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Journal of Sport and Health Science 2024年第3期13卷 368-372页

作者： Weimo zhu Wenguang Geng lingling Huang Xiong Qin Zezhao Chen Hai Yan Yunnan Plateau Thermal Health Industry Innovation Research Institute Tengchong 679100China Department of Kinesiology&Community Health University of Illinois at Urbana-ChampaignUrbanaIL 61801USA Department of Physical Education Nanjing Agricultural UniversityNanjing 210095China School of Sports Engineering Beijing Sport UniversityBeijing 100084China School of Strength and Conditioning Training Beijing Sport UniversityBeijing 100084China

Benefits of exercise for personal health,as well as preventing and treating chronic diseases,have been well documented during the past several decades.1 Exercise prescription is a specialized field that involves assessing an individual’s health status,fitness level,and specific goals to create a tailored exercise program based often on the FITT-VP principle.

关键词： prescription diseases assessing

Multiple factors to assist human-derived induced pluripotent stem cells to efficiently differentiate into midbrain dopaminergic neurons

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Neural Regeneration Research 2024年第4期19卷 908-914页

作者： Yalan Chen Junxin Kuang Yimei Niu Hongyao zhu Xiaoxia Chen Kwok-Fai So Anding Xu lingling Shi Guangdong-Hong Kong-Macao Institute of CNS Regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan University Department of Neurology and Stroke Center The First Affiliated HospitalJinan University Department of Psychiatry The First Affiliated HospitalJinan University Co-innovation Center of Neuroregeneration Nantong University

Midbrain dopaminergic neurons play an important role in the etiology of neurodevelopmental and neurodegenerative diseases.They also represent a potential source of transplanted cells for therapeutic applications.In vitro differentiation of functional midbrain dopaminergic neurons provides an accessible platform to study midbrain neuronal dysfunction and can be used to examine obstacles to dopaminergic neuronal development.Emerging evidence and impressive advances in human induced pluripotent stem cells,with tuned neural induction and differentiation protocols,makes the production of induced pluripotent stem cell-derived dopaminergic neurons feasible.Using SB431542 and dorsomorphin dual inhibitor in an induced pluripotent stem cell-derived neural induction protocol,we obtained multiple subtypes of neurons,including 20%tyrosine hydroxylase-positive dopaminergic neurons.To obtain more dopaminergic neurons,we next added sonic hedgehog(SHH)and fibroblast growth factor 8(FGF8)on day 8 of induction.This increased the proportion of dopaminergic neurons,up to 75%tyrosine hydroxylase-positive neurons,with 15%tyrosine hydroxylase and forkhead box protein A2(FOXA2)co-expressing neurons.We further optimized the induction protocol by applying the small molecule inhibitor,CHIR99021(CHIR).This helped facilitate the generation of midbrain dopaminergic neurons,and we obtained 31-74%midbrain dopaminergic neurons based on tyrosine hydroxylase and FOXA2 staining.Thus,we have established three induction protocols for dopaminergic neurons.Based on tyrosine hydroxylase and FOXA2 immunostaining analysis,the CHIR,SHH,and FGF8 combined protocol produces a much higher proportion of midbrain dopaminergic neurons,which could be an ideal resource for tackling midbrain-related diseases.

关键词： dopaminergic neurons FGF signal induced pluripotent stem cells midbrain neural differentiation SHH signal SMAD signal WNT signal

Estrogen receptor beta suppresses the androgen receptor oncogenic effects in triple-negative breast cancer

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Chinese Medical Journal 2024年第3期137卷 338-349页

作者： Feng Xu Kun Xu lingling Fan Xintong Li Yiqiu Liu Fang Yang Chengjun zhu Xiaoxiang Guan Department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China Department of Oncology Jiangsu Cancer HospitalThe Affiliated Cancer Hospital of Nanjing Medical UniversityJiangsu Institute of Cancer ResearchNanjingJiangsu 210009China The Comprehensive Cancer Center of Nanjing Drum Tower Hospital Affiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu 210008China Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Personalized Cancer MedicineNanjing Medical UniversityNanjingJiangsu 211166China

