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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

Synergistic effects of three traditional herbs green tea,mulberry leaf and corn silk on glucose uptake level of L6 myoblasts and the hypoglycemic mechanism

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Traditional Medicine Research 2024年第7期9卷 1-12页

作者： Jing-Na Zhou Ming-Yue Li Ting-Ting Zhang Jing-Yang Lu Min Zhang Peng-Wei Zhuang Hai-Xia Chen tianjin key laboratory for modern drug delivery&high-efficiency School of Pharmaceutical Science and TechnologyTianjin UniversityTianjin 300072China. School of Food Science and Bioengineering Tianjin Agricultural UniversityTianjin 300384China. State key laboratory of Nutrition and Safety Tianjin University of Science&TechnologyTianjin 300457China. Haihe laboratory of modern Chinese Medicine Chinese Materia Medica CollegeTianjin University of Traditional Chinese MedicineTianjin 301617China.

Background:Green tea,mulberry leaf and corn silk are traditional herbs used in the prevention and treatment of diabetes in China for a long time,but their synergistic hypoglycemic effects and mechanisms remain ***:The effective components of green tea,mulberry leaf and corn silk were extracted and *** design of experiments was used to study the influences of different combinations on the cell viability and glucose uptake level of L6 myoblasts,so as to determine the optimal synergistic hypoglycemic *** possible hypoglycemic mechanism of the optimal synergistic combination was explored by cytotoxicity assay,glucose uptake assay,and western ***:Three polyphenol enrichment fractions of the herbs,30%ethanol elution fraction of green tea(GT),50%ethanol elution fraction of mulberry leaf(ML)and 60%ethanol elution fraction of corn silk(CS)were *** antioxidant activities of GT-30%,ML-50%and CS-60%were superior to those of crude extracts,and showed strong potential inα-amylase andα-glucosidase inhibition *** optimal synergistic combination of crude extracts G7(crude extract of green tea:crude extract of mulberry leaf:crude extract of corn silk=1:5:3),polyphenol enrichment fractions R3(GT-30%:ML-50%:CS-60%=1:7:1)and monomers X2(epigallocatechin gallate:morusin:formononetin=3:1:2)were selected,respectively.G7,R3,and X2 showed promoting effects on the cell viability and glucose uptake of L6 myoblasts within the detected concentration *** addition,G7,R3,and X2 could increase the expression levels of p-PI3K/PI3K and p-Akt/Akt in L6 myoblasts,and promote the translocation of Glut4,but G7 and R3 showed more significant ***:The synergistic hypoglycemic effects of green tea,mulberry leaf and corn silk had the characteristics of multiple-components and multiple-targets with p-PI3K/PI3K,p-Akt/Akt and the translocation of Glut4 signal pathways *** three traditional herbs might have the potential

关键词： green tea mulberry leaf corn silk synergistic effect type 2 diabetes mellitus mechanism

Different Types of Bone Fractures Observed by Terahertz Time-Domain Spectroscopy

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Acta Mechanica Solida Sinica 2024年第3期37卷 468-477页

作者： Minghao Zhang Xianjia Meng Zhiyong Wang Chuanyong Qu Chuan Qu Donghui Fu Department of Mechanics Tianjin UniversityTianjin300072China tianjin key laboratory of modern Engineering Mechanics Tianjin300072China

Microcracks are common in compact bone,but their continued propagation can lead to macroscopic *** microcracks cannot be visualized radiographically,necessitating alternative noninvasive methods to identify excessive microcracking and prevent *** this study,terahertz time-domain spectroscopy(THz-TDS)was used to examine bone interiors near cracks resulting from loading in bovine tibia *** loading configurations,such as impact,quasi-static loading,and fatigue loading,known to induce different types of micro-scale damage,were *** values of refractive index and absorption coefficient of the bone samples were then determined from the THz-TDS spectra acquired before loading and after *** study revealed that different loading configurations led to varying terahertz optical coefficients associated with various types of bone ***,the refractive index notably increased under fatigue loading but remained relatively stable during quasi-static *** absorption coefficient of bone decreased only under fatigue ***,samples were subjected to axial and radial impacts without sustaining *** indicated that in the undamaged state,the change in refractive index was smaller compared to after impact failure,while the change in absorption coefficient remained consistent after *** radial impact loading,changes in refractive index and absorption coefficient were significantly more pronounced than under axial *** to loading,the measured value of refractive index was 2.72±0.11,and the absorption coefficient was 6.33±0.09 mm^(−1)at 0.5 THz.

