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Leucine regulates lipid metabolism in adipose tissue through adipokine-mTOR-SIRT1 signaling pathway and bile acid—microbe axis in a finishing pig model

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Animal Nutrition 2024年第1期16卷 158-173页

作者： Yunju Yin Saiming Gong Mengmeng Han Jingzun Wang Hanjing Shi Xianji Jiang Liu Guo Yehui Duan Qiuping Guo Qinghua Chen Fengna Li key Laboratory of Agro-ecological Processes in Subtropical Region Institute of Subtropical AgricultureChinese Academy of SciencesHunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic ProcessHunan Provincial Engineering Research Center for Healthy Livestock and Poultry ProductionChangsha 410125China College of Animal Science and Technology Hunan Agricultural UniversityChangsha 410128China College of Modern Agricultural Sciences University of Chinese Academy of SciencesBeijing 100049China College of Life Science and Engineering Northwest Minzu UniversityLanzhou 730124China College of Life Sciences Hunan Normal UniversityChangsha 410128China

This study was conducted to explore the regulatory mechanism of leucine(Leu)on lipid metabolism of finishing ***-four Duroc×Landrace×Large cross pigs with an average body weight of68.33±0.97 kg were randomly allocated into 3 treatment groups with 8 replicates per group(1 pig per replicate).The dietary treatments were as follows:control group(CON),0.25%Leu group and 0.50%Leu *** experimental period was 42 *** results showed as follows.(1)Compared with the CON,0.25%and 0.50%Leu increased(P<0.01)the average daily gain(ADG),while the average backfat thickness(ABT)and the ratio of feed intake to body weight gain(F:G ratio)were decreased(P<0.05).(2)In the 0.25%Leu group,the relative mRNA expression levels of sterol regulatory element binding protein-1c(SREBP1c),recombinant fatty acid transport protein 1(FATP1),chemerin and peroxisome proliferatoractivated receptorγ(PPARγ)were decreased but the level of fatty acid binding protein 4(FABP4)and fatty acid translocase(FAT/CD36)were increased in backfat *** the 0.25%Leu group,the protein levels of p-Rictor,p-Raptor,p-eIF4E-binding protein 1(p-4EBP1),p-silent mating type information regulator 2homolog 1(p-SIRT1)and acetylation ribosome s6 protein kinase 1(Ac—S6K1)were increased(P<0.05).(3)Compared to the CON,the diversity of gut microbiota in the 0.25%Leu group was *** component analysis showed that the relative abundance of Bacteroidetes,Lactobacillus and Desulfovibrio was higher in the 0.25%Leu group than the CON,but the relative abundance of Firmicutes,Treponema and Shigella was lower than in the CON(P<0.05).(4)Four different metabolites were screened out from the serum of finishing pigs including allolithocholic acid(alloLCA),isolithocholic acid(isoLCA),ursodeoxycholic acid(UDCA)and hyodeoxycholic acid(HDCA),which correlate to various degrees with the above *** conclusion,Leu could promote adipose tissue lipolysis of finishing pigs through the mTOR-SIRT1 signaling pathway,a

关键词： Leu Lipid metabolism Gut microbiota Bile acid

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Asymmetric Synthesis of Dihydrospirotryprostatin B via a Silica Gel-Mediated Cyclization of Tryptamine-Ynamide

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Chinese Journal of Chemistry 2024年第12期42卷 1355-1359页

作者： Changhong Han Lu Yang Kaizong Yao Sen Zhang Jiayue Fu Hanyang Sun Hongsheng Xu Bin Lin Maosheng Cheng Yongxiang Liu key Laboratory of Structure:Based Drug Design and Discovery of Ministry of Education Shenyang Pharmaceutical UniversityShenyangLiaoning 110016China Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyangLiaoning 110016China Institute of Drug Research in Medicine Capital of China BenxiLiaoning 117000China Zhejiang Shapuaisi Pharmaceutical Co. LtdPinghuZhejiang 314299China

Comprehensive Summary An asymmetric synthesis of dihydrospirotryprostatin B was achieved in 15 steps(8 purifications)from *** main feature of our synthetic strategy is the efficient construction of spirocyclic oxindole intermediate containing a chiral quaternary carbon center,involving the silica gel-mediated cyclization of tryptamine-ynamide and oxidation under neat conditions.

