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Impact of short-term ambient air pollution exposure on the risk of severe COVID-19

Journal of Environmental Sciences 2024年第1期135卷 610-618页

作者： Baihuan Feng Jiangshan Lian Fei Yu Dan Zhang Weizhen Chen QiWang Yifei Shen Guoliang Xie Ruonan Wang Yun Teng Bin Lou Shufa Zheng Yida Yang Yu Chen Department of Laboratory Medicine The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China Key Laboratory of Clinical In vitro Diagnostic Techniques of Zhejiang Province Hangzhou 310000China Institute of Laboratory Medicine Zhejiang UniversityHangzhou 310000China Department of Infectious Diseases The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious Diseasesthe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China

Ecological studies suggested a link between air pollution and severe COVID-19 outcomes,while studies accounting for individual-level characteristics are *** the present study,we aimed to investigate the impact of short-term ambient air pollution exposure on disease severity among a cohort of 569 laboratory confirmed COVID-19 patients admitted to designated hospitals in Zhejiang province,China,from January 17 to March 3,2020,and elucidate the possible biological processes involved using *** with mild cases,severe cases had higher proportion of medical conditions as well as unfavorable results in most of the laboratory tests,and manifested higher air pollution exposure *** exposure to air pollutants was associated with increased risk of severe COVID-19 with odds ratio(OR)of 1.89(95%confidence interval(CI):1.01,3.53),2.35(95%CI:1.20,4.61),2.87(95%CI:1.68,4.91),and 2.01(95%CI:1.10,3.69)for PM_(2.5),PM_(10),NO_(2)and CO,*** for NO_(2)remained significant in two-pollutant models after adjusting for other *** analysis showed 884 differentially expressed genes which mainly were enriched in virus clearance related biological processes between patients with high and low NO_(2)exposure levels,indicating that compromised immune response might be a potential underlying mechanistic *** findings highlight the impact of shortterm air pollution exposure,particularly for NO_(2),on COVID-19 severity,and emphasize the significance in mitigating the COVID-19 burden of commitments to improve air quality.

关键词： Air pollution COVID-19 Severity Transcriptomics Immune response

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Enhancing metformin-induced tumor metabolism destruction by glucose oxidase for triple-combination therapy

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Journal of Pharmaceutical Analysis 2024年第3期14卷 321-334页

作者： Rangrang Fan Linrui Cai Hao Liu Hongxu Chen Caili Chen Gang Guo Jianguo Xu Department of Neurosurgery and Institute of Neurosurgery Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu610041China NMPA Key Laboratory for Technical Research on Drug Products in vitro and in Vivo Correlation Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOENational Drug Clinical-Trial InstitutionWest China Second HospitalSichuan UniversityChengdu610041China Department of Immunology School of Basic Medical SciencesXinxiang Medical UniversityXinxiangHenan453000China

Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in *** the metabolism destruction effect of metformin(Met)and cancer cell starvation induced by glucose oxidase(GOx),after their efficient delivery to tumor sites,GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in ***,a pH-responsive epigallocatechin gallate(EGCG)-conjugated low-molecular-weight chitosan(LC-EGCG,LE)nanoparticle(Met–GOx/Fe@LE NPs)was *** coordination between iron ions(Fe3+)and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton ***–GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its ***,this pH-responsive nanoplatform presents controllable drug release *** in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nanoplatform was 3.6-fold higher than that of the free *** in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their *** triple-combination therapy approach is promising for efficient and targeted cancer treatment.

关键词： Metformin Glucose oxidase Metabolism disruption Tumor starvation Combination cancer therapy

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Zinc-based metal-organic frameworks as efficient carriers for anticancer drug to reduce toxicity and increase efficacy

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Rare Metals 2024年第10期43卷 5152-5163页

作者： Dong-Wei Ma Jing-Sheng Lu Xiang-Xin Cao Yan-Wei Cheng Gang Wang Zi-Qian Zhang Bo-Cheng Chen Ning Lin Qing Chen College of Pharmacy Guangxi Scientific Research Center of Traditional Chinese MedicineGuangxi University of Chinese Medicine Guangxi Zhuang Yao Medicine center of Engineering and Technology

The rational design of a specific co-drug delivery platform that can address the unavoidable resistance, toxic side effects and low targeting efficiency of traditional cancer treatments is of great ***, Zn-based MOF-zeolitic imidazole framework-90(ZIF-90) was selected as the drug delivery carrier, with the cancer therapeutic drug mercaptopurine(6-MP) and glucose oxidase(GOD) as the drug models, hyaluronic acid(HA) was used for protection and targeted delivery, which designed and fabricated an intelligent drug delivery platform(6-MP@ZIF-90@GOD@HA). This platform aims to reduce the toxic side effects of 6-MP and enhance its efficacy while improving the targeting ability of GOD,thereby further enhancing the treatment outcome. Notably,results from both in vitro and in vivo experiments demonstrate that the targeted synergistic chemo/reactive oxygen species(ROS)-mediated/starvation therapy inhibited the cancer cell growth while reducing the chemotherapy toxicity, which provides new possibilities for the development of more precise and effective treatment strategies.

