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| 1 | Chimeric antigen receptor T cell targeting EGFRvIII for metastatic lung cancer therapy显示文摘Lung cancer is the most common incident cancer and the leading cause of cancer death. In recent years, the development of tumor immunotherapy especially chimeric antigen receptor T (CAR-T) cell has shown a promising future. Epidermal growth factor receptor variant III (EGFRvlll) is a tumor-specific mutation expressed in various types of tumors and has been detected in non-small cell lung cancer with a mutation rate of 10%. Thus, EGFRvIII is a potential antigen for targeted lung cancer therapy. In this study, CAR vectors were constructed and transfected into virus-packaging cells. Then, activated T cells were infected with retrovirus harvested from stable virus-producing single clone cell lines. CAR expression on the surfaces of the T cells was detected by flow cytometry and Western blot. The function of CAR-T targeting EGFRvIII was then evaluated. The EGFRvIII-CAR vector was successfully constructed and confirmed by DNA sequencing. A stable virus-producing cell line was produced from a single clone by limited dilution. The culture conditions for the cell line, including cell density, temperature, and culture medium were optimized. After infection with retrovirus, CAR was expressed on more than 90% of the T cells. The proliferation of CAR-T cells were induced by cytokine and specific antigen in vitro. More importantly, EGFRvIII-CART specifically and efficiently recognized and killed A549-EGFRvIII cells with an effector/target ratio of 10:1 by expressing and releasing cytokines, including perforin, granzyme B, IFN-γ, and TNF-α. The in vivo study indicated that the metastasis of A549-EGFRvIII cells in mice were inhibited by EGFRvIII-CART cells, and the survival of the mice was significantly prolonged with no serious side effects. EGFRvIII-CART showed significantly efficient antitumor activity against lung cancer cells expressing EGFRvlll in vivo and in vitro. Therefore, CAR-T targeting EGFRvIII is a potential therapeutic strategy in preventing recurrence and metastasis of lung cancer after surgery. | Zhao Zhang Jun Jiang Xiaodong Wu Mengyao Zhang Dan Luo Renyu Zhang Shiyou Li Youwen He Huijie Bian Zhinan Chen | 2019 | Frontiers of Medicine2019，13，1： | 11 |
| 2 | Microstructure evolution and texture tailoring of reduced graphene oxide reinforced Zn scaffold显示文摘Zinc(Zn)possesses desirable degradability and favorable biocompatibility,thus being recognized as a promising bone implant material.Nevertheless,the insufficient mechanical performance limits its further clinical application.In this study,reduced graphene oxide(RGO)was used as reinforcement in Zn scaffold fabricated via laser additive manufacturing.Results showed that the homogeneously dispersed RGO simultaneously enhanced the strength and ductility of Zn scaffold.On one hand,the enhanced strength was ascribed to(i)the grain refinement caused by the pinning effect of RGO,(ii)the efficient load shift due to the huge specific surface area of RGO and the favorable interface bonding between RGO and Zn matrix,and(iii)the Orowan strengthening by the homogeneously distributed RGO.On the other hand,the improved ductility was owing to the RGO-induced random orientation of grain with texture index reducing from 20.5 to 7.3,which activated more slip systems and provided more space to accommodate dislocation.Furthermore,the cell test confirmed that RGO promoted cell growth and differentiation.This study demonstrated the great potential of RGO in tailoring the mechanical performance and cell behavior of Zn scaffold for bone repair. | Youwen Yang Yun Cheng Shuping Peng Liang Xu Chongxian He Fangwei Qi Mingchun Zhao Cijun Shuai | 2021 | Bioactive Materials2021，6，5： | 4 |
| 3 | Roles of autophagy in lymphocytes: reflections and directions显示文摘最近的研究揭示了那 autophagy,基本细胞内部的进程,在淋巴细胞开发和功能起许多不同作用。Autophagy 调整天真的 T 淋巴细胞动态平衡,明确地由调整 mitochondrial 质量和周转,并且为成熟 T 房间的增长是必要的。Autophagy 也在淋巴细胞充当一条细胞的死亡小径,在延长 cytokine 退却之上并且在尖锐抗原受体刺激期间如果不正确地调整了。在 HIV 感染期间,而且, autophagy 的 hyperinduction 在 uninfected CD4+ T 房间导致巨大的 T 房间死亡,并且被禁止 autophagic 救开始。在 thymic 的 autophagy 组成地高级上皮的房间为最佳的处理和内长的抗原的表示是必要的,并且为开发 thymocytes 的合适的积极、否定的选择要求。Autophagy 也支持早 B 房间祖先的 B 淋巴细胞,以及发展的幸存。在 B 房间, autophagy 是一条其他的死亡小径,当当 costimulation 不在时的抗原受体刺激导致有势力 autophagic 死亡。因此, autophagy 在淋巴细胞起一个复杂作用并且在他们的 lifespan 期间被调整保证一个健康免疫系统。 | Ian X McLeod Youwen He | 2010 | Cellular & Molecular Immunology2010，7，2： | 2 |
