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| 1 | How complex is the 2016 Mw 7.8 Kaikoura earthquake, South Island, New Zealand?显示文摘A powerful earthquake of moment magnitude(Mw)7.8occurred in the Kaikoura region,South Island,New Zealand,at00:02:56 AM(local time),14 November 2016.According to the Institute of Geological and Nuclear Sciences(GNS)in New Zealand, | Xuhua Shi Yu Wang Jing Liu-Zeng Ray Weldon Shengji Wei Teng Wang Kerry Sieh | 2017 | Science Bulletin2017，62，5： | 6 |
| 2 | Chondroitin sulfate proteoglycan 4 functions as the cellular receptor for Clostridium difficile toxin B显示文摘作为克积极的、形成孢子的厌氧的杆菌, Clostridium 顽固(C。顽固) 为严重、致命的 pseudomembranous 大肠炎负责,并且形成世界范围的最迫切的抗菌素抵抗威胁。流行 C。顽固全球性是联系抗菌素的腹泻的领先的原因,特别由于 hypervirulent 的出现,种类与高死亡和病态联系了的腹泻。TcdB,关键毒力因素之一由这个细菌藏匿了,通过糟糕理解的机制进入主人房间得到它的病原的效果。这里,我们报导 TcdB 细胞的受体的第一鉴定, chondroitin 硫酸盐 proteoglycan 4 (CSPG4 ) 。CSPG4 开始从屏蔽的一个整个染色体的人的 shRNAmir 图书馆被孤立,并且它的角色被证实由调停 TALEN 并且在人的房间的 CRISPR/Cas9-mediated 基因大美人。CSPG4 为对房间表面有约束力的 TcdB 是批评的,导致细胞骨架混乱和房间死亡。在 CSPG4 的 N 终点和 TcdB 的 C 终点之间的一个直接相互作用被证实,并且 CSPG4 的毒素绑定领域的可溶的肽能保护房间免受 TcdB 的行动的伤害。尤其是, CSPG4/NG2 的完全的损失减少了在没有显著地影响动物死亡的老鼠的被触发 TcdB 的 interleukin-8 正式就职。基于两个在里面 vitro 并且在 vivo 研究,我们为 TcdB endocytosis 建议一个双受体的模型。第一 TcdB 受体的发现为 CSPG4 揭示一个以前不受怀疑的角色并且为 C 的处理提供一个新治疗学的目标。顽固感染。 | Pengfei Yuan Hongmin Zhang Changzu Cai Shiyou Zhu Yuexin Zhou Xiaozhou Yang Ruina He Chan Li Shengjie Guo Shan Li Tuxiong Huang Gregorio Perez-Cordon Hanping Feng Wensheng Wei | 2015 | Cell Research2015，25，2： | 6 |
| 3 | Functional Metabolomics Reveals that Astragalus Polysaccharides Improve Lipids Metabolism through Microbial Metabolite 2-Hydroxybutyric Acid in Obese Mice显示文摘Polysaccharides are widely present in herbs with multiple activities,especially immunity regulation and metabolic benefits for metabolic disorders.However,the underlying mechanisms are not well under-stood.Functional metabolomics is increasingly used to investigate systemic effects on the host by iden-tifying metabolites with particular functions.This study explores the mechanisms underlying the metabolic benefits of Astragalus polysaccharides(APS)by adopting a functional metabolomics strategy.The effects of APS were determined in eight-week high-fat diet(HFD)-fed obese mice.Then,gas chromatography–time-of-flight mass spectrometry(GC–TOFMS)-based untargeted metabolomics was performed for an analysis of serum and liver tissues,and liquid chromatography–tandem mass spectrom-etry(LC–MS/MS)-based targeted metabolomics was performed.The potential functions of the metabo-lites were tested with in vitro and in vivo models of metabolic disorders.Our results first confirmed the metabolic benefits of APS in obese mice.Then,metabolomics analysis revealed that APS supplemen-tation reversed the HFD-induced metabolic changes,and identified 2-hydroxybutyric acid(2-HB)as a potential functional metabolite for APS activity that was significantly decreased by a HFD and reversed by APS.Further study indicated that 2-HB inhibited oleic acid(OA)-induced triglyceride(TG)accumula-tion.It was also found to stimulate the expression of proteins in lipid degradation in hepatocytes and TG lipolysis in 3T3-L1 cells.Moreover,it was found to reduce serum TG and regulate the proteins involved in lipid degradation in high-fat and high-sucrose(HFHS)-fed mice.In conclusion,our study demonstrates that the metabolic benefits of APS are at least partially due to 2-HB generation,which modulated lipid metabolism both in vitro and in vivo.Our results also highlight that functional metabolomics is practical for investigating the mechanism underlying the systemic benefits of plant polysaccharides. | Bingbing Li Ying Hong Yu Gu Shengjie Ye Kaili Hu Jian Yao Kan Ding Aihua Zhao Wei Jia Houkai Li | 2022 | Engineering2022，8，2： | 6 |
