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Gut liver brain axis in diseases:the implications for therapeutic interventions

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Signal Transduction and Targeted Therapy 2024年第1期9卷 79-104页

作者： Mengyao Yan Shuli Man Benyue Sun Long Ma Lanping Guo Luqi Huang Wenyuan Gao State key laboratory of Food Nutrition and Safety Key Laboratory of Industrial MicrobiologyMinistry of EducationTianjin Key Laboratory of Industry MicrobiologyNational and Local United Engineering Lab of Metabolic Control Fermentation TechnologyChina International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal ChemistryCollege of BiotechnologyTianjin University of Science&Technology300457 TianjinChina National Resource Center for Chinese Materia Medica China Academy of Chinese Medical Sciences100700 BeijingChina Tianjin key laboratory for Modern Drug Delivery&High-Efficiency School of Pharmaceutical Science and TechnologyTianjin UniversityWeijin Road300072 TianjinChina

Gut-liver-brain axis is a three-way highway of information interaction system among the gastrointestinal tract,liver,and nervous *** the past few decades,breakthrough progress has been made in the gut liver brain axis,mainly through understanding its formation mechanism and increasing treatment *** this review,we discuss various complex networks including barrier permeability,gut hormones,gut microbial metabolites,vagus nerve,neurotransmitters,immunity,brain toxic metabolites,β-amyloid(Aβ)metabolism,and epigenetic regulation in the gut-liver-brain *** therapies containing antibiotics,probiotics,prebiotics,synbiotics,fecal microbiota transplantation(FMT),polyphenols,low FODMAP diet and nanotechnology application regulate the gut liver brain ***,some special treatments targeting gut-liver axis include farnesoid X receptor(FXR)agonists,takeda G protein-coupled receptor 5(TGR5)agonists,glucagon-like peptide-1(GLP-1)receptor antagonists and fibroblast growth factor 19(FGF19)*** gut-brain axis embraces cognitive behavioral therapy(CBT),antidepressants and tryptophan metabolism-related *** liver-brain axis contains epigenetic regulation and Aβmetabolism-related *** the future,a better understanding of gut-liver-brain axis interactions will promote the development of novel preventative strategies and the discovery of precise therapeutic targets in multiple diseases.

关键词： metabolism therapeutic immunity

Genome-edited rabbits:Unleashing the potential of a promising experimental animal model across diverse diseases

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Zoological Research 2024年第2期45卷 253-262页

作者： Yang Han Jiale Zhou Renquan Zhang Yuru Liang Liangxue Lai Zhanjun Li key laboratory of Zoonosis Research Ministry of EducationCollege of Animal ScienceJilin UniversityChangchunJilin 130062China CAS key laboratory of Regenerative Biology Guangdong Provincial Key Laboratory of Stem Cell and Regenerative MedicineSouth China Institute for Stem Cell Biology and Regenerative MedicineGuangzhou Institutes of Biomedicine and HealthChinese Academy of SciencesGuangzhouGuangdong 510530China Guangzhou Regenerative Medicine and Health Guang Dong laboratory(GRMH-GDL) GuangzhouGuangdong 510005China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China

Animal models are extensively used in all aspects of biomedical research,with substantial contributions to our understanding of diseases,the development of pharmaceuticals,and the exploration of gene *** field of genome modification in rabbits has progressed ***,recent advancements,particularly in CRISPR/Cas9-related technologies,have catalyzed the successful development of various genome-edited rabbit models to mimic diverse diseases,including cardiovascular disorders,immunodeficiencies,agingrelated ailments,neurological diseases,and ophthalmic *** models hold great promise in advancing biomedical research due to their closer physiological and biochemical resemblance to humans compared to *** review aims to summarize the novel gene-editing approaches currently available for rabbits and present the applications and prospects of such models in biomedicine,underscoring their impact and future potential in translational medicine.

