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Science China Chemistry 2024年第10期67卷 3193-3194页

作者： Jingfang Zhang Yi Huang Engineering Research Center of Phosphorus Resources Development and Utilization of Ministry of Education School of Chemical Engineering&PharmacyWuhan Institute of TechnologyWuhan 430205China College of Chemistry Central China Normal UniversityWuhan 430079China

Furfural(FF),an important bio-based platform molecule,can be valorized to high-value-added chemicals(e.g.,furfuryl alcohol(FA)or 2-methylfuran(MF))through catalytic hydrogenation[1].The traditional thermocatalytic transformation of FF always requires high-temperature and highpressure conditions[2].Accordingly,electrocatalytic hydrogenation is emerging as a promising approach for the selective reduction of FF to FA or MF under environmentally friendly and benign conditions.

关键词： hydrogenation electrolyte selectivity

Innovative hydrogel-based delivery systems for immunotherapy:A review of pre-clinical progress

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Nano Research 2024年第10期17卷 9031-9043页

作者： Narsimha Mamidi Michael Poellmann Kaila Javius-Jones KiChang Nam Seungpyo Hong Wisconsin Center for NanoBioSystems University of Wisconsin-MadisonMadisonWI 53705USA Pharmaceutical Sciences Division School of PharmacyUniversity of Wisconsin-MadisonMadisonWI 53705USA Department of Medical Engineering College of MedicineDongguk UniversityGoyang 10326Republic of Korea Department of pharmacy Yonsei UniversityIncheon 21983Republic of Korea Lachman institute for Pharmaceutical Development University of Wisconsin-MadisonMadisonWI 53705USA

Immunotherapy has markedly reinvented how we treat cancer,as shown by numerous Food and Drug Administration(FDA)drug approvals that have made significant clinical impact and ongoing clinical ***,undesirable side effects,such as autoimmunity and inflammation,and inconsistent clinical outcomes remain a major *** response rates across various immunotherapeutic reagents is imperative to enhance overall effectiveness and reduce adverse side *** address this challenge,interdisciplinary approaches have been explored by incorporating immunotherapies into hydrogels,enabling finecontrolled delivery to target *** review focuses on recent progress in the utilization of hydrogel-based delivery systems for cancer immunotherapy and their potential to further enhance treatment response ***,recent preclinical advances in hydrogels implemented with immune checkpoint inhibitors,combination therapies,and vaccines,along with selfassembled peptide hydrogels,are *** also discuss technological advances and drawbacks in this area and provide insights to ultimately realize the clinical application of hydrogels in cancer immunotherapy.

关键词： cancer immunotherapy drug delivery hydrogels immunotherapeutic agents immune modulation clinical outcomes

A novel cabazitaxel liposomes modified with ginsenoside Rk1 for cancer targeted therapy

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Acupuncture and Herbal Medicine 2024年第1期4卷 113-121页

作者： Dandan Huang Zhongjie Tang Xiao Pu Tianqi Wang Feiyan Gao Chong Li Medical Research institute College of Pharmaceutical SciencesSouthwest UniversityChongqingChina Department of pharmacy National University of SingaporeSingapore 117545Singapore

Objective:In this study,we aim to enhance the anti-prostate cancer efficacy of cabazitaxel(CTX)and reduce its immunosuppression and systemic toxicity by developing CTX-loaded liposomes modified with ginsenoside Rk1(Rk1/CTX-Lip).Methods:Physical and chemical properties of Rk1/CTX-Lip were *** evaluated the biological functions of Rk1/CTXLip,both in vitro and in vivo.A subcutaneous prostate cancer(RM-1)-bearing mouse model was established to study the efficacy of Rk1/CTX-Lip inhibition in ***,a Candida albicans infection model was established in tumor-bearing mice to study the infection-relieving efficacy of Rk1/***,biocompatibility and in vivo safety of Rk1/CTX-Lip were ***:We successfully prepared Rk1/CTX-Lip,achieving high CTX encapsulation efficiency(97.24±0.75)%and physical ***1/CTX-Lip demonstrated evasion of macrophage phagocytosis,effective tumor tissue targeting,and a significant reduction(>50%)in average tumor volume compared with Chol/***,it relieved the concurrent infection burden and effectively regulated immune organs and cells,demonstrating superior ***:Rk1/CTX-Lip presents a promising new therapy for prostate cancer and holds potential for relieving concurrent fungal infections in cancer patients with low immunity.

