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| 1 | Plant abiotic stress response and nutrient use efficiency显示文摘Abiotic stresses and soil nutrient limitations are major environmental conditions that reduce plant growth,productivity and quality.Plants have evolved mechanisms to perceive these environmental challenges,transmit the stress signals within cells as well as between cells and tissues,and make appropriate adjustments in their growth and development in order to survive and reproduce.In recent years,significant progress has been made on many fronts of the stress signaling research,particularly in understanding the downstream signaling events that culminate at the activation of stress-and nutrient limitation-responsive genes,cellular ion homeostasis,and growth adjustment.However,the revelation of the early events of stress signaling,particularly the identification of primary stress sensors,still lags behind.In this review,we summarize recent work on the genetic and molecular mechanisms of plant abiotic stress and nutrient limitation sensing and signaling and discuss new directions for future studies. | Zhizhong Gong Liming Xiong Huazhong Shi Shuhua Yang Luis R.Herrera-Estrella Guohua Xu Dai-Yin Chao Jingrui Li Peng-Yun Wang Feng Qin Jigang Li Yanglin Ding Yiting Shi Yu Wang Yongqing Yang Yan Guo Jian-Kang Zhu | 2020 | Science China(Life Sciences)2020，63，5： | 94 |
| 2 | BZR1 Positively Regulates Freezing Tolerance via CBF-Dependent and CBF-Independent Pathways in Arabidopsis显示文摘冷应力是不利地影响植物生长和开发的一个主要环境因素。C 重复有约束力的 factor/DRE 绑定因素 1 (CBF/DREB1 ) 规章的串联被显示出在对的植物反应起重要作用的 transcriptional 冷。这里,我们证明发信号的 brassinosteroid (BR ) 的二个关键部件调制 Arabidopsis 植物的结冰忍耐。象 GSK3 一样 kinases 的 loss-of-function 异种在 BR 发信号包含了, bin2-3 bil1 bil2,显示出的增加的结冰公差,而 BIN2 的 overexpression 导致了超敏性到结冰,在 non-acclimated 和 acclimated 下面的应力调节。由对比,显示的抄写因素 BZR1 和 BES1 的 gain-of-function 异种提高了结冰忍耐,和一致地冷的处理能导致 dephosphorylated BZR1 的累积。生物化学、基因的分析证明 BZR1 行动 CBF1 和 CBF2 到在上游直接调整他们的表示。而且,我们发现 BZR1 也调整了另外的英国管基因与 CBF 解开了例如 WKRY6, PYL6, SOC1, JMT,和 SAG21,种反应调制到冷应力。一致地, wrky6 异种显示出减少的结冰忍耐。一起拿,我们的结果显示 BZR1 断然调制通过 CBF 依赖、 CBF 独立的小径冻结忍耐的植物。 | Hui Li Keyi Ye Yiting Shi Jinkui Cheng Xiaoyan Zhang Shuhua Yang | 2017 | Molecular Plant2017，10，4： | 37 |
| 3 | The Antagonistic Action of Abscisic Acid and Cytokinin Signaling Mediates Drought Stress Response in Arabidopsis显示文摘 | Xiaozhen Huang Lingyan Hou Jingjing Meng Huiwen You Zhen Li Zhizhong Gong Shuhua Yang Yiting Shi | 2018 | Molecular Plant2018，11，7： | 15 |
| 4 | Cold-Induced CBF–PIF3 Interaction Enhances Freezing Tolerance by Stabilizing the phyB Thermosensor in Arabidopsis显示文摘Growth inhibition and cold-acclimation strategies help plants withstand cold stress,which adversely affects growth and survival.PHYTOCHROME B(phyB)regulates plant growth through perceiving both light and ambient temperature signals.However,the mechanism by which phyB mediates the plant response to cold stress remains elusive.Here,we show that the key transcription factors mediating cold acclimation,C-REPEAT BINDING FACTORs(CBFs),interact with PHYTOCHROME-INTERACTING FACTOR 3(PIF3)under cold stress,thus attenuating the mutually assured destruction of PIF3–phyB.Cold-stabilized phyB acts downstream of CBFs to positively regulate freezing tolerance by modulating the expression of stress-responsive and growth-related genes.Consistent with this,phyB mutants exhibited a freezing-sensitive phenotype,whereas phyB-overexpression transgenic plants displayed enhanced freezing tolerance.Further analysis showed that the PIF1,PIF4,and PIF5 proteins,all of which negatively regulate plant freezing tolerance,were destabilized by cold stress in a phytochrome-dependent manner.Collectively,our study reveals that CBFs–PIF3–phyB serves as an important regulatory module for modulating plant response to cold stress. | Bochen Jiang Yiting Shi Yue Peng Yuxin Jia Yan Yan Xiaojing Dong Hui Li Jie Dong Jigang Li Zhizhong Gong Michael F.Thomashow Shuhua Yang | 2020 | Molecular Plant2020，13，6： | 13 |