Background:Triple-negative breast cancer(TNBC)is an aggressive type of breast cancer associated with poor prognosis and limited treatment options.The androgen receptor(AR)has emerged as a potential therapeutic target for luminal androgen receptor(LAR)TNBC.However,multiple studies have claimed that anti-androgen therapy for AR-positive TNBC only has limited clinical benefits.This study aimed to investigate the role of AR in TNBC and its detailed mechanism.Methods:Immunohistochemistry and TNBC tissue sections were applied to investigate AR and nectin cell adhesion molecule 4(NECTIN4)expression in TNBC tissues.Then,in vitro and in vivo assays were used to explore the function of AR and estrogen receptor beta(ERβ)in TNBC.Chromatin immunoprecipitation sequencing(ChIP-seq),co-immunoprecipitation(co-IP),molecular docking method,and luciferase reporter assay were performed to identify key molecules that affect the function of AR.Results:Based on the TNBC tissue array analysis,we revealed that ERβand AR were positive in 21.92%(32/146)and 24.66%(36/146)of 146 TNBC samples,respectively,and about 13.70%(20/146)of TNBC patients were ERβpositive and AR positive.We further demonstrated the pro-tumoral effects of AR on TNBC cells,however,the oncogenic biology was significantly suppressed when ERβtransfection in LAR TNBC cell lines but not in AR-negative TNBC.Mechanistically,we identified that NECTIN4 promoter–42 bp to–28 bp was an AR response element,and that ERβinteracted with AR thus impeding the AR-mediated NECTIN4 transcription which promoted epithelial–mesenchymal transition in tumor progression.Conclusions:This study suggests that ERβfunctions as a suppressor mediating the effect of AR in TNBC prognosis and cell proliferation.Therefore,our current research facilitates a better understanding of the role and mechanisms of AR in TNBC carcinogenesis.

关键词： Androgen receptor Estrogen receptor beta Triple-negative breast cancer NECTIN4 Oncogenic effects Tumor progression

Differential expression of miRNAs and mRNAs in the livers of largemouth bass Micropterus salmoides under heat stress

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Journal of Oceanology and Limnology 2024年第2期42卷 594-608页

作者： Xuqian ZHAO Zijie LIN Caijuan LI Hao zhu lingling LI Wenjia MAO Qufei LING School of Biology and Basic Medical Sciences Suzhou Medical College of Soochow UniversitySuzhou 215000China

Global warming threatens freshwater ecosystems and compromises fish survival.To elucidate the role of miRNAs in the livers of heat stressed largemouth bass,juvenile fish was subject to heat stress under 37°C.Both mRNA-seq and miRNA-seq were conducted on the liver tissues under control and heat stress conditions.Differential gene expression analysis and enrichment analysis were performed on mRNA and miRNA expression profiles.A total of 406 differentially expressed genes(DEGs)were discovered,of which 212 were up-regulated and 194 were down-regulated.Most of the DEGs were significantly implicated in the regulation of“protein processing in endoplasmic reticulum”,“proteasome”,“steroid biosynthesis”,and“ornithine decarboxylase inhibitor activity”pathways.In addition,47 differentially expressed miRNAs(DEMs)were identified in largemouth bass livers under heat stress,including 21 up-regulated and 25 down-regulated miRNAs.A negatively regulated miRNA-mRNA network including 12 miRNAs and 19 mRNAs was constructed with DEMs involved in“protein degradation”,“calcium ion regulation”,“cell apoptosis”,and“lipid metabolism”.Moreover,this study indicated novel-miR-144 activated the IRE1 signaling pathway by targeting txndc5 to induce liver apoptosis in largemouth bass under heat stress.This study revealed the involvement of miRNA regulation in largemouth bass in response to heat stress.

