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Branched glycopolymer prodrug-derived nanoassembly combined with a STING agonist activates an immuno-supportive status to boost anti-PD-l1 antibody therapy

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2194-2209页

作者： Zhilin li Qianfeng Zhang Zhiqian li long Ren Dayi Pan Qiyong Gong Zhongwei Gu Hao cai Kui luo Department of Radiology Huaxi MR Research Center(HMRRC)Clinical Research Center for BreastDepartment of Breast SurgeryDepartment of Thoracic Surgery and Institute of Thoracic OncologyFrontiers Science Center for Disease-Related Molecular NetworkState Key Laboratory of BiotherapyWest China Hospital Sichuan UniversityChengdu 610041China Functional and Molecular Imaging Key laboratory of Sichuan Province and Research Unit of PsychoradiologyChinese Academy of Medical SciencesChengdu 610041China Department of Radiology West China Xiamen Hospital of Sichuan UniversityXiamen 361021China Key laboratory of Medicinal Chemistry for Natural Resource Ministry of EducationYunnan Key Laboratory of Research and Development for Natural ProductsSchool of PharmacyYunnan UniversityKunming 650500China

Despite the great potential of anti-PD-l1 antibodies for immunotherapy,their low response rate due to an immunosuppressive tumor microenvironment has hampered their *** address this issue,we constructed a cell membrane-coated nanosystem(mB4S)to reverse an immunosuppressive microenvironment to an immuno-supportive one for strengthening the anti-tumor *** this system,Epirubicin(EPI)as an immunogenic cell death(ICD)inducer was coupled to a branched glycopolymer via hydrazone bonds and diABZI as a stimulator of interferon genes(STING)agonist was encapsulated into *** internalization of mB4S,EPI was acidic-responsively released to induce ICD,which was characterized by an increased level of calreticulin(CRT)exposure and enhanced ATP ***,diABZI effectively activated the STING *** with mB4S in combination with an anti-PD-l1 antibody elicited potent immune responses by increasing the ratio of matured dendritic cells(DCs)and CD8+T cells,promoting cytokines secretion,up-regulating M1-like tumor-associated macrophages(TAMs)and down-regulating immunosuppressive myeloid-derived suppressor cells(MDSCs).Therefore,this nanosystem for co-delivery of an ICD inducer and a STING agonist achieved promotion of DCs maturation and CD8+T cells infiltration,creating an immuno-supportive microenvironment,thus potentiating the therapy effect of the anti-PD-l1 antibody in both 4T1 breast and CT26 colon tumor mice.

关键词： Glycopolymer Polymer prodrug Immunogenic cell death Nanoassembly Epirubicin STING pathway Immuno-supportive microenvironment Immunotherapy

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Ganoderma lucidum Spore Oil enhances the effect of cyclophosphamide via inhibiting programmed death-1 and prolongs the survival of H22 tumor-bearing mice

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Journal of Traditional Chinese Medicine 2024年第4期44卷 652-659页

作者： JIANG Zhaojian cai Hongfei YUAN Cheng CAO lin xU Wendong HAN Yaming ZHANG Qin lI Jing WANG Qin lIU Juyan Guangzhou HanFang Pharmaceutical Company limited National Engineering Research Center of Pharmaceutical Processing Technology of Traditional Chinese Medicine and Drug InnovationGuangdong Provincial Key Laboratory of Medicinal LipidsGuangzhou 510240China Zhongshan Medical College Sun Yat-sen UniversityGuangzhou 510080China Guangzhou Pharmaceutical Holdings limited Guangzhou 510130China National Engineering Research Center of Pharmaceutical Processing Technology of Traditional Chinese Medicine and Drug Innovation Guangzhou 510240China