关键词： Cabazitaxel Fungal infection Ginsenoside Rk1 Liposome-drug delivery system Prostate cancer

LPA_(1) antagonist-derived LNPs deliver A20 mRNA and promote anti-fibrotic activities

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Nano Research 2024年第10期17卷 9095-9102页

作者： Jingyue Yan Diana D.Kang Chang Wang Xucheng Hou Shi Du Siyu Wang Yonger Xue Zhengwei Liu Haoyuan Li Yichen Zhong Binbin Deng David W.McComb Yizhou Dong Division of Pharmaceutics&Pharmacology College of PharmacyThe Ohio State UniversityColumbusOH 43210USA Icahn Genomics institute Precision Immunology InstituteDepartment of Immunology and ImmunotherapyDepartment of Oncological SciencesTisch Cancer InstituteBiomedical Engineering and Imaging InstituteFriedman Brain InstituteIcahn School of Medicine at Mount SinaiNew YorkNY 10029USA Center for Electron Microscopy and Analysis The Ohio State UniversityColumbusOH 43212USA Department of Materials Science and Engineering The Ohio State UniversityColumbusOH 43210USA

Activated fibroblasts are major mediators of pulmonary *** are generally found in the connective tissue but upon activation can generate excess extracellular matrix(ECM)in the lung interstitial ***,fibroblasts are one of the most targeted cells for treating idiopathic pulmonary fibrosis(IPF).Here,we develop an anti-fibrotic platform that can modulate both the lysophosphatidic acid receptor 1(LPA_(1))and the inflammatory pathway through tumor necrosis factorα-induced protein 3(TNFAIP3,also known as A20)in ***,we synthesized a series of LPA_(1) antagonists,AM095 and AM966,derived amino lipids(LA lipids)which were formulated into LA-lipid nanoparticles(LA-LNPs)encapsulating ***,LA5-LNPs,with AM966 head group and biodegradable acetal lipid tails,showed efficient A20 mRNA delivery to lung fibroblasts in vitro(80.2%±1.5%)and ex vivo(17.2%±0.4%).When treated to primary mouse lung fibroblasts(MLF),this formulation inhibited fibroblast migration and collagen production,thereby slowing the progression of ***,LA5-LNPs encapsulated with A20 mRNA is a novel platform offering a potential approach to regulate fibroblast activation for the treatment of IPF.

关键词： lysophosphatidic acid receptor 1(LPA_(1))antagonist tumor necrosis factorα-induced protein 3(A20) lung fibrosis lipid nanoparticles mRNA

Discovery and characterization of naturally occurring covalent inhibitors of SARS-CoV-2 M^(pro)from the antiviral herb Ephedra

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Chinese Journal of Natural Medicines 2024年第9期22卷 797-807页

作者： HU Qing ZHANG Yiwen CHEN Pengcheng ZHANG Yani ZHU Guanghao LIU Wei WANG Chaoran ZHENG Shuilian SHEN Nonger WANG Haonan HUANG Ping GE Guangbo Center for Clinical pharmacy Cancer CenterDepartment of PharmacyZhejiang Provincial People’s Hospital(Affiliated People’s Hospital)Hangzhou Medical CollegeHangzhou 310014China Shanghai Frontiers Science Center of TCM Chemical Biology Institute of Interdisciplinary Integrative Medicine ResearchShanghai University of Traditional Chinese MedicineShanghai 201203China Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Shanghai 200021China Dalian institute of Chemical Physics Chinese Academy of SciencesDalian 116023China

The Chinese herb Ephedra(also known as Mahuang)has been extensively utilized for the prevention and treatment of coronavirus-induced diseases,including coronavirus disease 2019(COVID-19).However,the specific anti-SARS-CoV-2 compounds and mechanisms have not been fully *** main protease(M^(pro))of SARS-CoV-2 is a highly conserved enzyme responsible for proteolytic processing during the viral life cycle,making it a critical target for the development of antiviral *** study aimed to identify naturally occurring covalent inhibitors of SARS-CoV-2 M^(pro)from Ephedra and to investigate their covalent binding *** results demonstrated that the non-alkaloid fraction of Ephedra(ENA)exhibited a potent inhibitory effect against the SARS-CoV-2 M^(pro)effect,whereas the alkaloid fraction did ***,the chemical constituents in ENA were identified,and the major constituents'anti-SARS-CoV-2 M^(pro)effects were *** the tested constituents,herbacetin(HE)and gallic acid(GA)were found to inhibit SARS-CoV-2 M^(pro)in a time-and dose-dependent *** combination displayed a significant synergistic effect on this key ***,various techniques,including inhibition kinetic assays,chemoproteomic methods,and molecular dynamics simulations,were employed to further elucidate the synergistic anti-M^(pro)mechanisms of the combination of HE and ***,this study deciphers the naturally occurring covalent inhibitors of SARS-CoV-2 M^(pro)from Ephedra and characterizes their synergistic anti-M^(pro)synergistic effect,providing robust evidence to support the anti-coronavirus efficacy of Ephedra.