| 5 | Biosynthesis of Triacylglycerol Molecules with a Tailored PUFA Profile in Industrial Microalgae显示文摘The composition of polyun saturated fatty acids (PUFAs) in triacylglycerols (TAGs) is key to health ben efits and for oil applications, yet the underlying genetic mechanism remains poorly understood. In this study, by in si Iico, ex vivo, and in vivo profili ng of type-2 diacylglycerol acyltransferases (DGAT2s) in Nannochloropsis oceanica we revealed two novel PUFA-preferring enzymes that discriminate individual PUFA species in TAG assembly, with NoDGAT2J for linoleic acid (LA) and NoDGAT2K for eicosapentaenoic acid (EPA). The LA and EPA composition of TAG molecules is mediated in vivo via the functional partitioning between NoDGAT2J and 2K, both of which are localized in the chloroplast envelope. By modulating transcript abundance of the DGAT2s, an N. oceanica strain bank was created, where proportions of LA and EPA in TAG vary by 18.7-fold (between 0.21% and 3.92% dry weight) and 34.7-fold (between 0.09% and 3.12% dry weight), respective!y. These findings lay the foundation for producing designer TAG molecules with tailored health benefits or for biofuel applications in industrial microalgae and higher-plant crops. | Yi Xin Chen Shen Yiting She Hong Chen Cong Wang Li Wei Kangsup Yoon Danxiang Han Qiang Hu Jian Xu | 2019 | Molecular Plant2019，12，4： | 10 |
| 6 | Clinical Application of Chromosome Microarray Analysis in Han Chinese Children with Neurodevelopmental Disorders显示文摘Chromosome microarray analysis(CMA) is a cost-effective molecular cytogenetic technique that has been used as a first-line diagnostic test in neurodevelopmental disorders in the USA since 2011. The impact of CMA results on clinical practice in China is not yet well studied, so we aimed to better evaluate this phenomenon.We analyzed the CMA results from 434 patients in our clinic, and characterized their molecular diagnoses, clinical features, and follow-up clinical actions based on these results. The overall diagnostic yield for our patients was 13.6%(59 out of 434). This gave a detection rate of 14.7%for developmental delay/intellectual disability(DD/ID,38/259) and 12% for autism spectrum disorders(ASDs,21/175). Thirty-three recurrent(n≥2) variants were found, distributed at six chromosomal loci involving known chromosome syndromes(such as DiGeorge, Williams Beuren, and Angelman/Prader-Willi syndromes).The spectrum of positive copy number variants in our study was comparable to that reported in Caucasian populations, but with specific characteristics. Parental origin tests indicated an effect involving a significant maternal transmission bias to sons. The majority of patients with positive results(94.9%) had benefits, allowing earlier diagnosis(36/59), prioritized full clinical management(28/59), medication changes(7/59), a changed prognosis(30/59), and prenatal genetic counseling(15/59). Our results provide information on de novo mutations in Chinese children with DD/ID and/or ASDs. Our data showed that microarray testing provides immediate clinical utility for patients. It is expected that the personalized medical care of children with developmental disabilities will lead to improved outcomes in long-term developmental potential.We advocate using the diagnostic yield of clinically actionable results to evaluate CMA as it provides information of both clinical validity and clinical utility. | Mingyu Xu Yiting Ji Ting Zhang Xiaodong Jiang Yun Fan Juan Geng Fei Li | 2018 | Neuroscience Bulletin2018，34，6： | 8 |