OBJECTIVE:To investigate the effect of Ganoderma lucidum Spore Oil(GlSO)on the tumor growth and survival of H22 tumor-bearing mice treated with cyclophosphamide(CTx),and explore the underlying ***:Allograft H22 hepatocellular carcinoma mouse model was applied to investigate the effect of GlSO on the tumor growth and survival of animals,and Kaplan-Meier survival analysis was used to analyze the life *** biochemical examination was used to determine the levels of alanine aminotransferase(AlT),aspartate aminotransferase(AST),urea(UREA)and creatinine(CRE).Western blot analysis was performed to detect Programmed Death-1(PD-1),Programmed Death ligand 1(PD-l1),Janus Kinase 2(JAK2),phosphorylated Signal Transducer and Activator of Transcription 3(p-STAT3),and Signal Transducer and Activator of Transcription 3(STAT3)***:GlSO increased the anti-tumor effect of CTx and prolonged the survival of H22 tumor-bearing mice treated with ***,GlSO increased the thymus index and showed no obvious toxicity to liver functions of *** also decreased the level of UREA in H22 tumor-bearing mice treated with ***,GlSO could inhibit the expression of PD-1 in spleen,which was independent of JAK2 expression and STAT3 ***,GlSO did not affect the expression of PD-l1,JAK2,and p-STAT3 in tumor ***:GlSO could strengthen the anti-tumor effect of CTx and prolong the life span of H22 tumorbearing mice,while the underlying mechanism might be relevant to the amelioration effect of thymus function and inhibition of PD-1 expression in ***,these findings implied the promising role of GlSO in combination with CTx to extend the survival of patients in clinical chemotherapy of hepatocellular carcinoma.

关键词： carcinoma,hepatocellular cyclophosphamide survival programmed cell death 1 receptor Ganoderma lucidum SporeOil

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Ru-Ni alloy nanosheets as tandem catalysts for electrochemical reduction of nitrate to ammonia

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Nano Research 2024年第6期17卷 4815-4824页

作者： xingchao You Jiawei xu Zechao Zhuang Junkai xia Suwen Wang Haiyan Wei Yongfu li Yanjiang cai Hai xiang Bing Yu State Key laboratory of Subtropical Silviculture Zhejiang A&F UniversityHangzhou 311300China Ecological-Environment&Health College(EEHC) Zhejiang A&F UniversityHangzhou 311300China Jiangsu Key laboratory of Numerical Simulation of large Scale Complex Systems and School of Chemistry and Materials Science Nanjing Normal UniversityNanjing 210023China Department of Chemistry Tsinghua UniversityBeijing 100084China Department of Chemical Engineering Columbia UniversityNew YorkNY 10027USA

Developing electrocatalysts that exhibit both high activity and ammonia selectivity for nitrate reduction is a significant and demanding challenge,primarily due to the complex nature of the multiple-electron reduction process *** encouraging approach involves coupling highly active precious metals with transition metals to enhance catalytic performance through ***,we report a ruthenium-nickel alloy catalyst with nanosheets(Ru-Ni NSs)structure that achieves a remarkable ammonia Faradaic efficiency of approximately 95.93%,alongside a yield rate of up to 6.11 g·h^(−1)·cm^(−2).Moreover,the prepared Ru-Ni NSs exhibit exceptional stability during continuous nitrate reduction in a flow reactor for 100 h,maintaining a Faradaic efficiency of approximately 90%and an ammonia yield of 37.4 mg·l^(−1)·h^(−1)using 0.05 M nitrate alkaline *** studies reveal that the catalytic process follows a two-step pathway,in which HONO serves as a migration *** presence of a partially oxidized Ru(002)surface enhances the adsorption of nitrate and facilitates the release of the migration intermediate by adjusting the strength of the electrostatic and covalent interactions between the adsorbate and the surface,*** the other hand,the Ni(111)surface promotes the utilization of the migration intermediate and requires less energy for NH_(3)*** tandem process contributes to a high catalytic activity of Ru-Ni NSs towards nitrate reduction.