关键词： Cancer treatment Combination therapy Drug delivery Metal-organic framework Reduced toxicity

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Fabrication of micro-nano patterned materials mimicking the topological structure of extracellular matrix for biomedical applications

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Nano Research 2024年第5期17卷 4244-4258页

作者： Yifeng Nie Dong Han Xiang Li CAS center for Excellence in Nanoscience National Center for Nanoscience and TechnologyBeijing 100190China School of Future Technology University of Chinese Academy of SciencesBeijing 100049China

With the advent of tissue engineering and biomedicine,the creation of extracellular matrix(ECM)biomaterials for in vitro applications has become a prominent and promising *** ECM materials provide physical,biochemical,and mechanical properties that guide cellular behaviors,such as proliferation,differentiation,migration,and *** micro-and nano-patterned materials have a unique surface topology and low energy replication process that directly affect cellular biological behaviors at the interface,the fabrication of micro-nano pattern biomaterials and the regulation of surface physical and chemical properties are of great significance in the fields of cell regulation,tissue engineering,and regenerative ***,we provide a comprehensive review of the progress in the fabrication and application of patterned materials based on the coupling of mechanical action at the micro-and nano-meter scale,including photolithography,micro-contact printing,electron beam lithography,electrospinning,and 3D printing ***,a summary of the fabrication process,underlying principles,as well as the advantages and disadvantages of various technologies are *** also discuss the influence of material properties on the fabrication of micro-and nano-patterns.

关键词： micro/nano hybrid materials patterning fabrication techniques extracellular matrix substrate-cell interaction biomedical engineering

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The Effect and Mechanism of Fructus lycii on Improvement of Exercise Fatigue Using a Network Pharmacological Approach with in vitro Experimental Verification

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Biomedical and Environmental Sciences 2024年第1期37卷 42-53页

作者： JI Xiao Ning LIU Zhao Ping ZHANG Chao Zheng CHEN Min LIANG Jiang LU Jiang ZHANG Lei National Resource center for Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing 100700China China National center for Food Safety Risk Assessment Beijing 100022China Chinese center for Disease Control and Prevention Beijing 102206China

Objective This study aimed to investigate the effect and underlying mechanism of Fructus lycii in improving exercise *** A network pharmacological approach was used to explore potential mechanisms of action of Fructus *** muscle C2C12 cells and immunofluorescence were employed to verify the effect and mechanism of the representative components in Fructus lycii predicted by network pharmacological *** Six potential active components,namely quercetin,β-sitosterol,stigmasterol,7-Omethylluteolin-6-C-beta-glucoside_qt,atropine,and glycitein,were identified to have potency in improving exercise fatigue via multiple pathways,such as the PI3K-Akt,neuroactive ligand-receptor interaction,IL-17,TNF,and MAPK signaling *** immunofluorescence results indicated that quercetin,a significant active component in Fructus lycii,increased the mean staining area of 2-NBDG,TMRM,and MitoTracker,and decreased the area of CellRox compared to the ***,the protein expression levels of p-38 MAPK,p-MAPK,p-JNK,p-PI3K,and p-AKT markedly increased after quercetin *** Fructus lycii might alleviate exercise fatigue through multiple components and *** these,quercetin appears to improve exercise fatigue by enhancing energy metabolism and reducing oxidative *** PI3K-AKT and MAPK signaling pathways also appear to play a role in this process.

