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Two NPF transporters mediate iron long-distance transport and homeostasis in Arabidopsis

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Plant Communications 2021年第6期2卷 71-81页

作者： Si-Ying Chen Tian-yu Gu Zi-Ai Qi Jing Yan Zi-Jun Fang yu-ting lu Hui Li Ji-Ming Gong National Key Laboratory of Plant Molecular Genetics CAS Center for Excellence in Molecular Plant SciencesShanghai Institute of Plant Physiology and EcologyChinese Academy of SciencesShanghai 200032China University of the Chinese Academy of Sciences Beijing 100049China School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China State Key Laboratory of Crop Stress Adaptation and Improvement School of Life SciencesHenan UniversityKaifeng 475004China

Iron(Fe)transport and reallocation are essential to Fe homeostasis in plants,but it is unclear how Fe homeostasis is regulated,especially under stress.Here we report that NPF5.9 and its close homolog NPF5.8 redundantly regulate Fe transport and reallocation in Arabidopsis.NPF5.9 is highly upregulated in response to Fe deficiency.NPF5.9 expresses preferentially in vasculature tissues and localizes to the trans-Golgi network,and NPF5.8 showed a similar expression pattern.Long-distance Fe transport and allocation into aerial parts was significantly increased in NPF5.9-overexpressing lines.In the double mutant npf5.8 npf5.9,Fe loading in aerial parts and plant growth were decreased,which were partially rescued by Fe supplementation.Further analysis showed that expression of PYE,the negative regulator for Fe homeostasis,and its downstream target NAS4 were significantly altered in the double mutant.NPF5.9 and NPF5.8 were shown to also mediate nitrate uptake and transport,although nitrate and Fe application did not reciprocally affect each other.Our findings uncovered the novel function of NPF5.9 and NPF5.8 in long-distance Fe transport and homeostasis,and further indicated that they possibly mediate nitrate transport and Fe homeostasis independently in Arabidopsis.

关键词： NPF transporter iron homeostasis nitrate transport and allocation trans-Golgi network

Fc receptor-like 5(FCRL5)-directed CAR-T cells exhibit antitumor activity against multiple myeloma

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Signal Transduction and Targeted Therapy 2024年第2期9卷 724-737页

作者： Zhengyu yu Hexian Li Qizhong lu Zongliang Zhang Aiping Tong ting Niu Department of Hematology State Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengdu 610041China

Multiple myeloma(MM)remains a challenging hematologic malignancy despite advancements in chimeric antigen receptor T-cell(CAR-T)therapy.Current targets of CAR-T cells used in MM immunotherapy have limitations,with a subset of patients experiencing antigen loss resulting in relapse.Therefore,novel targets for enhancing CAR-T cell therapy in MM remain needed.Fc receptor-like 5(FCRL5)is a protein marker with considerably upregulated expression in MM and has emerged as a promising target for CAR-T cell therapeutic interventions,offering an alternative treatment for MM.To further explore this option,we designed FCRL5-directed CAR-T cells and assessed their cytotoxicity in vitro using a co-culture system and in vivo using MM cell-derived xenograft models,specifically focusing on MM with gain of chromosome 1q21.Given the challenges in CAR-T therapies arising from limited T cell persistence,our approach incorporates interleukin-15(IL-15),which enhances the functionality of central memory T(TCM)cells,into the design of FCRL5-directed CAR-T cells,to improve cytotoxicity and reduce T-cell dysfunction,thereby promoting greater CAR-T cell survival and efficacy.Both in vitro and xenograft models displayed that FCRL5 CAR-T cells incorporating IL-15 exhibited potent antitumor efficacy,effectively inhibiting the proliferation of MM cells and leading to remarkable tumor suppression.Our results highlight the capacity of FCRL5-specific CAR-T cells with the integration of IL-15 to improve the therapeutic potency,suggesting a potential novel immunotherapeutic strategy for MM treatment.