关键词： alloy catalyst nitrate reduction ammonia synthesis Faradaic efficiency

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Re-usable Cd_(0.9)Zn_(0.1)S-ZnO@C/PVDF piezo-photocatalytic film with exceptional hydrogen evolution capability triggered by the synergetic advantages of piezoelectricity and S-Scheme heterojunction

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Journal of Energy Chemistry 2024年第9期96卷 164-176页

作者： Ping Su Dong Zhang Minghui Zhu Tengteng liang Nan Yang Huaihao Zhao Dafeng Zhang Junchang liu Peiqing cai xipeng Pu School of Materials Science and Engineering Shandong Provincial Key Laboratory of Chemical Energy Science and Novel Cell TechnologyLiaocheng UniversityLiaocheng 252000ShandongChina School of Physics Science and Information Technology Shandong Key Laboratory of Optical Communication Sciencend TechnologyLiaocheng UniversityLiaocheng 252000ShandongChina College of Optical and Electronic Technology China Jiliang UniversityHangzhou 310018ZhejiangChina

Piezoelectric materials have advantages of fine-tuning photocatalytic performance through harvesting mechanical energy and open a new avenue in facilitating green catalytic ***,polyvinylidene fluoride(PVDF),a flexible piezoelectric material,was introduced to synthesize a novel Cd_(0.9)Zn_(0.1)S-ZnO@C/PVDF(CZS-ZO@C/PVDF)piezo-photocatalytic film by spin coating and immersion phase conversion *** from the piezoelectricity of PVDF and the internal electric field(IEF)of CZS-ZO@C Step-scheme(S-Scheme)heterojunction,CZS-ZO@C/PVDF was able to induce a hydrogen generation rate of 34.9 mmol g^(−1)h^(−1)activated by ultrasound and visible light(U-l),which is∼17.5 times of Cd_(0.9)Zn_(0.1)S/PVDF(CZS/PVDF)and∼7.4 times of the photocatalysis rate activated by visible light only(l).Piezoelectric measurements and COMSOl simulation illustrated the excellent piezoelectricity of CZS-ZO@C/PVDF film,which exhibits a piezoelectric coefficient(d33)of 9.9 pm V−1 and a piezoelectric potential of 874 mV(under 0.5 MPa).The reaction mechanism for the exceptional piezo-photocatalytic performance was finally disclosed through density functional theory(DFT)calculation and electrochemical *** study enriches the application scope of piezoelectric materials in sustainable energy catalysis and provides a new direction to develop efficient piezoelectric photocatalysts.

关键词： Piezo-photocatalysis Heterojunction Cd_(0.9)Zn_(0.1)S Zno@c PVDF

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Multi-cohort comprehensive analysis unveiling the clinical value and therapeutic effect of GNAl in glioma

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Oncology Research 2024年第5期32卷 965-981页

作者： ZHEN lIU lIANGWANG YANG ZHENGxING xIE HUI YU TIANYI GU DAOMING SHI NING cai SHENGHUA ZHUO Department of Neurosurgery Affiliated Hospital of Jiangsu UniversityZhenjiang212000China Department of Neurosurgery First Affiliated Hospital of Hainan Medical UniversityHaikou570100China Department of Cardiothoracic Surgery Affiliated Hospital of Jiangsu UniversityZhenjiang212000China Department of General Surgery Affiliated Hospital of Jiangsu UniversityZhenjiang212000China