| 4 | A study on the uncertainties of the centroid depth of the 2013 Lushan earthquake from teleseimic body wave data显示文摘Centroid depth of earthquakes is essential for seismic hazard mitigation.But,various studies provided different solutions for the centroid depth of the damaging2013 Lushan earthquake,thus hindering further studies of the earthquake processes.To resolve its centroid depth and assess the uncertainties,we apply the teleseismic cut and paste method to invert for centroid depth with teleseismic body waves in the epicentral distance of 30°–90°.We performed the inversion for P waves only as well the case of both P and SH waves and found that both cases lead to depth solutions with difference less than 0.5 km.We also investigated the effects on depth inversion from azimuth gap of seismic stations,source duration,and corner frequency of filter.These various tests show that even azimuthal distribution of seismic stations is helpful for accurate depth inversion.It is also found that estimate of centroid depth is sensitive to source duration.Moreover,the depth is biased to larger values when corner frequency of low-pass filter is very low.The uncertainty in the velocity model can also generate some error in the depth estimation(*1.0 km).With all the above factors considered,the centroid depth of Lushan earthquake is proposed to be around 12 km,with uncertainty about 2 km. | Weiwen Chen Decai Wang Shengji Wei | 2013 | Earthquake Science2013，26，3： | 6 |
| 5 | Mobility in China,2020:a tale of four phases显示文摘2020 was an unprecedented year;with rapid and drastic changes in human mobility due to the COVID-19 pandemic.To understand the variation in commuting patterns among the Chinese population across stable and unstable periods,we used nationwide mobility data from 318 million mobile phone users in China to examine the extreme fluctuations of population movements in 2020,ranging from the Lunar New Year travel season(chunyun),to the exceptional calm of COVID-19 lockdown,and then to the recovery period.We observed that cross-city movements;which increased substantially in chunyun and then dropped sharply during the lockdown,are primarily dependent on travel distance and the socio-economic development of cities.Following the Lunar New Year holiday,national mobility remained low until mid-February,and COVID-19 interventions delayed more than 72.89 million people returning to large cities.Mobility network analysis revealed clusters of highly connected cities,conforming to the social-economic division of urban agglomerations in China.While the mass migration back to large cities was delayed,smaller cities connected more densely to form new clusters.During the recovery period after travel restrictions were lifted,the netflows of over 55%city pairs reversed in direction compared to before the lockdown.These findings offer the most comprehensive picture of Chinese mobility at fine resolution across various scenarios in China and are of critical importance for decision making regarding future public-health-emergency response,transportation planning and regional economic development,among others. | Suoyi Tan Shengjie Lai Fan Fang Ziqiang Cao Bin Sai Bing Song Bitao Dai Shuhui Guo Chuchu Liu Mengsi Cai Tong Wang Mengning Wang Jiaxu Li Saran Chen Shuo Qin Jessica R.Floyd Zhidong Cao Jing Tan Xin Sun Tao Zhou Wei Zhang Andrew J.Tatem Petter Holme Xiaohong Chen Xin Lu | 2021 | National Science Review2021，8，11： | 3 |
| 6 | Source model of the 11th July 2004 Zhongba earthquake revealed from the joint inversion of InSAR and seismological data显示文摘We use interferometric synthetic aperture radar (InSAR) and broadband seismic waveform data to estimate a source model of the 11th July, 2004 M W 6.2 Zhongba earthquake, Tibet of China. This event occurred within the seismically active zone of southwestern Tibetan Plateau where the east-west extension of the upper crust is observed. Because of limitations in one pair of InSAR data available, there are trade-offs among centroid depth, rupture area and amount of slip. Available seismic data tightly constrain