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Tumor Suppressor Folliculin Regulates mTORC1 through Primary Cilia

JOURNAL OF BIOLOGICAL CHEMISTRY 2016年第22期291卷 11689-11697页

作者： Zhong, Mingming zhao, xuwen Li, Jinmei Yuan, Wenjie Yan, Gonghong Tong, Mingming Guo, Shuguang Zhu, Yichao Jiang, Yong Liu, Yongjian Jiang, Yu Southern Med Univ Minist Educ China State Key Lab Organ Failure ResDept Pathophysiol Key Lab Transcript & ProteGuangdong Prov Key Lab Guangzhou 510515 Guangdong Peoples R China Univ Pittsburgh Sch Med Dept Pharmacol & Chem Biol Pittsburgh PA 15261 USA Nanjing Med Univ Dept Physiol Nanjing 211166 Jiangsu Peoples R China

Folliculin (FLCN) is the tumor suppressor associated with Birt-Hogg-Dube (BHD) syndrome that predisposes patients to incident of hamartomas and cysts in multiple organs. Its inactivation causes deregulation in the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. However, the underlying mechanism is poorly defined. In this study, we show that FLCN is a ciliary protein that functions through primary cilia to regulate mTORC1. In response to flow stress, FLCN associates with LKB1 and recruits the kinase to primary cilia for activation of AMPK resided at basal bodies, which causes mTORC1 down-regulation. In cells depleted of FLCN, LKB1 fails to accumulate in primary cilia and AMPK at the basal bodies remains inactive, thus nullifying the inhibitory effect of flow stress on mTORC1 activity. Our results demonstrate that FLCN is part of a flow sensory mechanism that regulates mTORC1 through primary cilia.

关键词： AMP-activated kinase (AMPK) mammalian target of rapamycin (mTOR) mTOR complex (mTORC) primary cilium tumor suppressor gene FLCN LKB1 folliculin

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Manganese-based virus-mimicking nanomedicine with triple immunomodulatory functions inhibits breast cancer brain metastasis

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BIOMATERIALS 2025年 320卷 123262-123262页

作者： zhao, Zhenhao Zhou, Jingyi Li, xuwen Zhang, Tongyu Tian, Zonghua Sun, Tao Jiang, Chen Fudan Univ Sch Pharm Dept Pharmaceut Minist EducKey Lab Smart Drug DeliveryState Key Shanghai 201203 Peoples R China MOE Frontiers Ctr Brain Sci Shanghai 201203 Peoples R China Fujian Med Univ Affiliated Hosp 1 Natl Reg Med Ctr Dept Digest Dis Binhai Campus Fuzhou 350212 Peoples R China

Hindered by the challenges of blood-brain barrier (BBB) hindrance, tumor heterogeneity and immunosuppressive microenvironment, patients with breast cancer brain metastasis have yet to benefit from current clinical treatments, experiencing instead a decline in quality of life due to radiochemotherapy. While virus-mimicking nanosystems (VMN) mimicking viral infection processes show promise in treating peripheral tumors, the inability to modulate the immunosuppressive microenvironment limits the efficacy against brain metastasis. Accordingly, a VMN-based triple immunomodulatory strategy is initially proposed, aiming to activate innate and adaptive immune responses and reverse the immunosuppressive microenvironment. Here, manganese-based virus-mimicking nanomedicine (Vir-HD@HM) with intratumoral drug enrichment is engineered. Vir-HD@HM can induce the immune response through the activation of cGAS-STING by mimicking the in vivo infection process of herpesviruses. Meanwhile, DNAzyme mimicking the genome can rescue the epigenetic silencing of PTEN with the assistance of Mn2+, thus ameliorating the immunosuppressive metastatic microenvironment and achieving synergistic sensitizing therapeutic efficacy. In vivo experiments substantiate the efficacy of VirHD@HM in recruiting NK cells and CD8+ T cells to metastatic foci, inhibiting Treg cells infiltration, and prolonging murine survival without adjunctive radiochemotherapy. This study demonstrates that Vir-HD@HM with triple immunomodulation offers an encouraging therapeutic option for patients with brain metastasis.