关键词： Asymmetric synthesis Alkaloids Dihydrospirotryprostatin B Tryptamine-ynamide Cross-coupling Silica gel-mediated cyclization Oxidation

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Fine-tuning the activation behaviors of ternary modular cabazitaxel prodrugs for efficient and on-target oral anti-cancer therapy

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Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 188-203页

作者： Mingyang Zhang Yifan Miao Can Zhao Tong Liu Xiyan Wang Zixuan Wang Wenxin Zhong Zhonggui He Chutong Tian Jin Sun Department of Pharmaceutics Wuya College of InnovationShenyang Pharmaceutical UniversityShenyang 110016China key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province Hangzhou 310058China Joint International Research Laboratory of Intelligent Drug Delivery Systems Ministry of EducationShenyang 110016China liaoning provincial Institute of Drug Inspection and Testing Shenyang 110036China

The disulfide bond plays a crucial role in the design of anti-tumor prodrugs due to its exceptional tumor-specific redox responsiveness. However, premature breaking of disulfide bonds is triggered by small amounts of reducing substances (e.g., ascorbic acid, glutathione, uric acid and tea polyphenols) in the systemic circulation. This may lead to toxicity, particularly in oral prodrugs that require more frequent and high-dose treatments. Fine-tuning the activation kinetics of these prodrugs is a promising prospect for more efficient on-target cancer therapies. In this study, disulfide, steric disulfide, and ester bonds were used to bridge cabazitaxel (CTX) to an intestinal lymph vessel-directed triglyceride (TG) module. Then, synthetic prodrugs were efficiently incorporated into self-nanoemulsifying drug delivery system (corn oil and Maisine CC were used as the oil phase and Cremophor EL as the surfactant). All three prodrugs had excellent gastric stability and intestinal permeability. The oral bioavailability of the disulfide bond-based prodrugs (CTX-(C)S-(C)S-TG and CTX-S-S-TG) was 11.5- and 19.1-fold higher than that of the CTX solution, respectively, demonstrating good oral delivery efficiency. However, the excessive reduction sensitivity of the disulfide bond resulted in lower plasma stability and safety of CTX-S-S-TG than that of CTX-(C)S-(C)S-TG. Moreover, introducing steric hindrance into disulfide bonds could also modulate drug release and cytotoxicity, significantly improving the anti-tumor activity even compared to that of intravenous CTX solution at half dosage while minimizing off-target adverse effects. Our findings provide insights into the design and fine-tuning of different disulfide bond-based linkers, which may help identify oral prodrugs with more potent therapeutic efficacy and safety for cancer therapy.

关键词： Steric disulfide bond Triglyceride-like pr odrugs Cabazitaxel Lymphatic transport Oral chemotherapy

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Terahertz Irradiation Improves Cognitive Impairments and Attenuates Alzheimer’s Neuropathology in the APPSWE/PS1DE9 Mouse:A Novel Therapeutic Intervention for Alzheimer’s Disease

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Neuroscience Bulletin 2024年第7期40卷 857-871页

作者： Jun Zhang Yixin Chen Yarui Zhao Panpan Wang Hongbin Ding Cong Liu Junhong Lyu Weidong Le liaoning provincial key Laboratory for Research on the Pathogenic Mechanisms of Neurological Diseases the First Affiliated HospitalDalian Medical UniversityDalian 116011China School of Physics Dalian University of TechnologyDalian 116024China Interdisciplinary Research Center on Biology and Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 201210China Advanced Research Institute Chinese Academy of SciencesShanghai 201203China Department of Neurology and Institute of Neurology Sichuan Academy of Medical Sciences‑Sichuan Provincial HospitalMedical SchoolUniversity of Electronic Science and Technology of ChinaChengdu 610072China

