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| 1 | Artemisinin, the Magic Drug Discovered from Traditional Chinese Medicine显示文摘Artemisinin and its derivatives represent the most important and influential class of drugs in the fight against malaria. Since the discovery of artemisinin in the early 1970s, the global community has made great strides in characterizing and understanding this remarkable phytochemical and its unique chemical and pharmacological properties. Today, even as artemisinin continues to serve as the foundation for antimalarial therapy, numerous challenges have surfaced in the continued application and development of this family of drugs. These challenges include the emergence of delayed treatment responses to artemisinins in malaria and efforts to apply artemisinins for non-malarial indications. Here, we provide an overview of the story of artemisinin in terms of its past, present, and future. In particular, we comment on the current understanding of the mechanism of action (MOA) of artemisinins, and emphasize the importance of relating mechanistic studies to therapeutic outcomes, both in malarial and non-malarial contexts. | Jigang Wang Chengchao Xu Yin Kwan Wong Yujie Li Fulong Liao Tingliang Jiang Youyou Tu | 2019 | Engineering2019，5，1： | 16 |
| 2 | Impairment of the autophagy-lysosomal pathway in Alzheimer’s diseases: Pathogenic mechanisms and therapeutic potential显示文摘Alzheimer’s disease(AD),the most common neurodegenerative disorder,is characterized by memory loss and cognitive dysfunction.The accumulation of misfolded protein aggregates including amyloid beta(Aβ)peptides and microtubule associated protein tau(MAPT/tau)in neuronal cells are hallmarks of AD.So far,the exact underlying mechanisms for the aetiologies of AD have not been fully understood and the effective treatment for AD is limited.Autophagy is an evolutionarily conserved cellular catabolic process by which damaged cellular organelles and protein aggregates are degraded via lysosomes.Recently,there is accumulating evidence linking the impairment of the autophagy-lysosomal pathway with AD pathogenesis.Interestingly,the enhancement of autophagy to remove protein aggregates has been proposed as a promising therapeutic strategy for AD.Here,we first summarize the recent genetic,pathological and experimental studies regarding the impairment of the autophagy-lysosomal pathway in AD.We then describe the interplay between the autophagy-lysosomal pathway and two pathological proteins,Aβand MAPT/tau,in AD.Finally,we discuss potential therapeutic strategies and small molecules that target the autophagy-lysosomal pathway for AD treatment both in animal models and in clinical trials.Overall,this article highlights the pivotal functions of the autophagy-lysosomal pathway in AD pathogenesis and potential druggable targets in the autophagy-lysosomal pathway for AD treatment. | Wei Zhang Chengchao Xu Jichao Sun Han-Ming Shen Jigang Wang Chuanbin Yang | 2022 | Acta Pharmaceutica Sinica B2022，12，3： | 6 |
| 3 | Regulation of the stability and ABA import activity of NRT1.2/NPF4.6 by CEPR2-mediated phosphorylation in Arabidopsis显示文摘Abscisic acid(ABA)transport plays an important role in systemic plant responses to environmental factors.However,it remains largely unclear about the precise regulation of ABA transporters in plants.In this study,we show that the C-terminally encoded peptide receptor 2(CEPR2)directly interacts with the ABA transporter NRT1.2/NPF4.6.Genetic and phenotypic analyses revealed that NRT1.2/NPF4.6 positively regulates ABA response and that NRT1.2/NPF4.6 is epistatically and negatively regulated by CEPR2.Further biochemical assays demonstrated that CEPR2 phosphorylates NRT1.2/NPF4.6 at serine 292 to promote its degradation under normal conditions.However,ABA treatment and non-phosphorylation at serine 292 prevented the degradation of NRT1.2/NPF4.6,indicating that ABA inhibits the phosphorylation of this residue.Transport assays in yeast and Xenopus oocytes revealed that non-phosphorylated NRT1.2/NPF4.6 had high levels of ABA import activity,whereas phosphorylated NRT1.2/NPF4.6 did not import ABA.Analyses of complemented nrt1.2 mutants that mimicked non-phosphorylated and phosphorylated NRT1.2/NPF4.6 confirmed that non-phosphorylated NRT1.2S292A had high stability and ABA import activity in planta.Additional experiments showed that NRT1.2/NPF4.6 was