关键词： Genome editing Animal model Rabbit CRISPR/Cas9 Genetic diseases

Electrochemical Mono-Deuterodefluorination of Trifluoromethyl Aromatic Compounds with Deuterium Oxide

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CCS Chemistry 2024年第1期6卷 230-240页

作者： Jie Sheng Xu Cheng Institute of Chemistry and Biomedical Sciences Jiangsu Key Laboratory of Advanced Organic MaterialsSchool of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023 State key laboratory of Elemento-Organic Chemistry Nankai UniversityTianjin 30071

The deuterodifluoromethyl group CF_(2)D combines the structural features of CF_(3) and CD_(3) groups,finding wide applications in diverse pharmaceutical *** this work,the electrochemical monodeuterodefluorination of Ar-CF_(3) to Ar-CF_(2)D is achieved with an unreported deuterium atom transfer-coupled electron transfer pathway using D_(2)O as the only D source for the first time.A series of Ar-CF_(3) substances,including commercial pharmaceuticals,were converted to corresponding CF_(2)D products in up to 91% yield and 97% D-incorporation.A variety of functional groups,including pyridine,pyrrole,furan,thiophene,borate,thio ether,amine,amide,sulfonamide,and halide,are well tolerated in this protocol.t-BuOLi was an essential reagent to achieve chemoselective mono-defluorination.

关键词： electrochemistry C-F activation fluorinecontaining drugs deuterated drugs deuterium oxide

Pathological BBB Crossing Melanin-Like Nanoparticles as Metal-Ion Chelators and Neuroinflammation Regulators against Alzheimer’s Disease

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Research 2024年第1期6卷 687-706页

作者： Qianqian Huang Chaoqing Jiang Xue Xia Yufan Wang Chenxing Yan Xiaorong Wang Ting Lei Xiaotong Yang Wenqin Yang Guo Cheng Huile Gao key laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry West China School of PharmacySichuan UniversityChengdu 610041P.R.China laboratory of Molecular Translational Medicine Center for Translational MedicineKey Laboratory of Birth Defects and Related Diseases of Women and Children(Sichuan University)Ministry of EducationDepartment of PediatricsWest China Second University HospitalSichuan UniversityChengdu 610041P.R.China

Inflammatory responses,manifested in excessive oxidative stress and microglia overactivation,together with metal ion-triggered amyloid-beta(Aβ)deposition,are critical hallmarks of Alzheimer’s disease(AD).The intricate pathogenesis causes severe impairment of neurons,which,in turn,exacerbates Aβaggregation and facilitates AD ***,multifunctional melanin-like metal ion chelators and neuroinflammation regulators(named PDA@K)were constructed for targeted treatment of *** this platform,intrinsically bioactive material polydopamine nanoparticles(PDA)with potent metal ion chelating and ROS scavenging effects were decorated with the KLVFF peptide,endowing the system with the capacity of enhanced pathological blood–brain barrier(BBB)crossing and lesion site accumulation via Aβ*** vitro and in vivo experiment revealed that PDA@K had high affinity toward Aβand were able to hitch a ride on Aβto achieve increased pathological BBB *** engineered PDA@K effectively mitigated Aβaggregate and alleviated neuroinflammation.

关键词： oxidative aggregation chelating

The transgenerational effects of maternal low-protein diet during lactation on offspring

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Journal of Genetics and Genomics 2024年第8期51卷 824-835页

作者： Lin-Jian Gu Li Li Qian-Nan Li Ke Xu Wei Yue Jing-Yi Qiao Tie-Gang Meng Ming-Zhe Dong Wen-Long Lei Jia-Ni Guo Zhen-Bo Wang Qing-Yuan Sun State key laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Institute of laboratory Animal Sciences CAMS&PUMCBeijing 100021China Guangzhou key laboratory of Metabolic Diseases and Reproductive Health Guangdong-Hong Kong Metabolism&Reproduction Joint LaboratoryReproductive Medicine CenterGuangdong Second Provincial General HospitalGuangzhouGuangdong 510317China