the focal mechanism and centroid depth of the earthquake but not the horizontal location. Together, two complementary data sets can be used to identify the actual fault plane, better constrain the slip model and event location. We first use regional seismic waveform to estimate point source mechanism, then InSAR data is used to obtain better location. Finally, a joint inversion of teleseismic P-waves and InSAR data is performed to obtain a distributed model. Our preferred point source mechanism indicates a seismic moment of ~2.2×10 18 N·m (~M W 6.2), a fault plane solution of 171° (342 ° )/42 ° (48 ° )/-83 ° (-97 ° ), corresponding to strike/dip/rake, and a depth of 11 km. The fault plane with strike of 171 ° and dip of 42° is identified as the ruptured fault with the aid of InSAR data. The preferred source model features compact area of slips between depth of 5-11 km and 10 km along strike with maximum slip amplitude of about 1.5 m. | Shengji Wei Sidao Ni Xianjie Zha Don Helmberger | 2011 | Earthquake Science2011，24，2： | 3 |
| 7 | Low-density lipoprotein receptor-related protein 1 is a CROPs-associated receptor for Clostridioides infection toxin B显示文摘As the leading cause of worldwide hospital-acquired infection,Clostridioides difficile(C.difficile)infection has caused heavy economic and hospitalized burden,while its pathogenesis is not fully understood.Toxin B(Tcd B)is one of the major virulent factors of C.difficile.Recently,CSPG4 and FZD2 were reported to be the receptors that mediate Tcd B cellular entry.However,genetic ablation of genes encoding these receptors failed to completely block Tcd B entry,implicating the existence of alternative receptor(s)for this toxin.Here,by employing the CRISPR-Cas9 screen in CSPG4-deficient He La cells,we identified LDL receptor-related protein-1(LRP1)as a novel receptor for Tcd B.Knockout of LRP1 in both CSPG4-deficient He La cells and colonic epithelium Caco2 cells conferred cells with increased Tcd B resistance,while LRP1 overexpression sensitized cells to Tcd B at a low concentration.Co-immunoprecipitation assay showed that LRP1 interacts with full-length Tcd B.Moreover,CROPs domain,which is dispensable for Tcd B’s interaction with CSPG4 and FZD2,is sufficient for binding to LRP1.As such,our study provided evidence for a novel mechanism of Tcd B entry and suggested potential therapeutic targets for treating C.difficile infection. | Shengjie Guo Yiou Chen Jingze Liu Xinyi Zhang Zhiheng Liu Zhuo Zhou Wensheng Wei | 2022 | Science China(Life Sciences)2022，65，1： | 2 |
| 8 | Effect of Mg on Microstructure and Growth Kinetics of Zn-22.3Al-1.1Si Coating显示文摘The effects of Mg on the microstructure and growth kinetics of the hot-dip Zn-22.3 Al-1.1 Si-x Mg(x = 0, 0.2, 0.4, and 0.6) coatings were investigated in detail. Scanning electron microscopy with energy dispersive spectroscopy and X-ray diffraction studies revealed the presence of η-Zn, α-Al, Zn/Al eutectoid,(Si), Al/Si eutectic, and Zn/Al/Mg_2 Zn11 ternary eutectic on the top surface of these Mg-containing coatings. Especially, a small amount of MgZn2 phase appears in top surface of Zn-22.3 Al-1.1 Si-0.6 Mg coating. Five phases are found in the alloy layers, i e, Fe_2 Al_5, FeAl_3, τ_(5C), τ_(5H), and τ_1. The addition of 0.2% Mg can delay the emergence of FeAl_3 phase. When the Mg content is more than 0.2%, the outer layers of coating change from τ_(5C) to τ_(5H) phase. The growth of the inhibition layer is diffusion controlled for various Mg content baths. Mg improves the corrosion resistance of the Mg-containing coatings, and the Zn-22.3 Al-1.1 Si-0.6 Mg coating possesses the highest protective properties. | 涂浩 WEI Dasheng ZHOU Shengjie LIU Ya WU Changjun WANG Jianhua 苏旭平 | 2019 | Journal of Wuhan University of Technology(Materials Science)2019，34，2： | 2 |