Clinical data indicates that glioma patients have poor treatment outcomes and clinical *** role of olfactory signaling pathway-related genes(OSPRGs)in glioma has not been fully *** this study,we aimed to investigate the role and relationship between OSPRGs and *** and multivariate Cox regression analyses were performed to assess the relationship between OSPRGs and the overall survival of glioma based on public cohorts,and the target gene(G Protein Subunit Alpha l,GNAl)was *** association of GNAl expression with clinicopathological characteristics,gene mutation landscape,tumor immune microenvironment(TIME),deoxyribonucleic acid(DNA)methylation,and naris-occlusion controlled genes(NOCGs)was *** was used to evaluate GNAl level in *** analysis was conducted to evaluate the drug sensitivity,immunotherapy response,and functional enrichment of *** was an independent prognostic factor,and patients with low GNAl expression have a poor *** of GNAl was closely associated with clinicopathological characteristics,DNA methylation,and several immune-related *** infiltration analysis indicated that GNAl levels were negatively correlated with immune *** low-expression group showed efficacy with anti-PD-1 *** compounds with significantly different half-maximal inhibitory concentration(IC50)values between the GNAl high and low-expression groups were ***,its expression was associated with several immune cells,immune-related genes,and *** expression of GNAl is closely associated with clinicopathological characteristics,TIME,and the response to therapeutic interventions,highlighting its potential as a prognostic biomarker for glioma.

关键词： Glioma Olfaction GNAl Tumor immune microenvironment Immunotherapy/chemotherapy response

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Identification of 3-ketocapnine reductase activity within the human microbiota

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mlife 2024年第2期3卷 307-316页

作者： xiaotong Wu lukuan Hou Haili Zhang Yi Ma Jufang Wang Mingwei cai xiaoyu Tang School of Biology and Biological Engineering South China University of TechnologyGuangzhouChina Institute of Chemical Biology Shenzhen Bay LaboratoryShenzhenChina College of Chemistry and Pharmacy Northwest A&F UniversityYanglingChina

The microbial synthesis of sulfonolipids within the human body is likely involved in maintaining human health or causing ***,the enzymes responsible for their biosynthesis remain largely *** this study,we identified and verified the role of 3-ketocapnine reductase,the third-step enzyme,in the four-step conversion of l-phosphoserine into sulfobacin B both in vivo and in *** finding builds upon our previous research into sulfonolipid biosynthesis,which focused on the vaginal bacterium Chryseobacterium gleum DSM 16776 and the gut bacterium Alistipes finegoldii DSM *** comprehensive gene mapping,we demonstrate the widespread presence of potential sulfonolipid biosynthetic genes across diverse bacterial species inhabiting various regions of the human *** findings shed light on the prevalence of sulfonolipid-like metabolites within the human microbiota,suggesting a potential role for these lipid molecules in influencing the intricate biointeractions within the complex microbial ecosystem of the human body.

关键词： 3-ketocapnine reductase capnines human microbiota sulfonolipids

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Biomimetic“Gemini nanoimmunoregulators”orchestrated for boosted photoimmunotherapy by spatiotemporally modulating PD-l1 and tumor-associated macrophages

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1345-1361页

作者： Honglin Huang Ningxi li xiaodan Wei Qingzhi li Junhan Guo Geng Yang Hong Yang lulu cai Yiyao liu Chunhui Wu Department of Pharmacy Personalized Drug Therapy Key Laboratory of Sichuan ProvinceSichuan Provincial People’s Hospitaland School of Life Science and TechnologyUniversity of Electronic Science and Technology of ChinaChengdu 610054China TCM Regulating Metabolic Diseases Key laboratory of Sichuan Province Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072China

