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Pseudomonas aeruginosa:pathogenesis,virulence factors,antibiotic resistance,interaction with host,technology advances and emerging therapeutics

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Signal Transduction and Targeted Therapy 2022年第7期7卷 2396-2422页

作者： Shugang Qin Wen Xiao Chuanmin zhou qinqin Pu Xin Deng Lefu Lan Haihua Liang Xiangrong Song Min Wu Department of Critical Care Medicine Frontiers Science Center for Disease-related Molecular NetworkState Key Laboratory of Biotherapy and Cancer CenterWest China HospitalSichuan UniversityChengduChina State Key Laboratory of Virology School of Public HealthWuhan UniversityWuhan 430071P.R.China Department of Biomedical Sciences School of Medicine and Health SciencesUniversity of North DakotaGrand ForksND 58203USA Department of Biomedical Sciences City University of Hong KongHong KongPeople’s Republic of China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China College of Life Sciences Northwest UniversityXi’anShaanXi 710069China

Pseudomonas aeruginosa(***)is a Gram-negative opportunistic pathogen that infects patients with cystic fibrosis,burn wounds,immunodeficiency,chronic obstructive pulmonary disorder(COPD),cancer,and severe infection requiring ventilation,such as *** is also a widely-used model bacterium for all biological *** addition to continued,intense efforts in understanding bacterial pathogenesis of *** including virulence factors(LPS,quorum sensing,two-component systems,6 type secretion systems,outer membrane vesicles(OMVs),CRISPR-Cas and their regulation),rapid progress has been made in further studying host-pathogen interaction,particularly host immune networks involving autophagy,inflammasome,noncoding RNAs,cGAS,***,numerous technologic advances,such as bioinformatics,metabolomics,scRNA-seq,nanoparticles,drug screening,and phage therapy,have been used to improve our understanding of *** pathogenesis and host ***,much remains to be uncovered about interactions between *** and host immune responses,including mechanisms of drug resistance by known or unannotated bacterial virulence factors as well as mammalian cell signaling *** widespread use of antibiotics and the slow development of effective antimicrobials present daunting challenges and necessitate new theoretical and practical platforms to screen and develop mechanism-tested novel drugs to treat intractable infections,especially those caused by multi-drug resistance *** from has advancing in research tools and technology,dissecting this pathogen’s feature has entered into molecular and mechanistic details as well as dynamic and holistic ***,we comprehensively review the progress and discuss the current status of *** biophysical traits,behaviors,virulence factors,invasive regulators,and host defense patterns against its infection,which point out new directions for future investigation and add to

关键词： pathogenesis resistance interaction

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ANAC087 transcription factor positively regulates age-dependent leaf senescence through modulating the expression of multiple target genes in Arabidopsis

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Journal of Integrative Plant Biology 2023年第4期65卷 967-984页

作者： qinqin Chen Jingli Yan Tiantian Tong Peiyu Zhao Shuangshuang Wang Na zhou Xing Cui Moyu Dai Yuan‐Qing Jiang Bo Yang State Key Laboratory of Crop Stress Biology for Arid Areas College of Life SciencesNorthwest A&F UniversityYangling 712100China College of Plant Protection Henan Agricultural UniversityZhengzhou 450002China

Leaf senescence is the final stage of leaf development and appropriate onset and progression of leaf senescence are critical for reproductive success and *** great progress has been made in identifying key genes regulating leaf senescence and elucidating the underlining mechanisms in the model plant Arabidopsis,there is still a gap to understanding the complex regulatory *** this study,we discovered that Arabidopsis ANAC087 transcription factor(TF)positively modulated leaf *** of ANAC087 was induced in senescing leaves and the encoded protein acted as a transcriptional *** constitutive and inducible overexpression lines of ANAC087 showed earlier senescence than control plants,whereas T-DNA insertion mutation and dominant repression of the ANAC087 delayed senescence rate.A quantitative reverse transcription-polymerase chain reaction(qRT-PCR)profiling showed that the expression of an array of senescence-associated genes was upregulated in inducible ANAC087 overexpression plants including BFN1,NYE1,CEP1,RbohD,SAG13,SAG15,and VPEs,which are involved in programmed cell death(PCD),chlorophyll degradation and reactive oxygen species(ROS)*** addition,electrophoretic mobility shift assay(EMSA)and chromatin immunoprecipitation-quantitative polymerase chain reaction(ChIP-qPCR)assays demonstrated that ANAC087 directly bound to the canonical NAC recognition sequence(NACRS)motif in promoters of its target ***,mutation of two representative target genes,BFN1 or NYE1 alleviated the senescence rate of ANAC087-overexpression plants,suggesting their genetic regulatory *** together,this study indicates that ANAC087serves as an important regulator linking PCD,ROS,and chlorophyll degradation to leaf senescence.

