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| 1 | Anti-PD-L1/TGF-BR fusion protein (SHR-1701) overcomes disrupted lymphocyte recovery-induced resistance to PD-1/PD-L1 inhibitors in lung cancer显示文摘Background:Second-generation programmed cell death-protein 1/pro-grammed death-ligand 1(PD-1/PD-L1)inhibitors,such as bintrafusp alfa(M7824),SHR-1701,and YM101,have been developed to simultaneously block PD-1/PD-L1 and transforming growth factor-beta/transforming growth factor-beta receptor(TGF-P/TGF-βR).Consequently,it is necessary to identify predictive factors of lung cancer patients who are not only resistant to PD-1/PD-LI inhibitors but also sensitive to bifunctional drugs.The purpose of this study was to search for such predictors.Methods:Multivariable Cox regression was used to study the association between the clinical outcome of treatment with PD-1/PD-L1 inhibitors and lym-phocyte recovery after lymphopenia in lung cancer patients.Murine CMT167 lung cancer cells were engineered to express the firefly luciferase gene and implanted orthotopically in the lung of syngeneic mice.Bioluminescence imag-ing,flow cytometry,and immunohistochemistry were employed to detrmine response to immunotherapy and function of tumor-infiltrating immune cells.Results:For lung cancer patients treated with anti-PD-1/PD-LI antibodies,poor lymphocyte recovery was associated with a shorter progression-free survival(PFS;P<0.001),an accumulation of regulatory T cells(Tregs),and an elimi-nation of CD8+T cells in the peripheral blood.Levels of CD8+T cells and Treg cells were also imbalanced in the tumors and peripheral immune organs of mice with poor lymphocyte recovery after chemotherapy.Moreover,these mice failed to respond to anti-PD-1 antibodies but remained sensitive to the anti-PD-LI/TGF-βR fusion protein(SHR-1701).Consistently,SHR-1701 but not anti-PD-1 antibod-ies,markedly enhanced IFN-γproduction and Ki-67 expression in peripheral CD8+T cells from patients with impaired lymphocyte recovery.Conclusions:Lung cancer patients with poor lymphocyte recovery and suffer-ing from persistent lymphopenia after previous chemotherapy are resistant to anti-PD-1/PD-L1 antibodies but might be sensitive to second-generation agents such as SHR-1701. | Bo Cheng Kaikai Ding Pengxiang Chen Jianxiong Ji Tao Luo Xiaofan Guo Wei Qiu Chunhong Ma Xue Meng Jian Wang Jinming Yu Yuan Liu | 2022 | Cancer Communications2022，42，1： | 5 |
| 2 | Investigation and analysis of the linkage mechanism and whole process cost of livestock manure organic fertilizer显示文摘In recent years,the utilization of manure resources for livestock and poultry farming has attracted a widespread attention,and manure resources utilization models suitable for different regional characteristics have formed gradually.Among them,the production of organic fertilizer from animal manure is a vital utilization method.However,there are still some problems such as high production costs,difficult sales,and the unwillingness of farmers to use organic fertilizers which have affected the breeding cycle and the sustainability of manure treatment in livestock and poultry breeding.This article selected 371 organic fertilizer plants,related farms and farmers in China,focusing on the main links of the entire process of livestock manure-organic fertilizer-farm application,and studied the mode of animal manure collection by organic fertilizer plants.The costs of organic fertilizer production and farmland application were discussed.Moreover,suggestions were made for the promotion and implementation of large-scale organic fertilizers to make good utilization of manure resources in livestock and poultry farming. | Shanshan Dong Bin Sui Yujun Shen Haibo Meng Lixin Zhao Jingtao Ding Haibin Zhou Xi Zhang Hongsheng Cheng Jian Wang Ran Li Liqiu Song Pengxiang Xu Ji Li | 2020 | International Journal of Agricultural and Biological Engineering2020，13，2： | 2 |