| 7 | Shear-responsive boundary-lubricated hydrogels attenuate osteoarthritis显示文摘Lipid-based boundary layers formed on liposome-containing hydrogels can facilitate lubrication.However,these boundary layers can be damaged by shear,resulting in decreased lubrication.Here,a shear-responsive boundary-lubricated drug-loaded hydrogel is created by incorporating celecoxib(CLX)-loaded liposomes within dynamic covalent bond-based hyaluronic acid(HA)hydrogels(CLX@Lipo@HA-gel).The dynamic cross-linked network enables the hydrogel to get restructured in response to shear,and the HA matrix allows the accumulation of internal liposome microreservoirs on the sliding surfaces,which results in the formation of boundary layers to provide stable lubrication.Moreover,hydration shells formed surrounding the hydrogel can retard the degradation process,thus helping in sustaining lubrication.Furthermore,in vitro and in vivo experiments found that CLX@Lipo@HA-gels can maintain anabolic-catabolic balance,alleviate cartilage wear,and attenuate osteoarthritis progression by delivering CLX and shear-responsive boundary lubrication.Overall,CLX@Lipo@HA-gels can serve as shear-responsive boundary lubricants and drug-delivery vehicles to alleviate friction-related diseases like osteoarthritis. | Yiting Lei Xingkuan Wang Junyi Liao Jieliang Shen Yuling Li Zhengwei Cai Ning Hu Xiaoji Luo Wenguo Cui Wei Huang | 2022 | Bioactive Materials2022，7，10： | 4 |
| 8 | Terrain relief periods of loess landforms based on terrain profiles of the Loess Plateau in northern Shaanxi Province,China显示文摘The Loess Plateau is densely covered by numerous types of gullies which represent different soil erosion intensities.Therefore,research on topographic variation features of the loess gullies is of great significance to environmental protection and ecological management.Using a5 m digital elevation model and data from a national geographic database,this paper studies different topographical areas of the Loess Plateau,including Shenmu,Suide,Yanchuan,Ganquan,Yijun,and Chunhua,to derive representative gully terrain profile data of the sampled areas.First,the profile data are standardized in MATLAB and then decomposed using the ensemble empirical mode decomposition method.Then,a significance test is performed on the results;the test confidence is 95% to 99%.The most reliable decomposition component is then used to calculate the relief period and size of the gullies.The results showed that relief periods of the Chunhua,Shenmu,Yijun,Yuanchuan,Ganquan,and Suide gullies are 1110.14 m,1096.85 m,1002.49 m,523.48 m,498.12 m,and 270.83 m,respectively.In terms of gully size,the loess landforms are sorted as loess fragmented tableland,aeolian and dune,loess tableland,loess ridge,loess hill and loess ridge,and loess hill,in descending order.Taken together,the gully terrain features of the sample areas and the results of the study are approximately consistent with the actual terrain profiles.Thus,we conclude that ensemble empirical mode decomposition is a reliable method for the study of the relief and topography of loess gullies. | Jianjun CAO Guoan TANG Xuan FANG Jilong LI Yongjuan LIU Yiting ZHANG Ying ZHU Fayuan LI | 2019 | Frontiers of Earth Science2019，13，2： | 4 |
| 9 | Integration of light and temperature signaling pathways in plants显示文摘As two of the most important environmental factors,light and temperature regulate almost all aspects of plant growth and development.Under natural conditions,light is accompanied by warm temperatures and darkness by cooler temperatures,suggesting that light and temperature are tightly associated signals for plants.Indeed,accumulating evidence shows that plants have evolved a wide range of mechanisms to simultaneously perceive and respond to dynamic changes in light and temperature.Notably,the photoreceptor phytochrome B(phy B)was recently shown to function as a thermosensor,thus reinforcing the notion that light and temperature signaling pathways are tightly associated in plants.In this review,we summarize and discuss the current understanding of the molecular mechanisms integrating light and temperature signaling pathways in plants,with the emphasis on recent progress in temperature sensing,light control of plant freezing tolerance,and thermomorphogenesis.We also discuss the questions that are crucial for a further understanding of the interactions between light and temperature signaling pathways in plants. | Lijuan Qi Yiting Shi William Terzaghi Shuhua Yang Jigang Li | 2022 | Journal of Integrative Plant Biology2022，64，2： | 4 |