Alzheimer's disease(AD)is a progressive neurodegenerative disease characterized by the deposition of amyloid-β(Aβ),neurofibrillary tangles,neuroinflammation,and neurodegeneration in the *** recent years,considering the unsatisfied benefits of pharmacological therapies,non-pharmacological therapy has become a research hotspot for AD ***(THz)waves with a range between microwave and infrared regions in the electromagnetic spectrum and high permeability to a wide range of materials have great potential in the bioengineering ***,its biological impacts on the central nervous system,under either physiological or pathological conditions,are poorly *** this study,we first measured the 0.14 THz waves penetration across the skull of a C57BL/6 mouse and found the percentage of THz penetration to be~70%,guaranteeing that THz waves can reach the relevant brain *** then exposed the APPSWE/PS1DE9 mouse model of AD to repeated low-frequency THz waves on the *** demonstrated that THz waves treatment significantly improved the cognitive impairment and alleviated AD neuropathology including Aβdeposition and tau hyperphosphorylation in the AD ***,THz waves treatment effectively attenuated mitochondrial impairment,neuroinflammation,and neuronal loss in the AD mouse *** findings reveal previously unappreciated beneficial effects of THz waves treatment in AD and suggest that THz waves may have the potential to be used as a novel therapeutic intervention for this devastating disease.

关键词： Alzheimer's disease Cognitive impairment Senile plaque Tau protein Terahertz

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Effects of weaning on intestinal longitudinal muscle-myenteric plexus function in piglets

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Science China(Life Sciences) 2024年第2期67卷 379-390页

作者： Jing Li Fenfen Liu Kaibin Mo Hengjia Ni Yulong Yin key Laboratory of Agro-Ecological Processes in Subtropical Region Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic ProcessHunan Research Center of Livestock and Poultry SciencesSouth Central Experimental Station of Animal Nutrition and Feed Science in the Ministry of AgricultureInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha 410125China University of Chinese Academy of Sciences Beijing 100008China Guangdong key Laboratory for Veterinary Drug Development and Safety Evaluation College of Veterinary MedicineSouth China Agricultural UniversityGuangzhou 510642China

Weaning piglets usually suffer from severe diarrhea(commonly known as postweaning diarrhea,PWD)along with intestinal motility *** peristalsis is mainly regulated by the longitudinal muscle-myenteric plexus(LM-MP).To understand the relationship between intestinal LM-MP function and the development of PWD,we compared the intestinal electrical activity,and the transcriptional profile of the LM-MP between 21-day-old piglets(just weaned,n=7)and 24-day-old piglets(suffered the most severe weaning stress,n=7).The results showed that 24-day-old piglets exhibited different degrees of diarrhea.A significant increase in the slow-wave frequency in the ileum and colon was observed in 24-day-old piglets,while c-kit expression in the intestinal LM-MPs was significantly decreased,indicating that PWD caused by elevated slow-wave frequency may be associated with loss of *** real-time quantitative PCR(RT-q PCR)and enzyme-linked immunosorbent assay(ELISA)showed that intestinal LM-MPs in 24-day-old piglets may undergo inflammation and oxidative *** increases in 8-hydroxy-2′-deoxyguanosine and decreases in thioredoxin suggest that weaning may lead to DNA damage in the LM-MP of 24-day-old *** addition,activating transcription factor 3 was significantly upregulated,indicating nerve damage in the LM-MP of 24-day-old *** transcriptomic results showed that most of the differentially expressed genes in the ileal LM-MP after weaning were downregulated and closely related to the cell cycle *** RT-q PCR analysis showed that the relative expression of p21 was upregulated,while the expression of cyclin A2,cyclin B1,and proliferating cell nuclear antigen was downregulated in the ileal and colonic LM-MP of 24-day-old piglets,suggesting that weaning may inhibit cell proliferation and cause G1/S cell cycle arrest in ileal and colonic *** conclusion,weaning may lead to cell cycle arrest by causing DNA damage in the LM-MP,impairing i

