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Science China Chemistry 2024年第1期67卷 368-373页

作者： Xing-Yu Wang Pei Xu Wen-Wen Liu Hao-Qiang Jiang Song-Lei Zhu Dong Guo Xu Zhu Jiangsu key laboratory of New drug Research and Clinical Pharmacy School of PharmacyXuzhou Medical UniversityXuzhou 22100China

Unprecedented divergent synthesis of gem-difluorovinylacetic acid and glutaric acid derivatives fromα-CF_(3)alkenes with formate as the carbonyl source was *** reaction can undergo selective mono-or triple C-F bond cleavage by simply switching the photocatalyst and hydrogen atom transfer(HAT)catalyst under visible-light-induced conditions at room *** acts as both the C1 source and the reductant through the generation of CO_(2)^(·-)species,which underwent Giese radical addition to electron-deficient alkenes to trigger the consecutive C-F bond cleavage and carboxylation process.

关键词： C-F bond activation defluorocarboxylation carbon dioxide radical anion visible light

Lymph node-biomimetic scaffold boosts CAR-T therapy against solid tumor

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National Science Review 2024年第4期11卷 206-215页

作者： Ziyan Liao Jie Jiang Wei Wu Jiaqi Shi Yanfang Wang Yuejun Yao Tao Sheng Feng Liu Wei Liu Peng Zhao Feifei Lv Jie Sun Hongjun Li Zhen Gu Department of General Surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University National key laboratory of Advanced drug delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University key laboratory of Advanced drug delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang University Liangzhu laboratory Zhejiang University Bone Marrow Transplantation Center of the First Affiliated Hospital and Department of Cell Biology Zhejiang University School of Medicine Department of Medical Oncology The First Affiliated Hospital School of Medicine Zhejiang University Department of laboratory Medicine The First Affiliated Hospital Zhejiang University School of Medicine Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated HospitalSchool of MedicineZhejiang University Jinhua Institute of Zhejiang University MOE key laboratory of Macromolecular Synthesis and Functionalization of Ministry of Education Department of Polymer Science and EngineeringZhejiang University

The limited infiltration and persistence of chimeric antigen receptor(CAR)-T cells is primarily responsible for their treatment deficits in solid tumors. Here, we present a three-dimensional scaffold, inspired by the physiological process of T-cell proliferation in lymph nodes. This scaffold gathers the function of loading,delivery, activation and expansion for CAR-T cells to enhance their therapeutic effects on solid tumors. This porous device is made from poly(lactic-co-glycolic acid) by a microfluidic technique with the modification of T-cell stimulatory signals, including anti-CD3, anti-CD28 antibodies, as well as cytokines. This scaffold fosters a 50-fold CAR-T cell expansion in vitro and a 15-fold cell expansion in vivo. Particularly, it maintains long-lasting expansion of CAR-T cells for up to 30 days in a cervical tumor model and significantly inhibits the tumor growth. This biomimetic delivery strategy provides a versatile platform of cell delivery and activation for CAR-T cells in treating solid tumors.

关键词： drug delivery cell therapy bioinspired biomaterials cancer immunotherapy

Multifunctional nano-herb based on tumor microenvironment for enhanced tumor therapy of gambogic acid

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Chinese Chemical Letters 2024年第5期35卷 307-313页

作者： Fengyun Li Zerong Pei Shuting Chen Gen li Mengyang Liu Liqin Ding Jingbo Liu Feng Qiu School of Chinese Materia Medica Tianjin University of Traditional Chinese MedicineTianjin 301617China College of Horticulture and Landscape Architecture Tianjin Agricultural UniversityTianjin 300384China State key laboratory of Component-based Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China

