 knockout mESCs,respectively.Mettl14 knockout led to a globally decreased nascent RNA synthesis,whereas Mettl3 depletion resulted in transcription upregulation,suggesting that METTL14 might possess an mA-independent role in gene regulation.We found that METTL14 colocalizes with the repressive H3K27me3 modification.Mechanistically,METTL14,but not METTL3,binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3.Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression.The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs.This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m^(6)A,and critically impacts transcriptional regulation,stemness maintenance,and differentiation ofmESCs. | Xiaoyang Dou Lulu Huang Yu Xiao Chang Liu Yini Li Xinning Zhang Lishan Yu Ran Zhao Lei Yang Chuan Chen Xianbin Yu Boyang Gao Meijie Qi Yawei Gao Bin Shen Shuying Sun Chuan He Jun Liu | 2023 | Protein & Cell2023，14，9： | 0 |
| 8 | Nm-Mut-seq:a base-resolution quantitative method for mapping transcriptome-wide 2′-O-methylation显示文摘Dear Editor,2'-O-methylation(Nm)(Fig.1a)is a prevalent post-transcriptional RNA modification present in many cellular RNAs and plays critical roles in modulating both physical properties and functions of eukaryotic RNA.Studies of Nm modifications in RNA havelong been hampered by a lack of effective mapping methods. | Li Chen Li-Sheng Zhang Chang Ye Huiqing Zhou Bei Liu Boyang Gao Zixin Deng Changming Zhao Chuan He Bryan C.Dickinson | 2023 | Cell Research2023，33，9： | 0 |
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