关键词： Terahertz time-domain spectroscopy Bone Microdamage Noninvasive method

Discovery of Novel Anthranilic Diamide Derivatives Bearing Sulfoximine Group as Potent Insecticide Candidates

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Chemical Research in Chinese Universities 2024年第1期40卷 96-108页

作者： ZHANG Hongyuan PENG Jinmin ZHONG Yuanhan CHEN Yue WANG Qing Haditullah HADIATULLAH XIE Weibin XIONG Lixia YUCHI Zhiguang LIU Jingbo LI Yuxin State key laboratory of Elemento-Organic Chemistry College of ChemistryNankai UniversityTianjin300071P.R.China Nankai University&Cangzhou Bohai New Area Institute of Green Chemical Engineering Changzhou062550P.R.China College of Horticulture and Landscape Architecture Tianjin Agricultural UniversityTianjin300392P.R.China tianjin key laboratory for modern drug delivery and high-efficiency Collaborative Innovation Center of Chemical Science and EngineeringSchool of Pharmaceutical Science and TechnologyTianjin UniversityTianjin300072P.R.China

The fall armyworm,Spodoptera frugiperda(***),represents the most resistant insect species and poses serious threat to grain ***(CHL),which targets the ryanodine receptors(RyRs)in insects,has demonstrated the efficacy in controlling ***,this has led to emerging resistance in several *** counter this resistance,a viable approach involves the development of novel compounds that bind against RyRs via distinct binding sites or *** this study,a series of 22 novel anthranilic diamide derivatives was designed and synthesized,and their insecticidal activities were *** of these derivatives showed moderate to good insecticidal activity against *** and Mythimna ***-lapse fluorescence measurements of endoplasmic reticulum luminal calcium revealed that most derivatives elicited cellular responses similar as CHL when assessed on HEK293 cells expressing *** ryanodine receptors(SfRyRs).The mode of action of compound 13a was studied and verified on the isolated neurons by calcium imaging ***,molecular docking analysis was employed to predict the binding mechanism of compound 13a against ***,these novel diamide derivatives hold promise as a valuable resource for guiding the future design of insecticidal compounds targeting RyRs.

关键词： Anthranilic diamide derivative Sulfoximine Spodoptera frugiperda Mode of action Molecular docking

Terahertz wide-angle metalens with nearly ideal object-image relation

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Chinese Optics Letters 2024年第1期22卷 147-152页

作者：王宇程洁嵘冀允允范飞常胜江 Institute of modern Optics Nankai UniversityTianjin 300350China tianjin key laboratory of Micro-scale Optical Information Science and Technology Tianjin 300350China tianjin key laboratory of Optoelectronic Sensor and Sensing Network Technology Tianjin 300350China

Metalenses are essential components in terahertz imaging ***,without careful design,they show limited field of view and their practical applications are ***,a wide-angle metalens is proposed whose structure is optimized for focusing within the incident angles of±25°.Simulation and experiment results show that the focusing efficiency,spot size,and modulation transfer function of this lens are not sensitive to the incident *** importantly,this wide-angle metalens follows the ideal Gaussian formula for the object-image relation,which ensures a wider field of view and better contrast in the imaging experiment.

关键词： terahertz metalens wide-angle Gaussian formula

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Organic thin-film transistors and related devices in life and health monitoring

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Nano Research 2024年第2期17卷 426-444页

作者： Chenfang Sun Tie Wang tianjin key laboratory of drug Targeting and Bioimaging Life and Health Intelligent Research InstituteTianjin University of TechnologyTianjin 300384China

The early determination of disease-related biomarkers can significantly improve the survival rate of ***,a series of explorations for new diagnosis technologies,such as optical and electrochemical methods,have been devoted to life and health *** thin-film transistor(OTFT),as a state-of-the-art nano-sensing technology,has attracted significant attention from construction to application owing to the merits of being label-free,low-cost,facial,and rapid detection with multi-parameter ***,interference from non-specific adsorption is inevitable in complex biological samples such as body liquid and exhaled gas,so the reliability and accuracy of the biosensor need to be further improved while ensuring sensitivity,selectivity,and ***,we overviewed the composition,mechanism,and construction strategies of OTFTs for the practical determination of disease-related biomarkers in both body fluids and exhaled *** results show that the realization of bio-inspired applications will come true with the rapid development of high-effective OTFTs and related devices.

关键词： organic thin-film transistors biosensors biomarkers organic bioelectronics organic semiconductors healthcare

Multidimensional autophagy nano-regulator boosts Alzheimer's disease treatment by improving both extra/intraneuronal homeostasis

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1380-1399页

作者： Yixian Li Peng Yang Ran Meng Shuting Xu Lingling Zhou Kang Qian Pengzhen Wang Yunlong Cheng Dongyu Sheng Minjun Xu Tianying Wang Jing Wu Jinxu Cao Qizhi Zhang key laboratory of Smart drug delivery Ministry of EducationSchool of PharmacyFudan UniversityShanghai 201203China

Intraneuronal dysproteostasis and extraneuronal microenvironmental abnormalities in Alzheimer’s disease(AD)collectively culminate in neuronal *** the context of AD,autophagy dysfunction,a multi-link obstacle involving autophagy downregulation and lysosome defects in neurons/microglia is highly implicated in intra/extraneuronal pathological ***,multidimensional autophagy regulation strategies co-manipulating“autophagy induction”and“lysosome degradation”in dual targets(neuron and microglia)are more reliable for AD ***,we designed an RP-1 peptide-modified reactive oxygen species(ROS)-responsive micelles(RT-NM)loading rapamycin or gypenoside *** by RP-1 peptide,the ligand of receptor for advanced glycation end products(RAGE),RT-NM efficiently targeted neurons and microglia in AD-affected *** nanocombination therapy activated the whole autophagy-lysosome pathway by autophagy induction(rapamycin)and lysosome improvement(gypenoside XVII),thus enhancing autophagic degradation of neurotoxic aggregates and inflammasomes,and promoting Aβ ***,it decreased aberrant protein burden,alleviated neuroinflammation,and eventually ameliorated memory defects in 3×Tg-AD transgenic *** research developed a multidimensional autophagy nano-regulator to boost the efficacy of autophagy-centered AD therapy.

