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Radiation-based immunogenic vaccine combined with a macrophage“checkpoint inhibitor”for boosting innate and adaptive immunity against metastatic colon cancers

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2247-2262页

作者： Hongbo Xu Xianya Qin Yuanyuan Guo Siyu Zhao Xingxing Feng Runzan Zhang Tianyi Tian Li Kong Conglian Yang Zhiping Zhang Tongji School of Pharmacy Huazhong University of Science and TechnologyWuhan 430030China hubei engineering research center for novel drug delivery system Wuhan 430030China Wuhan Liyuan Hospital of Tongji School of Pharmacy Huazhong University of Science and TechnologyWuhan 430077China

Immunogenic dying tumor cells hold promising prospects as cancer vaccines to activate systemic immunity against both primary and metastatic tumors.Especially,X-ray-induced dying tumor cells are rich in highly immunogenic tumor-associated antigens and self-generated dsDNA as potent adjuvants.However,we found that the X-ray induction process can result in the excessive exposure of phosphatidylserine in cancer vaccines,which can specifically bind with the MerTK receptor on macrophages,acting as a“checkpoint”to facilitate immune silence in the tumor microenvironment.Therefore,we developed a novel strategy combining X-ray-induced cancer vaccines with UNC2250,a macrophage MerTK“checkpoint inhibitor,”for treating peritoneal carcinomatosis in colon cancer.By incorporating UNC2250 into the treatment regimen,immunosuppressive efferocytosis of macrophages,which relies on MerTK-directed recognition of phosphatidylserine on vaccines,was effectively blocked.Consequently,the immune analysis revealed that this combination strategy promoted the maturation of dendritic cells and M1-like repolarization of macrophages,thereby simultaneously eliciting robust adaptive and innate immunity.This innovative approach utilizing X-ray-induced vaccines combined with a checkpoint inhibitor may provide valuable insights for developing effective cancer vaccines and immunotherapies targeting colon cancer.

关键词： Immunogenic cell death Cancer vaccine X-ray Efferocytosis Macrophage STING Adaptive immunity Innate immunity

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Cooperative NHC/Photoredox Catalysis:Three-Component Reaction of Aroyl Fluorides,Styrenes and Oxalates

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Chinese Journal of Chemistry 2024年第5期42卷 511-515页

作者： Zheng Lin Guanghui Lv Jianghong Liu Jiangyan Tang Binsong Mu Jian Chen Tianle Huang Zhongzhen Yang 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 UniversityChengduSichuan610041 China Department of Pharmacy Hubei Provincial Clinical Research Center for Umbilical Cord Blood Hematopoietic Stem CellsTaihe HospitalHubei University of MedicineShiyanHubei442000 China

Cooperative NHC/photoredox catalysis has emerged as an important research field in recent years.Herein,this article describes the use of cesium salt derivatives of tert-alcohols as alkyl radical precursors in a three-component reaction with styrene and aromatic acyl fluorides to synthesizeα-arylalkyl aryl ketones.The aroyl fluoride reacts with the NHC catalyst,leading to the formation of an acyl azolium ion.This acyl azolium ion can then be reduced by the photoredox catalyst,generating the corresponding ketyl radical anion.The C-radical generated from oxalate oxidation undergoes an addition reaction with the styrene derivative,followed by cross-coupling of the addition radical with the ketone radical,which is fragmented by NHC to give the target ketone.

关键词： Three-component Photoredox NHC Aryl ketones Iridium Radical C—C coupling Amides

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Combination of AAV-delivered tumor suppressor PTEN with anti-PD-1 loaded depot gel for enhanced antitumor immunity

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Acta Pharmaceutica Sinica B 2024年第1期14卷 350-364页

作者： Yongshun Zhang Lan Yang Yangsen Ou Rui Hu Guangsheng Du Shuang Luo Fuhua Wu Hairui Wang Zhiqiang Xie Yu Zhang Chunting He Cheng Ma Tao Gong Ling Zhang Zhirong Zhang Xun Sun 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 UniversityChengdu 610041China Med-X center for Materials College of Polymer Science and EngineeringSichuan UniversityChengdu 610065China

Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10(PTEN)gene in cancer cells may be associated with immunosuppressive tumor microenvironment(TME)and poor response to immune checkpoint blockade(ICB)therapy.Therefore,efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy.Here,we screened an adeno-associated virus(AAV)capsid for efficient PTEN gene delivery into B16F10 tumor cells.We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death(ICD)and increasing immune cell infiltration.Moreover,we developed an anti-PD-1 loaded phospholipid-based phase separation gel(PPSG),which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo.In order to effectively inhibit the recurrence of melanoma,we further applied a triple therapy based on AAV6-PTEN,PPSG^(@anti-PD-1)and CpG,and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory,which completely rejected tumor recurrence.We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

关键词： Triple therapy Adeno-associated virus PTEN PPSG@anti-PD-1 CpG Immunogenic cell death Antitumor immune response Immune memory