关键词： weaning piglets diarrhea longitudinal muscle-myenteric plexus

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Fenofibrate-promoted hepatomegaly and liver regeneration are PPARα-dependent and partially related to the YAP pathway

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Acta Pharmaceutica Sinica B 2024年第7期14卷 2992-3008页

作者： Shicheng Fan Yue Gao Pengfei Zhao Guomin Xie Yanying Zhou Xiao Yang Xuan Li Shuaishuai Zhang Frank JGonzalez Aijuan Qu Min Huangb Huichang Bi NMPA key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong provincial key Laboratory of New Drug Screening&Guangdong-Hongkong-Macao Joint Laboratory for New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Guangdong provincial key Laboratory of New Drug Design and Evaluation School of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China Department of physiology and Pathophysiology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China Laboratory of Metabolism Center for Cancer ResearchNational Cancer InstituteNational Institutes of HealthBethesdaMD 20892USA The State key Laboratory of Chemical Oncogenomics School of Chemical Biology and BiotechnologyShenzhen Graduate School of Peking UniversityShenzhen 518055China

Fenofibrate,a peroxisome proliferator-activated receptor α(PPARα)agonist,is widely prescribed for hyperlipidemia *** studies also showed that it has therapeutic potential in various liver ***,its effects on hepatomegaly and liver regeneration and the involved mechanisms remain ***,the study showed that fenofibrate significantly promoted liver enlargement and regeneration post-partial hepatectomy in mice,which was dependent on hepatocyteexpressed PPARα.Yes-associated protein(YAP)is pivotal in manipulating liver growth and *** further identified that fenofibrate activated YAP signaling by suppressing its K48-linked ubiquitination,promoting its K63-linked ubiquitination,and enhancing the interaction and transcriptional activity of the YAP-TEAD *** inhibition of YAP-TEAD interaction using verteporfin or suppression of YAP using AAV Yap shRNA in mice significantly attenuated fenofibrate-induced *** factors,such as MYC,KRT23,RAS,and RHOA,might also participate in fenofibrate-promoted hepatomegaly and liver *** studies demonstrate that fenofibratepromoted liver enlargement and regeneration are PPARα-dependent and partially through activating the YAP signaling,with clinical implications of fenofibrate as a novel therapeutic agent for promoting liver regeneration.

关键词： Fenofibrate PPARa Hepatomegaly Partial hepatectomy Liver regeneration YAP TEAD Ubiquitination

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Zinc lactate alleviates oxidative stress by modulating crosstalk between constitutive androstane receptor signaling pathway and gut microbiota profile in weaned piglets

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Animal Nutrition 2024年第1期16卷 23-33页

作者： Wenjie Tang Xuan Xiang Houfu Wang Wentao Zhou Liuqin He Yulong Yin Tiejun Li College of Animal Science and Technology Hunan Agricultural UniversityChangsha 410128China Hunan provincial key Laboratory of Animal Nutritional physiology and Metabolic Process CAS Key Laboratory of Agro-Ecological Processes in Subtropical RegionNational Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry ProductionInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha 410125China Hunan provincial key Laboratory of Animal Intestinal Function and Regulation Laboratory of Animal Nutrition and Human HealthCollege of Life SciencesHunan Normal UniversityChangsha 410081China College of Advanced Agricultural Science University of Chinese Academy of SciencesBeijing 100049China Sichuan Academy of Animal Sciences Animal Breeding and Genetics Key Laboratory of Sichuan ProvinceChengdu 610066China Livestock and Poultry Biological Products key Laboratory of Sichuan Province Sichuan Animtech Feed Co.LtdChengdu 610000China