| 10 | Genetic architecture and key genes controlling the diversity of oil composition in rice grains显示文摘Rice grain oil is a valuable nutrient source.However,the genetic basis of oil biosynthesis in rice grains remains unclear.In this study,we performed a genome-wide association study on oil composition and oil concentration in a diverse panel of 533 cultivated rice accessions.High variation for 11 oil-related traits was observed,and the oil composition of rice grains showed differentiation among the subpopulations.We identified 46 loci that are significantly associated with grain oil concentration or composition,16 of which were detected in three recombinant inbred line populations.Twenty-six candidate genes encoding enzymes involved in oil metabolism were identified from these 46 loci,four of which(PAL6,LIN6,MYR2,and ARA6)were found to contribute to natural variation in oil composition and to show differentiation among the subpopulations.Interestingly,population genetic analyses revealed that specific haplotypes of PAL6 and LIN6 have been selected in japonica rice.Based on these results,we propose a possible oil biosynthetic pathway in rice grains.Collectively,our results provide new insights into the genetic basis of oil biosynthesis in rice grains and can facilitate marker-based breeding of rice varieties with enhanced oil and grain quality. | Hao Zhou Duo Xia Pingbo Li Yiting Ao Xiaodong Xu Shanshan Wan Yanhua Li Bian Wu Huan Shi Kaiyue Wang Guanjun Gao Qinglu Zhang Gongwei Wang Jinghua Xiao Xianghua Li Sibin Yu Xingming Lian Yuqing He | 2021 | Molecular Plant2021，14，3： | 4 |
| 11 | Scaffolding protein Gab1 regulates myeloid dendritic cell migration in allergic asthma显示文摘气喘是在多重基因、环境的因素之中包含复杂相互影响的普通过敏混乱。最近的研究作为一个新奇气喘危险性因素识别了人的 GAB1 的基因变体。然而,在肺的 Gab1 的功能仍然保持大部分未经勘探。在这研究,我们首先在尖锐恶化期间从气喘的病人在外部血 mononuclear 房间观察了 Gab1 水平的举起与康复相比。有在 myeloid 的有选择地破坏的 Gab1 的老鼠树枝状的房间(mDCs ) 更加在气喘的试验性的模型稀释了过敏发炎。进一步的调查在 Gab1 缺乏的 mDCs 的调停 CCL19 的移植揭示了突出的减小到排干淋巴节点和驾驶 Th2 的适应激活的随后的缺陷。机械学地, Gab1 是在气喘的回答期间调整 mDC 移植的 CCL19/CCR7 chemokine 轴的一个必要部件。一起,这些调查结果在肺为 Gab1 的角色提供第一条证据,给我们气喘的致病的更深的理解。 | Yun Zhang Yun Xu Shuwan Liu Xiaohong Guo Dong Cen Jiaqi Xu Heyuan Li Kaijun Li Chunlai Zeng Linrong LU Yiting Zhou Huahao Shen Hongqiang Cheng Xue Zhang Yuehai Ke | 2016 | Cell Research2016，26，11： | 3 |
| 12 | The direct targets of CBFs:In cold stress response and beyond显示文摘Cold acclimation in Arabidopsis thaliana triggers a significant transcriptional reprogramming altering the expression patterns of thousands of cold-responsive(COR) genes. Essential to this process is the C-repeat binding factor(CBF)-dependent pathway, involving the activity of AP2/ERF(APETALA2/ethylene-responsive factor)-type CBF transcription factors required for plant cold acclimation. In this study, we performed chromatin immunoprecipitation assays followed by deep sequencing(ChIP-seq) to determine the genomewide binding sites of the CBF transcription factors. Cold-induced CBF proteins specifically bind to the conserved C-repeat(CRT)/dehydrationresponsive elements(CRT/DRE;G/ACCGAC) of their target genes. A Gene Ontology enrichment analysis showed that 1,012 genes are targeted by all three CBFs. Combined with a transcriptional analysis of the cbf1,2,3 triple mutant, we define 146 CBF regulons as direct CBF targets. In addition, the CBF-target genes are significantly enriched in functions associated with hormone, light,and circadian rhythm signaling, suggesting that the CBFs act as key integrators of endogenous and external environmental cues. Our findings not only define the genome-wide binding patterns of the CBFs during the early cold response, but also provide insights into the role of the CBFs in regulating multiple biological processes of plants. | Yue Song Xiaoyan Zhang Minze Li Hao Yang Diyi Fu Jian Lv Yanglin Ding Zhizhong Gong Yiting Shi Shuhua Yang | 2021 | Journal of Integrative Plant Biology2021，63，11： | 3 |