关键词： Main protease Ephedra Ephedra non-alkaloid fraction Covalent inhibitors Synergistic effect

Structural insight into the dual-antagonistic mechanism of AB928 on adenosine A_(2)receptors

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Science China(Life Sciences) 2024年第5期67卷 986-995页

作者： Yuan Weng Xinyu Yang Qiansen Zhang Ying Chen Yueming Xu Chenyu Zhu Qiong Xie Yonghui Wang Huaiyu Yang Mingyao Liu Weiqiang Lu Gaojie Song Shanghai Key Laboratory of Regulatory Biology Institute of Biomedical Sciences and School of Life SciencesEast China Normal UniversityShanghai 200241China Department of Medicinal Chemistry School of PharmacyFudan UniversityShanghai 201203China

The adenosine subfamily G protein-coupled receptors A_(2A)R and A_(2B)R have been identified as promising cancer immunotherapy *** of the A_(2A)R/A_(2B)R dual antagonists,AB928,has progressed to a phaseⅡclinical trial to treat rectal ***,the precise mechanism underlying its dual-antagonistic properties remains ***,we report crystal structures of the A_(2A)R complexed with AB928 and a selective A_(2A)R antagonist *** structures revealed a common binding mode on A_(2A)R,wherein the ligands established extensive interactions with residues from the orthosteric and secondary *** contrast,the cAMP assay and A_(2A)R and A_(2B)R molecular dynamics simulations indicated that the ligands adopted distinct binding modes on A_(2B)*** analysis of their chemical structures suggested that AB928 readily adapted to the A_(2B)R pocket,while 2-118 did not due to intrinsic *** disparity potentially accounted for the difference in inhibitory efficacy between A_(2B)R and A_(2A)*** study serves as a valuable structural template for the future development of selective or dual inhibitors targeting A_(2A)R/A_(2B)R for cancer therapy.

关键词： adenosine receptor A2AR A2BR inhibitor dual-antagonism drug discovery

Lyophilized lymph nodes:A paradigm shift in CAR T-cell delivery for solid tumor therapy

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3774-3776页

作者： Qiuhua Luo Xiaojing Yan Hong-Xu Liu Heran Li Department of pharmacy the First Hospital of China Medical UniversityShenyang 110001China School of pharmacy China Medical UniversityShenyang 110122China Department of Hematology the First Hospital of China Medical UniversityShenyang 110001China Liaoning Cancer Hospital&institute Cancer Hospital of Dalian University of TechnologyShenyang 110042China

CAR T(chimeric antigen receptor T-cell)therapy represents a paradigm shift in cancer *** empowering immune cells to target malignant cells directly,it opens another door to precision medicine,promising cures for once refractory ***,the extension of CAR T therapy to solid tumors confronts formidable *** physical and biochemical barriers within the tumor microenvironment,such as dense extracellular matrices and immunosuppressive factors,impede CAR T cell infiltration and function,leading to diminished success rates in solid tumor treatment2.

关键词： CAR therapy tumor

Contrast-enhanced guided endoscopic ultrasound procedures

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World Journal of Gastroenterology 2024年第17期30卷 2311-2320页

作者： Marcel Ioan Gheorghiu Andrada Seicean Cristina Pojoga Claudia Hagiu Radu Seicean Zeno Sparchez Department of Gastroenterology “Prof.Dr.Octavian Fodor”Regional Institute of Gastroenterology and Hepatology"Iuliu Hatieganu"University of Medicine and PharmacyCluj-Napoca 400162ClujRomania Department of Clinical Psychology and Psychotherapy International Institute for Advanced Study of Psychotherapy and Applied Mental HealthBabeș-Bolyai UniversityCluj-Napoca 400375ClujRomania The First Surgical Clinic "Iuliu Hatieganu"University of Medicine and PharmacyCluj Napoca 400006ClujRomania

Contrast-enhanced endoscopic ultrasound(CH-EUS)can overcome the limi-tations of endoscopic ultrasound-guided acquisition by identifying microvessels inside inhomogeneous tumours and improving the characterization of these *** the initial enthusiasm that oriented needle sampling under CH-EUS guidance could provide better diagnostic yield in pancreatic solid lesions,further studies did not confirm the supplementary values in cases of tissue acquisition guided by *** review details the knowledge based on the available data on contrast-guided *** indications for CH-EUS tissue acquisition include isoechoic EUS lesions with poor visible delineation where CH-EUS can differentiate the lesion vascularisation from the surrounding parenchyma and also the mural nodules within biliopancreatic cystic lesions,which occur in select ***,the roles of CH-EUS-guided therapy in patients whose pancreatic fluid collections or bile ducts that have an echogenic content have indications for drainage,and patients who have nonvisualized vessels that need to be highlighted via Doppler EUS are *** indication is represented if there is a need for an immediate assessment of the post-radiofrequency ablation of pancreatic neuroendocrine tumours,in which case CH-EUS can be used to reveal the incomplete tumour destruction.