Multifunctional drug delivery systems(DDSs)have shown great prospects in overcoming the heterogeneous barrier of delivery drugs to the complex tumor microenvironment(TME).In this study,multifunctional AS/Ge-pNAB microgels with dual-active targeting,triple environment responsiveness,and fluorescence imaging capability were prepared through a straightforward *** was aimed to improve the antitumor therapeutic application of gambogic acid(GA)based on the biological characteristics of *** microgels have a uniform double-layer structure with aptamer in the outer layer which helps in recognizing receptors on the tumor *** GA loaded nano-herb exhibited environment-responsive drug release profiles under acidic pH,reductant and high *** nano-herb significantly improved the accumulation of GA in tumor sites through the synergistic combination of the enhanced permeability and retention effect and dual-ligand mediated ***,it accelerated intracellular drug release and killed tumor ***,the nano-herb had specific therapeutic effects on the tumor in vitro and in vivo as they remarkably inhibited tumor growth while depicting optimal biosafety and lower levels of off-target ***,these findings demonstrate the great potential of the multifunctional AS/Ge-pNAB microgels for precisely targeted GA delivery and open a new avenue for the facile preparation of multifunctional DDSs.

关键词： Tumor microenvironment Microgels Gambogic acid Dual-active targeting Triple environment responsiveness Silver nanoclusters

Discovery of proqodine A derivatives with antitumor activity targeting NAD(P)H:quinone oxidoreductase 1 and nicotinamide phosphoribosyltransferase

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Chinese Journal of Natural Medicines 2024年第1期22卷 75-88页

作者： SONG Jiangzhou ZOU Guiqing ZHAO Zhou ZHU Ya XUE Jiayu AO Lanjia SUN Huiyong HAO Haiping ZHANG Bo XU Xiaowei State key laboratory of Natural Medicines Key Lab of Drug Metabolism and PharmacokineticsChina Pharmaceutical UniversityNanjing 210009China State key laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China

NAD(P)H:quinone oxidoreductase 1(NQO1)is a flavin protease highly expressed in various cancer ***1 catalyzes a futile redox cycle in substrates,leading to substantial reactive oxygen species(ROS)*** ROS generation results in extensive DNA damage and elevated poly(ADP-ribose)polymerase 1(PARP1)-mediated consumption of nicotinamide adenine dinucleotide(NAD^(+)),ultimately causing cell *** phosphoribosyltransferase(NAMPT),the rate-limiting enzyme in the NAD^(+)salvage synthesis pathway,emerges as a critical target in cancer *** concurrent inhibition of NQO1 and NAMPT triggers hyperactivation of PARP1 and intensive NAD+*** this study,we designed,synthesized,and assessed a novel series of proqodine A derivatives targeting both NQO1 and *** these,compound T8 demonstrated potent antitumor ***,T8 selectively inhibited the proliferation of MCF-7 cells and induced apoptosis through mechanisms dependent on both NQO1 and *** discovery offers a promising new molecular entity for advancing anticancer research.

关键词： NQO1 ROS NAMPT NAD^(+) T8

Unlocking the potential of amorphous calcium carbonate: A star ascending in the realm of biomedical application

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Acta Pharmaceutica Sinica B 2024年第2期14卷 602-622页

作者： Han Liu Zhiyang Wen Zihan Liu Yanfang Yang Hongliang Wang Xuejun Xia Jun Ye Yuling Liu State key laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Beijing key laboratory of drug delivery Technology and Novel Formulation Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

Calcium-based biomaterials have been intensively studied in the field of drug delivery owing to their excellent biocompatibility and ***-based materials can also deliver contrast agents,which can enhance real-time imaging and exert a Ca^(2+)-interfering therapeutic *** on these characteristics,amorphous calcium carbonate(ACC),as a brunch of calcium-based biomaterials,has the potential to become a widely used *** functional ACC can be either discovered in natural organisms or obtained by chemical synthesis However,the standalone presence of ACC is unstable in *** are required to be used as stabilizers or core-shell structures formed by permeable layers or lipids with modified molecules constructed to maintain the stability of ACC until the ACC carrier reaches its *** has high chemical instability and can produce biocompatible products when exposed to an acidic condition in vivo,such as Ca^(2+) with an immune-regulating ability and CO_(2) with an imaging-enhancing *** to these characteristics,ACC has been studied for selfsacrificing templates of carrier construction,targeted delivery of oncology drugs,immunomodulation,tumor imaging,tissue engineering,and calcium *** in this paper has been placed on the origin,structural features,and multiple applications of ***,ACC faces many challenges in clinical translation,and long-term basic research is required to overcome these *** hope that this study will contribute to future innovative research on ACC.