关键词： Fructus lycii Exercise fatigue Network pharmacology

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RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

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Military Medical Research 2024年第1期11卷 34-49页

作者： Yi-Qun Li Fang-Zhou Sun Chun-Xiao Li Hong-Nan Mo Yan-Tong Zhou Dan Lv Jing-Tong Zhai Hai-Li Qian Fei Ma Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor *** the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment *** evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully *** Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of *** investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo *** signaling pathway components were evaluated using multi-omics *** were performed to elucidate the regulation of lipid metabolic reprogramming of *** We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic ***,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain *** Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of ***2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

关键词： RARRES2 Lipid metabolic reprogramming Brain metastasis(BrM) Breast cancer

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MicroRNA-502-3p regulates GABAergic synapse function in hippocampal neurons

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Neural Regeneration Research 2024年第12期19卷 2698-2707页

作者： Bhupender Sharma Melissa MTorres Sheryl Rodriguez Laxman Gangwani Subodh Kumar center of Emphasis in Neuroscience Department of Molecular and Translational MedicinePaul L.Foster School of MedicineTexas Tech University Health Sciences CenterEl PasoTXUSA Bond Life Sciences center and Department of Veterinary Pathobiology University of MissouriColumbiaMOUSA L.Frederick Francis Graduate School of Biomedical Sciences Texas Tech University Health Sciences CenterEl PasoTXUSA

Gamma-aminobutyric acid(GABA)ergic neurons,the most abundant inhibitory neurons in the human brain,have been found to be reduced in many neurological disorders,including Alzheimer's disease and Alzheimer's disease-related *** previous study identified the upregulation of microRNA-502-3p(miR-502-3p)and downregulation of GABA type A receptor subunitα-1 in Alzheimer's disease *** study investigated a new molecular relationship between miR-502-3p and GABAergic synapse *** vitro studies were perfo rmed using the mouse hippocampal neuronal cell line HT22 and miR-502-3p agomiRs and *** silico analysis identified multiple binding sites of miR-502-3p at GABA type A receptor subunitα-1 *** assay confirmed that miR-502-3p targets the GABA type A receptor subunitα-1 gene and suppresses the luciferase ***,quantitative reve rse transcription-polymerase chain reaction,miRNA in situ hybridization,immunoblotting,and immunostaining analysis confirmed that overexpression of miR-502-3p reduced the GABA type A receptor subunitα-1 level,while suppression of miR-502-3p increased the level of GABA type A receptor subunitα-1 ***,as a result of the overexpression of miR-502-3p,cell viability was found to be reduced,and the population of necrotic cells was found to be *** whole cell patch-clamp analysis of human-GABA receptor A-α1/β3/γ2L human embryonic kidney(HEK)recombinant cell line also showed that overexpression of miR-502-3p reduced the GABA current and overall GABA function,suggesting a negative correlation between miR-502-3p levels and GABAergic synapse ***,the levels of proteins associated with Alzheimer s disease were high with miR-502-3p overexpression and reduced with miR-502-3p *** present study provides insight into the molecular mechanism of regulation of GABAergic synapses by *** propose that micro-RNA,in particular miR-502-3p,could be a potential the

关键词： Alzheimer's disease GABAergic synapse gamma-aminobutyric acid type A receptor subunitα-1(GABRα1) microRNA-502-3p(miR-502-3p) miRNA in situ hybridization Patch-clamp

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Novel PLCZ1 mutation caused polyspermy during in vitro fertilization

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Asian Journal of Andrology 2024年第4期26卷 389-395页

作者： Ke-Ya Tong Wei-Wei Liu Li-Wei Sun Dong-Yun Liu Ye-Zhou Xiang Chong Li Lu-Wei Chai Ke Chen Guo-Ning Huang Jing-Yu Li Chongqing Key Laboratory of Human Embryo Engineering Center for Reproductive MedicineWomen and Children’s Hospital of Chongqing Medical UniversityChongqing 400012China Chongqing Clinical Research center for Reproductive Medicine Center for Reproductive MedicineChongqing Health Center for Women and ChildrenChongqing 400012China.

Failure of oocyte activation,including polyspermy and defects in pronuclear(PN)formation,triggers early embryonic developmental *** studies have shown that phospholipase C zeta 1(PLCZ1)mutations cause failure of PN formation following intracytoplasmic sperm injection(ICSI);however,whether PLCZ1 mutation is associated with polyspermy during in vitro fertilization(IVF)remains ***-exome sequencing(WES)was performed to identify candidate mutations in couples with primary *** sequencing was used to validate the *** PLCZ1-mutated sperm were injected into human and mouse oocytes to explore whether PN formation was *** oocyte activation(AOA)after ICSI was performed to overcome the failure of oocyte *** identified three PLCZ1 mutations in three patients who experienced polyspermy during IVF cycles,including a novel missense mutation c.1154C>T,*** formation failure was observed during the ICSI ***,injection of multiple PLCZ1-mutated sperm induced PN formation,suggesting that the Ca2+oscillations induced by the sperm exceeded the necessary threshold for PN *** after ICSI enabled normal fertilization,and all patients achieved successful *** findings expand the mutational spectrum of PLCZ1 and suggest an important role for PLCZ1 in terms of blocking ***,this study may benefit genetic diagnoses in cases of abnormal fertilization and provide potential appropriate therapeutic measures for these patients with sperm-derived polyspermy.

