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Lipid droplets in the nervous system:involvement in cell metabolic homeostasis

Neural Regeneration Research 2025年第3期20卷 740-750页

作者： Yuchen Zhang Yiqing Chen Cheng Zhuang Jingxuan Qi Robert Chunhua Zhao Jiao Wang School of Life Sciences Shanghai UniversityShanghaiChina School of Medicine Shanghai UniversityShanghaiChina Institute of Basic medical Sciences Chinese Academy of medical Sciences School of Basic MedicinePeking Union Medical CollegeBeijingChina center of Excellence in Tissue Engineering Chinese Academy of Medical SciencesBeijingChina Beijing Key Laboratory of New drug development and Clinical Trial of Stem Cell Therapy BeijingChina

Lipid droplets serve as primary storage organelles for neutral lipids in neurons,glial cells,and other cells in the nervous *** droplet formation begins with the synthesis of neutral lipids in the endoplasmic ***,lipid droplets were recognized for their role in maintaining lipid metabolism and energy homeostasis;however,recent research has shown that lipid droplets are highly adaptive organelles with diverse functions in the nervous *** addition to their role in regulating cell metabolism,lipid droplets play a protective role in various cellular stress ***,lipid droplets exhibit specific functions in neurons and glial *** of lipid droplet formation leads to cellular dysfunction,metabolic abnormalities,and nervous system *** review aims to provide an overview of the role of lipid droplets in the nervous system,covering topics such as biogenesis,cellular specificity,and ***,it will explore the association between lipid droplets and neurodegenerative *** the involvement of lipid droplets in cell metabolic homeostasis related to the nervous system is crucial to determine the underlying causes and in exploring potential therapeutic approaches for these diseases.

关键词： Alzheimer's disease lipid droplet biogenesis lipid droplets lipid metabolism nervous system neurodegenerative disorders oxidative stress Parkinson's disease

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Enhanced oral drug delivery by mimicking natural amino acid and oligopeptide absorption route

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Nano Research 2025年第2期18卷 525-540页

作者： Ruinan Wu Xiaoxing Fan Licheng Wu Liyun Xing Jinxia Kong Zhou Zhou Jingyuan Wen Lian Li Yuan Huang 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 School of Pharmacy Faculty of Medical and Health SciencesUniversity of AucklandAuckland 1023New Zealand

Oral delivery of protein and peptide drugs presents considerable challenges due to their susceptibility to digestive enzymes in gastrointestinal(Gl)tract and low efficiency of transepithelial ***,inspired by efficient absorption of protein-based nutrients,we constructed several kinds of oral drug delivery systems by mimicking natural amino acid and oligopeptide absorption *** kinds of amino acids and two kinds of oligopeptides were chosen as targeting ligands to mediate transportation of orally administered nanoparticles(NPs).Liraglutide(Lira),a kind of glucagon like peptide-1(GLP-1)receptor agonist,was used as model *** functionalized NPs could protect Lira from enzymatic degradation in Gl ***,compared with amino acid-modified NPs,oligopeptide-modified NPs exhibited greater transepithelial transport efficiency and were primarily absorbed in the proximal small intestine due to the high expression and transportation mediated by proton coupled oligopeptide transporter 1(PEPT1).These Lira-loaded NPs could effectively control the blood glucose level,reduce plasma lipid level,and repair tissue damage on type 2 diabetic mice and even showed comparable hypoglycemic effects of subcutaneous injection(s.c.)free *** study demonstrates the potential of mimicking natural oligopeptide absorption route to enhance oral delivery of protein and peptide drugs.