关键词： ANAC087 chlorophyll degradation leaf senescence NAC transcription factor programmed cell death reactive oxygen species

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Overexpression of low-density lipoprotein receptor prevents neurotoxic polarization of astrocytes via inhibiting NLRP3 inflammasome activation in experimental ischemic stroke

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Neural Regeneration Research 2025年第2期20卷 491-502页

作者： Shuai Feng Juanji Li Tingting Liu Shiqi Huang Xiangliang Chen Shen Liu Junshan zhou Hongdong Zhao Ye Hong Department of Neurology Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina Department of Neurology Nanjing Jinling HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu ProvinceChina

Neurotoxic astrocytes are a promising therapeutic target for the attenuation of cerebral ischemia/reperfusion ***-density lipoprotein receptor,a classic cholesterol regulatory receptor,has been found to inhibit NLR family pyrin domain containing protein 3(NLRP3)inflammasome activation in neurons following ischemic stroke and to suppress the activation of microglia and astrocytes in individuals with Alzheimer’s ***,little is known about the effects of low-density lipoprotein receptor on astrocytic activation in ischemic *** address this issue in the present study,we examined the mechanisms by which low-density lipoprotein receptor regulates astrocytic polarization in ischemic stroke ***,we examined low-density lipoprotein receptor expression in astrocytes via immunofluorescence staining and western blotting *** observed significant downregulation of low-density lipoprotein receptor following middle cerebral artery occlusion reperfusion and oxygen-glucose deprivation/***,we induced the astrocyte-specific overexpression of low-density lipoprotein receptor using astrocyte-specific adeno-associated ***-density lipoprotein receptor overexpression in astrocytes improved neurological outcomes in middle cerebral artery occlusion mice and reversed neurotoxic astrocytes to create a neuroprotective ***,we found that the overexpression of low-density lipoprotein receptor inhibited NLRP3 inflammasome activation in oxygen-glucose deprivation/reoxygenation injured astrocytes and that the addition of nigericin,an NLRP3 agonist,restored the neurotoxic astrocyte *** findings suggest that low-density lipoprotein receptor could inhibit the NLRP3-meidiated neurotoxic polarization of astrocytes and that increasing low-density lipoprotein receptor in astrocytes might represent a novel strategy for treating cerebral ischemic stroke.

关键词： inflammation ischemia/reperfusion injury ischemic stroke low-density lipoprotein receptor neuroprotective astrocytes neurotoxic astrocytes NLRP3 inflammasome polarization

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Photo-manipulated polyunsaturated fatty acid-doped liposomal hydrogel for flexible photoimmunotherapy

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Chinese Chemical Letters 2024年第4期35卷 268-274页

作者： Xinyue Lan Junguang Liang Churan Wen Xiaolong Quan Huimin Lin qinqin Xu Peixian Chen Guangyu Yao Dan zhou Meng Yu Breast Center Department of General SurgeryNanfang HospitalSouthern Medical UniversityGuangzhou 510515China NMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Breast Surgery The First People's Hospital of FoshanFoshan 528100China Zhujiang Hospital Southern Medical UniversityGuangzhou 510282China

