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| 1 | Targeting a novel inducible GPX4 alternative isoform to alleviate ferroptosis and treat metabolic-associated fatty liver disease显示文摘Metabolic-associated fatty liver disease(MAFLD),which is previously known as non-alcoholic fatty liver disease(NAFLD),represents a major health concern worldwide with limited therapy.Here,we provide evidence that ferroptosis,a novel form of regulated cell death characterized by iron-driven lipid peroxidation,was comprehensively activated in liver tissues from MAFLD patients.The canonical-GPX4(cGPX4),which is the most important negative controller of ferroptosis,is downregulated at protein but not mRNA level.Interestingly,a non-canonical GPX4 transcript-variant is induced(inducible-GPX4,iGPX4)in MAFLD condition.The high fat-fructose/sucrose diet(HFFD)and methionine/choline-deficient diet(MCD)-induced MAFLD pathologies,including hepatocellular ballooning,steatohepatitis andfibrosis,were attenuated and aggravated,respectively,in cGPX4-and iGPX4-knockin mice.cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes.Knockdown of iGPX4 by siRNA alleviated lipid stress,ferroptosis and cell injury.Mechanistically,the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress,and thus promotes ferroptosis.Co-immunoprecipitation and nano LC–MS/MS analyses confirmed the interaction between iGPX4 and cGPX4.Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis,and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD. | Jie Tong Dongjie Li Hongbo Meng Diyang Sun Xiuting Lan Min Ni Jiawei Ma Feiyan Zeng Sijia Sun Jiangtao Fu Guoqiang Li Qingxin Ji Guoyan Zhang Qirui Shen Yuanyuan Wang Jiahui Zhu Yi Zhao Xujie Wang Yi Liu Shenxi Ouyang Chunquan Sheng Fuming Shen Pei Wang | 2022 | Acta Pharmaceutica Sinica B2022，12，9： | 3 |
| 2 | Molecular basis for ligand activation of the human KCNQ2 channel显示文摘The voltage-gated potassium channel KCNQ2 is responsible for M-current in neurons and is an important drug target to treat epilepsy,pain and several other diseases related to neuronal hyper-excitability.A list of synthetic compounds have been developed to directly activate KCNQ2,yet our knowledge of their activation mechanism is limited,due to lack of high-resolution structures.Here,we report cryo-electron microscopy(cryo-EM)structures of the human KCNQ2 determined in apo state and in complex with two activators,ztz240 or retigabine,which activate KCNQ2 through different mechanisms.The activator-bound structures,along with electrophysiology analysis,reveal that ztz240 binds at the voltage-sensing domain and directly stabilizes it at the activated state,whereas retigabine binds at the pore domain and activates the channel by an allosteric modulation.By accurately defining ligand-binding sites,these KCNQ2 structures not only reveal different ligand recognition and activation mechanisms,but also provide a structural basis for drug optimization and design. | Xiaoxiao Li Qiansen Zhangc Peipei Guo Jie Fu Lianghe Mei Dashuai Lv Jiangqin Wang Dongwu Lai Sheng Ye Huaiyu Yang Jiangtao Guo | 2021 | Cell Research2021，31，1： | 3 |
| 3 | An analytical model to optimize rotation speed and travel speed of friction stir welding for defect-free joints显示文摘 | Jinwen Qian Jinglong Li Fu Sun Jiangtao Xiong Fusheng Zhang Xin Lin | 2013 | Scripta Materialia (-)2013，，3： | 1 |
| 4 | Exploring exosomes to provide evidence for the treatment and prediction of Alzheimer’s disease显示文摘Exosomes are extracellular vesicles with a 30–150 nm diameter originating from endosomes.In recent years,scientists have regarded exosomes as an ideal small molecule carrier for the targeted treatment of Alzheimer’s disease(AD)across the blood-brain barrier due to their nanoscale size and low immunogenicity.A large amount of evidence shows that exosomes are rich in biomarkers,and it has been found that the changes in biomarker content in blood,cerebrospinal fluid,and urine are often associated with the onset of AD patients.In this paper,some recent advances in the use of exosomes in the treatment of AD are reviewed,and various exosome markers and some latest detection methods are summarized to provide some evidence for the detection or treatment of AD by exosomes. | XIANGYU QUAN XUETING MA GUODONG LI XUEQI FU JIANGTAO LI LINLIN ZENG | 2023 | BIOCELL2023，47，10： | 0 |