| 13 | Recent progress in perovskite solar cells:material science显示文摘Perovskite solar cells represent a promising third-generation photovoltaic technology with low fabrication cost and high power conversion efficiency.In light of the rapid development of perovskite materials and devices,a systematic survey on the latest advancements covering a broad range of related work is urgently needed.This review summarizes the recent major advances in the research of perovskite solar cells from a material science perspective.The discussed topics include the devices based on different type of perovskites(organic-inorganic hybrid,all-inorganic,and lead-free perovskite and perovskite quantum dots),the properties of perovskite defects,different type of charge transport materials(organic,polymeric,and inorganic hole transport materials and inorganic and organic electron transport materials),counter electrodes,and interfacial materials used to improve the efficiency and stability of devices.Most discussions focus on the key progresses reported within the recent five years.Meanwhile,the major issues limiting the production of perovskite solar cells and the prospects for the future development of related materials are discussed. | Jiang-Yang Shao Dongmei Li Jiangjian Shi Chuang Ma Yousheng Wang Xiaomin Liu Xianyuan Jiang Mengmeng Hao Luozheng Zhang Chang Liu Yiting Jiang Zhenhan Wang Yu-Wu Zhong Shengzhong(Frank)Liu Yaohua Mai Yongsheng Liu Yixin Zhao Zhijun Ning Lianzhou Wang Baomin Xu Lei Meng Zuqiang Bian Ziyi Ge Xiaowei Zhan Jingbi You Yongfang Li Qingbo Meng | 2023 | Science China Chemistry2023，66，1： | 3 |
| 14 | Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors显示文摘 | Benjamin J Moeller Yiting Cao Chuan Y Li Mark W Dewhirst | 2004 | Cancer Cell2004，，5： | 2 |
| 15 | Colonization of endophyte Acremonium sp. D212 in Panax notoginseng and rice mediated by auxin and jasmonic acid显示文摘Endophytic fungi can be beneficial to plant growth. However, the molecular mechanisms under-lying colonization of Acremonium spp. remain unclear. In this study, a novel endophytic Acremonium strain was isolated from the buds of Panax notoginseng and named Acremonium sp. D212. The Acremonium sp. D212 could colonize the roots of P. notoginseng, enhance the resistance of P. notoginseng to root rot disease, and promote root growth and saponin bio-synthesis in P. notoginseng. Acremonium sp. D212 could secrete indole-3-acetic acid (IAA) and jasmonic acid (JA), and inoculation with the fungus increased the endogenous levels of IAA and JA in P. noto-ginseng. Colonization of the Acremonium sp. D212 in the roots of the rice line Nipponbare was dependent on the concentration of methyl jasmonate (MeJA) (2–15μmol/L) and 1-naphthalenacetic acid (NAA) (10–20μmol/L). Moreover, the roots of the JA signaling-defective coi1-18 mutant were colonized by Acremonium sp. D212 to a lesser degree than those of the wild-type Nipponbare and miR393b-overexpressing lines, and the colonization was res-cued by MeJA but not by NAA. It suggests that the cross-talk between JA signaling and the auxin biosynthetic pathway plays a crucial role in the colonization of Acremonium sp. D212 in host plants. | Li Han Xuan Zhou Yiting Zhao Shusheng Zhu Lixia Wu Yunlu He Xiangrui Ping Xinqi Lu Wuying Huang Jie Qian Lina Zhang Xi Jiang Dan Zhu Chongyu Luo Saijie Li Qian Dong Qijing Fu Kaiyuan Deng Xin Wang Lei Wang Sheng Peng Jinsong Wu Weimin Li JiǐíFriml Youyong Zhu Xiahong He Yunlong Du | 2020 | Journal of Integrative Plant Biology2020，62，9： | 2 |
| 16 | Mechanism of micro-wetting of highly hydrophobic coal dust in underground mining and new wetting agent development显示文摘The internal mechanism of the high hydrophobicity of the coal samples from the Pingdingshan mining area was studied through industrial,element,and surface functional group analysis.Laboratory testing and molecular dynamics simulations were employed to study the impact of three types of surfactants on the surface adsorption properties and wettability of highly hydrophobic bituminous coal.The results show that the surface of highly hydrophobic bituminous coal is compact,rich in inorganic minerals,and poorly