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| 1 | Three-dimensional bioprinted glioblastoma microenvironments model cellular dependencies and immune interactions显示文摘Brain tumors are dynamic complex ecosystems with multiple cell types.To model the brain tumor microenvironment in a reproducible and scalable system,we developed a rapid three-dimensional(3D)bioprinting method to construct clinically relevant biomimetic tissue models.In recurrent glioblastoma,macrophages/microglia prominently contribute to the tumor mass.To parse the function of macrophages in 3D,we compared the growth of glioblastoma stem cells(GSCs)alone or with astrocytes and neural precursor cells in a hyaluronic acid-rich hydrogel,with or without macrophage.Bioprinted constructs integrating macrophage recapitulate patient-derived transcriptional profiles predictive of patient survival,maintenance of stemness,invasion,and drug resistance.Whole-genome CRISPR screening with bioprinted complex systems identified unique molecular dependencies in GSCs,relative to sphere culture.Multicellular bioprinted models serve as a scalable and physiologic platform to interrogate drug sensitivity,cellular crosstalk,invasion,context-specific functional dependencies,as well as immunologic interactions in a species-matched neural environment. | Min Tang Qi Xie Ryan C.Gimple Zheng Zhong Trevor Tam Jing Tian Reilly L.Kidwell Qiulian Wu Briana C.Prager Zhixin Qiu Aaron Yu Zhe Zhu Pinar Mesci Hui Jing Jacob Schimelman Pengrui Wang Derrick Lee Michael H.Lorenzini Deobrat Dixit Linjie Zhao Shruti B.hargava Tyler E.Miller Xueyi Wan Jing Tang Bingjie Sun Benjamin F.Cravatt Alysson R.Muotri Shaochen Chen Jeremy N.Rich | 2020 | Cell Research2020，30，10： | 6 |
| 2 | COVID-19:immunopathogenesis and Immunotherapeutics显示文摘The recent novel coronavirus disease(COVID-19)outbreak,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is seeing a rapid increase in infected patients worldwide.The host immune response to SARS-CoV-2 appears to play a critical role in disease pathogenesis and clinical manifestations.SARS-CoV-2 not only activates antiviral immune responses,but can also cause uncontrolled inflammatory responses characterized by marked pro-inflammatory cytokine release in patients with severe COVID-19,leading to lymphopenia,lymphocyte dysfunction,and granulocyte and monocyte abnormalities.These SARS-CoV-2-induced immune abnormalities may lead to infections by microorganisms,septic shock,and severe multiple organ dysfunction.Therefore,mechanisms underlying immune abnormalities in patients with COVID-19 must be elucidated to guide clinical management of the disease.Moreover,rational management of the immune responses to SARSCoV-2,which includes enhancing anti-viral immunity while inhibiting systemic inflammation,may be key to successful treatment.In this review,we discuss the immunopathology of COVID-19,its potential mechanisms,and clinical implications to aid the development of new therapeutic strategies against COVID-19. | Li Yang Shasha Liu Jinyan Liu Zhixin Zhang Xiaochun Wan Bo Huang Youhai Chen Yi Zhang | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 4 |
| 3 | Influence of division cone angles between the fuel-rich and the fuelleanducts on gas-particle flow and combustion near swirl burners显示文摘 | Li Zhengqi Wan Zhixin Sun Rui | 2002 | Energy2002，27，： | 1 |
| 4 | An experimental study of HF passive bistatic radar via hybrid sky-surface wave mode显示文摘 | ZHAO Zhixin WAN Xianrong ZHANG Delei | 2013 | IEEE Trarisac-tions on antennas and propagation2013，61，1： | 1 |
| 5 | Gas-particle flow and combustion in the near-burner zone of the swirl-stabilized pulverized coal burner显示文摘 | Li Zhengqi Sun Rui Wan Zhixin | 2003 | Combustion Science and Techonolgy2003，175，11： | 1 |
| 6 | Influence of division cone angles between the fuel-rich and the fuel-lean ducts on gas-particle flow and combustion near swirl burners显示文摘 | Li Zhengqi Wan Zhixin Sun Rui | 2002 | Energy2002，27，12： | 1 |