degraded via the 26S proteasome and vacuolar degradation pathways.Furthermore,we found that three E2 ubiquitin-conjugating enzymes,UBC32,UBC33,and UBC34,interact with NRT1.2/NPF4.6 in the endoplasmic reticulum and mediate its ubiquitination.NRT1.2/NPF4.6 is epistatically and negatively regulated by UBC32,UBC33,and UBC34 inplanta.Taken together,these results suggest that the stability and ABA import activity of NRT1.2/NPF4.6 are precisely regulated by its phosphorylation and degradation in response to environmental stress. | Lei Zhang Zipeng Yu Yang Xu Miao Yu Yue Ren Shizhong Zhang Guodong Yang Jinguang Huang Kang Yan Chengchao Zheng Changai Wu | 2021 | Molecular Plant2021，14，4： | 2 |
| 4 | Discovery and repurposing of artemisinin显示文摘Malaria is an ancient infectious disease that threatens millions of lives globally even today.The discovery of artemisinin,inspired by traditional Chinese medicine(TCM),has brought in a paradigm shift and been recognized as the“best hope for the treatment of malaria”by World Health Organization.With its high potency and low toxicity,the wide use of artemisinin effectively treats the otherwise drug-resistant parasites and helps many countries,including China,to eventually eradicate malaria.Here,we will first review the initial discovery of artemisinin,an extraordinary journey that was in stark contrast with many drugs in western medicine.We will then discuss how artemisinin and its derivatives could be repurposed to treat cancer,inflammation,immunoregulation-related diseases,and COVID-19.Finally,we will discuss the implications of the“artemisinin story”and how that can better guide the development of TCM today.We believe that artemisinin is just a starting point and TCM will play an even bigger role in healthcare in the 21st century. | Qiaoli Shi Fei Xia Qixin Wang Fulong Liao Qiuyan Guo Chengchao Xu Jigang Wang | 2022 | Frontiers of Medicine2022，16，1： | 2 |
| 5 | Regulation of the stability and ABA import activity of NRT1.2/NPF4.6 by CEPR2-mediated phosphorylation in Arabidopsis显示文摘(Molecular Plant 14,633–646;April 52021)In Figure 1D in our original manuscript,we demonstrated by the mating-based split ubiquitin system(MbSUS)assay that the functional domains of CEPR2 interact with the loop region of NRT1.2/NPF4.6(NRT1.2loop,aa 232-346).However,the sub-image of-WLU in Figure 1D was mistakenly assembled. | Lei Zhang Zipeng Yu Yang Xu Miao Yu Yue Ren Shizhong Zhang Guodong Yang Jinguang Huang Kang Yan Chengchao Zheng Changai Wu | 2022 | Molecular Plant2022，15，10： | 1 |
| 6 | Predicting pipe failure in water distribution network显示文摘 | Jowitt P W Chengchao Xu | 1993 | Journal of Water Resources Planning and Management1993，119，1： | 1 |
| 7 | Predicting Pipe Failure Effects in Water Distribution Networks 显示文摘 | P W Jowitt Chengchao Xu | 1993 | Journal of Water Resources Planning and Management1993，119，1： | 1 |
| 8 | Cortical and Subcortical Grey Matter Abnormalities in White Matter Hyperintensities and Subsequent Cognitive Impairment显示文摘Grey matter(GM)alterations may contribute to cognitive decline in individuals with white matter hyperintensities(WMH)but no consensus has yet emerged.Here,we investigated cortical thickness and grey matter volume in 23 WMH patients with mild cognitive impairment(WMH-MCI),43 WMH patients without cognitive impairment,and 55 healthy controls.Both WMH groups showed GM atrophy in the bilateral thalamus,fronto-insular cortices,and several parietal-temporal regions,and the WMH-MCI group showed more extensive and severe GM atrophy.The GM atrophy in the thalamus and fronto-insular cortices was associated with cognitive decline in the WMH-MCI patients and may mediate the relationship between WMH and cognition in WMH patients.Furthermore,the main results were well replicated in an independent dataset from the Alzheimer's Disease Neuroimaging Initiative database and in other control analyses.These comprehensive results provide robust evidence of specific GM alterations underlying WMH and subsequent cognitive impairment. | Wenhao Zhu Hao Huang Shiqi Yang Xiang Luo Wenzhen Zhu Shabei Xu Qi Meng Chengchao Zuo Yong Liu Wei Wang Alzheimer’s Disease Neuroimaging Initiative | 2021 | Neuroscience Bulletin2021，37，6： | 1 |