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Rhodium-catalyzed Doyle-Kirmse rearrangement reactions of sulfoxoniun ylides

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Chinese Chemical Letters 2024年第4期35卷 363-366页

作者： Ying-Di Hao Zhi-Qian Lin Xiao-Yu Guo Jiao Liang Can-Kun Luo Qian-Tao Wang Li Guo Yong Wu Key Laboratory of drug-Targeting and drug delivery system of the Education Ministry and Department of Medicinal Chemistry Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China

Doyle-Kirmse rearrangement reactions have received continuous attention as an important method for constructing complex chemical structures. Herein, we disclosed an efficient rhodium-catalyzed DoyleKirmse rearrangement reaction, which can simultaneously construct C–C bonds and C–X(X = S/Se) bonds using sulfoxonium ylides as starting materials to obtain sulfur-or selenium-containing compounds. This strategy is characterized by the safer and greener carbene precursor, high yields and broad substrate scope, possessing a wide range of application.

关键词： Sulfoxonium ylides Rhodium(Ⅱ)-catalyzed Carbene Rearrangement reactions One-pot process

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

Green Synthesis and Catalysis

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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 investigated.The utilization of pyridotriazoles as the carbene precursors in this kind of reaction efficiently constructed the C(sp3)-S and C(sp3)-Se bond with broad substrate scope and great functional group tolerance.

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

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Mild construction of N-fused polycyclic compounds via Rh(Ⅲ)/EosinY co-catalyze C—H activation

Green Synthesis and Catalysis

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Green Synthesis and Catalysis 2024年第2期5卷 108-111页

作者： Zhouping Wu Guanghui Lv Zheng Lin Jiangyan Tang Jian Chen Jianghong Liu 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 UniversityChengdu 610041China Department of Pharmacy Taihe HospitalHubei University of MedicineNo.32 South Renmin RoadShiyan 442000China

The construction of N-fused polycyclic compounds at room temperature via the combination of transition-metal catalyst and photocatalyst has been reported.This novel work has successfully realized LED irradiated C—H activation of iodonium ylides.The strategy shows wide substrate scope and ideal functional group tolerance.Our work would be useful for the construction of various heterocyclic compounds.

关键词： N-fused polycyclic compounds C—H activation Rh(Ⅲ)catalyst and photocatalyst Iodonium ylides Energy transfer process

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Deployment optimization for target perpetual coverage in energy harvesting wireless sensor network

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Digital Communications and Networks 2024年第2期10卷 498-508页

作者： Zhenkun Jin Yixuan Geng Chenlu Zhu Yunzhi Xia Xianjun Deng Lingzhi Yi Xianlan Wang Wuhan Business University 430056China Wuhan research Institute of Post and Telecommunication Wuhan430074China hubei Key Laboratory of Distributed system Security Hubei Engineering Research Center on Big Data SecuritySchool of Cyber Science and EngineeringHuazhong University of Science and TechnologyWuhan430074China hubei Chutian Expressway Digital Technology Co.Ltd Wuhan430074China School of Information and Safety engineering Zhongnan University of Economics and LawWuhan430073China

Energy limitation of traditional Wireless Sensor Networks(WSNs)greatly confines the network lifetime due to generating and processing massive sensing data with a limited battery.The energy harvesting WSN is a novel network architecture to address the limitation of traditional WSN.However,existing coverage and deployment schemes neglect the environmental correlation of sensor nodes and external energy with respect to physical space.Comprehensively considering the spatial correlation of the environment and the uneven distribution of energy in energy harvesting WSN,we investigate how to deploy a collection of sensor nodes to save the deployment cost while ensuring the target perpetual coverage.The Confident Information Coverage(CIC)model is adopted to formulate the CIC Minimum Deployment Cost Target Perpetual Coverage(CICMTP)problem to minimize the deployed sensor nodes.As the CICMTP is NP-hard,we devise two approximation algorithms named Local Greedy Threshold Algorithm based on CIC(LGTA-CIC)and Overall Greedy Search Algorithm based on CIC(OGSA-CIC).The LGTA-CIC has a low time complexity and the OGSA-CIC has a better approximation rate.Extensive simulation results demonstrate that the OGSA-CIC is able to achieve lower deployment cost and the performance of the proposed algorithms outperforms GRNP,TPNP and EENP algorithms.