| 3 | An invasive zone in human liver cancer identified by Stereo-seq promotes hepatocyte–tumor cell crosstalk,local immunosuppression and tumor progression显示文摘Dissecting and understanding the cancer ecosystem,especially that around the tumor margins,which have strong implications for tumor cell infiltration and invasion,are essential for exploring the mechanisms of tumor metastasis and developing effective new treatments.Using a novel tumor border scanning and digitization model enabled by nanoscale resolution-SpaTial Enhanced REsolution Omics-sequencing(Stereo-seq),we identified a 500µm-wide zone centered around the tumor border in patients with liver cancer,referred to as“the invasive zone”.We detected strong immunosuppression,metabolic reprogramming,and severely damaged hepatocytes in this zone.We also identified a subpopulation of damaged hepatocytes with increased expression of serum amyloid A1 and A2(referred to collectively as SAAs)located close to the border on the paratumor side.Overexpression of CXCL6 in adjacent malignant cells could induce activation of the JAK-STAT3 pathway in nearby hepatocytes,which subsequently caused SAAs’overexpression in these hepatocytes.Furthermore,overexpression and secretion of SAAs by hepatocytes in the invasive zone could lead to the recruitment of macrophages and M2 polarization,further promoting local immunosuppression,potentially resulting in tumor progression.Clinical association analysis in additional five independent cohorts of patients with primary and secondary liver cancer(n=423)showed that patients with overexpression of SAAs in the invasive zone had a worse prognosis.Further in vivo experiments using mouse liver tumor models in situ confirmed that the knockdown of genes encoding SAAs in hepatocytes decreased macrophage accumulation around the tumor border and delayed tumor growth.The identification and characterization of a novel invasive zone in human cancer patients not only add an important layer of understanding regarding the mechanisms of tumor invasion and metastasis,but may also pave the way for developing novel therapeutic strategies for advanced liver cancer and other solid tumors. | Liang Wu Jiayan Yan Yinqi Bai Feiyu Chen Xuanxuan Zou Jiangshan Xu Ao Huang Liangzhen Hou Yu Zhong Zehua Jing Qichao Yu Xiaorui Zhou Zhifeng Jiang Chunqing Wang Mengnan Cheng Yuan Ji Yingyong Hou Rongkui Luo Qinqin Li Liang Wu Jianwen Cheng Pengxiang Wang Dezhen Guo Waidong Huang Junjie Lei Shang Liu Yizhen Yan Yiling Chen Sha Liao Yuxiang Li Haixiang Sun Na Yao Xiangyu Zhang Shiyu Zhang Xi Chen Yang Yu Yao Li Fengming Liu Zheng Wang Shaolai Zhou Huanming Yang Shuang Yang Xun Xu Longqi Liu Qiang Gao Zhaoyou Tang Xiangdong Wang Jian Wang Jia Fan Shiping Liu Xinrong Yang Ao Chen Jian Zhou | 2023 | Cell Research2023，33，8： | 1 |
| 4 | Angiopoietin-like 4 promotes epidermal stem cell proliferation and migration and contributes to cutaneous wound re-epithelialization显示文摘Proliferation and migration of epidermal stem cells(EpSCs)are essential for epithelialization during skin wound healing.Angiopoietin-like 4(ANGPTL4)has been reported to play an important role in wound healing,but the mechanisms involved are not fully understood.Here,we investigate the contribution of ANGPTL4 to full-thickness wound re-epithelialization and the underlying mechanisms using Angptl4-knockout mice.Immunohistochemical staining reveals that ANGPTL4 is significantly upregulated in the basal layer cells of the epidermis around the wound during cutaneous wound healing.ANGPTL4 deficiency impairs wound healing.H&E staining shows that ANGPTL4 deficiency significantly reduces the thickness,length and area of the regenerated epidermis postwounding.Immunohistochemical staining for markers of EpSCs(α6 integrin andβ1 integrin)and cell proliferation(PCNA)shows that the number and proliferation of EpSCs in the basal layer of the epidermis are reduced in ANGPTL4-deficient mice.In vitro studies show that ANGPTL4 deficiency impedes EpSC proliferation,causes cell cycle arrest at the G1 phase and reduces the expressions of cyclins D1 and A2,which can be reversed by ANGPTL4 overexpression.ANGPTL4 deletion suppresses EpSC migration,which is also rescued by ANGPTL4 overexpression.Overexpression of ANGPTL4 in EpSCs accelerates cell proliferation and migration.Collectively,our results indicate that ANGPTL4 promotes EpSC proliferation by upregulating cyclins D1 and A2 expressions and accelerating the cell cycle transition from G1 to S phase and that ANGPTL4 promotes skin wound re-epithelialization by stimulating EpSC proliferation and migration.Our study reveals a novel mechanism underlying EpSC activation and re-epithelialization during cutaneous wound healing. | Yuan Yang Chenghao Yu Yingying Le Weijuan Gong Jihui Ju Guangliang Zhang Pengxiang Ji Rui Zuo Zhe Liu Ping Zhang Ruixing Hou Yi Fu | 2023 | Acta Biochimica et Biophysica Sinica2023，55，8： | 0 |