关键词： AOA PLCZ1 polyspermy pronuclear formation

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Drug repurposing screening and mechanism analysis based on human colorectal cancer organoids

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Protein & Cell 2024年第4期15卷 285-304页

作者： Yunuo Mao Wei Wang Jingwei Yang Xin Zhou Yongqu Lu Junpeng Gao Xiao Wang Lu Wen Wei Fu Fuchou Tang School of Life Sciences Biomedical Pioneering Innovation CenterDepartment of General SurgeryThird HospitalPeking UniversityBeijing 100871China Beijing Advanced Innovation center for Genomics(ICG) Ministry of Education Key Laboratory of Cell Proliferation and DifferentiationBeijing 100871China Peking-Tsinghua center for Life Sciences Peking UniversityBeijing 100871China Peking University Third Hospital Cancer center Beijing 100871China The Research center of Stem Cell and Regenerative Medicine School of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China

Colorectal cancer(CRC)is a highly heterogeneous cancer and exploring novel therapeutic options is a pressing issue that needs to be ***,we established human CRC tumor-derived organoids that well represent both morphological and molecular heterogeneities of original *** efficiently identify repurposed drugs for CRC,we developed a robust organoid-based drug screening *** combining the repurposed drug library and computation-based drug prediction,335 drugs were tested and 34 drugs with anti-CRC effects were *** importantly,we conducted a detailed transcriptome analysis of drug responses and divided the drug response signatures into five representative patterns:differentiation induction,growth inhibition,metabolism inhibition,immune response promotion,and cell cycle *** anticancer activities of drug candidates were further validated in the established patient-derived organoids-based xenograft(PDOX)system in *** found that fedratinib,trametinib,and bortezomib exhibited effective anticancer ***,the concordance and discordance of drug response signatures between organoids in vitro and pairwise PDOX in vivo were *** study offers an innovative approach for drug discovery,and the representative transcriptome features of drug responses provide valuable resources for developing novel clinical treatments for CRC.

关键词： colorectal cancer organoids drug repurposing patient-derived organoids-based xenograft mechanism of action

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Force-induced Caspase-1-dependent pyroptosis regulates orthodontic tooth movement

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International Journal of Oral Science 2024年第2期16卷 238-250页

作者： Liyuan Chen Huajie Yu Zixin Li Yu Wang Shanshan Jin Min Yu Lisha Zhu Chengye Ding Xiaolan Wu Tianhao Wu Chunlei Xun Yanheng Zhou Danqing He Yan Liu Department of Orthodontics Central LaboratoryPeking University School and Hospital for Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical Devices&Beijing Key Laboratory of Digital Stomatology&Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health&NMPA Key Laboratory for Dental Materials&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijingChina Peking University Hospital of Stomatology Fourth Division BeijingChina

Pyroptosis,an inflammatory caspase-dependent programmed cell death,plays a vital role in maintaining tissue homeostasis and activating inflammatory *** tooth movement(OTM)is an aseptic force-induced inflammatory bone remodeling process mediated by the activation of periodontal ligament(PDL)progenitor ***,whether and how force induces PDL progenitor cell pyroptosis,thereby influencing OTM and alveolar bone remodeling remains *** this study,we found that mechanical force induced the expression of pyroptosis-related markers in rat OTM and alveolar bone remodeling *** or enhancing pyroptosis level could suppress or promote OTM and alveolar bone remodeling *** Caspase-1^(−/−)mice,we further demonstrated that the functional role of the force-induced pyroptosis in PDL progenitor cells depended on ***,mechanical force could also induce pyroptosis in human ex-vivo force-treated PDL progenitor cells and in compressive force-loaded PDL progenitor cells in vitro,which influenced ***,transient receptor potential subfamily V member 4 signaling was involved in force-induced Caspase-1-dependent pyroptosis in PDL progenitor ***,this study suggested a novel mechanism contributing to the modulation of osteoclastogenesis and alveolar bone remodeling under mechanical stimuli,indicating a promising approach to accelerate OTM by targeting Caspase-1.

关键词： homeostasis movement thereby

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