关键词： heat stress largemouth bass miRNA-mRNA interaction

Graphene reinforced nanoarchitectonics of 3D interconnected magnetic-dielectric frameworks for high-efficient and anti-corrosive microwave absorbers

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Journal of Materials Science & Technology 2024年第1期168卷 194-207页

作者： Chenchen Liu Xiaofang Feng Shuning Liu Guo Lin Zhongxiang Bai lingling Wang Ke zhu Xiulan Li Xiaobo Liu School of Materials and Energy University of Electronic Science and Technology of ChinaChengdu611731China Sichuan Province Engineering Technology Research Center of Novel CN Polymeric Materials Chengdu611731China School of Chemical Engineering Northwest UniversityXi’an710069China Guangdong Provincial Key Laboratory of Environmental Pollution Control and Remediation Technology School of Environmental Science and EngineeringSun Yat-sen UniversityGuangzhou510275China

The combination of high efficiency and environmental stability is vital to promote the commercial appli-cations of microwave absorption(MA)materials,yet remains challenging in the absence of facile routes.Here,we put forward a graphene-reinforced construct approach for one-pot synthesis of 3D intercon-nected magnetic-dielectric frameworks via pre-functionalization and subsequent assembly.Multiple in-teractions among discrete precursors are capable of manipulating the confined growth and interfacial self-assembly.Significant enhancements in MA properties are triggered in a straightforward manner us-ing ultralow feeding fractions of graphene oxide nanosheet.The minimum reflection loss is up to-60.1 dB(99.9999%wave absorption)and the effective absorption bandwidth reaches 5.9 GHz(almost covering the Ku band).Remarkably,based on the optimization by ultralow concentrations of graphene,the as-prepared nanoarchitecture simultaneously integrates strong absorption,broad bandwidth,and low matching thick-ness.The embedded graphene nanosheets serve as high-speed electron transmission channels and hollow resonance cavities,facilitating multimode attenuations and impedance-matching characteristics.Mean-while,the graphene-reinforced framework suppresses the corrosion of magnetic components,whose cor-rosion rate reduces by an order of magnitude.This study provides a simple procedure to boost magnetic-dielectric absorbers for comprehensive MA performances and enhanced corrosion resistance.

关键词： 3D Magnetic-dielectric framework Graphene nanosheet Microwave absorption Anti-corrosion

Genetic mutation of Tas2r104/Tas2r105/Tas2r114 cluster leads to a loss of taste perception to denatonium benzoate and cucurbitacin B

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Animal Models and Experimental Medicine 2024年第3期7卷 324-336页

作者： Bowen Niu lingling Liu Qian Gao Meng-Min zhu Lixiang Chen Xiu-Hua Peng Boying Qin Xiaohui Zhou Feng Li Department of Laboratory Animal Science Shanghai Public Health Clinical CenterFudan UniversityShanghaiChina Department of Biology College of Life SciencesShanghai Normal UniversityShanghaiPeople's Republic of China

Background:Bitter taste receptors(Tas2rs)are generally considered to sense various bitter compounds to escape the intake of toxic substances.Bitter taste receptors have been found to widely express in extraoral tissues and have important physiological functions outside the gustatory system in vivo.Methods:To investigate the physiological functions of the bitter taste receptor cluster Tas2r106/Tas2r104/Tas2r105/Tas2r114 in lingual and extraoral tissues,multiple Tas2rs mutant mice and Gnat3 were produced using CRISPR/Cas9 gene-editing technique.A mixture containing Cas9 and sgRNA mRNAs for Tas2rs and Gnat3 gene was microinjected into the cytoplasm of the zygotes.Then,T7EN1 assays and sequencing were used to screen genetic mutation at the target sites in founder mice.Quantitative real-time polymerase chain reaction(qRT-PCR)and immunostaining were used to study the expression level of taste signaling cascade and bitter taste receptor in taste buds.Perception to taste substance was also studied using twobottle preference tests.Results:We successfully produced several Tas2rs and Gnat3 mutant mice using the CRISPR/Cas9 technique.Immunostaining results showed that the expression of GNAT3 and PLCB2 was not altered in Tas2rs mutant mice.But qRT-PCR results revealed the changed expression profile of m Tas2rs gene in taste buds of these mutant mice.With two-bottle preference tests,these mutant mice eliminate responses to cycloheximide due to genetic mutation of Tas2r105.In addition,these mutant mice showed a loss of taste perception to quinine dihydrochloride,denatonium benzoate,and cucurbitacin B(CuB).Gnat3-mediated taste receptor and its signal pathway contribute to CuB perception.Conclusions:These findings implied that these mutant mice would be a valuable means to understand the biological functions of TAS2Rs in extraoral tissues and investigate bitter compound-induced responses mediated by these TAS2Rs in many extraoral tissues.

