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| 1 | Nucleocytoplasmic Trafficking of the Arabidopsis WD40 Repeat Protein XIW1 Regulates ABI5 Stability and Abscisic Acid Responses显示文摘WD40 repeat-containing proteins(WD40 proteins)serve as versatile scaffolds for protein-protein interac-tions,modulating a variety of cellular processes such as plant stress and hormone responses.Here we report the identification of a WD40 protein,XIW1(for XPO1-interacting WD40 protein 1),which positively regulates the abscisic acid(ABA)response in Arabidopsis.XIW1 is located in the cytoplasm and nucleus.We found that it interacts with the nuclear transport receptor XPO1 and is exported by XPO1 from the nucleus.Mutation of XIW1 reduces the induction of ABA-responsive genes and the accumulation of ABA Insensitive 5(ABI5),causing mutant plants with ABA-insensitive phenotypes during seed germination and seedling growth,and decreased drought stress resistance.ABA treatment upregulates the expression of XIW1,and both ABA and abiotic stresses promote XIW1 accumulation in the nucleus,where it interacts with ABI5.Loss of XIW1 function results in rapid proteasomal degradation of ABI5.Taken together,these findings suggest that XIW1 is a nucleocytoplasmic shuttling protein and plays a positive role in ABA responses by interacting with and maintaining the stability of ABI5 in the nucleus. | Xuezhong XU Wang Wan Guobin Jiang Yue Xi Haijian Huang Jiajia Cai Yanan Chang Cheng-Guo Duan Satendra KMangrauthia Xinxiang Peng Jian-Kang Zhu Guohui Zhu | 2019 | Molecular Plant2019，12，12： | 8 |
| 2 | N^6-Methyladenosine modification: a novel pharmacological target for anti-cancer drug development显示文摘N6-Methyladenosine(m6 A) modification is the most pervasive modification of human mRNA molecules. It is reversible via regulation of m6 A modification methyltransferase, demethylase and proteins that preferentially recognize m6 A modification as 'writers', 'erasers' and 'readers', respectively. Altered expression levels of the m6 A modification key regulators substantially affect their function, leading to significant phenotype changes in the cell and organism. Recent studies have proved that the m6 A modification plays significant roles in regulation of metabolism, stem cell self-renewal, and metastasis in a variety of human cancers. In this review, we describe the potential roles of m6 A modification in human cancers and summarize their underlying molecular mechanisms. Moreover, we will highlight potential therapeutic approaches by targeting the key m6 A modification regulators for cancer drug development.& 2018 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license(http://creativecommons.org/licenses/by-nc-nd/4.0/). | Yi Niu Arabella Wan Ziyou Lin Xiongbin Lu Guohui Wan | 2018 | Acta Pharmaceutica Sinica B2018，8，6： | 5 |
| 3 | miR-203 induces oxaliplatin resistance in colorectal cancer cells by negatively regulating ATM kinase显示文摘 | Yunfei Zhou Guohui Wan Riccardo Spizzo Cristina Ivan Rohit Mathur Xiaoxiao Hu Xiangcang Ye Jia Lu Fan Fan Ling Xia George A. Calin Lee M. Ellis Xiongbin Lu | 2014 | Molecular Oncology2014，，1： | 3 |
| 4 | A New Growth Model of Fault Attributes in a Strike-Slip Fault System in the Tarim Basin显示文摘Fault attributes generally display a consistent power–law-scaling relationship.Based on new 3 D seismic data,however,we found some exceptional fault attribute relationships of lengths(L)–throw(T)(vertical component of displacement),overlap zone length(Lo)–width(Wo)from a strike-slip fault system of the Ordovician carbonates in the Tarim Basin.The L–T relationship shows two linear segments with breakup at^40 km in fault length.This presents an exceptional throw increase in the second stage,which is attributed to a localization of vertical displacement and deformation in overlapping zones other than the different fault scales in a mature fault zone.The Lo–Wo relationship in the overlapping zones shows multiply stepped-shape patterns,suggesting multiple fault differential growth and periodic increase in fault size.Therefore,we propose a new alternative growth model of fault attributes in strike-slip fault zones,in which the overlapping zones accumulated localized displacement and deformation in the intracratonic strike-slip fault zone. | ZHANG Yintao WU Guanghui WANG Junfang LI Guohui WAN Xiaoguo YANG Tianyi | 2020 | Acta Geologica Sinica(English Edition)2020，94，5： | 1 |
| 5 | Direct analysis of trans-resveratrol in red wine by high performance liquid chromatography with ehemiluminescent detection显示文摘 | Jian Zhou Hua Cui Guohui Wan | 2004 | Food Chemistry2004，88，： | 1 |