关键词： oral drug delivery amino acid absorption route oligopeptide absorption route liraglutide

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I_(2)-DMSO mediated tetra-functionalization of enaminones for the construction of novel furo[2,3:4,5]pyrimido[1,2-b]indazole skeletons via in situ capture of ketenimine cations

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Chinese Chemical Letters 2025年第1期36卷 277-282页

作者： You Zhou Li-Sheng Wang Shuang-Gui Lei Bo-Cheng Tang Zhi-Cheng Yu Xing Li Yan-Dong Wu Kai-Lu Zheng An-Xin Wu National Key Laboratory of Green Pesticide International Joint Research Center for Intelligent Biosensor Technology and HealthCollege of ChemistryCentral China Normal UniversityWuhan 430079China Guangdong Provincial Key Laboratory of Research and development of Natural drugs The First Dongguan Affiliated HospitalSchool of PharmacyGuangdong Medical UniversityDongguan 523808China State Key Laboratory of Chemical Biology and drug Discovery Department of Applied Biology and Chemical TechnologyThe Hong Kong Polytechnic UniversityHong Kong SAR 999077China

The first-ever synthesis of the unknown furo[2,3:4,5]pyrimido[1,2-b]indazole skeleton was demonstrated based on the undiscovered tetra-functionalization of enaminones,with simple substrates and reaction *** key to realizing this process lies in the multiple trapping of the in situ generated ketenimine cation by the 3-aminoindazole,which results in the formation of four new chemical bonds and two new rings in one ***,the products of this new reaction were found to exhibit aggregationinduced emission(AIE)without modification.

关键词： Unknown skeleton Tetra-functionalization Ketenimine cations Aggregation-induced emission

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Research progress of small-molecule natural medicines for the treatment of ischemic stroke

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Chinese Journal of Natural Medicines 2025年第1期23卷 21-30页

作者： Kui Liu Ling Wang Tao Pang State Key Laboratory of Natural Medicines New Drug Screening and Pharmacodynamics Evaluation Center China Pharmaceutical University

Stroke is the second leading cause of disability and mortality worldwide, imposing a substantial socioeconomic burden on individuals and healthcare systems. Annually, approximately 14 million people experience stroke, with ischemic stroke comprising nearly 85% of cases, of which 10% to 20% involve large vessel occlusions. Currently, recombinant tissue plasminogen activator(tPA) remains the only approved pharmacological intervention. However, its utility is limited due to a narrow therapeutic window and low recanalization rates, making it applicable to only a minority of patients. Therefore, there is an urgent need for novel therapeutic strategies, including pharmacological advancements and combinatory ***-molecule natural medicines, particularly those derived from traditional Chinese herbs,have demonstrated significant therapeutic potential in ischemic stroke management. These compounds exert multiple neuroprotective effects, such as antioxidation, anti-inflammatory action, and inhibition of apoptosis, all of which are critical in mitigating stroke-induced cerebral damage. This review comprehensively examines the pathophysiology of acute ischemic stroke(AIS) and highlights the recent progress in the development of small-molecule natural medicines as promising therapeutic agents for cerebral ischemic stroke.

关键词： Antioxidants Ischemic stroke Natural medicines Neuroinflammation. Small molecule

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End-to-end dataflow engineering framework of honey manufacturing from intermediates to process by TAS1R2@AuNPs/SPCE biosensor coupled with quality transfer principle

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Fundamental Research 2025年第1期5卷 407-418页

作者： Xiaoyan Hu Jingqi Zeng Lijuan M Xiaomeng Wang Jing Du Lu Yao Zhisheng Wu Fujian University of Traditional Chinese Medicine Fuzhou 350122China Engineering Research center for Pharmaceutics of Chinese Materia Medica and New drug development Ministry of EducationBeijing 100102China Beijing University of Chinese Medicine Beijing 100102China china Beijing Tongrentang Group Co. Ltd.Beijing 100062China