关键词： directed thereby offering

Tailoring electron vortex beams with customizable intensity patterns by electron diffraction holography

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Opto-Electronic Advances 2024年第2期7卷 14-21页

作者： Pengcheng Huo Ruixuan yu Mingze Liu Hui Zhang Yan-qing lu ting Xu National Laboratory of Solid-State Microstructures and Collaborative Innovation Center of Advanced Microstructures Nanjing UniversityNanjing 210093China College of Engineering and Applied Sciences Key Laboratory of Intelligent Optical Sensing and Manipulation and Jiangsu Key Laboratory of Artificial Functional MaterialsNanjing UniversityNanjing 210093China

An electron vortex beam(EVB) carrying orbital angular momentum(OAM) plays a key role in a series of fundamental scientific researches, such as chiral energy-loss spectroscopy and magnetic dichroism spectroscopy. So far, almost all the experimentally created EVBs manifest isotropic doughnut intensity patterns. Here, based on the correlation between local divergence angle of electron beam and phase gradient along azimuthal direction, we show that free electrons can be tailored to EVBs with customizable intensity patterns independent of the carried OAM. As proof-of-concept, by using computer generated hologram and designing phase masks to shape the incident free electrons in the transmission electron microscope, three structured EVBs carrying identical OAM are tailored to exhibit completely different intensity patterns. Furthermore, through the modal decomposition, we quantitatively investigate their OAM spectral distributions and reveal that structured EVBs present a superposition of a series of different eigenstates induced by the locally varied geometries. These results not only generalize the concept of EVB, but also demonstrate an extra highly controllable degree of freedom for electron beam manipulation in addition to OAM.

关键词： electron vortex beam orbital angular momentum diffraction holography

Identification and functional analysis of CG3526 in spermatogenesis of Drosophila melanogaster

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Insect Science 2024年第1期31卷 79-90页

作者： Qihao Hu Yanhong Xiao Runnan Wei ting Tang Liang Wen yuzhen lu Xiao-Qiang yu Guangdong Provincial Key Laboratory of Insect Developmental Biology and Applied Technology Guangzhou Key Laboratory of Insect Development Regulation and Application ResearchInstitute of Insect Science and TechnologySchool of Life SciencesSouth China Normal UniversityGuangzhou510631 China

Spermatogenesis is a critical part of reproduction in insects;however,its molecular mechanism is still largely unknown.In this study,we identified a testis-specific gene CG3526 in Drosophila melanogaster.Bioinformatics analysis showed that CG3526 contains a zinc binding domain and 2 C2H2 type zinc fingers,and it is clustered to the vertebrate really interesting new gene(RING)family E3 ubiquitin-protein ligases.When CG3526 was knocked down by RNA interference(RNAi),the testis became much smaller in size,and the apical tip exhibited a sharp and thin end instead of the blunt and round shape in the control testis.More importantly,compared to the control flies,only a few mature sperm were present in the seminal vesicle of C587-Gal4>CG3526 RNAi flies.Immunofluorescence staining of the testis from CG3526 RNAi flies showed that the homeostasis of testis stem cell niche was disrupted,cell distribution in the apical tip was scattered,and the process of spermatogenesis was not completed.Furthermore,we found that the phenotype of CG3526 RNAi flies’testis was similar to that of testis of Stat92E RNAi flies,the expression level of CG3526 was significantly downregulated in the Stat92EF06346 mutant flies,and the promoter activity of CG3526 was upregulated by STAT92E.Taken together,our results indicated that CG3526 is a downstream effector gene in the JAK-STAT signaling pathway that plays a key role in the spermatogenesis of Drosophila.