| 6 | Pharmacological inhibition of BAP1 recruits HERC2 to competitively dissociate BRCA1-BARD1, suppresses DNA repair and sensitizes CRC to radiotherapy显示文摘Radiotherapy is widely used in the management of advanced colorectal cancer(CRC).However,the clinical efficacy is limited by the safe irradiated dose.Sensitizing tumor cells to radiotherapy via interrupting DNA repair is a promising approach to conquering the limitation.The BRCA1-BARD1 complex has been demonstrated to play a critical role in homologous recombination(HR)DSB repair,and its functions may be affected by HERC2 or BAP1.Accumulated evidence illustrates that the ubiquitination-deubiquitination balance is involved in these processes;however,the precise mechanism for the cross-talk among these proteins in HR repair following radiation hasn’t been defined.Through activity-based profiling,we identified PT33 as an active entity for HR repair suppression.Subsequently,we revealed that BAP1 serves as a novel molecular target of PT33 via a CRISPR-based deubiquitinase screen.Mechanistically,pharmacological covalent inhibition of BAP1 with PT33 recruits HERC2 to compete with BARD1 for BRCA1 interaction,interrupting HR repair.Consequently,PT33 treatment can substantially enhance the sensitivity of CRC cells to radiotherapy in vitro and in vivo.Overall,these findings provide a mechanistic basis for PT33-induced HR suppression and may guide an effective strategy to improve therapeutic gain. | Xin Yue Tingyu Liu Xuecen Wang Weijian Wu Gesi Wen Yang Yi Jiaxin Wu Ziyang Wang Weixiang Zhan Ruirui Wu Yuan Meng Zhirui Cao Liyuan Le Wenyan Qiu Xiaoyue Zhang Zhenyu Li Yong Chen Guohui Wan Xianzhang Bu Zhenwei Peng Ran-yi Liu | 2023 | Acta Pharmaceutica Sinica B2023，13，8： | 1 |
| 7 | Determination of quinolones residues in prawn using high-performance liquid chromatography with Ce (Ⅳ)-Ru ( bpy ) 3 2 + -HNO3 chemiluminescence detection 显示文摘 | WAN Guohui CUI Hua PAN Yilan | 2006 | J Chromatogr B2006，，： | 1 |
| 8 | miRNA response to DNA damage显示文摘 | Guohui Wan Rohit Mathur Xiaoxiao Hu Xinna Zhang Xiongbin Lu | 2011 | Trends in Biochemical Sciences2011，，9： | 1 |
| 9 | Direct analysis of trans-resveratrol in red wine by high performance liquid chromatography with chemiluminescent detection显示文摘 | Jian Zhou Hua Cui Guohui Wan | 2004 | Food Chemistry2004，88，4： | 1 |
| 10 | Enhancing and inhibiting effects of aromatic compounds on luminal - dimethylsulfoxide - OH - chemiluminescence and determination of intermediates in oxidative hair dyes by HPLC with chemiluminescence detection 显示文摘 | Zhou Jian Xu Hong Wan Guohui | 2004 | Talanta2004，64，： | 1 |
| 11 | A multidimensional platform of patient-derived tumors identifies drug susceptibilities for clinical lenvatinib resistance显示文摘Lenvatinib,a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer,facing limitations due to drug resistance.Here,we applied a multidimensional,high-throughput screening platform comprising patient-derived resistant liver tumor cells(PDCs),organoids(PDOs),and xenografts(PDXs)to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant settings.Expansion and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment,expediting drug repurposing screens.Pharmacological screening identified romidepsin,YM155,apitolisib,NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO models.Notably,romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway.A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX models.Collectively,our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer,providing a feasible multidimensional platform for personalized medicine. | Lei Sun Arabella H.Wan Shijia Yan Ruonian Liu Jiarui Li Zhuolong Zhou Ruirui Wu Dongshi Chen Xianzhang Bu Jingxing Ou Kai Li Xiongbin Lu Guohui Wan Zunfu Ke | 2024 | Acta Pharmaceutica Sinica B2024，14，1： | 0 |
| 12 | Effect of solvent on directional drift in Brownian motion of particle/molecule with broken symmetry显示文摘The directional drifting of particles/molecules with broken symmetry has received increasing attention. Through molecular dynamics simulations, we investigate the effects of various solvents on the time-dependent directional drifting of a particle with broken symmetry. Our simulations show that the distance of directional drift of the asymmetrical particle is reduced while the ratio of the drift to the mean displacement of the particle is enhanced with increasing mass, size, and interaction strength of the solvent atoms in a short time range. Among the parameters considered, solvent atom size is a particularly influential factor for enhancing the directional drift of asymmetrical particles, while the effects of the interaction strength and the mass of the solvent atoms are relatively weaker. These findings are of great importance to the understanding and control of the Brownian motion of particles in various physical, chemical, and biological processes within finite time spans. | FanDong Kong Nan Sheng RongZheng Wan GuoHui Hu HaiPing Fang | 2016 | Science China(Physics,Mechanics & Astronomy)2016，59，8： | 0 |