| 9 | Chemical proteomic profling with photoaffinity labeling strategy identifies antimalarial targets of artemisinin显示文摘Present research on the antimalarial mechanisms of artemisinin(ART)is mainly focused on covalent drug binding targets alkylated by free radicals,while non-covalent binding targets have rarely been reported.Here,we developed a novel photoaffinity probe of ART to globally capture and identify the antimalarial target proteins of ART through chemical proteomics.The results demonstrated that ART can bind to par-asite proteins by both covalent and non-covalent modification,and these may jointly contribute to the antimalarial effects.Our work enriches the research on the antimalarial targets of ART,and provides a new perspective for further exploring the antimalarial mechanism of ART. | Peng Gao Jiayun Chen Peng Sun Jianyou Wang Huan Tang Fei Xia Liwei Gu Huimin Zhang Chen Wang Yin Kwan Wong Yinhua Zhu Chengchao Xu Jigang Wang | 2023 | Chinese Chemical Letters2023，34，12： | 1 |
| 10 | The effect of antibody against vascular endothelial growth factor on tumor growth and metastasis显示文摘 | Guiqui Wang Zhiwei Dong Guangwei Xu Zhihua Yang Chengchao Shou Naiqin Wang Tong Liu | 1998 | Journal of Cancer Research and Clinical Oncology1998，，11： | 1 |
| 11 | Reliability-based optimal design of water distribution network显示文摘 | Xu Chengchao Goulter I C | 1999 | J Water Resources Planning and Management1999，125，6： | 1 |
| 12 | Effect of nano-TiC dopant size on magnetic properties and corrosion resistance of hot-deformed NdFeB显示文摘Effects of dopant size on the magnetic properties and corrosion behavior of hot-deformed NdFeB with the intergranular additions of nano-TiC were investigated using X-ray diffraction(XRD),X-ray photoelectron spectrometer(XPS),scanning electron microscopy(SEM),electrochemical and magnetic measurement technologies.Additions of 50 nm-TiC,unlike 30 nm- and 40 nm-TiC,are found to increase the magnetic energy product and comprehensive magnetic properties,due in main to the improvement of magnet orientation by more strip-shaped Nd-rich phases.Nano-TiC dopants especially with a size of40 nm can increase the electrochemical corrosion resistance of magnets.It is attributed to the hindrance of additives on the reaction channel formation and their barrier effect on the oxidations of Nd and Fe.For 40 nm-TiC doped magnet,the charge transfer resistance in electric double layer structure reaches 15000 Ω·cm^(2) that is one order of magnitude higher than other cases,which is responsible for the lowe st corrosion current density and accordingly the best anti-corrosion properties. | Xiaoqiang Li Jian Li Kai Xu Zhiwei Wang Yu Bian Yuxuan Shao Chengchao Hu Junjie Ni | 2022 | Journal of Rare Earths2022，40，6： | 1 |
| 13 | Probabilistic model for water distribution reliability 显示文摘 | Xu Chengchao Goulter I C | 1998 | Water Resources Planning and Management1998，124，4： | 1 |
| 14 | Reliability-based optimal design of water distribution network 显示文摘 | Xu Chengchao Gonlter I C | 1999 | J Water Resour Plan Manage1999，125，6： | 1 |
| 15 | The Brassicaceae-specific secreted peptides,STMPs,function in plant growth and pathogen defense显示文摘Low molecular weight secreted peptides have recently been shown to affect multiple aspects of plant growth,development,and defense responses.Here,we performed stepwise BLAST filtering to identify unannotated peptides from the Arabidopsis thaliana protein database and uncovered a novel secreted peptide family,secreted transmembrane peptides(STMPs).These low molecular weight peptides,which consist of an N-terminal signal peptide and a transmembrane domain,were primarily localized to extracellular compartments but were also detected in the endomembrane system of the secretory pathway,including the endoplasmic reticulum and Golgi.Comprehensive bioinformatics analysis identified 10 STMP family members that are specific to the Brassicaceae family.Brassicaceae plants showed dramatically inhibited root growth uponexposure to chemically synthesized STMP1 and STMP2.Arabidopsis overexpressing STMP1,2,4,6,or 10 exhibited severely arrested growth,suggesting that STMPs are involved in regulating plant growth and development.In addition,in vitro bioassays demonstrated that STMP1,STMP2,and STMP10 have antibacterial effects against Pseudomonas syringae pv.tomato DC3000,Ralstonia solanacearum,Bacillus subtilis,and Agrobacterium tumefaciens,demonstrating that STMPs are antimicrobial peptides.These findings suggest that STMP family members play important roles in various developmental events and pathogen defense responses in Brassicaceae plants. | Zipeng Yu Yang Xu Lifei Zhu Lei Zhang Lin Liu Di Zhang Dandan Li Changai Wu Jinguang Huang Guodong Yang Kang Yan Shizhong Zhang Chengchao Zheng | 2020 | Journal of Integrative Plant Biology2020，62，4： | 1 |
