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The receptor-like cytosolic kinase RIPK activates NADP-malic enzyme 2 to generate NADPH for fueling ROS production

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Molecular Plant 2022年第5期15卷 887-903页

作者： Binyan Wu Ping Li xiufang Hong Cuihong xu Ran Wang Yan Liang Ministry of Agriculture Key Laboratory of Molecular Biology of Crop Pathogens and Insects Institute of BiotechnologyZhejiang UniversityHangzhou 310058China

Reactive oxygen species(ROS)production is a conserved immune response in Arabidopsis primarily medi-ated by respiratory burst oxidase homolog D(RBOHD),a nicotinamide adenine dinucleotide phosphate(NADPH)oxidase associated with the plasma membrane.A rapid increase in NADPH is necessary to fuel RBOHD proteins and thus maintain ROS production.However,the molecular mechanism by which NADPH is generated to fuel RBOHD remains unclear.In this study,we isolated a new mutant allele of FLAGELLIN-INSENSITIVE 4(FIN4),which encodes the first enzyme in de novo NAD biosynthesis.fin4 mu-tants show reduced NADPH levels and impaired ROS production.However,FIN4 and other genes involved in NAD-and NADPH-generating pathways are not highly upregulated upon elicitor treatment,raising a pos-sibility that a cytosolic NADP-linked dehydrogenase might be post-transcriptionally activated to maintain the NADPH supply close to RBOHD.To verify this possibility,we isolated the proteins associated with RPM1-INDUCED PROTEIN KINASE(RIPK),a receptor-like cytoplasmic kinase that regulates broad-spectrum ROS signaling in plant immunity,and identified NADP-malic enzyme 2(NADP-ME2),an NADPH-generating enzyme.Compared with wild-type plants,nadp-me2 mutants display decreased NADP-ME activity,lower NADPH levels,and reduced ROS production in response to immune elicitors.Furthermore,we found that RIPK can directly phosphorylate NADP-ME2 and enhance its activity in vitro.The phosphorylation of the NADP-ME2 S371 residue contributes to ROS production upon immune elicitor treatment and susceptibility to the necrotrophic bacterium Pectobacterium carotovorum.Collectively,our study suggests that RIPK phosphorylates and activates NADP-ME2 to rapidly increase cytosolic NADPH,thus fueling RBOHD to sustain ROS production in plant immunity.

关键词： NADP-ME2 NADPH RBOHD reactive oxygen species plant immunity

The role of ribosomal proteins in the regulation of cell proliferation, tumorigenesis, and genomic integrity

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Science China(Life Sciences) 2016年第7期59卷 656-672页

作者： Xilong xu xiufang Xiong Yi Sun Institute of Translational Medicine Zhejiang University School of Medicine Collaborative Innovation Center for Diagnosis and Treatment of Infectious Disease Zhejiang University Division of Radiation and Cancer Biology Department of Radiation Oncology University of Michigan

Ribosomal proteins(RPs), the essential components of the ribosome, are a family of RNA-binding proteins, which play prime roles in ribosome biogenesis and protein translation. Recent studies revealed that RPs have additional extra-ribosomal functions, independent of protein biosynthesis, in regulation of diverse cellular processes. Here, we review recent advances in our understanding of how RPs regulate apoptosis, cell cycle arrest, cell proliferation, neoplastic transformation, cell migration and invasion, and tumorigenesis through both MDM2/p53-dependent and p53-independent mechanisms. We also discuss the roles of RPs in the maintenance of genome integrity via modulating DNA damage response and repair. We further discuss mutations or deletions at the somatic or germline levels of some RPs in human cancers as well as in patients of Diamond-Blackfan anemia and 5q- syndrome with high susceptibility to cancer development. Moreover, we discuss the potential clinical application, based upon abnormal levels of RPs, in biomarker development for early diagnosis and/or prognosis of certain human cancers. Finally, we discuss the pressing issues in the field as future perspectives for better understanding the roles of RPs in human cancers to eventually benefit human health.

关键词：核糖体蛋白细胞增殖肿瘤发生基因组调控整性蛋白质合成 RNA结合蛋白

Synergistic activation of photoswitchable supramolecular assembly based on sulfonated crown ether and dithienylethene derivative

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Chinese Chemical Letters 2022年第5期33卷 2447-2450页

作者： Conghui Wang Ying-Ming Zhang Haoran Li Jin Zhang Yu Zhou Guoxing Liu XIUFANG XU Yu Liu College of Chemistry State Key Laboratory of Elemento-Organic ChemistryNankai UniversityTianjin 300071China College of Computer Science Nankai UniversityTianjin 300350China College of Sciences Henan Agricultural UniversityZhengzhou 450001China

Conformational regulation among two or more distant sites is not only one of the main pathways to accomplish multiple tasks in complex biological systems but also represents a powerful strategy to obtain stimuli-responsive supramolecular nanoconstructs with tailored physicochemical performance.We herein report the fabrication of a photochromic supramolecular assembly,which can be synergistically activated by the conformational regulation with bis(4,8-disulfonato-1,5-naphtho)-32-crown-8 and then reversibly switched by the through-space communication between restricted stilbazolium salt and photochromic dithienylethene.This work demonstrates that the synergistic conformational modulation via intra-and intermolecular interactions can be developed as a generalizable approach to construct more advanced biomimetic nanomaterials.