| 13 | FOXO3 mutation predicting gefitinib-induced hepatotoxicity in NSCLC patients through regulation of autophagy显示文摘Hepatotoxicity is a common side effect for patients treated with gefitinib,but the related pathogenesis is unclear and lacks effective predictor and management strategies.A multi-omics approach integrating pharmacometabolomics,pharmacokinetics and pharmacogenomics was employed in non-small cell lung cancer patients to identify the effective predictor for gefitinib-induced hepatotoxicity and explore optional therapy substitution.Here,we found that patients with rs4946935 AA,located in Forkhead Box O3(FOXO3)which is a well-known autophagic regulator,had a higher risk of hepatotoxicity than those with the GA or GG variant(OR=18.020,95%CI=2.473 to 459.1784,P=0.018)in a gefitinib-concentration dependent pattern.Furthermore,functional experiments identified that rs4946935_A impaired the expression of FOXO3 by inhibiting the promotor activity,increasing the threshold of autophagy initiation and inhibiting the autophagic activity which contributed to gefitinib-induced liver injury.In contrast,erlotinib-induced liver injury was independent on the variant and expression levels of FOXO3.This study reveals that FOXO3 mutation,leading to autophagic imbalance,plays important role in gefitinib-induced hepatotoxicity,especially for patients with high concentration of gefitinib.In conclusion,FOXO3 mutation is an effective predictor and erlotinib might be an appropriately and well-tolerated treatment option for patients carrying rs4946935 AA. | Shaoxing Guan Xi Chen Youhao Chen Guohui Wan Qibiao Su Heng Liang Yunpeng Yang Wenfeng Fang Yan Huang Hongyun Zhao Wei Zhuang Shu Liu Fei Wang Wei Feng Xiaoxu Zhang Min Huang Xueding Wang Li Zhang | 2022 | Acta Pharmaceutica Sinica B2022，12，9： | 0 |
| 14 | Zipper head mechanism of telomere synthesis by human telomerase显示文摘Telomerase,a multi-subunit ribonucleoprotein complex,is a unique reverse transcriptase that catalyzes the processive addition of a repeat sequence to extend the telomere end using a short fragment of its own RNA component as the template.Despite recent structural characterizations of human and Tetrahymena telomerase,it is still a mystery how telomerase repeatedly uses its RNA template to synthesize telomeric DNA.Here,we report the cryo-EM structure of human telomerase holoenzyme bound with telomeric DNA at resolutions of 3.5 Åand 3.9 Åfor the catalytic core and biogenesis module,respectively.The structure reveals that a leucine residue Leu980 in telomerase reverse transcriptase(TERT)catalytic subunit functions as a zipper head to limit the length of the short primer–template duplex in the active center.Moreover,our structural and computational analyses suggest that TERT and telomerase RNA(hTR)are organized to harbor a preformed active site that can accommodate short primer–template duplex substrates for catalysis.Furthermore,our findings unveil a double-fingers architecture in TERT that ensures nucleotide addition processivity of human telomerase.We propose that the zipper head Leu980 is a structural determinant for the sequence-based pausing signal of DNA synthesis that coincides with the RNA element-based physical template boundary.Functional analyses unveil that the non-glycine zipper head plays an essential role in both telomerase repeat addition processivity and telomere length homeostasis.In addition,we also demonstrate that this zipper head mechanism is conserved in all eukaryotic telomerases.Together,our study provides an integrated model for telomerase-mediated telomere synthesis. | Futang Wan Yongbo Ding Yuebin Zhang Zhenfang Wu Shaobai Li Lin Yang Xiangyu Yan Pengfei Lan Guohui Li Jian Wu Ming Lei | 2021 | Cell Research2021，31，12： | 0 |
| 15 | Asymmetric self-diffusion with orientation-dependence of water molecule in finite timescale显示文摘Self-diffusion of water has been investigated by molecular dynamics simulations.It was found that the preference of the direction in self-diffusion of water is orientation dependent in a finite time.For a time of^100 ps,there are more possibilities for water molecules moving along the initial dipole orientation than in the opposite direction.This reveals that self-diffusion of water molecules is asymmetric in a finite time.We tested four water models and found that they all show similar asymmetric diffusion,indicating that asymmetric diffusion of water is intrinsic behavior rather than induced by the water model.These results are important for understanding and application of asymmetric diffusion in research fields such as biological water and confined water in small dimensions. | Xu Wei Nan Sheng RongZheng Wan GuoHui Hu HaiPing Fang | 2016 | Science China(Physics,Mechanics & Astronomy)2016，59，7： | 0 |
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