| 16 | The effect of antibody against vascular endothelial growth factor on tumor growth and metastasis显示文摘 | Guiqui Wang Zhiwei Dong Guangwei Xu Zhihua Yang Chengchao Shou Naiqin Wang Tong Liu | 1998 | Journal of Cancer Research and Clinical Oncology1998，，11： | 1 |
| 17 | 通过鉴定关键靶标蛋白探究青蒿素抗疟机制显示文摘The widespread use of artemisinin(ART)and its derivatives has significantly reduced the global burden of malaria;however,malaria still poses a serious threat to global health.Although significant progress has been achieved in elucidating the antimalarial mechanisms of ART,the most crucial target proteins and pathways of ART remain unknown.Knowledge on the exact antimalarial mechanisms of ART is urgently needed,as signs of emerging ART resistance have been observed in some regions of the world.Here,we used a combined strategy involving mass spectrometry-coupled cellular thermal shift assay(MS-CETSA)and transcriptomics profiling to identify a group of putative antimalarial targets of ART.We then conducted a series of validation experiments on five prospective protein targets,demonstrating that ART may function against malaria parasites by interfering with redox homeostasis,lipid metabolism,and protein synthesis processes.Taken together,this study provides fresh perspectives on the antimalarial mechanisms of ART and identifies several crucial proteins involved in parasite survival that can be targeted to combat malaria. | Peng Gao Jianyou Wang Jiayun Chen Liwei Gu Chen Wang Liting Xu Yin Kwan Wong Huimin Zhang Chengchao Xu Lingyun Dai Jigang Wang | 2023 | Engineering2023，31，12： | 0 |
| 18 | Recent Advances in Interventional Fluorescence Imaging: Toward the Precise Visualization of Transarterial Mini-Invasive Delivery Systems显示文摘CONSPECTUS:Interventional fluorescence imaging has gradually developed into a promising imaging strategy for the diagnosis of diseases in clinic.This strategy could benefit interventional targeted treatment because of the clear display of microstructures at the margins and boundaries.There are some stranded crucial issues in clinical application:(i)fast clearance of fluorescence probes;(ii)light instability and photobleaching;and(iii)residual and microsatellite lesions.The development of superstable homoge-neous intermixed formulation technology(SHIFT)can solve the aforementioned clinical problems for precision hepatectomy.Interventional fluorescence imaging based on SHIFT-prepared product has some advantages such as(i)strong stability,(ii)greatly extending imageable time window,and(iii)precisely visualizing microsatellite lesions.In this Account,we overview our current progress in interventional fluorescence imaging based on SHIFT method for surgical resection following long-lasting embolization conversion.To greatly realize interventional fluorescence imaging,we summarize clinical and preclinical application of interventional fluorescence imaging in a transarterial delivery system.Indeed,compared with conventional fluorescence imaging,interventional fluorescence imaging possesses non-negligible strengths on improved intensity in target location and step-down systemic toxicity.Unfortunately,a challenging issue is that immobile fluorescence performance is difficult to maintain after long-time embolization,resulting in a failed hepatectomy.On this basis,associated with our previous research,SHIFT was proposed and developed.Thus,we detailedly introduce and account the development and preponderance of SHIFT on interventional fluorescence imaging.Predictably,after lengthy embolization,its lightful fluorescence was still observable in tumor targets of a clinical trial.To regulate the fluorescence rendering of microsatellite lesion,SHIFT combining with pure nanoprobes(nanoICG)occurs,namely SHIFT nanoICG,and we dwell on its performance in transarterial invasive surgical navigation and its clinical application under interventional fluorescence imaging compared with conventional indocyanine green(ICG)formulations.Amazingly,the SHIFT nanoICG brings us an extraordinary imaging consequence for deep-seated tumor tissues and imperceptible microsatellite lesions.Finally,we offer perspectives on the future tendency