关键词： Amorphous calcium carbonate drugdelivery system Nanoparticle Acid sensitivity Water instability,Tumortherapy Tissue engineering Calcium supplement

Integrated causal inference modeling uncovers novel causal factors and potential therapeutic targets of Qingjin Yiqi granules for chronic fatigue syndrome

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Acupuncture and Herbal Medicine 2024年第1期4卷 122-133页

作者： Junrong Li Xiaobing Zhai Jixing Liu Chi Kin Lam Weiyu Meng Yuefei Wang Shu Li Yapeng Wang Kefeng Li Faculty of Applied Sciences Macao Polytechnic UniversityMacao SARChina Center for Artificial Intelligence Driven drug Discovery Faculty of Applied SciencesMacao Polytechnic UniversityMacao SARChina National key laboratory of Chinese Medicine Modernization Tianjin Key Laboratory of TCM Chemistry and AnalysisTianjin University of Traditional Chinese MedicineTianjinChina Haihe laboratory of Modern Chinese Medicine TianjinChina

Objective:Chronic fatigue syndrome(CFS)is a prevalent symptom of post-coronavirus disease 2019(COVID-19)and is associated with unclear disease *** herbal medicine Qingjin Yiqi granules(QJYQ)constitute a clinically approved formula for treating post-COVID-19;however,its potential as a drug target for treating CFS remains largely *** study aimed to identify novel causal factors for CFS and elucidate the potential targets and pharmacological mechanisms of action of QJYQ in treating ***:This prospective cohort analysis included 4,212 adults aged≥65 years who were followed up for 7 years with 435 incident CFS *** modeling and multivariate logistic regression analysis were performed to identify the potential causal determinants of CFS.A proteome-wide,two-sample Mendelian randomization(MR)analysis was employed to explore the proteins associated with the identified causal factors of CFS,which may serve as potential drug ***,we performed a virtual screening analysis to assess the binding affinity between the bioactive compounds in QJYQ and CFS-associated ***:Among 4,212 participants(47.5%men)with a median age of 69 years(interquartile range:69–70 years)enrolled in 2004,435 developed CFS by *** graph analysis with multivariate logistic regression identified frequent cough(odds ratio:1.74,95%confidence interval[CI]:1.15–2.63)and insomnia(odds ratio:2.59,95%CI:1.77–3.79)as novel causal factors of ***-wide MR analysis revealed that the upregulation of endothelial cell-selective adhesion molecule(ESAM)was causally linked to both chronic cough(odds ratio:1.019,95%CI:1.012–1.026,P=2.75 e^(−05))and insomnia(odds ratio:1.015,95%CI:1.008–1.022,P=4.40 e^(−08))in *** major bioactive compounds of QJYQ,ginsenoside Rb2(docking score:−6.03)and RG4(docking score:−6.15),bound to ESAM with high affinity based on virtual ***:Our integrated analytical framework combining epidemiological,genet

关键词： Causal factors Causal graph analysis Chronic fatigue syndrome drug targets Mendelian randomization Qingjin Yiqi

Preparation of baicalin colon-targeted granules and its intervention effect on ulcerative colitis in rats

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Particuology 2024年第2期85卷 13-21页

作者： Yongqing Huang Yuxin Zhou Yao Shen Jin Wang Liangliang Zhou Zhenhua Chen Jiangxi Provincial key laboratory of drug Design and Evaluation School of PharmacyJiangxi Science and Technology Normal UniversityNanchang330013China

Baicalin(BA)is a flavonoid extracted from the dried root of Scutellaria baicalensis Georgi with excellent antioxidant and anti-inflammatory biological *** this study,Eudragit S100 was used as the colonic target material to prepare BA colonic targeting granules(EBCGs)based on plasticizer dry powder coating technology to improve the targeting transportation performance of *** vitro studies showed that EBCGs with pH-sensitive properties were successfully prepared by plasticizer dry powder coating,and in vivo animal imaging studies showed that EBCGs could deliver BA to the colon and inhibit the release of BA in the upper gastrointestinal tract(GIT).In vivo studies showed that EBCGs had good therapeutic effects in colitis,which reduced expression levels of tumor necrosis factor alpha(TNF-α)and interleukin-1β(IL-1β)and increased superoxide dismutase(SOD)activities in the colonic tissues of rats with *** conclusion,Eudragit S100 could be used for the preparation of multi-unit oral colon-targeted formulations by plasticizer dry powder coating technology,and our prepared EBCGs had good colon-targeting properties,which could improve the therapeutic effect and provide a potential application for ulcerative colitis(UC).