wettable and that coal molecules are dominated by hydrophobic functional groups of aromatic rings and aliphatic structures.The wetting performance of surfactants as the intermediate carrier to connect coal and water molecules is largely determined by the interaction force between surfactants and coal(Fs-c)and the interaction force between surfactants and water(Fs-w),which effectively improve the wettability of modified coal dust via modifying its surface electrical properties and surface energy.A new type of wetting agent with a dust removal rate of 89%has been developed through discovery of a compound wetting agent solution with optimal wetting and settling performance.This paper provides theoretical and technical support for removing highly hydrophobic bituminous coal dust in underground mining. | Mingzhong Gao Hongmei Li Yun Zhao Yiting Liu Weiqi Zhou Luming Li Jing Xie Jie Deng | 2023 | International Journal of Mining Science and Technology2023，33，1： | 2 |
| 17 | Fine-tuning inverse metal-support interaction boosts electrochemical transformation of methanol into formaldehyde based on density functional theory显示文摘Different from traditional metal-support heterogenous catalysts,inverse heterogeneous catalysts,in which the surface of metal is decorated by metal oxide,have recently attracted increasing interests owing to the unique interracial effect and electronic structure.However,a deep insight into the effect of metaloxide interaction on the catalytic performance still remains a great challenge.In our work,an inverse hematite/palladium(Fe_(2) O_(3)/Pd) hybrid nanostructure,i.e.,the active Fe_(2) O_(3) ultrathin oxide layers partially covering on the surface of Pd nanoparticles(NPs),exhibited superior electrocatalytic performance towards methanol oxidation reaction(MOR) as compared to the bare Pd NPs based on density functional theory calculation.The charge could transfer from Pd to Fe_(2) O_(3) driven by the built-in potential at the interface of Pd and Fe_(2) O_(3),which favors the downshift of d band center of Pd.With the assistance of interfacial hydroxyl OH*,the cleavage of O—H and C—H in CH_(3) OH could take place much easily with lower barrier ene rgy on Fe_(2) O_(3)/Pd than that on pure Pd via two electrons transferring reaction pathways.Our results highlight that the syne rgy of Pd and Fe_(2) O_(3) at the interface could facilitate the electrochemical transformation of methanol into formaldehyde assisted with interfacial hydroxyl OH*. | Wenjuan Yang Junjun Li Xiaoya Cui Chenhuai Yang Yiting Liu Xianwei Zeng Zhicheng Zhang Qitao Zhang | 2021 | Chinese Chemical Letters2021，32，8： | 2 |
| 18 | Blockchain-based continuous data integrity checking protocol with zero-knowledge privacy protection显示文摘The cloud computing technology has emerged,developed,and matured in recent years,consequently commercializing remote outsourcing storage services.An increasing number of companies and individuals have chosen the cloud to store their data.However,accidents,such as cloud server downtime,cloud data loss,and accidental deletion,are serious issues for some applications that need to run around the clock.For some mission and business-critical applications,the continuous availability of outsourcing storage services is also necessary to protect users'outsourced data during downtime.Nevertheless,ensuring the continuous availability of data in public cloud data integrity auditing protocols leads to data privacy issues because auditors can obtain the data content of users by a sufficient number of storage proofs.Therefore,protecting data privacy is a burning issue.In addition,existing data integrity auditing schemes that rely on semi-trusted third-party auditors have several security problems,including single points of failure and performance bottlenecks.To deal with these issues,we propose herein a blockchain-based continuous data integrity checking protocol with zero-knowledge privacy protection.We realize a concrete construction by using a verifiable delay function with high efficiency and proof of retrievability,and prove the security of the proposal in a random oracle model.The proposed construction supports dynamic updates for the outsourced data.We also design smart contracts to ensure fairness among the parties involved.Finally,we implement the protocols,and the experimental results demonstrate the efficiency of the proposed protocol. | Yiting Huang Yong Yua Huilin Li Yannan Li Aikui Tian | 2022 | Digital Communications and Networks2022，8，5： | 2 |