关键词： Breast cancer brain metastasis Virus-mimicking nanosystem Immune activation Immunosuppressive microenvironment regulation PTEN cGAS-STING

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High-performance photodetectors based on two-dimensional perovskite crystals with alternating interlayer cations

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Journal of Materiomics 2023年第4期9卷 817-823页

作者： Yezhan Li Zhengxun Lai You Meng Wei Wang Yuxuan Zhang xuwen zhao Di Yin Weijun Wang Pengshan Xie Quan Quan SenPo Yip Johnny C.Ho Department of Materials Science and Engineering City University of Hong Kong999077Hong Kong SARChina Institute for Materials Chemistry and Engineering Kyushu UniversityFukuoka816-8580Japan State Key Laboratory of Terahertz and Millimeter Waves City University of Hong Kong999077Hong Kong SARChina

Organic-inorganic halide perovskite,as a low-cost,solution-processable material with remarkable optoelectronic properties,is ideal candidate to fabricate high-performance photodetectors and is expected to significantly reduce device *** to the common Dion-Jacobson and Ruddlesden-Popper two-dimensional(2D)layered hybrid perovskite compounds,the perovskites with alternating cations in the interlayer(ACI)phase show higher crystal symmetry and narrower optical bandgaps,which exhibit great potential for excellent photodetection ***,we report a high-performance photodetector based on the 2D bilayered hybrid lead halide perovskite single crystal with the ACI phase(GAMA_(2)Pb_(2)I_(7);GA=C(NH_(2))_(3)and MA=CH_(3)NH_(3)).The single-crystal photodetector exhibits high photoresponsivity of 1.56,2.54,and 2.60 A/W for incident light wavelengths of 405,532,and 635 nm under 9.82 nW,respectively,together with the correspondingly high detectivity values of 1.86×10^(12),3.04×10^(12),and 3.11×10^(12)Jones under the same operating ***,a high-resolution imaging sensor is built based on the GAMA_(2)Pb_(2)I_(7)single-crystal photodetector,confirming the high stability and photosensitivity of the imaging *** results show that the 2D hybrid lead halide perovskites with alternating interlayer cations are promising for high-performance visible light photodetectors and imaging systems.

关键词： Photodetector Two-dimensional Hybrid perovskite Alternating interlayer cation Imaging

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Energy Driving-Damage Degradation-Structural Failure Mechanism of Layered Sandstones Under Uniaxial Conditions

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ROCK MECHANICS AND ROCK ENGINEERING 2025年第3期58卷 3815-3853页

作者： Song, Zhixiang Zhang, Junwen Wu, Shaokang zhao, Shankun Zhang, Yang Dong, Xukai Zhang, xuwen Wang, Sihe China Univ Min & Technol Beijing Sch Energy & Min Engn Beijing 100083 Peoples R China China Coal Res Inst Mine Safety Technol Branch Beijing 100013 Peoples R China

It is of great theoretical significance to effectively reveal the energy driving-damage degradation-structural failure mechanism of rocks for the probability evaluation and prevention of rock burst in deep coal mines. Therefore, uniaxial loading and unloading tests of layered sandstones were conducted. Subsequently, the progressive failure process and stress-strain curves were obtained. Then, the evolution characteristics of strength, strain, energy, damage and macroscopic failure was characterized. Meanwhile, the damage proportion at each stage was quantified, and the linear damage deterioration law was obtained. Finally, the energy driving-damage degradation-structural failure mechanism was revealed. The results showed that: (1) increasing the unloading stress level did not necessarily reduce the bearing capacity, but the unloading effect could significantly affect the energy storage capacity;(2) there was the significant linear evolution relationship between the damage proportion and the unloading stress level under identical inclination angle in stages II and IV;(3) When the unloading stress level was over 0.7, the pre-peak structural adjustment behavior could strengthen the stability of post-peak structures and reduce the impact degree of rock burst. The conclusions could provide certain of theoretical basis for the prevention of rock burst in deep coal mines.

关键词： Structural evolution Unloading stress level Linear damage deterioration law Energy driving-damage degradation-structural failure mechanism Rock burst

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The Role of Glutathione S-Transferase in the Regulation of Plant Growth, and Responses to Environmental Stresses

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Phyton-International Journal of Experimental Botany 2025年第3期94卷 583-601页

作者： Chen Lin Zidan Zhang zhao Zhang Yuxiang Long xuwen Shen Jinghao Zhang Youping Wang Key Laboratory of Plant Functional Genomics of the Ministry of Education Yangzhou UniversityYangzhou225009China Jiangsu Key Laboratory of Crop Genomics and Molecular Breeding Yangzhou UniversityYangzhou225009China