| 4 | Mechanism for corrosion protection of β-TCP reinforced ZK60 via laser rapid solidification显示文摘It remains the primary issue to enhance the corrosion resistance of Mg alloys for their clinical applications.In this study,β-tricalcium phosphate(β-TCP)was composited with Mg-6Zn-1Zr(ZK60)using laser rapid solidification to improve the degradation behavior.Results revealed rapid solidification effectively restrained the aggregation ofβ-TCP,which thus homogenously distributed along grain boundaries ofα-Mg.Significantly,the uniformly distributedβ-TCP in the matrix promoted the formation of apatite layer on the surface,which contributed to the formation of a compact corrosion product layer,hence retarding the further degradation.Furthermore,ZK60/8β-TCP(wt.%)composite showed improved mechanical strength,as well as improved cytocompatibility.It was suggested that laser rapidly solidified ZK60/8β-TCP composite might be a potential materials for tissue engineering. | Youwen Deng Youwen Yang Chengde Gao Pei Feng Wang Guo Chongxian He Jian Chen Cijun Shuai | 2018 | International Journal of Bioprinting2018，4，1： | 2 |
| 5 | The extraeellular matrix protein mindin is a pattern-recognition molecule for microbial pathogens 显示文摘 | YouWen He Li H Zhang J | 2004 | Nat Immunol2004，5，1： | 1 |
| 6 | Formation of secondary inorganic aerosol in a frigid urban atmosphere显示文摘Formation of secondary inorganic aerosol(SIA)was investigated during a six-month long heating season in Harbin,China.Enhanced sulfate formation was observed at high relative humidity(RH),with the same threshold RH(80%)for both colder and warmer measurement periods.Compared to wintertime results from Beijing,the threshold RH was considerably higher in Harbin,whereas the RH-dependent enhancement of sulfur oxidation ratio(SOR)was less significant.In addition,the high RH events were rarely encountered,and for other periods,the SOR were typically as low as~0.1.Therefore,the sulfate formation was considered inefficient in this study.After excluding the several cases with high RH,both SOR and the nitrogen oxidation ratio(NOR)exhibited increasing trends as the temperature increased,with the increase of NOR being sharper.The nitrate to sulfate ratio tended to increase with increasing temperature as well.Based on a semi-quantitative approach,this trend was attributed primarily to the temperature-dependent variations of precursors including SO_(2) and NO_(2).The influence of biomass burning emissions on SIA formation was also evident.With stronger impact of biomass burning,an enhancement in NOR was observed whereas SOR was largely unchanged.The different patterns were identified as the dominant driver of the larger nitrate to sulfate ratios measured at higher concentrations of fine particulate matter. | Yuan Cheng Qinqin Yu Jiumeng Liu Youwen Sun Linlin Liang Zhenyu Du Guannan Geng Wanli Ma Hong Qi Qiang Zhang Kebin He | 2022 | Frontiers of Environmental Science & Engineering2022，16，2： | 0 |
| 7 | miR-126 mitigates the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by targeting the ERK1/2 and Bcl-2 pathways显示文摘Human bone marrow mesenchymal stem cells(hBMMSCs)are a promising cell source for bone engineering owing to their high potential to differentiate into osteoblasts.The objective of the present study is to assess microRNA-126(miR-126)and examine its effects on the osteogenic differentiation of hBMMSCs.In this study,we investigate the role of miR-126 in the progression of osteogenic differentiation(OD)as well as the apoptosis and inflammation of hBMMSCs during OD induction.OD is induced in hBMMSCs,and matrix mineralization along with other ODassociated markers are evaluated by Alizarin Red S(AR)staining and quantitative PCR(qPCR).Gain-and loss-offunction studies are performed to demonstrate the role of miR-126 in the OD of hBMMSCs.Flow cytometry and qPCR-based cytokine expression studies are performed to investigate the effect of miR-126 on the apoptosis and inflammation of hBMMSCs.The results indicate that miR-126 expression is downregulated during the OD of hBMMSCs.Gain-and loss-of function assays reveal that miR-126 upregulation inhibits the differentiation of hBMMSCs into osteoblasts,whereas the downregulation of miR-126 promotes hBMMSC differentiation,as assessed by the determination of osteogenic genes and alkaline phosphatase activity.Furthermore,the miR-126 level is positively correlated with the production of inflammatory cytokines and apoptotic cell death.Additionally,our results suggest that miR-126 negatively regulates not only B-cell lymphoma 2(Bcl-2)expression but also the phosphorylation of extracellular signal-regulated protein kinase(ERK)1/2.Moreover,restoring ERK1/2 activity and upregulating Bcl-2 expression counteract the miR-126-mediated suppression of OD in hBMMSCs by promoting inflammation and apoptosis,respectively.Overall,our findings suggest a novel molecular mechanism relevant to the differentiation of hBMMSCs into osteoblasts,which can potentially facilitate bone formation by counteracting miR-126-mediated suppression of ERK1/2 activity and Bcl-2 expression. | Ying Zhang Yiping Dong Qiushi Wei Zhikun Zhuang Youwen Liu Qiang Yuan Wei He Zhenhao Jing Jitian Li Peifeng Li Leilei Zhang Zhinan Hong Ning Zhang Haibin Wang Wuyin Li | 2023 | Acta Biochimica et Biophysica Sinica2023，55，3： | 0 |