Environmental factors such as diet and lifestyle can influence the health of both mothers and ***,its transgenerational transmission and underlying mechanisms remain largely ***,using a maternal lactation-period low-protein diet(LPD)mouse model,we show that maternal LPD during lactation causes decreased survival and stunted growth,significantly reduces ovulation and litter size,and alters the gut microbiome in the female LPD-F1 *** transcriptome of LPD-F1 metaphase II(MII)oocytes shows that differentially expressed genes are enriched in female pregnancy and multiple metabolic ***,maternal LPD causes early stunted growth and impairs metabolic health,which is transmitted over two *** methylome alteration of LPD-F1 oocytes can be partly transmitted to the F2 ***,our results reveal that LPD during lactation transgenerationally affects offspring health,probably via oocyte epigenetic changes.

关键词： Lactationdiet Maternal low-proteindiet DNAmethylation Transgenerational effect Oocyte

Screened peptides from one-bead one-compound technique extend half-life of peptide drugs in circulation through binding to albumin

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Chinese Chemical Letters 2024年第3期35卷 384-388页

作者： Yi-Jing Li Lingze Zhang Ming-Hao Pang Pei-Pei Yang Lu-Ming Guo Kuo Zhang Da-Yong Hou Lei Wang Hao Wang Hui Cao State key laboratory for Advanced Metals and Materials School of Materials Science and EngineeringUniversity of Science and Technology BeijingBeijing 100083China CAS Center for Excellence in Nanoscience CAS Key Laboratory for Biomedical Effects of Nanomaterials NanosafetyNational Center for Nanoscience and Technology(NCNST)Beijing 100190China

peptide drugs are known for their high biological ***,compared with small molecule drugs,peptide drugs are easily oxidized and hydrolyzed as well as short in ***,inspired by the long circulation of albumin in blood,we screened albumin binding peptides(ABPs)from a one-bead one-compound(OBOC)peptide library to increase the half-life of peptide *** displaying random peptides were screened using fluorescent labeled human serum *** beads with specific binding to albumin were isolated for *** selected ABPs can effectively bind to albumin,thus possessing the long circulation of *** dissociation constant(K_(D))of ABPs to albumin is up to 1×10^(-8)mol/*** one of ABPs(ABP2)was coupled to triptorelin,the circulation half-life of triptorelin in mice was significantly prolonged to 263.50 h much longer than that of triptorelin alone(179.07 h).In addition,the combination therapy using ABP-conjugated triptorelin and doxorubicin(DOX)can effectively inhibit the proliferation of tumor cells in *** OBOC screening strategy and resulting ABPs showed great potential for enhancing the delivery efficiency of peptide drugs.

关键词： One-bead one-compound Combinatorial library Albumin binding Drug delivery Triptorelin

The life-history trait trade-offs mediated by reproduction and immunity in the brown planthopper,Nilaparvata lugens Stål

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Journal of Integrative Agriculture 2024年第6期23卷 2018-2032页

作者： Dan Sun Hongfeng Wang Jiahui Zeng Qiuchen Xu Mingyun Wang Xiaoping Yu Xuping Shentu Zhejiang Provincial key laboratory of Biometrology and Inspection&Quarantine College of Life ScienceChina Jiliang UniversityHangzhou 310018China

