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Long-term exposure to aryl hydrocarbon receptor agonist neburon induces reproductive toxicity in male zebrafish(Danio rerio)

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Journal of Environmental Sciences 2024年第8期142卷 193-203页

作者： Fucong Zhang Chen Tang Yue Zhu Qian Wang Xin Huang Chunyan Yang Chengyong He Zhenghong Zuo key laboratory of the ministry of education for Coastal and Wetland Ecosystems School of Life SciencesXiamen UniversityXiamen 361102China

Neburon is a phenylurea herbicide that is widely used worldwide,but its toxicity is poorly studied.In our previous study,we found that neburon has strong aryl hydrocarbon receptor(AhR)agonist activity,but whether it causes reproductive toxicity is not clear.In the present study,zebrafish were conducted as a model organism to evaluate whether environmental concentrations of neburon(0.1,1 and 10μg/L)induce reproductive disorder in males.After exposure to neburon for 150 days from embryo to adult,that the average spawning egg number in high concentration group was 106.40,which was significantly lower than 193.00in control group.This result was mainly due to the abnormal male reproductive behavior caused by abnormal transcription of genes associated with reproductive behavior in the brain,such as secretogranin-2a.The proportions of spermatozoa in the medium and high concentration groups were 82.40%and 83.84%,respectively,which were significantly lower than 89.45%in control group.This result was mainly caused by hormonal disturbances and an increased proportion of apoptotic cells.The hormonal disruption was due to the significant changes in the transcription levels of key genes in the hypothalamus-pituitary-gonadal axis following neburon treatment.Neburon treatment also significantly activated the AhR signaling pathway,causing oxidative stress damage and eventually leading to a significant increase in apoptosis in the exposed group.Together,these data filled the currently more vacant profile of neburon toxicity and might provide information to assess the ecotoxicity of neburon on male reproduction at environmentally relevant concentrations.

关键词： Zebrafish Neburon Male reproductive toxicity HPG axis AhR agonist

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Moisture‑Electric–Moisture‑Sensitive Heterostructure Triggered Proton Hopping for Quality‑Enhancing Moist‑Electric Generator

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Nano-Micro Letters 2024年第3期16卷 351-366页

作者： Ya’nan Yang Jiaqi Wang Zhe Wang Changxiang Shao Yuyang Han Ying Wang Xiaoting Liu Xiaotong Sun Liru Wang Yuanyuan Li Qiang Guo Wenpeng Wu Nan Chen Liangti Qu key laboratory of Cluster Science Ministry of Education of ChinaKey Laboratory of Photoelectronic/Electrophotonic Conversion MaterialsSchool of Chemistry and Chemical EngineeringBeijing Institute of TechnologyBeijing 100081People’s Republic of China Yangtze Delta Region Academy of Beijing Institute of Technology Jiaxing 314019People’s Republic of China Department of Chemistry Key Laboratory of Organic Optoelectronics&Molecular EngineeringMinistry of EducationTsinghua UniversityBeijing 100084People’s Republic of China

Moisture-enabled electricity(ME)is a method of converting the potential energy of water in the external environment into electrical energy through the interaction of functional materials with water molecules and can be directly applied to energy harvesting and signal expression.However,ME can be unreliable in numerous applications due to its sluggish response to moisture,thus sacrificing the value of fast energy harvesting and highly accurate information representation.Here,by constructing a moisture-electric-moisture-sensitive(ME-MS)heterostructure,we develop an efficient ME generator with ultra-fast electric response to moisture achieved by triggering Grotthuss protons hopping in the sensitized ZnO,which modulates the heterostructure built-in interfacial potential,enables quick response(0.435 s),an unprecedented ultra-fast response rate of 972.4 mV s^(−1),and a durable electrical signal output for 8 h without any attenuation.Our research provides an efficient way to generate electricity and important insight for a deeper understanding of the mechanisms of moisture-generated carrier migration in ME generator,which has a more comprehensive working scene and can serve as a typical model for human health monitoring and smart medical electronics design.