关键词： Supramolecular assembly Crown ether Photochromism Energy transfer Conformational regulation

Mechanisms and applications of antitumor immunotherapy of responsive drug-loaded nanoparticles in breast cancer

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BIOCELL 2023年第7期47卷 1483-1498页

作者： LETIAN JIN HETING CHEN QI RUAN RUI LIU YIFENG FAN XIUFANG XU DAJIANG WANG JIAHUI LU School of Medical Imaging Hangzhou Medical CollegeHangzhou310053China

During the chemotherapy of tumors,the cytotoxic effect of drugs is vital to kill tumor cells,and the delivery of a chemotherapeutic agent is of great importance for optimal therapeutic effects.The high in vivo clearance rate and low delivery efficiency of conventional chemotherapeutic agents affect the therapeutic effect.In recent years,the responsive drug delivery nanosystem has received increasing concern owing to its excellent biocompatibility,stable delivery performance,and controlled drug release strategies.To lucidly explain the cytocidal and immunotherapeutic effects of such responsive nanosystems in breast cancer,this review discusses the various stimuli and responses of drug-loaded liposomal nanosystems.The light/magnetic response of drug-loaded bionic membranes nanosystems and the heat/magnetic response of drug-loaded iron oxide nanosystems are also elaborated.Their cancer cell-killing efficacy and antitumor immunotherapeutic effects are also scrutinized.

关键词： Responsive nanoparticles Antitumor immunotherapy Breast cancer

Research on multi-parametric sensors based on multi-mode microfiber

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Optoelectronics Letters 2024年第1期20卷 18-22页

作者： DONG Taiji LIU xu WANG Yunkai GAO Bingkun JIANG Chunlei WANG xiufang College of Electrical and Information Engineering Northeast Petroleum UniversityDaqing 163318China

A multi-parametric sensor based on multi-mode microfiber(MMF)is proposed,utilizing the modal interference between HE11mode and HE12mode in the elongated multi-mode fiber to achieve the temperature and pressure measurement.In this paper,the simulation model of modal interference based on MMF is established and the mechanism of modal interference is analyzed.Using the different mechanisms of modal response in the fiber at different wavelengths,the temperature was inverted using the offset of wavelengths in the spectrum,and the pressure was measured using the change of light intensity.The independent measurement of temperature and pressure was achieved.The experimental results show that the sensor has a temperature sensitivity of 1.305 nm/℃.In the case of pressure sensing,the sensor shows a sensitivity of-0.163 d Bm/g.

关键词： measurement mode modal

Theoretical analysis and experimental investigation on flexural performance of steel reinforced ultrahigh toughness cementitious composite (RUHTCC) beams

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Science China(Technological Sciences) 2009年第4期52卷 1068-1089页

作者： xu ShiLang ZHANG xiufang State Key Laboratory of Coastal and Offshore Engineering Dalian University of TechnologyDalian 116024China

UHTCC (ultrahigh toughness cementitious composite), which is a kind of ultrahigh toughness cemen- titious composites material, exhibits pseudo strain hardening feature when subjected to tension load, and has enormous ductility and prominent crack dispersal ability. Accordingly, UHTCC can improve mechanical behavior of ordinary concrete structure especially its durability, and has been regarded as historical breakthrough to traditional cementitious materials. In this paper, the study focuses on flexure behavior of steel reinforced beam made of UHTCC. Based on the plane section assumption, along with two equilibrium equations of force and moment, the formulae to calculate the flexural load capability for the reinforced ultrahigh toughness cementitious composite (RUHTCC) beam were developed under the assumption that the compression stress- strain relationship in the UHTCC material is a bilinear model. Following this, the simplified formulae were further evolved by effective rectangle stress distribution approach in order to facilitate design of practical engineering. Two effective parameters introduced in effective rectangle approach were determined. The mathematical expressions to evaluate limited rein- forcement ratio, flexural stiffness as well as ductility index were proposed, too. Last, two series of dif- ferent reinforcement ratios of the RUHTCC beams were tested in four-point flexure loading. For com- parison purposes, ordinary RC (reinforced concrete) beams also were prepared. Both moment curva- ture curves and load mid-span displacement curves were recorded and compared with the theoretical calculations. A good agreement between them was found, which validates the proposed theoretical formulae. For ductility index, a slightly big difference between the experimental values and the calcu- lated ones exists. The experimental results show that, compared to control RC beams, the RUHTCC beam can improve both flexural capacity and ductility index, and the degree of improvement will de- crease with the increase in

关键词： ultrahigh toughness cementitious composites (UHTCC) RUHTCC beam flexural capacity crack width ductility index reinforcement ratio