| 9 | The mechanism of dentine hypersensitivity:Stimuli-induced directional cation transport through dentinal tubules显示文摘Dentine hypersensitivity is an annoying worldwide disease,yet its mechanism remains unclear.The long-used hydrodynamic theory,a stimuli-induced fluid-flow process,describes the pain processes.However,no experimental evidence supports the statements.Here,we demonstrate that stimuli-induced directional cation transport,rather than fluid-flow,through dentinal tubules actually leads to dentine hypersensitivity.The in vitro/in vivo electro-chemical and electro-neurophysiological approaches reveal the cation current through the nanoconfined negatively charged dentinal tubules coming from external stimuli(pressure,pH,and temperature)on dentin surface and further triggering the nerve impulses causing the dentine hypersensitivity.Furthermore,the cationic-hydrogels blocked dentinal tubules could significantly reduce the stimuli-triggered nerve action potentials and the anionhydrogels counterpart enhances those,supporting the cation-flow transducing dentine hypersensitivity.Therefore,the inspired ion-blocking desensitizing therapies have achieved remarkable pain relief in clinical applications.The proposed mechanism would enrich the basic knowledge of dentistry and further foster breakthrough initiatives in hypersensitivity mitigation and cure. | Nuo Chen Jingjing Deng Shengjie Jiang Xiang-Yu Kong Teng Zhou Kai Zhao Zuohui Xiao Huimin Zheng Weipeng Chen Congcong Zhu Xinyu Liu Liping Wen Yan Wei Xuliang Deng Lei Jiang | 2023 | Nano Research2023，16，1： | 2 |
| 10 | Ethnobotanical study on medicinal plants from the Dragon Boat Festival herbal markets of Qianxinan, southwestern Guizhou, China显示文摘Dragon Boat Festival herbal markets in the Qianxinan Buyi and Miao Autonomous Prefecture of southwestern Guizhou have a long well-conserved history.These markets,which are a feature of Buyi and Miao traditional medicines,contain a rich diversity of medicinal plants and traditional medical knowledge.Today,people in southwestern Guizhou still believe that using herbs during the Dragon Boat Festival prevents and can treat disease.In this study,we identified the fresh herbal plants sold at the herbal markets of Xingren City and Zhenfeng County in Qianxinan Buyi and Miao Autonomous Prefecture and quantified their importance.We identified 141 plant species(belonging to 114 genera and 61 families).The plant family with the most species was Asteraceae(14 species).Informants reported that most medicinal plants are herbaceous,with 95.7%of plants used for decoction and 30.5%used for medicinal baths.Medicinal plants are most commonly used to treat rheumatism,injury,and abdominal diseases.The utilization frequency index and relative importance values indicated that Artemisia argyi and Acorus calamus are the most important plants sold at herbal markets during the Dragon Boat Festival.The price of medicinal materials sold in the market may serve as an indicator of the conservation status of species in the region.These findings indicate that the Dragon Boat Festival herbal markets in the Qianxinan Buyi and Miao Autonomous Prefecture fully embodies the characteristics of indigenous ethnomedicine and culture,and also exhibits the diversity of plant resources.We recommend that rare and endangered plants in this region be domesticated and protected. | Wei Gu Xiaojiang Hao Zehuan Wang Jiayu Zhang Liejun Huang Shengji Pei | 2020 | Plant Diversity2020，42，6： | 1 |