| 19 | Cartilage oligomeric matrix protein is an endogenous β-arrestin-2-selective allosteric modulator of AT1 receptor counteracting vascular injury显示文摘Compelling evidence has revealed that biased activation of G protein-coupled receptor(GPCR)signaling,including angiotensin II(AngII)receptor type 1(AT1)signaling,plays pivotal roles in vascular homeostasis and injury,but whether a clinically relevant endogenous biased antagonism of AT1 signaling exists under physiological and pathophysiological conditions has not been clearly elucidated.Here,we show that an extracellular matrix protein,cartilage oligomeric matrix protein(COMP),acts as an endogenous allosteric biased modulator of the AT1 receptor and its deficiency is clinically associated with abdominal aortic aneurysm(AAA)development.COMP directly interacts with the extracellular N-terminus of the AT1 via its EGF domain and inhibits AT1-β-arrestin-2 signaling,but not Gq or Gi signaling,in a selective manner through allosteric regulation of AT1 intracellular conformational states.COMP deficiency results in activation of AT1a-β-arrestin-2 signaling and subsequent exclusive AAA formation in response to AngII infusion.AAAs in COMP–/–or ApoE–/–mice are rescued by AT1a orβ-arrestin-2 deficiency,or the application of a peptidomimetic mimicking the AT1-binding motif of COMP.Explorations of the endogenous biased antagonism of AT1 receptor or other GPCRs may reveal novel therapeutic strategies for cardiovascular diseases. | Yi Fu Yaqian Huang Zhao Yang Yufei Chen Jingang Zheng Chenfeng Mao Zhiqing Li Zhixin Liu Bing Yu Tuoyi Li Meili Wang Chanjuan Xu Yiwei Zhou Guizhen Zhao Yiting Jia Wei Guo Xin Jia Tao Zhang Li Li Ziyi Liu Shengchao Guo Mingliang Ma Heng Zhang Bo Liu Junbao Du Wengong Wang Chaoshu Tang Pei Gao Qingbo Xu Xian Wang Jianfeng Liu Jinpeng Sun Wei Kong | 2021 | Cell Research2021，31，7： | 2 |
| 20 | A nanomedicine approach enables co-delivery of cyclosporin A and gefitinib to potentiate the therapeutic efficacy in drug-resistant lung cancer显示文摘Drug resistance,accounting for therapeutic failure in the clinic,remains a major challenge to effectively manage cancer.Cyclosporin A(CsA)can reverse multidrug resistance(MDR),especially resistance to epidermal growth factor receptor tyrosine kinase inhibitors.However,the application of both drugs in cancer therapies is hampered by their poor aqueous solubility and low bioavailability due to oral administration.CsA augments the potency of gefitinib(Gef)in both Gef-sensitive and Gef-resistant cell lines.Here,we show that the simultaneous encapsulation of CsA and Gef within polyethylene glycol-block-poly(D,L-lactic acid)(PEG-PLA)produced a stable and systemically injectable nanomedicine,which exhibited a sub-50-nm diameter and spherical structures.Impressively,the co-delivery of therapeutics via single nanoparticles(NPs)outperformed the oral administration of the free drug combination at suppressing tumor growth.Furthermore,in vivo results indicated that CsA formulated in NPs sensitized Gef-resistant cells and Gefresistant tumors to Gef treatment by inactivating the STAT3/Bcl-2 signaling pathway.Collectively,our nanomedicine approach not only provides an alternative administration route for the drugs of choice but also effectively reverses MDR,facilitating the development of effective therapeutic modalities for cancer. | Weidong Han Linlin Shi Lulu Ren Liqian Zhou Tongyu Li Yiting Qiao Hangxiang Wang | 2018 | Signal Transduction and Targeted Therapy2018，3，1： | 2 |
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