This study reported an original end-to-end dataflow engineering framework for the quality transfer principle to overcome the quality challenges in real-world honey ***,650 pivotal data points of physical and chemical quality attributes from 65 batches of honey intermediates were characterized through multiple sensors,which included rheological properties,acidity,moisture,and ***,a hypersensitized TAS1R2@AuNPs/SPCE biosensor was developed to identify biological quality attributes of honey,the powerful affinities between honey intermediates and the TAS1R2 receptor were discovered(KD<1×10^(−8)M),and the abnormal batches of B2,B23 and C23 were diagnosed by TAS1R2@AuNPs/SPCE biosensor and multivariable ***,the end-to-end dataflow containing physical,chemical and biological critical quality attributes was successfully established to interpret the quality transfer principle of honey manufacturing,which revealed that the front-end refining process was relatively unstable and the back-end refining process was a negligible influence on the quality of honey *** framework embraces quality management,quality transfer,and biosensor information,which will contribute to discovering the quality transfer principle in industrial innovation for intelligent manufacturing.

关键词： End-to-end dataflow Quality transfer principle Critical quality attributes Biosensor Honey manufacturing

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Blocking the PD-1 signal transduction by occupying the phosphorylated ITSM recognition site of SHP-2

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Science china(Life Sciences) 2025年第1期68卷 189-203页

作者： Wenjie Li Wenyi Mei Hewei Jiang Jie Wang Xiaoli Li Lina Quan Yanyan Diao Yanni Ma Sisi Fan Zhuwei Xie Mengdie Gong Huan Zhu Dewen Bi Feng Zhang Lei Ma Jian Zhang Yufeng Gao Aris Paschalidis Honghuang Lin Fangfang Liu Kangdong Liu Mingliang Ye Zhenjiang Zhao Yajun Duan Zhuo Chen Yufang Xu Weilie Xiao Shengce Tao Lili Zhu Honglin Li Shanghai Key Laboratory of New drug Design School of PharmacyEast China University of Science&TechnologyShanghai 200237China Shanghai center for Systems Biomedicine Key Laboratory of Systems Biomedicine(Ministry of Education)Shanghai Jiao Tong UniversityShanghai 200240China Key Laboratory of Medicinal Chemistry for Natural Resource Ministry of EducationYunnan Characteristic Plant Extraction LaboratoryYunnan Provincial Center for Research&Development of Natural ProductsState Key Laboratory for Conservation and Utilization of Bio-Resources in YunnanSchool of Pharmacy and School of Chemical Science and TechnologyYunnan UniversityKunming650500China CAS Key Laboratory of Separation Sciences for Analytical Chemistry National Chromatographic R&A CenterDalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China Department of Cardiology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230027China Department of Infectious Diseases The First Affiliated Hospital of Anhui Medical UniversityHefei 230022China Department of Medicine University of Massachusetts Chan Medical SchoolWorcester MA 01655USA Department of Pathophysiology School of Basic Medical SciencesAcademy of Medical ScienceCollege of MedicineZhengzhou UniversityZhengzhou 450001China Innovation center for AI and drug Discovery East China Normal UniversityShanghai 200062China Lingang Laboratory Shanghai 200031China

Targeting the PD-1/PD-L1 axis with small-molecular inhibitors is a promising approach for ***,we identify a natural pentacyclic triterpenoid,Pygenic Acid A(PA),as a PD-1 signaling *** exerts anti-tumor activity in hPD-1 knock-in C57BL/6 mice and enhances effector functions of T cells to promote immune responses by disrupting the PD-1 signaling ***,we identify SHP-2 as the direct molecular target of PA for inhibiting the PD-1 signaling ***,mechanistic studies suggest that PA binds to a new druggable site in the phosphorylated PD-1 ITSM recognition site of SHP-2,inhibiting the recruitment of SHP-2 by *** together,our findings demonstrate that PA has a potential application in cancer immunotherapy and occupying the phosphorylated ITSM recognition site of SHP-2 may serve as an alternative strategy to develop PD-1 signaling *** addition,our success in target recognition provides a paradigm of target identification and confirmation for natural products.