| 11 | Nano-channel-based physical and chemical synergic regulation for dendrite-free lithium plating显示文摘Uncontrollable dendrite growth resulting from the non-uniform lithium ion(Li^(+))flux and volume expansion in lithium metal(Li)negative electrode leads to rapid performance degradation and serious safety problems of lithium metal batteries.Although N-containing functional groups in carbon materials are reported to be effective to homogenize the Li^(+)flux,the effective interaction distance between lithium ions and N-containing groups should be relatively small(down to nanometer scale)according to the Debye length law.Thus,it is necessary to carefully design the microstructure of N-containing carbon materials to make the most of their roles in regulating the Li^(+)flux.In this work,porous carbon nitride microspheres(PCNMs)with abundant nanopores have been synthesized and utilized to fabricate a uniform lithiophilic coating layer having hybrid pores of both the nano-and micrometer scales on the Cu/Li foil.Physically,the three-dimensional(3D)porous framework is favorable for absorbing volume changes and guiding Li growth.Chemically,this coating layer can render a suitable interaction distance to effectively homogenize the Li^(+)flux and contribute to establishing a robust and stable solid electrolyte interphase(SEI)layer with Li-F,Li-N,and Li-O-rich contents based on the Debye length law.Such a physical-chemical synergic regulation strategy using PCNMs can lead to dendrite-free Li plating,resulting in a low nucleation overpotential and stable Li plating/stripping cycling performance in both the Li||Cu and the Li||Li symmetric cells.Meanwhile,a full cell using the PCNM coated Li foil negative electrode and a LiFePO4 positive electrode has delivered a high capacity retention of~80%after more than 200 cycles at 1 C and achieved a remarkable rate capability.The pouch cell fabricated by pairing the PCNM coated Li foil negative electrode with a NCM 811 positive electrode has retained~73%of the initial capacity after 150 cycles at 0.2 C. | Qiang Guo Wei Deng Shengjie Xia Zibo Zhang Fei Zhao Binjie Hu Sasa Zhang Xufeng Zhou George Zheng Chen Zhaoping Liu | 2021 | Nano Research2021，14，10： | 1 |
| 12 | Changes in extreme events of temperature and precipitation over Xinjiang, northwest China, during 1960–2009显示文摘 | Baolong Wang Mingjun Zhang Junlin Wei Shengjie Wang Shanshan Li Qian Ma Xiaofei Li Shukun Pan | 2012 | Quaternary International2012，，： | 1 |
| 13 | Changes in extreme events of temperature and precipitation over Xinjiang, northwest China, during 1960–2009显示文摘 | Baolong Wang Mingjun Zhang Junlin Wei Shengjie Wang Shanshan Li Qian Ma Xiaofei Li Shukun Pan | 2012 | Quaternary International2012，，： | 1 |
| 14 | Observational study of the physical and chemical characteristics of the winter radiation fog in the tropical rainforest in Xishuangbanna, China显示文摘We conducted a three-month field experiment focusing on the physical and chemical characteristics of fog in a tropical rainforest in Xishuangbanna,Southwest China,in the winter of 2019.In general,the fog would form at midnight and persist because of the increased long-wave radiative cooling combined with the high relative humidity,gentle breeze,and a relatively low aerosol number concentration in the forest;the fog would dissipate before noon due to the increasing turbulence near the surface.This diurnal cycle is typical for radiation fog.The microphysical fog properties included a relatively low number concentration of the fog droplet,large droplet size,high liquid water content,narrow droplet number-size distribution,and high supersaturation.The chemical properties showed that the fog water was slightly alkaline with low electrical conductivity,whereas the highest proportions of anions and cations therein were Cl^(−)and Ca^(2+),respectively;the chemical components were enriched in small fog droplets.In addition,we indirectly calculated the fog supersaturation according to theκ-Köhler theory.We found that condensation broadens the droplet number-size distribution at relatively low supersaturation,which is positively correlated with the fog-droplet number concentration and negatively correlated with the droplet mean-volume diameter;this affects the key microphysical processes of fog. | Yuan WANG Shengjie NIU Chunsong LU Jingjing LV Jing ZHANG Hongwei ZHANG Sirui ZHANG Naifu SHAO Wei SUN Yuchen JIN Qinghai SONG | 2021 | Science China Earth Sciences2021，64，11： | 1 |