Despite the synergy of immune checkpoint blockade(ICB) therapy and photodynamic therapy(PDT) holds great promise as countermeasures against breast cancer, exploring long-term or flexible short-time therapeutic strategies in “cold” tumors remains a great challenge. Here, we present a polyunsaturated fatty acid-doped liposomal hydrogel Lp(DHA)@CP Gel loaded with photosensitizer chlorin e6(Ce6) and programmed death-ligand 1 antibody(αPD-L1) for flexible local photoimmunotherapy with merely singledosed administration. The presence of polyunsaturated fatty acid(docosahexaenoic acid, DHA) doped in particle membrane endows liposomes with flexibly reactive oxygen species(ROS)-responsive release capability, which was attributed to the presence of abundant unsaturated groups. The αPD-L1 was repeatedly induced to in situ release in response to the PDT under photo-exposure. The immunogenic cell death(ICD) effect of PDT evoked “cold” breast tumor to “hot” one, and then assisted the cascade releasedαPD-L1 to synergistically boost the immunotherapy. After a single dose of peritumoral administration of Lp(DHA)@CP Gel, the on-demand treatment can maximize patient compliance and safety by adjusting therapeutic behaviors via a photo on-off switch. This work presents a flexible medication platform,showing promise in improving the objective response rate of ICB therapy and minimizing its systemic toxicity.

关键词： Photodynamic therapy Immunotherapy Responsive release Immunogenic cell death Liposomal hydrogel

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Recombinant chitinase-3-like protein 1 alleviates learning and memory impairments via M2 microglia polarization in postoperative cognitive dysfunction mice

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Neural Regeneration Research 2025年第9期20卷 2727-2736页

作者： Yujia Liu Xue Han Yan Su Yiming zhou Minhui Xu Jiyan Xu Zhengliang Ma Xiaoping Gu Tianjiao Xia Department of Anesthesiology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu ProvinceChina Medical School Nanjing UniversityNanjingJiangsu ProvinceChina Jiangsu Key Laboratory of Molecular Medicine Nanjing UniversityNanjingJiangsu ProvinceChina State Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjingJiangsu ProvinceChina Department of Anesthesiology Zhongshan HospitalFudan UniversityShanghaiChina

Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of *** date,there are no viable treatment options for postoperative cognitive *** identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future *** identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial *** dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub ***,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re *** were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning *** addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western *** with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expr

关键词： Chil1 hippocampus learning and memory M2 microglia neuroinflammation postoperative cognitive dysfunction(POCD) recombinant CHI3L1

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Establishment of human cerebral organoid systems to model early neural development and assess the central neurotoxicity of environmental toxins

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Neural Regeneration Research 2025年第1期20卷 242-252页

作者： Daiyu Hu Yuanqing Cao Chenglin Cai Guangming Wang Min zhou Luying Peng Yantao Fan Qiong Lai Zhengliang Gao Fundamental Research Center Shanghai Yangzhi Rehabilitation Hospital(Shanghai Sunshine Rehabilitation Center)School of MedicineTongji UniversityShanghaiChina Institute of Geriatrics(Shanghai University) Affiliated Nantong Hospital of Shanghai University(The Sixth People’s Hospital of Nantong)Shanghai University School of MedicineNantongJiangsu ProvinceChina Shanghai Engineering Research Center of Organ Repair Shanghai University School of MedicineShanghaiChina Key Laboratory of Arrhythmias Ministry of EducationShanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina

Human brain development is a complex process,and animal models often have significant *** address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and *** enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid *** involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid *** cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology *** a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental *** organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature *** exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic *** convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.

关键词： cadmium cell death cell proliferation cortical development environmental toxins neural progenitor cells neurogenesis neurotoxicology organoids stem cells

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Protein arginine methyltransferase-6 regulates heterogeneous nuclear ribonucleoprotein-F expression and is a potential target for the treatment of neuropathic pain

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Neural Regeneration Research 2025年第9期20卷 2682-2696页

作者： Xiaoyu Zhang Yuqi Liu Fangxia Xu Chengcheng zhou Kaimei Lu Bin Fang Lijuan Wang Lina Huang Zifeng Xu Department of Anesthesiology International Peace Maternity and Child Health HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Anesthesiology Shanghai General HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Shanghai Key Laboratory of Embryo Original Diseases ShanghaiChina

Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal ***,it remains unclear whether protein arginine methyl transferase-6 modifies neuropathic pain and,if so,what the mechanisms of this *** this study,protein arginine methyltransferase-6 expression levels and its effect on neuropathic pain were investigated in the spared nerve injury model,chronic constriction injury model and bone cancer pain model,using immunohistochemistry,western blotting,immunoprecipitation,and label-free proteomic *** results showed that protein arginine methyltransferase-6 mostly co-localized withβ-tubulinⅢin the dorsal root ganglion,and that its expression decreased following spared nerve injury,chronic constriction injury and bone cancer *** addition,PRMT6 knockout(Prmt6~(-/-))mice exhibited pain ***,the development of spared nerve injury-induced hypersensitivity to mechanical pain was attenuated by blocking the decrease in protein arginine methyltransferase-6 ***,when protein arginine methyltransferase-6 expression was downregulated in the dorsal root ganglion in mice without spared nerve injury,increased levels of phosphorylated extracellular signal-regulated kinases were observed in the ipsilateral dorsal horn,and the response to mechanical stimuli was ***,protein arginine methyltransferase-6 appeared to contribute to spared nerve injury-induced neuropathic pain by regulating the expression of heterogeneous nuclear ***,protein arginine methyltransfe rase-6-mediated modulation of hete rogeneous nuclear ribonucleoprotein-F expression required amino atids 319 to 388,but not classical H3R2 *** findings indicated that protein arginine methyltransferase-6 is a potential therapeutic target fo r the treatment of peripheral neuro pathic pain.

关键词： dorsal root ganglion heterogeneous nuclear ribonucleoprotein F neuropathic pain protein arginine methyltransferase-6 sensory neurons

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Cortico-striatal gamma oscillations are modulated by dopamine D3 receptors in dyskinetic rats

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Neural Regeneration Research 2025年第4期20卷 1164-1177页

作者： Pengfei Wang Yuewei Bi Min Li Jiazhi Chen Zhuyong Wang Huantao Wen Ming zhou Minjie Luo Wangming Zhang Neurosurgery Center Department of Pediatric NeurosurgeryGuangdong Provincial Key Laboratory on Brain Function Repair and RegenerationZhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong ProvinceChina

Long-term levodopa administration can lead to the development of levodopa-induced *** oscillations are a widely recognized hallmark of abnormal neural electrical activity in levodopa-induced ***,studies have reported increased oscillation power in cases of levodopa-induced ***,little is known about how the other electrophysiological parameters of gamma oscillations are altered in levodopa-induced ***,the role of the dopamine D3 receptor,which is implicated in levodopa-induced dyskinesia,in movement disorder-related changes in neural oscillations is *** found that the cortico-striatal functional connectivity of beta oscillations was enhanced in a model of Parkinson’s ***,levodopa application enhanced cortical gamma oscillations in cortico-striatal projections and cortical gamma aperiodic components,as well as bidirectional primary motor cortex(M1)↔dorsolateral striatum gamma *** of PD128907(a selective dopamine D3 receptor agonist)induced dyskinesia and excessive gamma oscillations with a bidirectional M1↔dorsolateral striatum ***,administration of PG01037(a selective dopamine D3 receptor antagonist)attenuated dyskinesia,suppressed gamma oscillations and cortical gamma aperiodic components,and decreased gamma causality in the M1→dorsolateral striatum *** findings suggest that the dopamine D3 receptor plays a role in dyskinesia-related oscillatory activity,and that it has potential as a therapeutic target for levodopa-induced dyskinesia.

关键词： aperiodic components dopamine D3 receptor dorsolateral striatum functional connectivity gamma oscillations levodopa-induced-dyskinesia local field potentials neuromodulation Parkinson’s disease primary motor cortex

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Cu-doped SnO_(2)/rGO nanocomposites for ultrasensitive H2S detection at low temperature

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Microsystems & Nanoengineering 2023年第3期9卷 61-71页