关键词： pygenic acid A programmed death-1 immunoreceptor tyrosine-based switch motif SH2 domain-containing protein-tyrosine phosphatase-2 target identification site recognition

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Rare tumor list provide vast opportunities for novel drug development in china

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Science Bulletin 2025年第2期70卷 132-134页

作者： Rongshou Zheng Shuhang Wang Guo Zhao Wenqiang Wei Ning Li National Central Cancer Registry National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Clinical Trial center National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

During the last decade,common cancer understanding and treatment have significantly improved[1,2,3].However,rare tumors are still poorly *** the low incidence of rare tumors,including soft tissue sarcoma,malignant peripheral nerve sheath tumor,malignant pleural mesothelioma,and others,they impose formidable clinical challenges due to inadequate information regarding their diagnosis and treatment,especially in ***,the rare tumor definition was the first issue encountered by researchers in this ***,no unanimous rare tumor definition has been established ***,there are disparities between rare tumor lists in different *** previously defined rare as those with a<50/100,000people prevalence in *** European Union initiated a project known as the Surveillance of Rare Cancer in Europe(RARECARE).

关键词： diagnosis rare Rare

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Stir-Fried Semen Armeniacae Amarum Suppresses Aristolochic AcidⅠ-Induced Nephrotoxicity and DNA Adducts

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Chinese Journal of Integrative Medicine 2025年第2期31卷 142-152页

作者： LI Cheng-xian XIAO Xiao-he LI Xin-yu XIAO Da-ke WANG Yin-kang WANG Xian-ling ZHANG Ping LI Yu-rong NIU Ming BAI Zhao-fang School of Chinese Materia Medica Beijing University of Chinese MedicineBeijing(100102)China Department of Hepatology Military Institute of Chinese Materiathe Fifth Medical CentreGeneral Hospital of PLABeijing(100039)China National Key Laboratory of Kidney Beijing(100039)China School of Pharmacy Chengdu University of Traditional Chinese MedicineChengdu(610075)China School of Traditional Chinese Medicine Capital Medical UniversityBeijing(100069)China School of Traditional Chinese Medicine Southern Medical UniversityGuangzhou(510515)China Department of Pharmacy Medical Supplies Center of PLA General HospitalBeijing(100039)China Department of Military Patient Management the Fifth Medical Center of PLA General HospitalBeijing(100039)China Department of Hematology the Fifth Medical Center of Chinese PLA General HospitalBeijing(100071)China

Objective:To investigate the protective effects of stir-fried Semen Armeniacae Amarum(SAA)against aristolochic acidⅠ(AAⅠ)-induced nephrotoxicity and DNA adducts and elucidate the underlying mechanism involved for ensuring the safe use of Asari Radix et ***:In vitro,HEK293T cells overexpressing Flag-tagged multidrug resistance-associated protein 3(MRP3)were constructed by Lentiviral transduction,and inhibitory effect of top 10 common pairs of medicinal herbs with Asari Radix et Rhizoma in clinic on MRP3 activity was verified using a self-constructed fluorescence screening *** m RNA,protein expressions,and enzyme activity levels of NAD(P)H quinone dehydrogenase 1(NQO1)and cytochrome P4501A2(CYP1A2)were measured in differentiated Hepa RG *** toxicity after inhibition of AAⅠmetabolite transport was detected using cell counting kit-8 *** vivo,C57BL/6 mice were randomly divided into 5 groups according to a random number table,including:control(1%sodium bicarbonate),AAⅠ(10 mg/kg),stir-fried SAA(1.75 g/kg)and AAⅠ+stir-fried SAA(1.75 and 8.75 g/kg)groups,6 mice in each *** 7 days of continuous gavage administration,liver and kidney damages were assessed,and the protein expressions and enzyme activity of liver metabolic enzymes NQO1 and CYP1A2 were determined ***:In vivo,combination of 1.75 g/kg SAA and 10 mg/kg AAⅠsuppressed AAⅠ-induced nephrotoxicity and reduced d A-ALI formation by 26.7%,and these detoxification effects in a dose-dependent manner(Pdrug candidate for the suppression of AAⅠ-induced liver and kidney dam

关键词： aristolochic acidⅠ stir-fried Semen Armeniacae Amarum detoxification principles of compatibility metabolic enzymes transporters