关键词： Moist-electric generators Grotthuss proton hopping Fast response Durable electrical output Personal health monitoring

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Targeting lncRNA16 by GalNAc-siRNA conjugates facilitates chemotherapeutic sensibilization via the HBB/NDUFAF5/ROS pathway

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Science China(Life Sciences) 2024年第4期67卷 663-679页

作者： Yanfang Liu Yan Wang Bing Liu Wenzhong Liu Yuanyuan Ma Yiren Cao Shi Yan Panpan Zhang Lixin Zhou Qimin Zhan Nan Wu key laboratory of Carcinogenesis and Translational Research(ministry of education/Beijing) Department of Thoracic Surgery IIPeking University Cancer Hospital and InstituteBeijing 100142China key laboratory of Carcinogenesis and Translational Research(ministry of education/Beijing) Laboratory of Molecular OncologyPeking University Cancer Hospital and InstituteBeijing 100142China key laboratory of Carcinogenesis and Translational Research(ministry of education/Beijing) Department of Thoracic Oncology IIPeking University Cancer Hospital and InstituteBeijing 100142China key laboratory of Carcinogenesis and Translational Research(ministry of education) Department of PathologyPeking University Cancer Hospital and InstituteBeijing 100142China Peking University International Cancer Institute Beijing 100191China Institute of Cancer Research Shenzhen Bay LaboratoryShenzhen 518132China

Chemoresistance is a significant barrier to effective cancer treatment.Potential mechanisms for chemoresistance include reactive oxygen species(ROS)accumulation and expression of chemoresistance-promoting genes.Here,we report a novel function of lncRNA16 in the inhibition of ROS generation and the progression of chemoresistance.By analyzing the serum levels of lncRNA16 in a cohort of 35 patients with non-small cell lung cancer(NSCLC)and paired serum samples pre-and post-treatment from 10 NSCLC patients receiving neoadjuvant platinum-based chemotherapy,performing immunohistochemistry(IHC)assays on 188 NSCLC tumor samples,using comprehensive identification of RNA-binding proteins by mass spectrometry(ChIRP-MS)assays,as well as RNA immunoprecipitation(RIP)and RNA pull-down analyses,we discovered that patients with increased serum levels of lncRNA16 exhibited a poor response to platinum-based chemotherapy.The expression of hemoglobin subunit beta(HBB)and NDUFAF5 significantly increases with the development of chemoresistance.LncRNA16 binds to HBB and promotes HBB accumulation by inhibiting autophagy.LncRNA16 can also inhibit ROS generation via the HBB/NDUFAF5 axis and function as a scaffold to facilitate the colocalization of HBB and NDUFAF5 in the mitochondria.Importantly,preclinical studies in mouse models of chemo-resistant NSCLC have suggested that lncRNA16 targeting by trivalent N-acetylgalactosamine(GalNAc)-conjugated siRNA restores chemosensitivity and results in tumor growth inhibition with no detectable toxicity in vivo.Overall,lncRNA16 is a promising therapeutic target for overcoming chemoresistance,and the combination of first-line platinum-based chemotherapy with lncRNA16 intervention can substantially enhance anti-tumor efficacy.

关键词： chemoresistance lncRNARNA interference ROs chemosensitizer

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Recent advances in protein conformation sampling by combining machine learning with molecular simulation

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Chinese Physics B 2024年第3期33卷 80-87页

作者：唐一鸣杨中元姚逸飞周运谈圆王子超潘瞳熊瑞孙俊力韦广红 Department of Physics State Key Laboratory of Surface Physicsand Key Laboratory for Computational Physical Sciences (Ministry of Education)Shanghai 200438China

The rapid advancement and broad application of machine learning(ML)have driven a groundbreaking revolution in computational biology.One of the most cutting-edge and important applications of ML is its integration with molecular simulations to improve the sampling efficiency of the vast conformational space of large biomolecules.This review focuses on recent studies that utilize ML-based techniques in the exploration of protein conformational landscape.We first highlight the recent development of ML-aided enhanced sampling methods,including heuristic algorithms and neural networks that are designed to refine the selection of reaction coordinates for the construction of bias potential,or facilitate the exploration of the unsampled region of the energy landscape.Further,we review the development of autoencoder based methods that combine molecular simulations and deep learning to expand the search for protein conformations.Lastly,we discuss the cutting-edge methodologies for the one-shot generation of protein conformations with precise Boltzmann weights.Collectively,this review demonstrates the promising potential of machine learning in revolutionizing our insight into the complex conformational ensembles of proteins.