Reproduction and immune defense are costly functions,and they are expected to tradeoff with each other to drive *** brown planthopper(BPH),Nilaparvata lugens Stål(Hemiptera,Delphacidae),is a global superpest that mostly damages rice ***-like symbionts(YLS)exist in the abdominal fat body tissue and are tightly associated with the development,growth,and reproduction of *** previous research demonstrated that mating behavior promotes the release of YLS from the fat body into the hemolymph in the BPH,thereby triggering an immune ***,the fitness costs related to life-history traits of BPH(such as survival rate)have a strong dependence on the relative abundance of ***,the possible relationship between reproduction and the immune response in BPH has not been *** this study,an omics-based approach was used to analyze the transcriptome of fat body tissues in mated and unmated BPH at 72 h post-eclosion,from which two antimicrobial peptide genes,NlDefensin A(NlDfA)and NlDefensin B(NlDfB),were selected since they were highly expressed in mated ***,the full-length cDNA sequences of the NlDfA and NlDfB genes were cloned and *** results showed up-regulation of the NlDfA and NlDfB genes in mated BPH when compared to unmated ***-temporal expression analysis indicated that the NlDfA and NlDfB genes were expressed in all tissues and developmental stages,and they were most highly expressed in the fat body at 24 h ***,the symbionts in BPH were significantly inhibited by the in vitro expression of the NlDfA and NlDfB ***,RNA interference(RNAi)-mediated suppression of NlDfA and NlDfB dramatically increased the relative abundance of YLS in the fat body,while YLS in the hemolymph decreased *** BPHs also displayed some fitness disadvantages in survival,fecundity,hatchability,and possibly the vertical transmission of YLS from hemolymph to *** results

关键词： Nilaparvata lugens reproduction immune defense trade-off

Exploring treatment options in cancer: Tumor treatment strategies

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3337-3380页

作者： Beilei Liu Hongyu Zhou Licheng Tan Kin To Hugo Siu Xin-Yuan Guan Department of Clinical Oncology The University of Hong Kong-Shenzhen HospitalShenzhenChina Department of Clinical Oncology The University of Hong KongHong KongChina state key laboratory for Liver Research The University of Hong KongHong KongChina Advanced Energy Science and Technology Guangdong laboratory HuizhouChina MOE key laboratory of Tumor Molecular Biology Jinan UniversityGuangzhouChina

Traditional therapeutic approaches such as chemotherapy and radiation therapy have burdened cancer patients with onerous physical and psychological ***,the landscape of tumor treatment has undergone a comprehensive and remarkable *** as fervently pursued modalities are small molecule targeted agents,antibody-drug conjugates(ADCs),cell-based therapies,and gene *** cutting-edge treatment modalities not only afford personalized and precise tumor targeting,but also provide patients with enhanced therapeutic comfort and the potential to impede disease ***,it is acknowledged that these therapeutic strategies still harbour untapped potential for further *** a comprehensive understanding of the merits and limitations of these treatment modalities holds the promise of offering novel perspectives for clinical practice and foundational research *** this review,we discussed the different treatment modalities,including small molecule targeted drugs,peptide drugs,antibody drugs,cell therapy,and gene *** will provide a detailed explanation of each method,addressing their status of development,clinical challenges,and potential *** aim is to assist clinicians and researchers in gaining a deeper understanding of these diverse treatment options,enabling them to carry out effective treatment and advance their research more effciently.

关键词： drugs treatment holds

Machine learning with active pharmaceutical ingredient/polymer interaction mechanism:Prediction for complex phase behaviors of pharmaceuticals and formulations

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Chinese Journal of Chemical Engineering 2024年第2期66卷 263-272页

作者： Kai Ge Yiping Huang Yuanhui Ji Jiangsu Province Hi-Tech key laboratory for Biomedical Research School of Chemistry and Chemical EngineeringSoutheast UniversityNanjing 211189China

The high throughput prediction of the thermodynamic phase behavior of active pharmaceutical ingredients(APIs)with pharmaceutically relevant excipients remains a major scientific challenge in the screening of pharmaceutical *** this work,a developed machine-learning model efficiently predicts the solubility of APIs in polymers by learning the phase equilibrium principle and using a few molecular *** the few-shot learning framework,thermodynamic theory(perturbed-chain statistical associating fluid theory)was used for data augmentation,and computational chemistry was applied for molecular descriptors'*** results showed that the developed machine-learning model can predict the API-polymer phase diagram accurately,broaden the solubility data of APIs in polymers,and reproduce the relationship between API solubility and the interaction mechanisms between API and polymer successfully,which provided efficient guidance for the development of pharmaceutical formulations.

关键词： Multi-task machine learning Density functional theory Hydrogen bond interaction Miscibility Solubility