| 5 | Interplay of transcription factors and microRNAs during embryonic hematopoiesis显示文摘Hematopoietic stem cells (HSCs), which are localized in the bone marrow of adult mammals, come from hematopoietic endothelium during embryonic stages. Although the basic processes of HSC generation and differentiation have been described in the past, the epigenetic regulation of embryonic hematopoiesis remains to be fully described. Here, by utilizing an in vitro differentiation system of mouse embryonic stem cells (ESCs), we identified more than 20 microRNAs that were highly enriched in embryonic hematopoietic cells, including some (e.g. miR-10b, miR-15b, and miR-27a) with previously unknown functions in blood formation. Luciferase and gene expression assays further revealed combinational binding and regulation of these microRNAs by key transcription factors in blood cells. Finally, bioinformatics and functional analyses supported an interactive regulatory control between transcription factors and microRNAs in hematopoiesis. | Xueping Gong Ruihua Chao Pengxiang Wang Xiaoli Huang Jingjing Zhang Xiaozhou Zhu Yanyang Zhang Xue Yang Chao Hou Xiangjun Ji Tieliu Shi Yuan Wang | 2017 | Science China(Life Sciences)2017，60，2： | 0 |
| 6 | Doping of group IVB elements for nickel-rich cobalt-free cathodes显示文摘Hetero-element doping is a promising strategy to improve the cycling stability of nickel-rich cobalt-free cathodes for the next-generation high energy-density Li ion batteries.To make doping effective,it is important to understand the mechanism of how the dopants regulate the electronic band,lattice parameter adjusting,or hetero-phase formation to achieve high stability.In this study,we investigate LiNi_(0.9)Mn_(0.1)O_(2)cathodes doped with IVB grouping elements via multiple characterization techniques.By utilizing in situ XRD and TEM methods,we found that the stronger Ti-O bond effectively improves the cathode stability via a dual protection mechanism.Specifically,the bulk lattice of cathode is wellpreserved during cycling as a result of the suppressed H_(2)-H_(3)phase transition,while a in situ formed Ti-rich surface layer can prevent continuous surface degradation.As a result,the 5%Ti doped LiNi_(0.9)Mn_(0.1)O_(2)cathode exhibits a high capacity retention of 96%after 100 cycles.Whereas,despite IVB group elements Zr and Hf have stronger bonding energy with oxygen,their larger ionic radii actually impede their diffusion into the cathode,thereby they can not improve the cycling stability.Our findings uncover the functional origin of doped elements with their dynamic modification on cathode structure,providing mechanistic insights into the design of nickel-rich cobalt-free cathodes. | Shengnan Guo Xincheng Lei Jiayi Wang Jie Su Yingying Wang Xiaozhi Liu Pengxiang Ji Kangning Zhao Xuefeng Wang Lin Gu Zhenpeng Yao Dong Su | 2023 | Journal of Energy Chemistry2023，，11： | 0 |
| 7 | Cationic ordering transition in oxygen-redox layered oxide cathodes显示文摘Understanding the structural origin of the competition between oxygen 2p and transition-metal 3d orbitals in oxygen-redox(OR)layered oxides is eminently desirable for exploring reversible and high-energy-density Li/Na-ion cathodes.Here,we reveal the correlation between cationic ordering transition and OR degradation in ribbon-ordered P3-Na_(0.6)Li_(0.2)Mn_(0.8)O_(2) via in situ structural analysis.Comparing two different voltage windows,the OR capacity can be improved approximately twofold when suppressing the in-plane cationic ordering transition.We find that the intralayer cationic migration is promoted by electrochemical reduction from Mn^(4+)to Jahn–Teller Mn^(3+)and the concomitant NaO_(6) stacking transformation from triangular prisms to octahedra,resulting in the loss of ribbon ordering and electrochemical decay.First-principles calculations reveal that Mn^(4+)/Mn^(3+)charge ordering and alignment of the degenerate eg orbital induce lattice-level collective Jahn–Teller distortion,which favors intralayer Mn-ion migration and thereby accelerates OR degradation.These findings unravel the relationship between in-plane cationic ordering and OR reversibility and highlight the importance of superstructure protection for the rational design of reversible OR-active layered oxide cathodes. | Xinyan Li Ang Gao Qinghua Zhang Hao Yu Pengxiang Ji Dongdong Xiao Xuefeng Wang Dong Su Xiaohui Rong Xiqian Yu Hong Li Yong-Sheng Hu Lin Gu | 2024 | Carbon Energy2024，6，1： | 0 |
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