关键词： machine learning molecular simulation protein conformational space enhanced sampling

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RebL1 is required for macronuclear structure stability and gametogenesis in Tetrahymena thermophila

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Marine Life Science & Technology 2024年第2期6卷 183-197页

作者： Huijuan Hao Yinjie Lian Chenhui Ren Sitong Yang Min Zhao Tao Bo Jing Xu Wei Wang key laboratory of Chemical Biology and molecular Engineering of ministry of education Institute of BiotechnologyShanxi UniversityTaiyuan 030006China School of Life Science Shanxi UniversityTaiyuan 030006China Shanxi key laboratory of Biotechnology Taiyuan 030006China

Histone modification and nucleosome assembly play important roles in chromatin-related processes.Histone chaperones form different complexes and coordinate histone transportation and assembly.Various histone chaperone complexes have been identified in different organisms.The ciliate protozoa(ciliates)have various chromatin structures and different nuclear morphology.However,histone chaperone components and functions of different subunits remain unclear in ciliates.Tet-rahymema thermophila contains a transcriptionally active macronucleus(MAC)and a transcriptionally inactive micronu-cleus(MIC)which exhibit multiple replication and various chromatin remodeling progresses during vegetative growth and sexual developmental stages.Here,we found histone chaperone RebL1 not only localized evenly in the transcriptionally active MAC but also dynamically changed in the MIC during vegetative growth and sexual developmental stages.REBL1 knockdown inhibited cellular proliferation.The macronuclear morphology became bigger in growing mutants.The abnormal macronuclear structure also occurred in the starvation stage.Furthermore,micronuclear meiosis was disturbed during sexual development,leading to a failure to generate new gametic nuclei.RebL1 potentially interacted with various factors involved in histone-modifying complexes and chromatin remodeling complexes in different developmental stages.REBL1 knockdown affected expression levels of the genes involved in chromatin organization and transcription.Taken together,RebL1 plays a vital role in maintaining macronuclear structure stability and gametogenesis in T.thermophila.

关键词： Gametogenesis Histone chaperone Macronuclear structure RebL1 Tetrahymena thermophilaIntroduction

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The biochemical behavior and mechanism of uranium(Ⅵ)bioreduction induced by natural Bacillus thuringiensis

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Journal of Environmental Sciences 2024年第2期136卷 372-381页

作者： Shunzhang Chen Junyuan Gong Yanxia Cheng Yuqi Guo Feize Li Tu Lan Yuanyou Yang Jijun Yang Ning Liu Jiali Liao key laboratory of Radiation Physics and Technology of the ministry of education Institute of Nuclear Science and TechnologySichuan UniversityChengdu 610064China

For a broader understanding of uranium migration affected by microorganisms in natural anaerobic environment,the bioreduction of uranium(Ⅵ)(U(Ⅵ))was revealed in Bacillus thuringiensis,a dominant bacterium strain with potential of uranium-tolerant isolated from uranium contaminated soil.The reduction behavior was systematically investigated by the quantitative analysis of U(Ⅳ)in bacteria,and mechanism was inferred from the pathway of electron transmission.Under anaerobic conditions,appropriate biomass and sodium lactate as electron donor,reduction behavior of U(Ⅵ)induced by B.thuringiensis was restricted by the activity of lactate dehydrogenase,which was directly affected by the initial pH,temperature and initial U(Ⅵ)concentration of bioreduction system.Bioreduction of U(Ⅵ)was driven by the generation of nicotinamide adenine dinucleotide(NADH)from enzymatic reaction of sodium lactate with various dehydrogenase.The transmission of the electrons from bacteria to U(Ⅵ)was mainly supported by the intracellular NADH dehydrogenase-ubiquinone system,this process could maintain the biological activity of cells.