关键词： bitter taste receptor CRISPR/Cas9 genetic mutation two-bottle preference test type 2 taste receptors(Tas2rs)

Clinical features and treatment modalities of rare choroid metastasis from lung malignancy

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Chinese Medical Journal 2022年第13期135卷 1628-1630页

作者： Zihan Qu Jiewei Liu lingling zhu Qinghua Zhou Lung Cancer Center West China Hospital of Sichuan UniversityChengduSichuan 610041China Lung Cancer Research Institute West China Hospital of Sichuan UniversityChengduSichuan 610041China Key Laboratory of Drug Targeting and Drug Delivery System of the Education Ministry Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyCollege of Polymer Science and EngineeringWest China School of PharmacySichuan UniversityChengduSichuan 610041China.

To the Editor:The incidence of intraocular metastases is approximately 8%to 10%,[1]of which choroidal metastasis(CM)is the most painful metastatic lesion.CM is a growing problem in the context of an aging population and improved survival among stage IV cancer patients.Lung cancer is the second most common primary malignancy associated with CM.Clinical symptoms vary greatly depending on the location of the lesion or the degree of invasion.Acute clinical symptoms will significantly impair quality of life among surviving patients.The main therapeutic modalities include systemic and local treatments,while observation is also a treatment option.Currently,the feasibility and effectiveness of various treatment options are controversial around the world.Given the rarity of this condition,it is almost impossible to conduct large-scale clinical trials to validate optimal treatment modalities,rather,clues and insights may derive from a series of small sample reports.Herein,we reviewed the related literature from 2009 to 2019,from which relevant information was extracted to elucidate the epidemiological and clinical characteristics of CM and to provide suggestions for the treatment of this condition.

关键词： metastasis modalities malignancy

Ni/Co bimetallic organic frameworks nanospheres for highperformance electrochemical energy storage

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Nano Research 2024年第6期17卷 5122-5130页

作者： Jianru Guan Minlu Liu Limin zhu Jiamei Wang Qing Han Xiaoxia Yang Weibo Hua lingling Xie Xiaoyu Cao School of Chemistry and Chemical Engineering Key Laboratory of High Specific Energy Materials for Electrochemical Power Sources of Zhengzhou CityHenan University of TechnologyZhengzhou 450001China School of Chemical Engineering and Technology Xi’an Jiaotong UniversityXi’an 710049China School of Environmental Engineering Henan University of TechnologyZhengzhou 450001China

In addition to their many well-known advantages(e.g.,ultra-high porosity,good pore size distribution,easy functionalization,and structural tolerability),metal-organic frameworks(MOFs)are a new class of advanced functional materials.However,their backbones are highly susceptible to deformation after exposure to acidic or alkaline conditions.As a result of lithium-ion batteries embedding or detaching directly from MOFs,they irreversibly collapse.As a result,they fail to maintain their electrochemical performance.These factors have hindered the development of MOFs as direct electrode materials,making the design of MOF materials with controlled morphology and stable dimensions a new challenge.In this study,we adopted a versatile and effective method to synthesize a novel MOF material(NiCo-BP(BP=BTC/phen and BTC=1,3,5-benzenetricarboxylic acid))using the rigid ligands 1,10-phenanthroline and homobenzotrizoic acid,and the emergence of the Ni-O/N and Co-O/N coordination layers was observed by extended X-ray absorption fine structure(EXAFS)tests,indicating that Ni and Co were coordinated with heterocyclic N-given atoms to form a stable p-πconjugated structure.Meanwhile,the metal-ion is attached to the carboxylic acid ligand on the other side,making the metal-organic skeleton complete and robust.The nanosphere structure of NiCo-BP(~400 nm)allows for full exposure and utilisation of the active sites,especially the Ni,Co,and phenanthroline units,and exhibit impressively high specific capacity and cycling stability.At a high current density of 1.0 A·g^(−1),a high discharge specific capacity of 631.6 mAh·g^(−1)was obtained after 1000 cycles.The co-participation of two organic ligands in the coordination is in accordance with the theory of soft and hard acids and bases,which contributes to the ability of the material to maintain a high capacity in cycling as well as its cyclic stability.