关键词： Energy harvesting WSN Deployment optimization Confident information coverage(CIC) Target perpetual coverage

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Improvement in hydrogen storage performance of MgH2 by vanadium doped with ZIF-8 derived a single-atom catalyst V-N-C

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Rare Metals 2024年第6期43卷 2623-2635页

作者： Fei-Fan Hong Wei-Tao Shi Ruo-Lin Zhao Yi Fan Zi-Qi Liu Si-Zhi Ding Hai-Zhen Liu Wen-Zheng Zhou Jin Guo Zhi-Qiang Lan Guangxi novel Battery Materials research center of engineering Technology and center on Nanoenergy research Guangxi Colleges and Universities Key Laboratory of Blue Energy and Systems IntegrationCarbon Peak and Neutrality Science and Technology Development InstituteSchool of Physical Science and TechnologyGuangxi University Nanning engineering Technology research center for Power Transmission system of New Energy Vehicle Transportation CollegeNanning University

Herein,the successful preparation of a singleatom catalyst V-N-C using vanadium-doped zeolitic imidazolate framework（ZIF）-8 as a precursor is reported.The experimental results showed that the V-N-C had a good promoting effect on the hydrogen storage performance of MgH2,and the optimal addition amount of V-N-C was 10wt%.The hydrogenation and dehydrogenation apparent activation energies of 10 wt% V-N-C-catalyzed MgH2were reduced by 44.9 and 53.5 kJ·mol-1,respectively,compared to those of additive-free MgH2.The 10 wt% V-N-C-catalyzed MgH2could reabsorb 5.92 wt% of hydrogen in 50 min at 150℃,with a capacity retention rate of 99.1% after 30 cycles of hydrogen absorption and desorption.Mechanism analysis showed that V-N-C was partially transformed into VN and metallic V when it was milled with MgH2;the in-situ-formed VN and metallic V played an important role in improving the hydrogen storage performance of MgH2.This approach provides a potential solution for obtaining high-performance Mg-based hydrogen storage materials through synergistic interactions between V,N and C.

关键词： MgH 2 Hydrogen storage materials Catalyst Hydrogen storage perormance

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Metochalcone induces senescence-associated secretory phenotype via JAK2/STAT3 pathway in breast cancer

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Oncology research 2024年第5期32卷 943-953页

作者： JIANBO ZHOU FENG WAN BIN XIAO XIN LI CHENG PENG FU PENG Department of Pharmacology West China School of PharmacySichuan UniversityChengduChina State Key Laboratory of Southwestern Chinese Medicine Resources Chengdu University of Traditional Chinese MedicineChengduChina 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 TechnologySichuan UniversityChengduChina Chengdu No.1 Pharmaceutical Co. Ltd.PengzhouChina Chengdu Push Bio-Technology Co. Ltd.ChengduChina

Breast and lung cancers are the leading causes of mortality and most frequently diagnosed cancers in women and men,respectively,worldwide.Although the antitumor activity of chalcones has been extensively studied,the molecular mechanisms of isoliquiritigenin analog 2',4',4-trihydroxychalcone(metochalcone;TEC)against carcinomas remain less well understood.In this study,we found that TEC inhibited cell proliferation of breast cancer BT549 cells and lung cancer A549 cells in a concentration-dependent manner.TEC induced cell cycle arrest in the S-phase,cell migration inhibition in vitro,and reduced tumor growth in vivo.Moreover,transcriptomic analysis revealed that TEC modulated the activity of the JAK2/STAT3 and P53 pathways.TEC triggered the senescence-associated secretory phenotype(SASP)by repressing the JAK2/STAT3 axis.The mechanism of metochalcone against breast cancer depended on the induction of SASP via deactivation of the JAK2/STAT3 pathway,highlighting the potential of chalcone in senescence-inducing therapy against carcinomas.

关键词： Metochalcone Breast cancer Lung cancer SASP JAK2/STAT3

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Adaptive observer-based integral event-triggered antivibration control of a full aircraft active landing gear system with irregular runway excitations

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Science China(Information Sciences) 2024年第6期67卷 248-261页

作者： Wenxiao HU Chenglong DU Fanbiao LI Xinmin CHEN Chunhua YANG Weihua GUI School of Automation Central South University research center in system engineering for Special Aircrafts Ningbo Institute of Materials Technology and EngineeringChinese Academy of Sciences

This study addresses the antivibration issue of a full aircraft active landing gear system(LGS)under landing impact and runway excitations via a novel adaptive observer-based integral event-triggered control method. First, a full aircraft active LGS comprising a front gear and two synchronized main left and right gears with active suspensions is established, where the information exchange among them is not implemented directly. Second, two adaptive observers are designed separately for the front and main LGSs to identify the varying damping parameters and estimate the system states simultaneously. Third, estimated states are transmitted to a shared network through a novel integral event-triggered mechanism(I-ETM);thus, the front and main LGSs are interconnected, and a networked control scheme for the aircraft LGS is constructed. Additionally, the integrated active control law is designed with the aid of the transmitted states of the front and main LGSs, enhancing the robustness against the pitch vibration of the aircraft.Furthermore, the L2-stability of the hybrid system is guaranteed to depress the vertical vibration effect of the landing impact and irregular runway excitations, thus improving passenger safety and comfort. Moreover,a codesign method is provided to obtain feasible solutions to the gain matrices of the observers and controllers simultaneously. Simulation and comparison results are presented to illustrate the effectiveness and superiority of the proposed control scheme in antivibration and saving communication resources.

关键词： aircraft active landing gear antivibration control integral event-triggered mechanism adaptive observer ${\mathcal{L}}_2$-stability

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