关键词： Uranium Bacillus thuringiensis Bioreduction Electron transmission

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Investigation of mechanical and electrical characteristics of selfsensing pneumatic torsional actuators

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Science China(Technological Sciences) 2024年第1期67卷 130-142页

作者： XIAO Wei HU DeAn HU GuoLiang XIAO YiHua key laboratory of Conveyance and Equipment Ministry of EducationEast China Jiaotong UniversityNanchang 330013China key laboratory of Advanced Design and Simulation Techniques for Special Equipment Ministry of EducationHunan UniversityChangsha 410082China

Soft pneumatic actuators are one of the most promising actuation for soft robots,and great achievements have been obtained.But it remains challenging to endow sensing capabilities to pneumatic actuators,especially for the sensing ability originating directly from the actuator architecture.Herein,a self-sensing pneumatic torsional actuator(SPTA)is designed based on the electromagnetic induction effect and magnetically responsive materials.The SPTA can generate feedback voltage and current with the deformation,in which the sensing function comes from its inherent structure.To investigate the mechanical and electrical characteristics,an experimental platform and a finite element model are established,respectively.We find that the torsion angle and output torque increase in nonlinear with the actuating pressure.The maximum torsion angle is 66.35°,which is 84.34%of that for the actuator fabricated by pure rubber.The maximum output torque(24.9 N mm)improves by 23.19%compared with the actuator made by pure rubber.As regards the electrical characteristics,the maximum feedback voltage and current are 2.90μV and 29.50 nA when the SPTA is actuated by a pressure of−40 kPa.We also demonstrate that the relationship between the torsion angle and the magnetic flux change is approximately linear.Finally,the number of turns of wires,magnetic powders contents,and magnetic direction on the feedback voltage and current are studied.Results show that the feedback voltage and current can be enhanced by increasing the number of turns and magnetic powders contents.We envision that the SPTA would be promising for soft robots to realize their accuracy control and intelligentization.

关键词： pneumatic torsional actuators self-sensing feedback voltage finite element modeling soft robots

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The early life immune dynamics and cellular drivers at single-cell resolution in lamb forestomachs and abomasum

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Journal of Animal Science and Biotechnology 2024年第1期15卷 218-235页

作者： Kailang Huang Bin Yang Zebang Xu Hongwei Chen Jiakun Wang Institute of Dairy Science College of Animal SciencesZhejiang UniversityHangzhou 310058China key laboratory of molecular Animal Nutrition Ministry of EducationZhejiang UniversityHangzhou 310058China

Background Four-chambered stomach including the forestomachs(rumen,reticulum,and omasum)and abomasum allows ruminants convert plant fiber into high-quality animal products.The early development of this four-chambered stomach is crucial for the health and well-being of young ruminants,especially the immune development.However,the dynamics of immune development are poorly understood.Results We investigated the early gene expression patterns across the four-chambered stomach in Hu sheep,at 5,10,15,and 25 days of age.We found that forestomachs share similar gene expression patterns,all four stomachs underwent widespread activation of both innate and adaptive immune responses from d 5 to 25,whereas the metabolic function were significantly downregulated with age.We constructed a cell landscape of the four-chambered stomach using single-cell sequencing.Integrating transcriptomic and single-cell transcriptomic analyses revealed that the immune-associated module hub genes were highly expressed in T cells,monocytes and macrophages,as well as the defense-associated module hub genes were highly expressed in endothelial cells in the four-stomach tissues.Moreover,the non-immune cells such as epithelial cells play key roles in immune maturation.Cell communication analysis predicted that in addition to immune cells,non-immune cells recruit immune cells through macrophage migration inhibitory factor signaling in the forestomachs.Conclusions Our results demonstrate that the immune and defense responses of four stomachs are quickly developing with age in lamb's early life.We also identified the gene expression patterns and functional cells associated with immune development.Additionally,we identified some key receptors and signaling involved in immune regulation.These results help to understand the early life immune development at single-cell resolution,which has implications to develop nutritional manipulation and health management strategies based on specific targets including key receptors and signaling pathways.