关键词： Plasticizer dry powder coating Colon-targeted granulesIn vivo imaging Ulcerative colitis

Sigmatropic rearrangements of B(MIDA)-propargylic alcohols towards the diverse synthesis of α-functionalized organoborons

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Science China Chemistry 2024年第2期67卷 568-575页

作者： Jiasheng Qian Li-Cai Liu Zhi-Hao Chen Yuan Liu Yin Li Qingjiang Li Honggen Wang Guangdong key laboratory of Chiral Molecule and drug Discovery School of Pharmaceutical SciencesSun Yat-Sen UniversityGuangzhou510006China

α-Functionalized organoborons are useful building blocks and key structural elements in functional *** previous synthesis relied on the famous Matteson reaction or the late-stage borylative modification of alkynes or ***,the synthetic transformation of borylated building blocks offers another useful strategy and is currently actively *** report herein that B(MIDA)-propargylic alcohols(BPAs) are a useful type of borylated building *** two complementary functional group handles(alkyne and hydroxyl) in close proximity,the redox-neutral [3,3] and [2,3] sigmatropic rearrangements of BPAs allow the efficient synthesis of several types of α-functionalized boronates,including α,β-unsaturated acylborons,α-S/P-substituted allenylborons,boryl-substituted thiazoles and a borylated α,β-unsaturated hydrazine,some of which are otherwise challenging targets using other synthetic methods.

关键词： organoboron diverse synthesis sigmatropic rearrangement heteroarene amide

Rh(Ⅱ)catalyzed efficient sigmatropic rearrangement reaction of pyridotriazoles and sulfides

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Green Synthesis and Catalysis

Green Synthesis and Catalysis 2024年第2期5卷 77-79页

作者： Yuting Chen Guanghui Lv Zhiyang Li Meiling Ye Tianle Huang Li Hai Yong Wu key laboratory of drug-Targeting and drug delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu610041China Department of Pharmacy Taihe HospitalHubei University of MedicineShiyan442000China

The[2,3]-and[1,2]-sigmatropic rearrangement reactions between pyridotriazoles and sulfides catalyzed by rhodium(II)were *** utilization of pyridotriazoles as the carbene precursors in this kind of reaction efficiently... 详细信息

关键词： Pyridotriazole Sulfide -Sigmatropic rearrangement -Sigmatropic rearrangement Rhodium catalysis

Microneedle patch loaded with ferritin-nanocaged doxorubicin for locally targeted drug delivery and efficient skin cancer treatment

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Particuology 2024年第5期88卷 282-289页

作者： Feng Li Yuan Yang Hua Yue Shuang Wang Xiao Zhang Wei Wei State key laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing100190China key laboratory of Biopharmaceutical Preparation and delivery Chinese Academy of SciencesBeijing100190China School of Chemical Engineering University of Chinese Academy of SciencesBeijing100049China

Ferritin has emerged as a promising nanocarrier for delivering therapeutic agents to ***,the limited drug loading and the off-target impacts after systemic administration remain challenges for cancer treatment with ferritin-based ***,we develop a microneedle patch loaded with ferritin-nanocaged doxorubicin(DoxFe@Fn/MN)for skin cancer ***,doxorubicin(Dox)is encapsulated in ferritin(Fn)using an iron core-assisted strategy,which results in a 3.4-fold increase in Dox loading compared to the direct loading ***,a polyvinyl alcohol-based microneedle(MN)patch is used for the transdermal delivery of DoxFe@Fn,enabling targeted tumour accumulation of DoxFe@Fn and preventing off-target *** released DoxFe@Fn can bind to CD71 highly expressed on skin cancer cells,facilitating its *** a result,the DoxFe@Fn/MN therapy presents a robust antitumour effect in a melanoma tumour model,showing its potential as a promising therapeutic modality for skin cancer treatment.

关键词： Ferritin Microneedle Skin cancer drug delivery