关键词： CG3526 JAK-STAT spermatogenesis STAT92E testis

Engineering classification recycling of spent lithium-ion batteries through pretreatment:a comprehensive review from laboratory to scale-up application

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Rare Metals 2024年第3期43卷 915-941页

作者： Shu-Xuan Yan You-Zhou Jiang Xiang-Ping Chen lu yuan ting-ting Min yu Cao Wan-Li Peng Tao Zhou Hunan Provincial Key Laboratory of Chemical Power Sources College of Chemistry and Chemical EngineeringCentral South UniversityChangsha 410083China College of Chemistry and Chemical Engineering Hunan Normal UniversityChangsha 410083China School of Public Policy and Management Tsinghua UniversityBeijing 100084China China Nonferrous Metal Industry's Foreign Engineering and Construction Co. LtdBeijing 100029China

The lithium-ion batteries(LIBs)have been widely equipped in electric/hybrid electric vehicles(EVs/HEVs)and the portable electronics due to their excellent electrochemical performances.However,a large number of retired LIBs that consist of toxic substances(e.g.,heavy metals,electrolytes)and valuable metals(e.g.,Li,Co)will inevitably flow into the waste stream,and their incineration or landfill treatment will cause severe risks to ecosystem and human beings.The sustainable and efficient treatment or recycling of valuable resources from spent LIBs should be fully recognized for environmental and resource security.As one of the most important processes for spent LIBs recycling,the pretreatment is an indispensable step,which is directly related to the subsequent metal extraction and separation processes.Although considerable progresses have been made regarding the pretreatment technologies,there are few summarized reports concerning critical processes of spent LIBs recycling,especially combination of currently available recycling technologies with industrialized applications during pretreatments.Therefore,comprehensive review of the current prevailing pretreatment technologies in laboratory to existing scale-up applications is quite necessary to reveal cutting-edge development in the field of pretreatment.In this review,the current pretreatment technologies are systematically categorized and introduced,along with critical discussions.This review focused on the various options for pretreatment processes itself,instead of general spent LIBs recycling technologies without the focused topics that have been sophisticatedly reviewed by previous studies.Here,the deactivation,discharge,dismantling,separation,liberation of active material and electrolyte treatment have been summarized with the in-depth discussion of the technology development and current status of each category.Finally,current states of industrial development are also reviewed and discussed for the development of efficient and environmentally friendly recyclin

关键词： Spent lithium-ion batteries(LIBs) Recycling Pretreatment Valuable metals Cutting-edge technologies Industrialized application

Permanent Magnet Temperature Estimation for PMSMs Using Virtual Position-offset Injection

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CES Transactions on Electrical Machines and Systems 2024年第1期8卷 51-60页

作者： Beichen Ding yuting lu Kaide Huang Guodong Feng Chunyan Lai IEEE the School of Intelligent Systems Engineering Sun Yat-sen UniversityShenzhen 518107China the Fosan University Foshan 528225China the Department of Electrical and Computer Engineering Concordia UniversityQCCanada

This paper proposes a virtual position-offset injection based permanent magnet temperature estimation approach for permanent magnet synchronous machines(PMSMs). The concept of virtual position-offset injection is mathematically transforming the machine model to a virtual frame with a position-offset. The virtual frame temperature estimation model is derived to calculate the permanent magnet temperature(PMT) directly from the measurements with computation efficiency. The estimation model involves a combined inductance term, which can simplify the establishment of saturation compensation model with less measurements. Moreover, resistance and inverter distorted terms are cancelled in the estimation model, which can improve the robustness to the winding temperature rise and inverter distortion. The proposed approach can achieve simplified computation in temperature estimation and reduced memory usage in saturation compensation. While existing model-based approaches could be affected by either the need of resistance and inverter information or complex saturation compensation. Experiments are conducted on the test machine to verify the proposed approach under various operating conditions.