关键词： Endosonography Contrast-enhanced endoscopic ultrasound Tissue acquisition Fine needle aspiration Fine needle biopsy Drainage Pancreatic fluid collections Biopsy Pancreas

Investigating the Mechanism of Qu Du Qiang Fei 1 Hao Fang Formula against Coronavirus Disease 2019 Based on Network Pharmacology Method

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World Journal of Traditional Chinese Medicine 2024年第1期10卷 93-103页

作者： Yuan-Hua Wang He-Yang Zhou Jin-Yun Ma Gui-Qing Ding Hua Yu Yong-Sheng Jin Xiao-Dong Cheng institute of Clinical Immunology Yue-Yang Hospital of Integrative MedicineShanghai University of Traditional Chinese MedicineShanghaiChina School of pharmacy Naval Medical UniversityShanghaiChina

Objective:Qu Du Qiang Fei 1 Hao Fang(QDQF1)is a novel Chinese herbal medicine formula used to treat coronavirus disease 2019(COVID-19).However,the pharmacological mechanisms of action of QDQF1 remain *** objective of this study was to identify the effective ingredients and biological targets of QDQF1 for COVID-19 *** and Methods:The effective ingredients and mechanisms of action of QDQF1 were analyzed by using network pharmacology methods,which included an analysis of the effective ingredients and corresponding targets,COVID-19-related target acquisition,compound-target network analyses,protein-protein interaction network analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)and Gene Ontology(GO)enrichment analyses,and molecular docking ***:In total,288 effective QDQF1 ingredients were *** identified 51 core targets from the 148 targets through an overlap between putative QDQF1 targets and COVID-19-related *** key components,including formononetin,kaempferol,luteolin,naringenin,quercetin,and wogonin were identified through component-target network *** functional enrichment analysis of the core targets revealed 1296 items,while KEGG pathway enrichment analysis identified 148 signaling *** central targets(CCL2,CXCL8,IL1B,IL6,MAPK1,MAPK3,MAPK8,STAT3,and TNF)related to the COVID-19 pathway were identified in the KEGG pathway enrichment ***,molecular docking analysis suggested that the docking scores of the six key components to the nine central targets were better than those to ***:QDQF1 may regulate multiple immune-and inflammation-related targets to inhibit the progression of severe acute respiratory syndrome coronavirus 2,and thus,may be suitable for the treatment of COVID-19.

关键词： Coronavirus disease 2019 molecular docking molecular mechanism network pharmacology Qu Du Qiang Fei 1 Hao Fang formula

Atroposelective Synthesis of 2-Arylindoles via Chiral Phosphoric Acid-Catalyzed Direct Amination of Indoles

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Chinese Journal of Chemistry 2024年第7期42卷 731-735页

作者： Wen Bao Ye-Hui Chen Yu-Wei Liu Shao-Hua Xiang Bin Tan School of pharmacy&StateKey Laboratory of Applied Organic Chemistry Lanzhou UniversityLanzhouGansu 730000China Shenzhen Grubbs institute Department of ChemistrySouthern University of Science and TechnologyShenzhenGuangdong 518055China

Indole-based atropisomers are a very important class of axially chiral ***,the atroposelective synthesis of axially chiral 2-arylindole remains largely *** this study,we report the successful synthesis of atropisomeric 2-arylindoles using direct amination of indoles with p-quinonediimines in the presence of chiral phosphoric acid as a *** acts as an aminating reagent through formal polarity inversion of *** malonate group on the 2-aryl of 2-indoles was found to be essen-tial for high enantioselectivity of the *** could be due to the additional interaction between the ester group and the cata-lyst,as well as the intramolecular hydrogen *** findings provide a new strategy for the asymmetric construction of 2-arylindole atropisomers.

关键词： Chiral phosphoric acid Quinonediimines Direct amination Nucleophilic addition Asymmetric catalysis Enantioselectivity Axially chiral 2-arylindole Atroposelective synthesis