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| 1 | Mechanisms and applications of antitumor immunotherapy of responsive drug-loaded nanoparticles in breast cancer显示文摘During the chemotherapy of tumors,the cytotoxic effect of drugs is vital to kill tumor cells,and the delivery of a chemotherapeutic agent is of great importance for optimal therapeutic effects.The high in vivo clearance rate and low delivery efficiency of conventional chemotherapeutic agents affect the therapeutic effect.In recent years,the responsive drug delivery nanosystem has received increasing concern owing to its excellent biocompatibility,stable delivery performance,and controlled drug release strategies.To lucidly explain the cytocidal and immunotherapeutic effects of such responsive nanosystems in breast cancer,this review discusses the various stimuli and responses of drug-loaded liposomal nanosystems.The light/magnetic response of drug-loaded bionic membranes nanosystems and the heat/magnetic response of drug-loaded iron oxide nanosystems are also elaborated.Their cancer cell-killing efficacy and antitumor immunotherapeutic effects are also scrutinized. | LETIAN JIN HETING CHEN QI RUAN RUI LIU YIFENG FAN XIUFANG XU DAJIANG WANG JIAHUI LU | 2023 | BIOCELL2023，47，7： | 0 |
| 2 | Medicinal chemistry strategies towards the development of non-covalent SARS-CoV-2 Mpro inhibitors显示文摘The main protease(M^(pro))of SARS-CoV-2 is an attractive target in anti-COVID-19 therapy for its high conservation and major role in the virus life cycle.The covalent M^(pro)inhibitor nirmatrelvir(in combination with ritonavir,a pharmacokinetic enhancer)and the non-covalent inhibitor ensitrelvir have shown efficacy in clinical trials and have been approved for therapeutic use.Effective antiviral drugs are needed to fight the pandemic,while non-covalent M^(pro)inhibitors could be promising alternatives due to their high selectivity and favorable druggability.Numerous non-covalent M^(pro)inhibitors with desirable properties have been developed based on available crystal structures of M^(pro).In this article,we describe medicinal chemistry strategies applied for the discovery and optimization of non-covalent M^(pro)inhibitors,followed by a general overview and critical analysis of the available information.Prospective viewpoints and insights into current strategies for the development of non-covalent M^(pro)inhibitors are also discussed. | Letian Song Shenghua Gao Bing Ye Mianling Yang Yusen Cheng Dongwei Kang Fan Yi Jin-Peng Sun Luis Menéndez-Arias Johan Neyts Xinyong Liu Peng Zhan | 2024 | Acta Pharmaceutica Sinica B2024，14，1： | 0 |
| 3 | Smart Design and Manufacturing the Welded Q350 Steel Frames via Lifecycle Management Strategy of Digital Twin显示文摘Artificial intelligent aided design and manufacturing have been recognized as one kind of robust data-driven and data-intensive technologies in the integrated computational material engi-neering(ICME)era.Motivated by the dramatical developments of the services of China Railway High-speed series for more than a decade,it is essential to reveal the foundations of lifecycle man-agement of those trains under environmental conditions.Here,the smart design and manufacturing of welded Q350 steel frames of CR200J series are introduced,presenting the capability and opportu-nity of ICME in weight reduction and lifecycle management at a cost-effective approach.In order to address the required fatigue life time enduring more than 9×10^(6)km,the response of optimized frames to the static and the dynamic loads are comprehensively investigated.It is highlighted that the maximum residual stress of the optimized welded frame is reduced to 69 MPa from 477 MPa of previous existing one.Based on the measured stress and acceleration from the railways,the fatigue life of modified frame under various loading modes could fulfil the requirements of the lifecycle man-agement.Moreover,our recent developed intelligent quality control strategy of welding process mediated by machine learning is also introduced,envisioning its application in the intelligent weld-ing. | Letian Fan Xinchao Wang Yongsheng Chen Li Wang Shumi Liu Yuanfei Wang Xinwei Li Kun Du Jia Zhang Xingyu Gao Feng Sun Haifeng Song William Yi Wang Jinshan Li | 2023 | Journal of Beijing Institute of Technology2023，32，4： | 0 |
| 4 | FFAR4 improves the senescence of tubular epithelial cells by AMPK/SirT3 signaling in acute kidney injury显示文摘Acute kidney injury(AKI)is a serious clinical complication with high morbidity and mortality rates.Despite substantial progress in understanding the mechanism of AKI,no effective therapy is available for treatment or prevention.We previously found that G protein-coupled receptor(GPCR)family member free fatty acid receptor 4(FFAR4)agonist TUG891 alleviated kidney dysfunction and tubular injury in AKI mice.However,the versatile role of FFAR4 in kidney has not been well characterized.In the study,the expression of FFAR4 was abnormally decreased in tubular epithelial cells(TECs)of cisplatin,cecal ligation/perforation and ischemia/reperfusion injury-induced AKI mice,respectively.Systemic and conditional TEC-specific knockout of FFAR4 aggravated renal function and pathological damage,whereas FFAR4 activation by TUG-891 alleviated the severity of disease in cisplatin-induced AKI mice.Notably,FFAR4,as a key determinant,was firstly explored to regulate cellular senescence both in injured kidneys of AKI mice and TECs,which was indicated by senescence-associatedβ-galactosidase(SA-β-gal)activity,marker protein p53,p21,Lamin B1,phospho-histone H2A.X,phospho-Rb expression,and secretory phenotype IL-6 level.Mechanistically,pharmacological activation and overexpression of FFAR4 reversed the decrease of aging-related SirT3 protein,where FFAR4 regulated SirT3 expression to exhibit anti-senescent effect via Gq subunit-mediated CaMKKβ/AMPK signaling in cisplatin-induced mice and TECs.These findings highlight the original role of tubular FFAR4 in cellular senescence via AMPK/SirT3 signaling and identify FFAR4 as a potential drug target against AKI. | Letian Yang Bo Wang Fan Guo Rongshuang Huang Yan Liang Lingzhi Li Sibei Tao Ting Yin Ping Fu Liang Ma | 2022 | Signal Transduction and Targeted Therapy2022，7，12： | 0 |
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