关键词： Early life Forestomachs Four-chambered stomach Immune cells Immune system maturation MIF signaling Rumen Ruminant development Single-cell transcriptomic sequencing

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Phosphorylation Promotes the Accumulation of PERIOD Protein Foci

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Research 2024年第1期2023卷 59-69页

作者： Mengna Li Shujing Li Luoying Zhang key laboratory of molecular biophysics of ministry of education College of Life Science and TechnologyHuazhong University of Science and TechnologyWuhanHubei 430074China Department of Life Sciences Bengbu Medical CollegeBengbuAnhui 233030China Hubei Province key laboratory of Oral and Maxillofacial Development and Regeneration WuhanHubei 430022China

Circadian clock drives the 24-h rhythm in our behavior and physiology.The molecular clock consists of a series of transcriptional/translational feedback loops operated by a number of clock genes.A very recent study reported that the clock protein PERIOD(PER)is organized into discrete foci at the nuclear envelope in fly circadian neurons,which is believed to be important for controlling the subcellular localization of clock genes.Loss of inner nuclear membrane protein lamin B receptor(LBR)leads to disruption of these foci,but how they are regulated is yet unknown.Here,we found that PER foci are likely phase-separated condensates,the formation of which is mediated by intrinsically disordered region in PER.Phosphorylation promotes the accumulation of these foci.Protein phosphatase 2A,which is known to dephosphorylate PER,hampers the accumulation of the foci.On the other hand,the circadian kinase DOUBLETIME(DBT)which phosphorylates PER enhances the accumulation of the foci.LBR likely facilitates PER foci accumulation by destabilizing the catalytic subunit of protein phosphatase 2A,MICROTUBULE STAR(MTS).In conclusion,here,we demonstrate a key role for phosphorylation in promoting the accumulation of PER foci,while LBR modulates this process by impinging on the circadian phosphatase MTS.

关键词： conclusion separated translational

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Multidimensional autophagy nano-regulator boosts Alzheimer's disease treatment by improving both extra/intraneuronal homeostasis

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1380-1399页

作者： Yixian Li Peng Yang Ran Meng Shuting Xu Lingling Zhou Kang Qian Pengzhen Wang Yunlong Cheng Dongyu Sheng Minjun Xu Tianying Wang Jing Wu Jinxu Cao Qizhi Zhang key laboratory of Smart Drug Delivery Ministry of EducationSchool of PharmacyFudan UniversityShanghai 201203China

Intraneuronal dysproteostasis and extraneuronal microenvironmental abnormalities in Alzheimer’s disease(AD)collectively culminate in neuronal deterioration.In the context of AD,autophagy dysfunction,a multi-link obstacle involving autophagy downregulation and lysosome defects in neurons/microglia is highly implicated in intra/extraneuronal pathological processes.Therefore,multidimensional autophagy regulation strategies co-manipulating“autophagy induction”and“lysosome degradation”in dual targets(neuron and microglia)are more reliable for AD treatment.Accordingly,we designed an RP-1 peptide-modified reactive oxygen species(ROS)-responsive micelles(RT-NM)loading rapamycin or gypenoside XVII.Guided by RP-1 peptide,the ligand of receptor for advanced glycation end products(RAGE),RT-NM efficiently targeted neurons and microglia in AD-affected region.This nanocombination therapy activated the whole autophagy-lysosome pathway by autophagy induction(rapamycin)and lysosome improvement(gypenoside XVII),thus enhancing autophagic degradation of neurotoxic aggregates and inflammasomes,and promoting Aβ phagocytosis.Resultantly,it decreased aberrant protein burden,alleviated neuroinflammation,and eventually ameliorated memory defects in 3×Tg-AD transgenic mice.Our research developed a multidimensional autophagy nano-regulator to boost the efficacy of autophagy-centered AD therapy.

关键词： Autophagy-lysosome pathway Alzheimer’s disease Proteostasis Neuroinflammation Multi-target therapy Rapamycin Gypenoside XVII Cascade dual-targeting

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