| 7 | Experimental research of CMMB-based passive radar under multipath environment显示文摘 | WAN Xianrong YI Jianxin ZHAO Zhixin | 2014 | IEEE Trans Aerosp Electron Syst2014，50，1： | 1 |
| 8 | An experimental study of HF passive bistatic radar via hybrid sky-surface wave mode显示文摘 | ZHAO Zhixin WAN Xianrong ZHANG Delei e1 al | 2013 | IEEE Trans Antennas Propag2013，61，1： | 1 |
| 9 | Influence of division cone angles between the fuel-rich and the fuel-lean ducts on gas-particle flow and combustion near swirl burners 显示文摘 | Li Zhengqi Wan Zhixin Sun Rui | 2002 | Energy2002，，27： | 1 |
| 10 | Gas-particle flow and combustion in the near-burner zone of the swirl-stabilized pulverized coal burner 显示文摘 | Li Zhengqi Sun Rui Wan Zhixin Sun Shaozeng | 2003 | Combust Sci and Tech2003，，175： | 1 |
| 11 | Influence of division cone angles between the fuel-rich and the fuel-lean ducts on gas-particle flow and combustion near swirl burners显示文摘 | Li Zhengqi Wan Zhixin Sun Rui | 2002 | Energy2002，27，12： | 1 |
| 12 | Targeting CRL4 suppresses chemoresistant ovarian cancer growth by inducing mitophagy显示文摘Chemoresistance has long been the bottleneck of ovarian cancer(OC)prognosis.It has been shown that mitochondria play a crucial role in cell response to chemotherapy and that dysregulated mitochondrial dynamics is intricately linked with diseases like OC,but the underlying mechanisms remain equivocal.Here,we demonstrate a new mechanism where CRL4^(CUL4A/DDB1)manipulates OC cell chemoresistance by regulating mitochondrial dynamics and mitophagy.CRL4^(CUL4A/DDB1)depletion enhanced mitochondrial fission by upregulating AMPKα^(Thr172)and MFF^(Ser172/Ser146)phosphorylation,which in turn recruited DRP1 to mitochondria.CRL4^(CUL4A/DDB1)loss stimulated mitophagy through the Parkin-PINK1 pathway to degrade the dysfunctional and fragmented mitochondria.Importantly,CRL4^(CUL4A/DDB1)loss inhibited OC cell proliferation,whereas inhibiting autophagy partially reversed this disruption.Our findings provide novel insight into the multifaceted function of the CRL4 E3 ubiquitin ligase complex in regulating mitochondrial fission,mitophagy,and OC chemoresistance.Disruption of CRL4^(CUL4A/DDB1)and mitophagy may be a promising therapeutic strategy to overcome chemoresistance in OC. | Yang Meng Lei Qiu Xinyi Zeng Xiaoyan Hu Yaguang Zhang Xiaowen Wan Xiaobing Mao Jian Wu Yongfeng Xu Qunli Xiong Zhixin Chen Bo Zhang Junhong Han | 2023 | Signal Transduction and Targeted Therapy2023，8，1： | 0 |
| 13 | Analogous comparison unravels heightened antiviral defense and boosted viral infection upon immunosuppression in bat organoids显示文摘Horseshoe bats host numerous SARS-related coronaviruses without overt disease signs.Bat intestinal organoids,a unique model of bat intestinal epithelium,allow direct comparison with human intestinal organoids.We sought to unravel the cellular mechanism(s)underlying bat tolerance of coronaviruses by comparing the innate immunity in bat and human organoids.We optimized the culture medium,which enabled a consecutive passage of bat intestinal organoids for over one year.Basal expression levels of IFNs and IFN-stimulated genes were higher in bat organoids than in their human counterparts.Notably,bat organoids mounted a more rapid,robust and prolonged antiviral defense than human organoids upon Poly(I:C)stimulation.TLR3 and RLR might be the conserved pathways mediating antiviral response in bat and human intestinal organoids.The susceptibility of bat organoids to a bat coronavirus CoV-HKU4,but resistance to EV-71,an enterovirus of exclusive human origin,indicated that bat organoids adequately recapitulated the authentic susceptibility of bats to certain viruses.Importantly,TLR3/RLR inhibition in bat organoids significantly boosted viral growth in the early phase after SARS-CoV-2 or CoV-HKU4 infection.Collectively,the higher basal expression of antiviral genes,especially more rapid and robust induction of innate immune response,empowered bat cells to curtail virus propagation in the early phase of infection. | Xiaojuan Liu Cun Li Zhixin Wan Man Chun Chiu Jingjing Huang Yifei Yu Lin Zhu Jian-Piao Cai Lei Rong You-qiang Song Hin Chu Zongwei Cai Shibo Jiang Kwok-yung Yuen Jie Zhou | 2023 | Signal Transduction and Targeted Therapy2023，8，1： | 0 |