| 5 | ‘C-type’ closed state and gating mechanisms of K2P channels revealed by conformational changes of the TREK-1 channel显示文摘Two-pore domain potassium (K2P) channels gate primarily within the selectivity filter, termed ‘C-type’ gating. Due to the lack of structural insights into the nonconductive (closed) state, ‘C-type’ gating mechanisms remain elusive. Here, molecular dynamics (MD) simulations on TREK-1, a K2P channel, revealed that M4 helix movements induce filter closing in a novel ‘deeper-down’ structure that represents a ‘C-type’ closed state. The ‘down’ structure does not represent the closed state as previously proposed and instead acts as an intermediate state in gating. The study identified the allosteric ‘seesaw’ mechanism of M4 helix movements in modulating filter closing. Finally, guided by this recognition of K2P gating mechanisms, MD simulations revealed that gain-of-function mutations and small-molecule activators activate TREK-1 by perturbing state transitions from open to closed states. Together, we reveal a ‘C-type’ closed state and provide mechanical insights into gating procedures and allosteric regulations for K2P channels. | Qiansen Zhang Jie Fu Shaoying Zhang Peipei Guo Shijie Liu Juwen Shen Jiangtao Guo Huaiyu Yang | 2022 | Journal of Molecular Cell Biology2022，14，1： | 0 |
| 6 | Uncertainty Quantification of Store-Separation Simulation Due to Ejector Modeling using a Monte Carlo Approach with Kriging Model显示文摘Precise calculation of the trajectory of store separation is critical in assess-ing whether the store can be released safely.Store ejection is the initial stage of the releasing process and any uncertainty introduced at this stage will propagate through the whole trajectory.In this work,the impact of the uncertainties in ejector modeling on the simulation of a generic store separation is investigated by using a Monte-Carlo-based approach.To reduce the extremely large computation cost resulted from the direct use CFD in Monte Carlo simulation,the CFD solutions are represented by a time-dependent Kriging model,which is constructed at each time step by using the samples from the URANS simulations.The stochastic outputs,including the distri-bution of probability density function,expected value and 95%confidence interval of store separation trajectory,are obtained by the Monte Carlo simulations.The sensitiv-ity analysis is also carried out by using the Monte-Carlo-based method to determine the most significant variables in ejector modeling,which affect the output uncertainty.Our results show that ejector modeling is one of the main uncertainty sources of store separation simulation and the approximation in ejector modeling can cause a signifi-cant deviation,especially in the angular displacement. | Shuling Tian Rongjie Li Jiawei Fu Zihan Jiao Jiangtao Chen | 2022 | Advances in Applied Mathematics and Mechanics2022，14，3： | 0 |
| 7 | Simple decision-making model for orchard air-assisted spraying airflow显示文摘Airflow speed is one of the three factors of air-assisted spraying.Optimizing the matching model between airflow speed and target canopy characteristics is an effective way to improve the orchard precision spraying technology,as airflow can significantly affect droplet deposition and drift loss.A simple model of airflow speed was established in this study.First,air-assisted spraying experiments were carried out on a standard simulation canopy to study the airflow speed depended on canopy width,leaf area index,and porosity rate.Second,determined by Ribbon Method and verified by droplet drift data,the airflow speed through the canopy was between 0.5 m/s and 0.7 m/s.Third,multiple tests were carried out under standard simulation canopy with different characteristics,and the airflow speed model was established ultimately:with a fixed leaf area index(LAI),the relationship between canopy upwind boundary airflow speed and canopy width satisfied the exponential model(y=ae^(bx)),and the coefficients a and b are well related to the density of branches and leaves in the canopy.When LAI=3.456,y=2.036e^(1.5887x),R^(2)=0.994;LAI=1.728,y=1.639e^(1.445x),R^(2)=0.972.Orchard growers can acquire needed airflow speed through this simple model,it is quick and precise and appropriate to most growth periods of a variety of fruit trees,such as apples,pears,and vines. | Xiang Wang Yuru Feng Wei Fu Jiangtao Qi Jianli Song | 2023 | International Journal of Agricultural and Biological Engineering2023，16，2： | 0 |