| 8 | Structural Characterization of Carbon-implanted GaSb显示文摘Ion implantation induced damage in GaSb and its removal by rapid thermal annealing(RTA)have been investigated by Raman spectroscopy.The evolution of the Raman modes as a function of implantation fluence,annealing temperature and time has been analyzed.Results indicate that a lattice quality that is close to as-grown GaSb has been obtained by annealing the implanted samples at 500℃for 45 s.However,consequent surface analyses by scanning electron microscope(SEM)and atomic force microscope(AFM)show that a heavily perturbed layer contains voids due to the outdifiusion of Sb atoms on the surface remains.Mechanism of the damage recovery and the structure of the implanted layer are discussed based on the experimental results. | SHEN Guiying ZHAO Youwen HE Jianjun | 2023 | Journal of Wuhan University of Technology(Materials Science)2023，38，5： | 0 |
| 9 | Performance improvement of c-Si solar cell by a combination of SiNx/SiOx passivation and double P-diffusion gettering treatment显示文摘SiN_x/SiO_x passivation and double side P-diffusion gettering treatment have been used for the fabrication of c-Si solar cells. The solar cells fabricated have high open circuit voltage and short circuit current after the double P-diffusion treatment. In addition to better surface passivation effect, SiN_x/SiO_x layer has lower reflectivity in long wavelength range than conventional SiN_x film. As a consequence, such solar cells exhibit higher conversion efficiency and better internal quantum efficiency, compared with conventional c-Si solar cells. | Xiaoyu Chen Youwen Zhao Zhiyuan Dong Guiying Shen Yongbiao Bai Jingming Liu Hui Xie Jiangbian He | 2017 | Journal of Semiconductors2017，38，11： | 0 |
| 10 | A continuous net-like eutectic structure enhances the corrosion resistance of Mg alloys显示文摘Mg alloys degrade rather rapidly in a physiological environment,although they have good biocompatibility and favorable mechanical properties.In this study,Ti was introduced into AZ61 alloy fabricated by selective laser melting,aiming to improve the corrosion resistance.Results indicated that Ti promoted the formation of Al-enriched eutecticαphase and reduced the formation ofβ-Mg17Al12 phase.With Ti content reaching to 0.5 wt.%,the Al-enriched eutecticαphase constructed a continuous net-like structure along the grain boundaries,which could act as a barrier to prevent the Mg matrix from corrosion progression.On the other hand,the Al-enriched eutecticαphase was less cathodic thanβ-Mg17Al12 phase in AZ61,thus alleviating the corrosion progress due to the decreased potential difference.As a consequence,the degradation rate dramatically decreased from 0.74 to 0.24 mg·cm-2·d-1.Meanwhile,the compressive strength and microhardness were increased by 59.4%and 15.6%,respectively.Moreover,the Ti-contained AZ61 alloy exhibited improved cytocompatibility.It was suggested that Ti-contained AZ61 alloy was a promising material for bone implants application. | Cijun Shuai Wenjing Yang Youwen Yang Chengde Gao Chongxian He Hao Pan | 2019 | International Journal of Bioprinting2019，5，2： | 0 |
| 11 | Structural genomics of the human dopamine receptor system显示文摘The dopaminergic system,including five dopamine receptors(D1R to D5R),plays essential roles in the central nervous system(CNS);and ligands that activate dopamine receptors have been used to treat many neuropsychiatric disorders,including Parkinson’s Disease(PD)and schizophrenia.Here,we report cryo-EM structures of all five subtypes of human dopamine receptors in complex with G protein and bound to the pan-agonist,rotigotine,which is used to treat PD and restless legs syndrome.The structures reveal the basis of rotigotine recognition in different dopamine receptors.Structural analysis together with functional assays illuminate determinants of ligand polypharmacology and selectivity.The structures also uncover the mechanisms of dopamine receptor activation,unique structural features among the five receptor subtypes,and the basis of G protein coupling specificity.Our work provides a comprehensive set of structural templates for the rational design of specific ligands to treat CNS diseases targeting the dopaminergic system. | Peiyu Xu Sijie Huang Brian E.Krumm Youwen Zhuang Chunyou Mao Yumu Zhang Yue Wang Xi-Ping Huang Yong-Feng Liu Xinheng He Huadong Li Wanchao Yin Yi Jiang Yan Zhang Bryan L.Roth H.Eric Xu | 2023 | Cell Research2023，33，8： | 0 |
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