| 14 | Effect of Cu-Rich Phase Precipitation on the Microstructure and Mechanical Properties of CoCrNiCux Medium-Entropy Alloys Prepared via Laser Directed Energy Deposition显示文摘CoCrNiCux(x=0.16,0.33,0.75,and 1)without macro-segregation medium-entropy alloys(MEAs)was prepared using laser directed energy deposition(LDED).The microstructure and mechanical properties of CoCrNiCux alloys with increasing Cu content were investigated.The results indicate that a single matrix phase changes into a dual-phase structure and the tensile fracture behaviors convert from brittle to plastic pattern with increasing Cu content in CoCrNiCux alloys.In addition,the tensile strength of CoCrNiCux alloys increased from 148 to 820 MPa,and the ductility increased from 1 to 11%with increasing Cu content.The nano-precipitated particles had a mean size of approximately 20 nm in the Cu-rich phase area,and a large number of neatly arranged misfit dislocations were observed at the interface between the two phases due to Cu-rich phase precipitation in the CoCrNiCu alloy.These misfit dislocations hinder the movement of dislocations during tensile deformation,as observed through transmission electron microscopy.This allows the CoCrNiCu alloy to reach the largest tensile strength and plasticity,and a new strengthening mechanism was achieved for the CoCrNiCu alloy.Moreover,twins were observed in the matrix phase after tensile fracture.Simultaneously,the dual-phase structure with different elastic moduli coordinated with each other during the deformation process,significantly improving the plasticity and strength of the CoCrNiCu alloy. | Yong Xie Zhixin Xia Jixin Hou Jiachao Xu Peng Chen Le Wan | 2021 | Acta Metallurgica Sinica(English Letters)2021，34，11： | 0 |
| 15 | The genetic basis of the leafy seadragon's unique camouflage morphology and avenues for its efficient conservation derived from habitat modeling显示文摘The leafy seadragon certainly is among evolution’s most“beautiful and wonderful”species aptly named for its extraordinary camouflage mimicking its coastal seaweed habitat.However,limited information is known about the genetic basis of its phenotypes and conspicuous camouflage.Here,we revealed genomic signatures of rapid evolution and positive selection in core genes related to its camouflage,which allowed us to predict population dynamics for this species.Comparative genomic analysis revealed that seadragons have the smallest olfactory repertoires among all ray-finned fishes,suggesting adaptations to the highly specialized habitat.Other positively selected and rapidly evolving genes that serve in bone development and coloration are highly expressed in the leaf-like appendages,supporting a recent adaptive shift in camouflage appendage formation.Knock-out of bmp6 results in dysplastic intermuscular bones with a significantly reduced number in zebrafish,implying its important function in bone formation.Global climate change-induced loss of seagrass beds now severely threatens the continued existence of this enigmatic species.The leafy seadragon has a historically small population size likely due to its specific habitat requirements that further exacerbate its vulnerability to climate change.Therefore,taking climate change-induced range shifts into account while developing future protection strategies. | Meng Qu Yingyi Zhang Zexia Gao Zhixin Zhang Yali Liu Shiming Wan Xin Wang Haiyan Yu Huixian Zhang Yuhong Liu Ralf Schneider Axel Meyer Qiang Lin | 2023 | Science China(Life Sciences)2023，66，6： | 0 |
| 16 | Peptide tyrosine-tyrosine combined with its receptors exhibits an anti-cancer potential in pancreatic cancer MiaPaCa-2 cell显示文摘 | Li Hongxia Wang Zhixin Dong Lei Jiang Jiong Xu Xinsen Zhou Lei Wan Yong | 2014 | Chinese Medical Journal2014，，24： | 0 |
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