| 8 | Clinical features of 162 fatal cases of COVID-19:a multi-center retrospective study显示文摘Background:The coronavirus disease 2019(COVID-19)has affected approximately 2 million individuals worldwide;however,data regarding fatal cases have been limited.Objective:To report the clinical features of 162 fatal cases of COVID-19 from 5 hospitals in Wuhan between December 30,2019 and March 12,2020.Methods:The demographic data,signs and symptoms,clinical course,comorbidities,laboratory findings,computed tomographic(CT)scans,treatments,and complications of the patients with fatal cases were retrieved from electronic medical records.Results:The median patient age was 69.5(interquartile range:63.0–77.25)years,and 80%of the patients were over 61 years.A total of 112(69.1%)patients were men.Hypertension(45.1%)was the most common comorbidity,while 59(36.4%)patients had no comorbidity.At admission,131(81.9%)patients had severe or critical COVID-19,whereas 39(18.1%)patients with hypertension or chronic lung disease had moderate COVID-19.In total,126(77.8%)patients received antiviral treatment,while 132(81.5%)patients received glucocorticoid treatment.A total of 116(71.6%)patients were admitted to the intensive care unit(ICU),and 137(85.1%)patients received mechanical ventilation.Most patients received mechanical ventilation before ICU admission.Approximately 93.2%of the patients developed respiratory failure or acute respiratory distress syndrome.There were no significant differences in the inhospital survival time among the hospitals(P=0.14).Conclusion:Young patients with moderate COVID-19 without comorbidity at admission could also develop fatal outcomes.The in-hospital survival time of the fatal cases was similar among the hospitals of different levels in Wuhan. | Xianlong Zhou Guoyong Ding Qing Fang Jun Guo Luyu Yang Ping Wang Shou-Zhi Fu Ang Li Jian Xia Jiangtao Yu Jianyou Xia Min Ma Zhuanzhuan Hu Lei Huang Ruining Liu Cheng Jiang Shaoping Li Mingxia Yu Xizhu Xu Yan Zhao Quan Hu Weijia Xing Zhigang Zhao | 2022 | Emergency and Critical Care Medicine2022，2，3： | 0 |
| 9 | Structural basis for the gating modulation of Kv4.3 by auxiliary subunits显示文摘Dear Editor,Kv4.3 is an A-type voltage-gated potassium channel that is characterized by fast activation at subthreshold membrane potentials,rapid inactivation,and quick recovery from inactiva-tionJ In neurons,Kv4.3 conducts the transient subthreshold somatodendritic A-type potassium current(Isa),knock down of which results in neuropathic pain and epilepsy.2 In cardiomyocytes,Kv4.3 generates the transient outward potassium current(lto)and its dysfunction is related to a variety of heart diseases,such as hypertrophy,heart failure,myocardial infarction,heart valvular disease,atrial fibrillation,and diabetic cardiomyopathy. | Demin Ma Cheng Zhao Xiaochen Wang Xiaoxiao Yi Zha Yan Zhang Guosheng Fu Ping Liang Jiangtao Guo Dongwu Lai | 2022 | Cell Research2022，32，4： | 0 |
| 10 | Receiver function imaging of dense seismic array and deep dynamic mechanism beneath the eastern South China显示文摘The Mesozoic tectonic framework of the eastern South China is mainly controlled by subduction,turning toward,and rollback of the Pacific Plate.Recent studies of receiver function imaging and ambient noise tomography have revealed the“Yshaped”thinnest crustal belt in the eastern South China under the overall extension of the lithosphere.However,the deep dynamic environment and formation mechanisms of the thin crustal belt remain debatable.Here we obtained high-resolution images of the crustal thickness and Poisson’s ratio in the eastern South China Block applying the recently proposed H-κ-c receiver function method,using data recorded by 305 dense portable broadband stations and 219 permanent stations surrounding.Additionally,we discussed the deep dynamic formation mechanism of the“Y-shaped”thinnest crustal belt coupled with two common conversion point stacked images at key locations.Results show that the average crustal thickness of the study area is 33 km(thin crust)and the average Poisson’s ratio is 0.24(low ratio).The overall crustal thinning toward the continental margin is likely because eastern South China was in a back-arc extension environment,which was induced by the rollback of the subducted plate in the Early Cretaceous.The crustal thickness of the“Y-shaped”thinnest crustal belt is<30 km,which is 3-5 km thinner than that outside the zone.The eastern branch is distributed along the trajectory of Nanchang-Ji’an-Ganzhou-Shaoguan-Guangzhou,and the western branch is around the Jianghan-Xiangzhong Basin,both of which intersect in Nanling.The eastern branch of the thin crustal zone indicates the potential location of the Pacific subduction slab breakoff,and the formation mechanism may be related to the interaction of deep-shallow processes,including the upwelling of mantle heat flow through the slab window and transtensional pre-existing faults.We developed a dynamic model that combines subduction-breakoff-rollback processes of the Paleo-Pacific Plate and accompanying deep fluid upwelling to explain the regional extension of the South China lithosphere,the formation mechanism of the thinnest crustal belt,and the distribution of granitic plutons. | Rubing HAN Dinghui YANG Qiusheng LI Rong HUANG Hongshuang ZHANG Jiangtao LI Hao CHEN Zhuo YE Wei FU | 2023 | Science China Earth Sciences2023，66，6： | 0 |
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