of interventional imaging-guided SHIFT products in clinical translation such as chemoembolization,radioembolization,and immunotherapy.Actually,these directions have been underway for some time,and even relative products are already applied for clinical trials,exhibiting effective therapeutic outcomes.Our green high-performance SHIFT products are concentrated on meeting clinical needs and solving clinical problems,breaking through the cure limitations of patients with advanced diseases.Thus,the discovery offers insight into the development and superiority of SHIFT products under interventional fluorescence imaging and simultaneously provides a new view on the development of clinically pragmatic products. | Xiaoxiao Shi Dazhuang Xu Hongwei Cheng Chengchao Chu Gang Liu | 2023 | Accounts of Materials Research2023，4，3： | 0 |
| 19 | A highly efficient protein corona-based proteomic analysis strategy for the discovery of pharmacodynamic biomarkers显示文摘The composition of serum is extremely complex,which complicates the discovery of new pharmacodynamic biomarkers via serum proteome for disease prediction and diagnosis.Recently,nanoparticles have been reported to efficiently reduce the proportion of high-abundance proteins and enrich lowabundance proteins in serum.Here,we synthesized a silica-coated iron oxide nanoparticle and developed a highly efficient and reproducible protein corona(PC)-based proteomic analysis strategy to improve the range of serum proteomic analysis.We identified 1,070 proteins with a median coefficient of variation of 12.56%using PC-based proteomic analysis,which was twice the number of proteins identified by direct digestion.There were also more biological processes enriched with these proteins.We applied this strategy to identify more pharmacodynamic biomarkers on collagen-induced arthritis(CIA)rat model treated with methotrexate(MTX).The bioinformatic results indicated that 485 differentially expressed proteins(DEPs)were found in CIA rats,of which 323 DEPs recovered to near normal levels after treatment with MTX.This strategy can not only help enhance our understanding of the mechanisms of disease and drug action through serum proteomics studies,but also provide more pharmacodynamic biomarkers for disease prediction,diagnosis,and treatment. | Yuqing Meng Jiayun Chen Yanqing Liu Yongping Zhu Yin-Kwan Wong Haining Lyu Qiaoli Shi Fei Xia Liwei Gu Xinwei Zhang Peng Gao Huan Tang Qiuyan Guo Chong Qiu Chengchao Xu Xiao He Junzhe Zhang Jigang Wang | 2022 | Journal of Pharmaceutical Analysis2022，12，6： | 0 |
| 20 | Function identification of Md TIR1 in apple root growth benefited from the predicted Md PPI network显示文摘Protein–protein interaction(PPI)network analysis is an effective method to identify key proteins during plant development,especially in species for which basic molecular research is lacking,such as apple(Malus domestica).Here,an MdPPI network containing 30806 PPIs was inferred in apple and its quality and reliability were rigorously verified.Subsequently,a rootgrowth subnetwork was extracted to screen for critical proteins in root growth.Because hormone-related proteins occupied the largest proportion of critical proteins,a hormonerelated sub-subnetwork was further extracted from the root-growth subnetwork.Among these proteins,auxin-related M.domestica TRANSPORT INHIBITOR RESISTANT 1(MdTIR1)served as the central,high-degree node,implying that this protein exerts essential roles in root growth.Furthermore,transgenic apple roots overexpressing an MdTIR1 transgene displayed increased primary root elongation.Expression analysis showed that MdTIR1 significantly upregulated auxin-responsive genes in apple roots,indicating that it mediates root growth in an auxin-dependent manner.Further experimental validation revealed that MdTIR1 interacted with and accelerated the degradation of MdIAA28,MdIAA43,andMdIAA46.Thus,MdTIR1-mediated degradation of MdIAAs is critical in auxin signal transduction and root growth regulation in apple.Moreover,our network analysis and high-degree node screening provide a novel research technique for more generally characterizing molecular mechanisms. | Lin Liu Zipeng Yu Yang Xu Cheng Guo Lei Zhang Changai Wu Guodong Yang Jinguang Huang Kang Yan Huairui Shu Chengchao Zheng Shizhong Zhang | 2021 | Journal of Integrative Plant Biology2021，63，4： | 0 |
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