关键词： Autophagy-lysosome pathway Alzheimer’s disease Proteostasis Neuroinflammation Multi-target therapy Rapamycin Gypenoside XVII Cascade dual-targeting

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Bionic immunoactivator copresenting autophagy promoting and costimulatory molecules for synergistic cancer immunotherapy

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Nano Research 2024年第3期17卷 1710-1724页

作者： Yiwei Peng Yiliang Yang Zhenzhen Yang Datong Gao Jiajia Li Qi Sun Yitian Du Meng Lin Xianrong Qi Beijing key laboratory of Molecular Pharmaceutics and New drug delivery System School of Pharmaceutical SciencesPeking UniversityBeijing 100191China

Immunotherapy has great promise in improving malignant tumor ***,the efficacy of existing strategies is often limited by the immunosuppressive ***,we demonstrate an in situ bionic immunoactivator,PLT-Bec1/DTA-1,with possessed natural advantages of platelets for tumor recruitment and activation,on which DTA-1(CD357 monoclonal antibody)and Bec1 were tethered as combined immune ***-Bec1/DTA-1,as a self-triggered release repository,can deliver the pre-tethered Bec1 and DTA-1 deeply through the secretion of platelet microparticles(PMPs),thereby cooperate tacitly and exhibit superiority in immune activation of dendritic cells(DCs)and T cells via autophagy inducibility,coupled with glucocorticoid-induced tumor necrosis factor receptor(GITR)-triggered T_(Reg) suppression,remodeled the immunosuppressive network of tumor ***-Bec1/DTA-1 promoted antigen presentation and T cell proliferation,and alleviated the low activity state of bone marrow-derived dendritic cells(BMDCs)in tumor suppressive ***-Bec1/DTA-1 inhibited tumor recurrence(5-and 13-fold lower of control group in tumor volume)and CD8^(+)T/T_(Reg) ratio(6.3-and 8.8-fold *** group)in mouse tumor model after intravenous or subcutaneous ***,PLT-Bec1/DTA-1 prevented tumor colonization in lung through in situ immune activation,and was slightly superior to the combined of Bec1 and *** findings highlight the promise of delivering immunostimulatory payloads via bionic carriers,eliciting automatic in situ activation of effector immune cells in tumor microenvironment for tumor *** these results provide promising prospects into the application of immunoactivator in improving cancer synergistic immunotherapy to overcome the bottlenecks in clinic.

关键词： in situ bionic immunoactivator autophagy glucocorticoid-induced tumor necrosis factor receptor(GITR)agonist platelets and platelet microparticles cancer immunotherapy

Effect of microstructure on lipolysis behavior of milk fat globules during gastrointestinal digestion

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Food Science and Human Wellness 2024年

作者： Xinyun Zhou Ting Guo Chen Chen Hadiatullah Hadiatullah Yunping Yao Changmo Li Xingguo Wang State key laboratory of Food Nutrition and Safety key laboratory of Food Nutrition and Safety Ministry of Education College of Food Science and Engineering tianjin University of Science & Technology tianjin key laboratory for modern drug delivery & high-efficiency Collaborative Innovation Center of Chemical Science and Engineering School of Pharmaceutical Science and Technology tianjin University Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province National Engineering Research Center for Functional Food School of Food Science and Technology Jiangnan University

Milk fat globules (MFG) are the primary source of energy and functional factor in dairy-based products. To evaluate the suitability of commercial MFG substitutes for infant and adult consumers， the lipolysis properties and regulatory factors in digesting bovine， caprine， and human MFG were compared. The lipolysis kinetic models of bovine and caprine MFG are comparable， with bovine MFG displaying the highest degree of lipolysis (50.21%) during gastric digestion in infants， resulting in the production short-chain saturated fatty acids. Caprine MFG has a high rate of lipolysis due to its weak phospholipid-glycoprotein layer， which is prominent in both infants’ and adults’ digestion. The effects of consuming bovine and caprine MFG for adults are comparable in terms of lipolysis properties and nutritional value of fatty acid. After gastrointestinal digestion， human MFG has the highest digestibility (93.98%). The advantages of human MFG include its phospholipid structure， exogenous lipase， and lipolysis-regulating proteins. This study provides recommendation for the selection of milk fat substitutes and improvements in commercial dairy.

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