This study aimed to determine the regulatory mechanism of dietary zinc lactate(ZL)supplementation on intestinal oxidative stress damage in a paraquat(PQ)-induced piglet ***-eight piglets(mean body weight 9.51±0.23 kg)weaned at 28 d of age were randomly divided into control,ZL,PQ,and ZL+PQ groups(n=7 in each group).The ZL-supplemented diet had little effect on growth performance under normal physiological ***,under PQ challenge,ZL supplementation significantly improved average daily gain(P<0.05)and reduced the frequency of *** improved intestinal morphology and ultrastructure by significantly increasing the expression level of the jejunal tight junction protein,zonula occludens-1(ZO-1)(P<0.05),and intestinal zinc transport and absorption in PQ-induced piglets,which reduced intestinal *** supplementation also enhanced the expression of antioxidant and antiinflammatory factor-related genes and decreased inflammatory cytokine expression and secretion in PQinduced ***,ZL treatment significantly inhibited the activation of constitutive androstane receptor(CAR)signaling(P<0.01)in PQ-induced piglets and altered the structure of the gut microbiota,especially by significantly increasing the abundance of beneficial gut microbes,including UCG_002,Ruminococcus,Rikenellaceae_RC9_gut_group,Christensenellaceae_R_7_group,Treponema,unclassified_Christensenellaceae,and unclassified_Erysipelotrichaceae(P<0.05).These data reveal that pre-administration of ZL to piglets can suppress intestinal oxidative stress by improving antioxidant and anti-inflammatory capacity and regulating the crosstalk between CAR signaling and gut microbiota.

关键词： Zinc lactate Intestinal barrier Oxidative stress Inflammation Constitutive androstane receptor Gut microbiota

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Effect of burial depth of a new tunnel on the seismic response of an existing tunnel

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Earthquake Engineering and Engineering Vibration 2024年第4期23卷 863-882页

作者： Ma Runbo Cao Qikun Lu Shasha Zhao Dongxu Zhang Yanan Xu Hong College of Civil Engineering Liaoning Technical UniversityFuxin 123000China key Laboratory of Urban Security and Disaster Engineering of Ministry of Education Beijing University of TechnologyBeijing 100124China

Burial depth is a crucial factor affecting the forces and deformation of tunnels during *** key issue is a lack of understanding of the effect of a change in the buried depth of a single-side tunnel on the seismic response of a double-tunnel *** this study,shaking table tests were designed and performed based on a tunnel under construction in Dalian,*** models were established using the equivalent linear method combined with ABAQUS finite element software to analyze the seismic response of the interacting *** results showed that the amplification coefficient of the soil acceleration did not change evidently with the burial depth of the new tunnel but decreased as the seismic amplitude *** addition,the existing tunnel acceleration,earth pressure,and internal force were hardly affected by the change in the burial depth;for the new tunnel,the acceleration and internal force decreased as the burial depth increased,while the earth pressure *** shows that the earth pressure distribution in a double-tunnel system is relatively complex and mainly concentrated on the arch spandrel and arch springing of the relative ***,when the horizontal clearance between the center of the two tunnels was more than twice the sum of the radius of the outer edges of the two tunnels,the change in the burial depth of the new tunnel had little effect on the existing one,and the tunnel structure was deemed *** results provide a preliminary understanding and reference for the seismic performance of a double-tunnel system.