A novel strategy of not only stimulating the immune cycle but also modulating the immunosuppressive tumor microenvironment is of vital importance to efficient cancer ***,a new type of spatiotemporal biomimetic“Gemini nanoimmunoregulators”was engineered to activate robust systemic photoimmunotherapy by integrating the triple-punch of amplified immunogenic cell death(ICD),tumor-associated macrophages(TAMs)phenotype reprogramming and programmed cell death ligand 1(PD-l1)***“Gemini nanoimmunoregulators”PM@RM-T7 and PR@RM-M2 were constructed by taking the biocompatible mesoporous polydopamine(mPDA)as nanovectors to deliver metformin(Met)and toll-like receptor 7/8 agonist resiquimod(R848)to cancer cells and TAMs by specific biorecognition via wrapping of red blood cell membrane(RM)inlaid with T7or M2 ***/Met@RM-T7(abbreviated as PM@RM-T7)was constructed to elicit an amplified in situ ICD effect through the targeted PTT and effectively stimulated the anticancer ***,PD-l1 on the remaining cancer cells was degraded by the burst metformin to prevent immune ***,mPDA/R848@RM-M2(abbreviated as PR@RM-M2)specifically recognized TAMs and reset the phenotype from M2 to M1 state,thus disrupting the immunosuppressive microenvironment and further boosting the function of cytotoxic T *** pair of sister nanoimmunoregulators cooperatively orchestrated the comprehensive anticancer activity,which remarkably inhibited the growth of primary and distant 4T1 tumors and prevented malignant *** study highlights the spatiotemporal cooperative modalities using multiple nanomedicines and provides a new paradigm for efficient cancer immunotherapy against metastatic-prone tumors.

关键词： Biomimetic immunoregulator Spatiotemporal delivery Targeted photothermal therapy Amplified immunogenic cell death Immunosuppressive tumor microenvironment PD-l1 degradation TAMs phenotype reversion Metastasis inhibition

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Identification of collagen subtypes of gastric cancer for distinguishing patient prognosis and therapeutic response

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Cancer Innovation 2024年第4期3卷 87-102页

作者： Di Wang Jing Zhang Jianchao Wang Zhonglin cai Shanfeng Jin Gang Chen Department of Molecular Pathology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhouChina Department of Pathology Clinical Oncology School of Fujian Medical UniversityFujian Cancer HospitalFuzhouChina Department of Urology Gongli Hospital of Shanghai Pudong New AreaShanghaiChina

Background:Gastric cancer is a highly heterogeneous disease,presenting a major obstacle to personalized *** markers of the immune checkpoint blockade response are needed for precise patient ***,therefore,divided patients with gastric cancer according to collagen gene expression to indicate their prognosis and treatment ***:We collected data for 1250 patients with gastric cancer from four *** the TCGA‐STAD cohort,we used consensus clustering to stratify patients based on expression levels of 44 collagen genes and compared the prognosis and clinical characteristics between collagen *** then identified distinct transcriptomic and genetic alteration signatures for the *** analyzed the associations of collagen subtypes with the responses to chemotherapy,immunotherapy,and targeted *** also established a platform‐independent collagen‐subtype *** verified the findings in three validation cohorts(GSE84433,GSE62254,and GSE15459)and compared the collagen subtyping method with other molecular subtyping ***:We identified two subtypes of gastric adenocarcinoma:a highexpression collagen subtype(CS‐H)and a low‐expression collagen subtype(CS‐l).Collagen subtype was an independent prognostic factor,with better overall survival in the CS‐l *** inflammatory response,angiogenesis,and phosphoinositide 3‐kinase(PI3K)/Akt pathways were transcriptionally active in the CS‐H subtype,while DNA repair activity was significantly greater in the CS‐l ***3CA was frequently amplified in the CS‐H subtype,while PIK3C2A,PIK3C2G,and PIK3R1 were frequently deleted in the CS‐l ***‐H subtype tumors were more sensitive to fluorouracil,while CS‐l subtype tumors were more sensitive to immune checkpoint ***‐l subtype was predicted to be more sensitive to HER2‐targeted drugs,and CS‐H subtype was predicted to be more sensitive to vascular endothelial growth factor and PI3K pathway‐target

关键词： biomarker cancer classification collagen gastric cancer phosphatidylinositol 3‐kinase

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The DUF579 proteins GhIRx15s regulate cotton fiber development by interacting with proteins involved in xylan synthesis

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The Crop Journal 2024年第4期12卷 1112-1125页