Glutathione S-transferases (GSTs) represent a large and diverse enzyme family ubiquitously distributed across the plant kingdom. These proteins catalyze the conjugation of glutathione (GSH) with electrophilic substrates in response to various stress conditions. Beyond their role in stress adaptation, certain GSTs are integral regulators of plant growth and development, contributing to a range of physiological processes. Most GST proteins exhibit dual enzymatic activities, functioning as both transferases and peroxidases, which enables their involvement in diverse cellular processes, including detoxification and stress responses. Recent advancements, particularly in X-ray crystallography, have enabled detailed structural analysis of GST proteins, significantly enhancing our understanding of their biological functions. This review offers a comprehensive overview of the classification and structural characteristics of GSTs in plants. It also highlights recent findings on their roles in plant growth and development, cell signaling, catalytic transport, and stress tolerance. Furthermore, key scientific challenges related to GSTs are discussed, focusing on their potential applications in agriculture. These insights aim to facilitate the screening of functional GST genes and support molecular breeding efforts across diverse crop species.

关键词： Glutathione S-transferase biotic and abiotic stress plant growth and development signal transduction biological functions

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Erosion wear resistance mechanism of erosion ripples

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PROCEEDINGS OF THE INSTITUTION OF MECHANICAL ENGINEERS PART C-JOURNAL OF MECHANICAL ENGINEERING SCIENCE 2022年第19期236卷 10359-10369页

作者： Zhang, Yan zhao, xuwen Wang, Qi Wang, Tianqi Tang, Yuling Tianjin Univ Sci & Technol Tianjin Key Lab Integrated Design & On Line Monit Tianjin Peoples R China Tianjin Univ Sci & Technol Coll Mech Engn Tianjin Peoples R China

Erosion ripples widely exist on natural and industrial surfaces suffering gas-solid flow erosion. During the steady state of erosion ripples formation, the material removal and plastic flow rate of the material basically reach a dynamic equilibrium. In this state, the erosion rate of the surface material is steady and at a low level. In this paper, the relationship between erosion ripples and the erosion characteristics of surface materials was explored by experimental and simulation methods. Under the conditions of air pressures of 0.3, 0.4 and 0.5 MPa and erosion angles of 30 degrees, 40 degrees and 50 degrees, several erosion ripples were prepared on the surface of 1060 aluminium alloy samples by sandblasting. According to the obtained morphological parameters and orthogonal test design, rippled samples with rectangular, triangular and semicircular groove sections were designed. The effect of morphology parameters on the erosion resistance of the sample was analysed by a sandblasting test. The results showed that the rippled samples have lower erosion rates than the plate sample. The cross-sectional shape of grooves is the most obviously affected factor. The velocity distribution and surface pressure distribution on the surface of rippled and plate samples were analysed by FLUENT software, and the results showed that the low-speed reflow vortex will be formed in grooves of erosion ripples that can change the near-wall flow field conditions. The differential pressure generated on two sides of the ridge between adjacent grooves, as well as the area decrease of erosion caused by the "shaded effect," may be the cause of the erosion resistance. The results of this study can provide new insight into the active erosive wear resistance method of mechanical components.

关键词： erosive wear erosion ripple gas-solid flow sandblasting near-wall flow field

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EXCEPTIONAL DATA TRANSMISSION METHOD, APPARATUS AND SYSTEM

EXCEPTIONAL DATA TRANSMISSION METHOD, APPARATUS AND SYSTEM

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作者： SHU, Lin zhao, xuwen

标准号: WO2018196761(A1)

Disclosed is an exceptional data transmission method, relating to the field of communications, and used for achieving that APN rate control is not executed on exceptional data sent by a UE to a core network. The exceptional data transmission method comprises: in the case where APN rate control is executed, a UE determining that there is exceptional data to be sent to a network side, then the UE sending a NAS message to a first core network device;after receiving the NAS message, the first core network device learning, according to exceptional data indicator information in the NAS message, that exceptional data is comprised in the NAS message;the first core network device sending a first message to a third core network via the second core network device;the third core network device receiving the first message when executing APN rate control, and when the APN rate control reaches a maximum rate limit, the third core network device sending the exceptional data to a data network according to the received exceptional data indicator information. The embodiments of the present application are applied to transmission of exceptional data in an emergency situation.

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Design of Intelligent Logistics System Based on JIT Material Distribution Plan

Design of Intelligent Logistics System Based on JIT Material...