关键词： burial depth new tunnel existing tunnel seismic response shaking table tests numerical simulations

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Overexpression of tonoplast Ca^(2+)-ATPase in guard cells synergistically enhances stomatal opening and drought tolerance

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Journal of Integrative Plant Biology 2024年第8期66卷 1587-1602页

作者： Jinghan Su Bingqing He Peiyuan Li Baiyang Yu Qiwen Cen Lingfeng Xia Yi Jing Feibo Wu Rucha Karnik Dawei Xue Michael R.Blatt Yizhou Wang Institute of Crop Science Zhejiang UniversityHangzhou 310058China Laboratory of Plant physiology and Biophysics University of GlasgowGlasgow G128QQUK BGI Research Sanya 572025China College of Life and Environmental Sciences Hangzhou Normal UniversityHangzhou 311121China Zhejiang provincial key Laboratory of Crop Germplasm Zhejiang UniversityHangzhou 310058China

Stomata play a crucial role in plants by controlling water status and responding to drought ***,simultaneously improving stomatal opening and drought tolerance has proven to be a significant *** address this issue,we employed the OnGuard quantitative model,which accurately represents the mechanics and coordination of ion transporters in guard *** the guidance of OnGuard,we successfully engineered plants that overexpressed the main tonoplast Ca^(2+)-ATPase gene,ACA11,which promotes stomatal opening and enhances plant ***,these transgenic plants also exhibited improved drought tolerance due to reduced water loss through their ***,OnGuard assisted us in understanding the mechanism behind the unexpected stomatal behaviors observed in the ACA11 overexpressing *** study revealed that the overexpression of ACA11 facilitated the accumulation of Ca^(2+)in the vacuole,thereby influencing Ca^(2+)storage and leading to an enhanced Ca^(2+)elevation in response to abscisic *** regulatory cascade finely tunes stomatal responses,ultimately leading to enhanced drought *** findings underscore the importance of tonoplast Ca^(2+)-ATPase in manipulating stomatal behavior and improving drought ***,these results highlight the diverse functions of tonoplast-localized ACA11 in response to different conditions,emphasizing its potential for future applications in plant enhancement.

关键词： ACA11 drought guard cells modeling stomata

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Integration of morphology and electronic structure modulation on cobalt phosphide nanosheets to boost photocatalytic hydrogen evolution from ammonia borane hydrolysis

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Green Energy & Environment 2024年第2期9卷 333-343页

作者： Chao Wan Yu Liang Liu Zhou Jindou Huang Jiapei Wang Fengqiu Chen Xiaoli Zhan Dang-guo Cheng School of Chemistry and Chemical Engineering Anhui Province Key Laboratory of Coal Clean Conversion and High Valued UtilizationAnhui University of TechnologyMa'anshan243002China College of Chemical and Biological Engineering Zhejiang UniversityZhejiang Provincial Key Laboratory of Advanced Chemical Engineering Manufacture Technology38 Zheda RoadHangzhou310027China key Laboratory of New Energy and Rare Earth Resource Utilization of State Ethnic Affairs Commission Key Laboratory of Photosensitive Materials&Devices of Liaoning ProvinceSchool of Physics and Materials EngineeringDalian Nationalities University 18 Liaohe West RoadDalian116600China Institute of Zhejiang University-Quzhou 78 Jiuhua Boulevard NorthQuzhou324000China Jiangsu key Laboratory of Advanced Catalytic Materials and Technology Changzhou University213164China

The controllable and safe hydrogen storage technologies are widely recognized as the main bottleneck for the accomplishment of sustainable hydrogen *** borane(AB)has regarded as a competitive candidate for chemical hydrogen ***,developing efficient yet high-performance catalysts towards hydrogen evolution from AB hydrolysis remains an enormous ***,cobalt phosphide nanosheets are synthesized by a facile salt-assisted along with low-temperature phosphidation strategy for simultaneously modulating its morphology and electronic structure,and function as hydrogen evolution ***,the Co_(2)P nanosheets display extraordinary performance with a record high turnover frequency of 44.9 min^(-1),outperforming most of the noble-metal-free catalysts reported to *** remarkable performance is attributed to its desired nanosheets structure,featuring with high specific surface area,abundant exposed active sites,and short charge diffusion *** findings provide a novel strategy for regulating metal phosphides with desired phase structure and morphology for energy-related applications and beyond.

关键词： Ammonia borane Hydrogen generation Hydrolysis Cobalt phosphide nanosheets Photocatalysis

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