作者： Tingting Chen Jianhai Sun Ning Xue Wen Wang Zongchang Luo qinqin Liang Tianye zhou Hao Quan Haoyuan Cai Kangsong Tang Kaisheng Jiang State Key Laboratory of Transducer Technology Aerospace Information Research InstituteChinese Academy of Sciences100194 BeijingChina School of Electronic Electrical and Communication EngineeringUniversity of Chinese Academy of Sciences100049 BeijingChina State Key Laboratory of Acoustics Institute of AcousticsChinese Academy of Sciences100190 BeijingChina Guangxi Key Laboratory of Intelligent Control and Maintenance of Power Equipment School of Electronic EngineeringGuangxi UniversityNanning 530004 GuangxiChina Electric Power Research Institute of Guangxi Power Grid Co. Ltd.Nanning 530013 GuangxiChina

Hydrogen sulfide(H_(2)S)detection remains a significant concern and the sensitivity,selectivity,and detection limit must be balanced at low ***,we utilized a facile solvothermal method to prepare Cu-doped SnO_(2)/rGO nanocomposites that have emerged as promising candidate materials for H_(2)S *** of the Cu-SnO_(2)/rGO was carried out to determine its surface morphology,chemical composition,and crystal *** optimal sensor response for 10 ppm H_(2)S was~1415.7 at 120℃,which was over 320 times higher than that seen for pristine SnO_(2)CQDs(R_(a)/R_(g)=4.4)at 280℃.Moreover,the sensor material exhibited excellent selectivity,a superior linear working range(R^(2)=0.991,1-150 ppm),a fast response time(31 s to 2 ppm),and ppb-level H_(2)S detection(R_(a)/R_(g)=1.26 to 50 ppb)at 120℃.In addition,the sensor maintained a high performance even at extremely high humidity(90%)and showed outstanding long-term *** superb H_(2)S sensing properties were attributed to catalytic sensitization by the Cu dopant and a synergistic effect of the Cu-SnO_(2)and rGO,which offered abundant active sites for O_(2)and H_(2)S absorption and accelerated the transfer of electrons/holes.

关键词： stability. selectivity attributed

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Silicon-based metal-organic frameworks(SiMOFs)for immunogenic cell death in cancer therapy

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Nano Research 2025年第1期18卷 628-641页

作者： Min Han Zishan Chen Shiying zhou Zunde Liao Xiangting Yi Yao He Yiling Zhong Kam W.Leong College of Pharmacy State Key Laboratory of Bioactive Molecules and Druggability AssessmentJinan UniversityGuangzhou 511443China Department of Biomedical Engineering Columbia UniversityNew YorkNY 10027USA Institute of Functional Nano and Soft Materials(FUNSOM) Soochow UniversitySuzhou 215123China

Silicon-based nanomaterials,known for their unique properties and favorable biocompatibility,significantly impact sectors like energy,electronics,and ***,metalorganic frameworks(MOFs)have emerged as promising candidates for biomedicine,characterized by adjustable chemical composition,high porosity,and ***,the combination of silicon with MOFs to create silicon-based MOF nanostructures(SiMOFs)remains ***,we establish a diverse library of SiMOFs with various nanostructures,including flower-like,capsule-like,hexagonal snowflake-like,and necklace-like morphologies via microwave-assisted *** SiMOFs,with their spacious interiors,are ideal for drug *** are used to load drugs and create drug-loaded SiMOFs(e.g.,SiFeO).SiFeO exhibits excellent photothermal effects and high reactive oxygen species(ROS)generation capacity,enabling synergistic treatments involving chemochemodynamic-photothermal *** approach efficiently triggers immunogenic cell death(ICD)and demonstrates excellent antitumor efficacy in *** staining reveals that the synergistic therapy can modulate the tumor microenvironment(TME)by reducing M2-phenotype macrophages,increasing the activation of antigen-presenting cells(APCs),enhancing the infiltration of CD4^(+)and CD8^(+)T cells,elevating Granzyme B production,and decreasing the presence of immunosuppressive regulatory T cells(Tregs).Consequently,drug-loaded SiMOFs-mediated combination therapy effectively reverses the immunosuppressive TME and activates robust antitumor immune responses by inducing ICD in tumor cells,ultimately achieving superior anticancer efficacy.

关键词： silicon-based nanomaterials nanocarriers immunogenic cell death antitumor immune responses

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