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The 2018 International Conference on Transportation & Logistics,Information & Communication,Smart City(TLICSC 2018)

作者： Yunrui Wang Zhengli Wu xuwen zhao School of Mechanical Engineering Xi'an University of Science and Technology

ISBN: (纸本)9781510876996

With increasingly high demands of personalized requirements and delivery time of customers,material distribution must be on time with guaranteeing the *** became one of the most critical technologies for companies to achieve the intelligent *** at the issues which is large batch size and serious accumulation in the material distribution of a specific enterprise,PCBA board was chosen as the research object in this *** analyzing the process of material distribution,the economic distribution batch model and the distribution kanban model were set ***,the ANDON system has been designed and a just-in-time distribution system for materials was eventually *** system greatly reduces material distribution personals and time,which saves distribution expenditures and combines this system with the currently used MES system by the company to achieve the cooperative control of plan and materials,thus providing guarantee for intelligent logistics *** present,this system has been used in enterprises,making good advancement.

关键词： Intelligent logistics JIT material distribution economic distribution batch distribution Kanban ANDON system

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Supercontinuum Generation Enhanced by Cross-phase Modulation in Dispersion-flattened and Decreasing Fiber

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Semiconductor Photonics and Technology 2005年第2期11卷 116-121页

作者： xuwen-cheng XUYong-zhao YUBing-tao CUIHu CHENYong-zhu LIUSong-hao InstituteofQuantumElectron. SouthChinaNormalUniversityGuangzhou510631CHN

Supercontinuum spectrum generation in a dispersion-flattened and decreasing fiber with two orthogonally polarized pulses was simulated and calculated. The research results indicated that the supercontinuum spectrum generated by two orthogonally polarized pulses is wider and flatter than that generated by single polarized pulse due to cross-phase modulation. The cross-phase modulation effect can enhance the supercontinuum spectrum generation. When the pump power of the input pulse is lower, the enhancement of supercontinuum spectrum generation by cross-phase modulation effect is more significant.

关键词： fiber optics supercontinuum spectrum dispersion-flattened and decreasingfiber cross-phase modulation soliton trapping

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A highly sensitive one-step nanobody-based immunoassay to specifically detect antibodies against fowl adenovirus serotype 4

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POULTRY SCIENCE 2025年第4期104卷 104970页

作者： Ji, Pinpin Zhang, Hao Xiri, Yangzong Li, Ziling Liu, Zhixiang Dan, Miao Li, Xiaoxuan Sun, xuwen zhao, Qin Sun, Yani Northwest A&F Univ Coll Vet Med Dept Prevent Vet Med Yangling 712100 Shaanxi Peoples R China Minist Agr Sci Observing & Expt Stn Vet Pharmacol & Diagnost Yangling 712100 Shaanxi Peoples R China

Hepatitis-hydropericardium syndrome, caused by fowl adenovirus serotype 4 (FAdV-4), has resulted in significant economic damage to the poultry industry. To monitor viral exposure and vaccine efficacy, some traditional antibody-based immunoassays have been developed for detecting anti-FAdV-4 antibodies. However, these assays have some drawbacks including multi-step operations and higher production cost. Recently, nanobodies are regarded as a promising tool for developing immunoassays. In the study, 23 nanobodies against FAdV-4 were screened and expressed with horseradish peroxidase (HRP) in the HEK293T cells. Then, the FAdV-4-Nb28-HRP fusion protein was selected for developing competitive enzyme-linked immunoassays (cELISA) to detect antiFAdV-4 antibodies in the chicken sera. The optimal concentrations and dilutions for the coating antigen, fusion protein and testing sera were determined to be 400 ng/well, 1:80 and 1:20, respectively. After the coated plates were vacuumized and stored, the operation of cELISA to detect clinical chicken sera was only one-step and the full time was 75 min. The cELISA also exhibited high sensitivity, specificity, reproducibility and good agreement with the commercial ELISA kit. When the sequential sera from the challenged chickens were tested, the cELISA showed superior sensitivity compared with the commercial ELISA kit. Moreover, epitope mapping revealed that the nanobody specifically recognized the sites GLN235 ASN236 SER238 of the fiber-1 protein, highly conserved among different FAdV-4 isolates and different from the FAdV-1 and-8. The results indicated that cELISA can specifically detect anti-FAdV-4 antibodies. Collectively, the developed one-step nanobody-based cELISA is an ideal method for epidemiological investigation and vaccine immune evaluation of FAdV-4.

关键词： Nanobody One-step competitive ELISA FAdV-4 antibodies Fiber-1 protein

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