关键词： lithium-ion batteries metal organic frame electrochemical energy storage dual ligand hard-soft-acid-base

Immune cell membrane-based biomimetic nanomedicine for treating cancer metastasis

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药学学报:英文版 2023年第6期13卷 2464-2482页

作者： lingling zhu Xianzhe Yu Ting Cao Hanyu Deng Xiaojun Tang Qing Lin Qinghua Zhou Lung Cancer Center/Lung Cancer Institute West China Hospital&West China School of PharmacyKey Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan ProvinceSichuan UniversityChengdu 610065China Department of Gastrointestinal Surgery Chengdu Second People's HospitalChengdu 610065China Laboratory of Infectious Diseases and Vaccine West China HospitalSichuan UniversityChengdu 610065China

Metastasis is the leading cause of cancer-related death.Despite extensive treatment,the prognosis for patients with metastatic cancer remains poor.In addition to conventional surgical resection,radiotherapy,immunotherapy,chemotherapy,and targeted therapy,various nanobiomaterials have attracted attention for their enhanced antitumor performance and low off-target effects.However,nanomedicines exhibit certain limitations in clinical applications,such as rapid clearance from the body,low biological stability,and poor targeting ability.Biomimetic methods utilize the natural biomembrane to mimic or hybridize nanoparticles and circumvent some of these limitations.Considering the involvement of immune cells in the tumor microenvironment of the metastatic cascade,biomimetic methods using immune cell membranes have been proposed with unique tumor-homing ability and high biocompatibility.In this review,we explore the impact of immune cells on various processes of tumor metastasis.Furthermore,we summarize the synthesis and applications of immune cell membrane-based nanocarriers increasing therapeutic efficacy against cancer metastases via immune evasion,prolonged circulation,enhanced tumor accumulation,and immunosuppression of the tumor microenvironment.Moreover,we describe the prospects and existing challenges in clinical translation.

关键词： Biomimetic nanoparticles Cancer metastasis Tumor microenvironment Immune system Immune cell membrane Tumor-homing Biocompatibility

Evolving landscape of treatments targeting the microenvironment of liver metastases in non-small cell lung cancer

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中华医学杂志(英文版) 2024年第9期137卷 2024 Jan 22页

作者： zhu lingling Yu Xianzhe Tang Xiaojun Hu Chenggong Wu Lei Liu Yanyang Zhou Qinghua Lung Cancer Center Lung Cancer Institute West China Hospital Sichuan University Chengdu Sichuan China Key Laboratory of Drug Targeting and Drug Delivery Systems Ministry of Education West China School of Pharmacy College of Polymer Science and Engineering Sichuan University Chengdu Sichuan China Department of Gastrointestinal Surgery Chengdu Second People’s Hospital Chengdu Sichuan China Department of Critical Care Medicine West China Hospital Sichuan University Chengdu Sichuan China Core Facility of West China Hospital Sichuan University Chengdu Sichuan China Department of Medical Oncology Cancer Center West China Hospital Sichuan University Chengdu Sichuan China

Liver metastases (LMs) are common in lung cancer. Despite substantial advances in diagnosis and treatment, the survival rate of patients with LM remains low as the immune-suppressive microenvironment of the liver allows tumor cells to evade the immune system. The impact of LMs on the outcomes of immune checkpoint inhibitors in patients with solid tumors has been the main focus of recent translational and clinical research. Growing evidence indicates that the hepatic microenvironment delivers paracrine and autocrine signals from non-parenchymal and parenchymal cells. Overall, these microenvironments create pre- and post-metastatic conditions for the progression of LMs. Herein, we reviewed the epidemiology, physiology, pathology and immunology, of LMs associated with non-small cell lung cancer and the role and potential targets of the liver microenvironment in LM in each phase of metastasis. Additionally, we reviewed the current treatment strategies and challenges that should be overcome in preclinical and clinical investigations. These approaches target liver elements as the basis for future clinical trials, including combinatorial interventions reported to resolve hepatic immune suppression, such as immunotherapy plus chemotherapy, immunotherapy plus radiotherapy, immunotherapy plus anti-angiogenesis therapy, and surgical resection.

关键词： Non-small cell lung cancer Liver metastasis Combination therapy Immune checkpoint inhibitors Immune tolerance Immunotherapy