Correlation between tension softening relation and crack extension resistance in concrete

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Frontiers of Structural and Civil Engineering 2009年第3期3卷 323-329页

作者： xiufang ZHANG Shilang xu Department of Civil and Hydraulic Engineering Dalian University of TechnologyDalian 116024China

Changes of the material fracture toughness with crack propagation can be described by a crack extension resistance curve,one of the fundamental fracture criteria in crack mechanics.Recently,experimental observation of the fracture behavior in concrete was used to develop a new fracture criterion,the crack extension GR resistance curve,to analyze crack propagation during the entire concrete fracture process.The variation of the crack extension resistance is mainly associated with the energy consumption in the fracture process zone ahead of the stress-free crack tip.The crack extension resistance is then a function of the softening curve,which is a basic mechanical property in the fracture process zone.The relationship between the softening curve and the crack extension GR resistance curve is then analyzed based on results of three-point bending beams tests.The results indicate that the characteristic points of the crack extension resistance GR curve is closely related to the characteristic point on used tension softening curve.

关键词： concrete fracture process zone crack exten-sion GR resistance tension softening curve

Discovery of a small molecule inhibitor of cullin neddylation that triggers ER stress to induce autophagy

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Acta Pharmaceutica Sinica B 2021年第11期11卷 3567-3584页

作者： Yanan Li Chaorong Wang Tiantian xu Peichen Pan Qing Yu Lei xu xiufang Xiong Tingjun Hou Sunliang Cui Yi Sun Cancer Institute of the 2nd Affiliated Hospital and Institute of Translational Medicine Zhejiang University School of MedicineHangzhou 310029China Cancer Center Zhejiang UniversityHangzhou 310012China College of Pharmaceutical Sciences Zhejiang UniversityHangzhou 310058China Institute of Bioinformatics and Medical Engineering School of Electrical and Information EngineeringJiangsu University of TechnologyChangzhou 212013China

Protein neddylation is catalyzed by a three-enzyme cascade,namely an E1 NEDD8-activating enzyme(NAE),one of two E2 NEDD8 conjugation enzymes and one of several E3 NEDD8 ligases.The physiological substrates of neddylation are the family members of cullin,the scaffold component of cullin RING ligases(CRLs).Currently,a potent E1 inhibitor,MLN4924,also known as pevonedistat,is in several clinical trials for anti-cancer therapy.Here we report the discovery,through virtual screening and structural modifications,of a small molecule compound HA-1141 that directly binds to NAE in both in vitro and in vivo assays and effectively inhibits neddylation of cullins 1 e5.Surprisingly,unlike MLN4924,HA-1141 also triggers non-canonical endoplasmic reticulum(ER)stress and PKR-mediated terminal integrated stress response(ISR)to activate ATF4 at an early stage,and to inhibit protein synthesis and mTORC1 activity at a later stage,eventually leading to autophagy induction.Biologically,HA-1141 suppresses growth and survival of cultured lung cancer cells and tumor growth in in vivo xenograft lung cancer models at a well-tolerated dose.Taken together,our study has identified a small molecule compound with the dual activities of blocking neddylation and triggering ER stress,leading to growth suppression of cancer cells.

关键词： Autophagy Cullin RING ligase ER stress mTORC1 Neddylation Small molecule inhibitor

Improved performance of aluminum pigments encapsulated in hybrid inorganic-organic films

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Particuology 2015年第2期13卷 93-98页

作者： Pihui Pi Chao Liu xiufang Wen Lianfu Zheng Shouping xu Jiang Cheng School of Chemistry and Chemical Engineering South China University of Technology

An organic silane acrylate resin （PMBK） was synthesized by free-radical solution polymerization using methyl methacrylate, butyl acrylate and （3-methacryloxypropyl）trimethoxysilane as monomers. Aluminum （AI） particles were then encapsulated in inorganic-organic hybrid films that were prepared by hydrolysis and condensation of PMBK and tetraethyl orthosilicate （TEOS） on the surface of AI pigments. Characterization results showed that PMBK and TEOS could simultaneously hydrolyze ancl condense with hydroxyl groups on the surface of the A1 particles to form composite AI particles coated with inorganic-organic hybrid films. Compared with raw AI particles, the corrosion resistance and adhesive properties of paint films containing the composite AI particles were improved greatly, while the glossiness of the paint films decreased slightly, from 48.6° to 47.0°. In alkaline media （pH 11 ）, the volume of evolved H2 of composite AI particles was only 3.5 mL, whereas that of raw AI was 83.5 mL. The glossiness of paint films containing composite A1 particles decreased by 1.66% after immersion in alkaline media for 24h, whereas that of raw AI decreased by 14.82%. Peel-off tests of the paint films showed that the composite particles moved slightly away from the paint films. In contrast, the raw A1 particles were seriously desquamated, suggesting encapsulation of hybrid films can greatly improve the adhesive properties of A1 particles in paint films.

关键词： Aluminum pigments Inorganic-organic hybrid encapsulation Corrosion resistance Adhesive performance Glossiness