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Emerging patterns of antimicrobial resistance:Concurrent presence of mcr-1.1 and mcr-8.1 in a ST15 Klebsiella pneumoniae isolated from poultry in china

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Journal of Integrative Agriculture 2025年第1期24卷 403-407页

作者： Dong'an Cui Panpan Liu Ling Wang Jiongjie He Yuzhang Yan Mengke Ru Baocheng Hao Yan Sun Shengyi Wang Key Laboratory of New Animal drug Project Gansu Province/Key Laboratory of Veterinary Pharmaceutical DevelopmentMinistry of Agriculture and Rural AffairsLanzhou Institute of Husbandry and Pharmaceutical SciencesChinese Academy of Agricultural SciencesLanzhou 730050China College of Animal Science and Technology Guangxi UniversityNanning 530005China china Institute of Veterinary drug Control Beijing 100081China

Colistin serves as a crucial treatment for multidrugresistant(MDR)Gram-negative bacterial ***,its excessive use has contributed to an increase in colistin-resistant strains within livestock production(Binsker et al.2022).The mobile colistin resistance gene,mcr,which reduces colistin affinity by incorporating phosphoethanolamine(pEtN)into the bacterial lipopolysaccharide,significantly compromises the effectiveness of colistin treatments(Liu et al.2016).

关键词： poultry treatment compromise

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Plasma metabolomics combined with mass spectrometry imaging reveals crosstalk between tumor and plasma in gastric cancer genesis and metastasis

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Chinese Chemical Letters 2025年第1期36卷 506-512页

作者： Yanhua Chen Xian Ding Jun Zhou Zhaoying Wang Yunhai Bo Ying Hu Qingce Zang Jing Xu Ruiping Zhang Jiuming He Fen Yang Zeper Abliz Key Laboratory of Mass Spectrometry Imaging and Metabolomics(State Ethnic affairs Commission) Center for Imaging and Systems BiologyCollege of Life and Environmental SciencesMinzu University of ChinaBeijing 100081China State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100050China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Center of Drug Clinical TrialPeking University Cancer Hospital and InstituteBeijing 100142China Beijing Engineering Research center of Food Environment and Public Health Minzu University of ChinaBeijing 100081China Key laboratory of Ethnomedicine of Ministry of Education School of PharmacyMinzu University of ChinaBeijing 100081China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of BioBankPeking University Cancer Hospital and InstituteBeijing 100142China Pharmacy Department of Beijing Chao–Yang Hospital Capital Medical UniversityBeijing 100020China

Gastric Carcinoma(GC)is a highly fatal malignant tumor with a poor *** elevated mortality rates are primarily due to its proclivity for late-stage *** the metabolic interactions between tumor microenvironment and the systemic bloodstream could help to clearly understand the mechanisms and identify precise biomarkers of tumor growth,proliferation,and *** this study,an integrative approach that combines plasma metabolomics with mass spectrometry imaging of tumor tissue was developed to investigate the global metabolic landscape of GC tumorigenesis and *** results showed that the oxidized glutathione to glutathione ratio(GSSH/GSH)became increased in non-distal metastatic GC(M0),which means an accumulation of oxidative stress in tumor ***,it was found that the peroxidation of polyunsaturated fatty acids,such as 9,10-EpOMe,9-HOTrE,etc.,were accelerated in both plasma and tumor tissues of distal metastatic GC(M1).These changes were further confirmed the potential effect of CYP2E1 and GGT1 in metastatic potential of GC by mass spectrometry imaging(MSI)and immunohistochemistry(IHC).Collectively,our findings reveal the integrated multidimensional metabolomics approach is a clinical useful method to unravel the bloodtumor metabolic crosstalk,illuminate reprogrammed metabolic networks,and provide reliable circulating biomarkers.

关键词： Metabolomics Spatial-resolved metabolomics Gastric cancer Blood-tumor metabolic crosstalk Lipid peroxidation

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