| 15 | Contribution of Mountain River Materials to the Continental Shelf off Southeastern Hainan Island Since the Mid-Holocene显示文摘The concentrations of rare earth elements(REEs)in the bulk sediment of Core X2,which was collected from southeastern Hainan Island,were analyzed to investigate the relative contributions of various provenance regions since mid-Holocene.The results show that sediments in Core X2 were primarily derived from Hainan Island with lesser amounts from Taiwan and limited input from the Pearl River.Based on the application of quantitative inversion to model the REE data,the average contributions of river materials from southeastern Hainan Island and southwestern Taiwan to the study area were 68%and 32%,respectively.Furthermore,starting at 4.0 kyr BP,the transport of fluvial sediments from Taiwan to the study region increased due to enhanced hydrodynamics in South China Sea(SCS).These results indicate that the contributions of mountain river materials from Hainan Island and Taiwan to the continental shelf of northern SCS are non-negligible.Furthermore,these results demonstrate that mountain rivers can play an important role in the material cycle of continental margins and may feature a greater impact than large river systems in specific continental shelf areas. | TIAN Xu JIANG Zuzhou GAO Wei LIU Zhaoqing LIU Xiling FAN Ying QIN Shengjie JING Chunlei XU Yue LIU Baohua XU Fangjian | 2019 | Journal of Ocean University of China2019，18，5： | 1 |
| 16 | Constitutive Activation OsbZIP62 Improves Plant Height and Yield through Regulating the Expression of Agronomic Traits Related Genes in Rice显示文摘Plant height is an important morphological trait that affects crop yield.Several genes related to plant height and yield have been reported in rice(Oryza sativa L.),however,the molecular mechanism underlying the regulation of these traits is still not completely understood.VP64 is widely used as a transcriptional activator to investigate the biological function of genes encoding transcription factors.Here,we identified a novel bZIP transcription factor OsbZIP62 that is involved in modulating agronomic traits in rice.Overexpression of OsbZIP62-VP64(OsbZIP62V)significantly increases the plant height and yield per plant in rice.RNA-seq analysis showed that some plant height and panicle development related genes(i.e.,OsEATB,OsDSS1 and OsGA3ox2)were up-regulated in OsbZIP62V overexpressing rice plants.Besides,OsbZIP62 could also bind to the promoters of several putative target genes.These results suggested that OsbZIP62 plays a role as transcriptional regulator in regulating the expression of genes associated with agronomic traits,and OsbZIP62 fused with VP64 would be useful in crop genetic modification with improved plant architecture and yield. | Shiqin Yang Tao Jiang Peilin Shen Shengjie Ren Zhun Gu Fangjun Feng Yunpeng Peng Wei Wang Kai Xu | 2022 | Phyton-International Journal of Experimental Botany2022，91，8： | 0 |
| 17 | The development of an iridium(Ⅲ) complex functionalized G-quadruplex probe for the stability of G-quadruplex and lifetime image in cytoplasm显示文摘G-quadruplex(G4) is widely known as a non-classical secondary structure of nucleic acid. With the indepth study of G4, it is an urgent need for a phosphorescent probe with a high G4 binding ability to evaluate the level of G4 in the cytoplasm. Thus, this study designed and synthesized Ir-PDP where an Ir(Ⅲ)complex was used as a phosphorescent emitter. Meanwhile, two installed PDPs(pyridostatin derivatives)were used to improve the combination ability with G4 and reduced the cytotoxicity of the Ir(Ⅲ) complex.Compared with other nucleic acid secondary structures, Ir-PDP produced a higher phosphorescence lifetime after interacting with G4. Ir-PDP was distributed in the cytoplasm of living cells, and two-photon phosphorescence lifetime imaging can detect the binding events of the probe in the cytoplasm. The addition of G4 binder PDS significantly regulated cytoplasmic phosphorescence lifetime. The project explored a new sensing pathway to observe the binding manners of probes in the cytoplasm through the phosphorescence lifetime of probes. | Shaokang Jia Wenjin Wang Shanshan Qin Shengjie Xie Lisi Zhan Qi Wei Ziang Lu Xiaolu Zhou Cong Chen Kun Chen Shen Yan Caiping Tan Zongwan Mao Xiang Zhou | 2023 | Chinese Chemical Letters2023，34，2： | 0 |