关键词： PMSM Magnet temperature estimation Virtual position offset injection Inverter nonlinearity

G protein-coupled receptors(GPCRs):advances in structures,mechanisms,and drug discovery

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1938-1980页

作者： Mingyang Zhang ting Chen Xun lu Xiaobing Lan Ziqiang Chen Shaoyong lu Key Laboratory of Protection Development and Utilization of Medicinal Resources in Liupanshan AreaMinistry of EducationPeptide&Protein Drug Research CenterSchool of PharmacyNingxia Medical UniversityYinchuan 750004China Medicinal Chemistry and Bioinformatics Center Shanghai Jiao Tong University School of MedicineShanghai 200025China Department of Cardiology Changzheng HospitalAffiliated to Naval Medical UniversityShanghai 200003China Department of Orthopedics Changhai HospitalAffiliated to Naval Medical UniversityShanghai 200433China

G protein-coupled receptors(GPCRs),the largest family of human membrane proteins and an important class of drug targets,play a role in maintaining numerous physiological processes.Agonist or antagonist,orthosteric effects or allosteric effects,and biased signaling or balanced signaling,characterize the complexity of GPCR dynamic features.In this study,we first review the structural advancements,activation mechanisms,and functional diversity of GPCRs.We then focus on GPCR drug discovery by revealing the detailed drug-target interactions and the underlying mechanisms of orthosteric drugs approved by the US Food and Drug Administration in the past five years.Particularly,an up-to-date analysis is performed on available GPCR structures complexed with synthetic small-molecule allosteric modulators to elucidate key receptor-ligand interactions and allosteric mechanisms.Finally,we highlight how the widespread GPCR-druggable allosteric sites can guide structure-or mechanism-based drug design and propose prospects of designing bitopic ligands for the future therapeutic potential of targeting this receptor family.

关键词： steric designing mechanisms

Relationship between Phenotypic Changes of Dendritic Cell Subsets and the Onset of Plateau Phase during Intermittent Interferon Therapy in Patients with CHB

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Biomedical and Environmental Sciences 2024年第3期37卷 303-314页

作者： YANG Liu WANG Shi yu JIANG ting ting DENG Wen CHANG Min WU Shu Ling CAO Wei Hua lu Yao SHEN Ge LIU Ru yu GAO yuan Jiao XU Meng Jiao HU Lei Ping ZHANG lu XIE Yao LI Ming Hui Department of Hepatology Division 2 Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Center for Infectious Diseases Second Affiliated Hospital of Air Force Medical UniversityXi'an 710038ShaanxiChina Department of Hepatology Division 2 Peking University Ditan Teaching HospitalBeijing 100015China

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86.Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer.Results In total,143 patients were enrolled(NH group,n=49;NA group,n=47;P group,n=47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P alllusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

关键词： CHB Dendritic Cells Intermittent Interferon Therapy Plateau Phase

Generation of mitochondrial replacement monkeys by female pronucleus transfer

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Zoological Research 2024年第2期45卷 292-298页

作者： Chun-Yang Li Xing-Chen Liu yu-Zhuo Li Yan Wang Yan-Hong Nie yu-ting Xu Xiao-Tong Zhang Yong lu Qiang Sun Institute of Neuroscience Center for Excellence in Brain Science and Intelligence TechnologyState Key Laboratory of NeuroscienceChinese Academy of SciencesShanghai 200031China Key Laboratory of Genetic Evolution and Animal Models Chinese Academy of SciencesKunming 650201China University of Chinese Academy of Sciences Beijing 100049China

Mutations in mitochondrial DNA(mtDNA)are maternally inherited and have the potential to cause severe disorders.Mitochondrial replacement therapies,including spindle,polar body,and pronuclear transfers,are promising strategies for preventing the hereditary transmission of mtDNA diseases.While pronuclear transfer has been used to generate mitochondrial replacement mouse models and human embryos,its application in non-human primates has not been previously reported.In this study,we successfully generated four healthy cynomolgus monkeys(Macaca fascicularis)via female pronuclear transfer.These individuals all survived for more than two years and exhibited minimal mtDNA carryover(3.8%–6.7%),as well as relatively stable mtDNA heteroplasmy dynamics during development.The successful establishment of this nonhuman primate model highlights the considerable potential of pronuclear transfer in reducing the risk of inherited mtDNA diseases and provides a valuable preclinical research model for advancing mitochondrial replacement therapies in humans.

关键词： Non-human primates Mitochondrial replacement Female pronuclear transfer