作者： Mengyun li Feng Chen Jingwen luo Yanan Gao Jinglong cai Wei Zeng Monika S.Doblin Gengqing Huang Wenliang xu Hubei Key laboratory of Genetic Regulation and Integrative Biology School of Life SciencesCentral China Normal UniversityWuhan 430079HubeiChina Zhejiang Provincial Key laboratory of Plant Evolutionary Ecology and Conservation School of Life SciencesTaizhou UniversityTaizhou 318000ZhejiangChina la Trobe Institute for Sustainable Agriculture&Food School of AgricultureBiomedicine and EnvironmentLa Trobe UniversityBundooraVIC 3086Australia

Cotton provides the most abundant natural fiber for the textile *** mature cotton fiber largely consists of secondary cell walls with the highest proportion of cellulose and a small amount of hemicellulose and *** dissect the roles of hemicellulosic polysaccharides during fiber development,four IRREGUlAR xYlEM 15(IRx15)genes,GhIRx15-1/-2/-3/-4,were functionally characterized in *** genes encode DUF579 domain-containing proteins,which are homologs of AtIRx15 involved in xylan *** four GhIRx15 genes were predominantly expressed during fiber secondary wall thickening,and the encoded proteins were localized to the Golgi *** GhIRx15 gene could restore the xylan deficient phenotype in the Arabidopsis irx15irx15l double *** of GhIRx15s in cotton resulted in shorter mature fibers with a thinner cell wall and reduced cellulose content as compared to the wild ***,GhIRx15-2 and GhIRx15-4 formed homodimers and *** addition,the GhIRx15s showed physical interaction with glycosyltransferases GhGT43C,GhGT47A and GhGT47B,which are responsible for synthesis of the xylan backbone and reducing end ***,the GhIRx15s can form heterocomplexes with enzymes involved in xylan modification and side chain synthesis,such as GhGUx1/2,GhGxM1/2 and *** findings suggest that GhIRx15s participate in fiber xylan biosynthesis and modulate fiber development via forming large multiprotein complexes.

关键词： Cotton fiber xylan biosynthesis GhIRx15s Protein-protein interaction Protein complexes

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Surgical or medical treatment of obesity-associated type 2 diabetesan increasing clinical conundrum

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World Journal of Diabetes 2024年第10期15卷 2036-2040页

作者： Ryan J Jalleh Karen l Jones Md Shahidul Islam lu cai Michael Horowitz Adelaide Medical School and Centre of Research Excellence in Translating Nutritional Science to Good Health University of Adelaide Endocrine and Metabolic Unit Royal Adelaide HospitalAdelaide 5000South AustraliaAustralia Department of Biochemistry School of Life SciencesUniversity of KwaZulu-NatalDurban 4000KwaZulu-NatalSouth Africa Pediatric Research Institute Departments of PediatricsRadiation OncologyPharmacology and ToxicologyUniversity of LouisvilleWendy Novak Diabetes InstituteNorton Children’s HospitalLouisvilleKY 40202United States

In this editorial,we comment on the article by He et al,specifically in relation to the efficacy of bariatric surgery vs glucagon-like peptide-1 receptor agonist(GlP-1RA)therapy in the management of type 2 diabetes(T2D)associated with *** surgery has now also been shown to be safe and effective in pre-teens and teenagers with obesity and T2D,but information on newer GlP-1RAs in these groups is predictably *** older individuals(age>65 years),both bariatric surgery and GlP-1RA therapy improve cardiovascular ***-tric surgery is not infrequently associated with post-operative postprandial hypoglycemia,which is not the case with GlP-1RAs and,paradoxically,there is evidence that GlP-1RAs may reduce both the frequency and severity of postprandial *** trials of the long-term efficacy of bariatric surgery and GlP-1RAs are indicated.

关键词： Glucagon-like peptide-1 Glucagon-like peptide-1 receptor agonist Obesity Diabetes Weight loss Bariatric surgery Metabolic surgery Hypoglycemia

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