| 18 | Risk Identification and Protection during High-Risk Forensic Autopsy显示文摘'High-risk'autopsies are those in which the anatomical examination of a corpse entails a substantial risk of contracting a serious infectious disease.Herein,we discuss the risks of infection associated with high-risk autopsies and factors pertaining to risk identification in high-risk autopsies,and we suggest potentially preventative measures focused on anatomy room protection and virtual imaging. | Xia Liu Jilong Zheng Shengjie Yang Cunrui Wei Xuesong Feng | 2020 | Journal of Forensic Science and Medicine2020，6，2： | 0 |
| 19 | Mediator complex subunit 12 is a gatekeeper of SARS-CoV-2 infection in breast cancer cells显示文摘Cancer patients are at increased risk for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection and mortality.Like other viruses in the SARS family,SARS-CoV-2 employs two host proteins,angiotensin-converting enzyme 2(ACE2)and transmembrane serine protease 2(TMPRSS2),for viral entry.1 Recent studies showed that many of the host proteins identified as potential targets for developing COVID therapies are dysregulated in cancer,2 prompting us to investigate whether human cancer cells are susceptible to SARS-CoV-2 infection,and whether chemotherapy could modulate a cancer patient's risk for infection. | Shengjie Zhang Fabao Liu Peter Halfmann Ryan TBehrens Peng Liu Sean JMcilwain Irene MOng Kristine Donahue Yidan Wang Yoshihiro Kawaoka Nathan Sherer Wei Xua | 2022 | Genes & Diseases2022，9，1： | 0 |
| 20 | Proximity-enabled covalent binding of IL-2 to IL-2Rα selectively activates regulatory T cells and suppresses autoimmunity显示文摘Interleukin-2(IL-2)is a pleiotropic cytokine that orchestrates bidirectional immune responses via regulatory T cells(Tregs)and effector cells,leading to paradoxical consequences.Here,we report a strategy that exploited genetic code expansion-guided incorporation of the latent bioreactive artificial amino acid fluorosulfate-L-tyrosine(FSY)into IL-2 for proximity-enabled covalent binding to IL-2Rαto selectively promote Treg activation.We found that FSY-bearing IL-2 variants,such as L72-FSY,covalently bound to IL-2Rαvia sulfur-fluoride exchange when in proximity,resulting in persistent recycling of IL-2 and selectively promoting the expansion of Tregs but not effector cells.Further assessment of L72-FSY-expanded Tregs demonstrated that L72-FSY maintained Tregs in a central memory phenotype without driving terminal differentiation,as demonstrated by simultaneously attenuated expression of lymphocyte activation gene-3(LAG-3)and enhanced expression of programmed cell death protein-1(PD-1).Subcutaneous administration of L72-FSY in murine models of pristane-induced lupus and graft-versus-host disease(GvHD)resulted in enhanced and sustained therapeutic efficacy compared with wild-type IL-2 treatment.The efficacy of L72-FSY was further improved by N-terminal PEGylation,which increased its circulatory retention for preferential and sustained effects.This proximity-enabled covalent binding strategy may accelerate the development of pleiotropic cytokines as a new class of immunomodulatory therapies. | Bo Zhang Jiaqi Sun Yeshuang Yuan Dezhong Ji Yeting Sun Yudong Liu Shengjie Li Xingxing Zhu Xunyao Wu Jin Hu Qiu Xie Ling Wu Lulu Liu Boyang Cheng Yuanjie Zhang Lingjuan Jiang Lidan Zhao Fei Yu Wei Song Min Wang Yue Xu Shiliang Ma Yunyun Fei Lihe Zhang Demin Zhou Xuan Zhang | 2023 | Signal Transduction and Targeted Therapy2023，8，2： | 0 |
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