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Endotoxin-induced alterations of adipose tissue function:a pathway to bovine metabolic stress

Journal of animal Science and Biotechnology 2024年第4期15卷 1391-1407页

作者： Miguel Chirivi G.Andres Contreras department of large animal Clinical Sciences Michigan State UniversityEast LansingMIUSA

During the periparturient period, dairy cows exhibit negative energy balance due to limited appetite and increased energy requirements for lactogenesis. The delicate equilibrium between energy availability and expenditure puts cows in a state of metabolic stress characterized by excessive lipolysis in white adipose tissues(AT), increased production of reactive oxygen species, and immune cell dysfunction. Metabolic stress, especially in AT, increases the risk for metabolic and inflammatory diseases. Around parturition, cows are also susceptible to endotoxemia. Bacterial-derived toxins cause endotoxemia by promoting inflammatory processes and immune cell infiltration in different organs and systems while impacting metabolic function by altering lipolysis, mitochondrial activity, and insulin sensitivity. In dairy cows, endotoxins enter the bloodstream after overcoming the defense mechanisms of the epithelial barriers, particularly during common periparturient conditions such as mastitis, metritis, and pneumonia, or after abrupt changes in the gut microbiome. In the bovine AT, endotoxins induce a pro-inflammatory response and stimulate lipolysis in AT, leading to the release of free fatty acids into the bloodstream. When excessive and protracted, endotoxin-induced lipolysis can impair adipocyte's insulin signaling pathways and lipid synthesis. Endotoxin exposure can also induce oxidative stress in AT through the production of reactive oxygen species by inflammatory cells and other cellular components. This review provides insights into endotoxins' impact on AT function, highlighting the gaps in our knowledge of the mechanisms underlying AT dysfunction, its connection with periparturient cows' disease risk, and the need to develop effective interventions to prevent and treat endotoxemia-related inflammatory conditions in dairy cattle.

关键词： Adipose tissue dysfunction Endotoxin Inflammation Insulin resistance

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Quercetin Alleviates Lipopolysaccharide-Induced Cardiac Inflammation via Inhibiting Autophagy and Programmed Cell Death

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Biomedical and Environmental Sciences 2024年第1期37卷 54-70页

作者： YU Jin Hai HU Guo Liang GUO Xiao Quan CAO Hua Bin XIA Zhao Fei AMIN Buhe Jiangxi Provincial Key Laboratory for animal Health Institute of Animal Population HealthCollege of Animal Science and TechnologyJiangxi Agricultural UniversityNanchang 330045JiangxiChina Internal medicine Laboratory Department of Veterinary Clinical MedicineCollege of Veterinary MedicineChina Agricultural UniversityBeijing 100091China department of Cancer surgery Beijing Shijitan Hospital Affiliated with Capital Medical UniversityBeijing 100038China

Objective The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide(LPS)induced septic cardiac *** Specific pathogen-free chicken embryos(n=120)were allocated untreated control,phosphate buffer solution(PBS)vehicle,PBS with ethanol vehicle,LPS(500 ng/egg),LPS with quercetin treatment(10,20,or 40 nmol/egg,respectively),Quercetin groups(10,20,or 40 nmol/egg).Fifteenday-old embryonated eggs were inoculated with abovementioned solutions via the allantoic *** embryonic day 19,the hearts of the embryos were collected for histopathological examination,RNA extraction,real-time polymerase chain reaction,immunohistochemical investigations,and Western *** They demonstrated that the heart presented inflammatory responses after LPS *** LPS-induced higher mRNA expressions of inflammation-related factors(TLR4,TNFα,MYD88,NF-κB1,IFNγ,IL-1β,IL-8,IL-6,IL-10,p38,MMP3,and MMP9)were blocked by quercetin with three *** significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS *** significantly decreased protein expressions of TLR4,IFNγ,MMP3,and MMP9 when compared with the LPS *** treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1,and significantly decreased protein expression of claudin 1 when compared with the LPS *** significantly downregulated autophagyrelated gene expressions(PPARα,SGLT1,APOA4,AMPKα1,AMPKα2,ATG5,ATG7,Beclin-1,and LC3B)and programmed cell death(Fas,Bcl-2,CASP1,CASP12,CASP3,and RIPK1)after LPS *** significantly decreased immunopositivity to APOA4,AMPKα2,and LC3-II/LC3-I in the treatment group when compared with the LPS *** significantly decreased protein expressions of AMPKα1,LC3-I,and *** significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or

关键词： Quercetin Lipopolysaccharide Inflammation Autophagy Programmed cell death Myocardiocytes permeability

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Neoadjuvant camrelizumab(an anti-PD-1 antibody)plus chemotherapy or apatinib(a VEGFR-2 inhibitor)for initially unresectable stage II–III non-small-cell lung cancer:a multicentre,two-arm,phase 2 exploratory study

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3015-3023页

作者： Haoran Xia Han Zhang Zheng Ruan Huibiao Zhang Liangdong Sun Hezhong Chen Yongxin Zhou Lele Zhang Dongliang Bian Xinsheng Zhu Jing Zhang Fenghuan Sun Huansha Yu Nan Song Xiaogang Liu Yuming Zhu Haiping Zhang Wenxin He Jian Chen Jie Yang Guohan Chen Shiliang Xie Dongfang Tang Xiaomiao Zhang Liang Duan Deping Zhao Qinchuan Li Peng Zhang Gening Jiang department of Thoracic surgery Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina department of Thoracic surgery Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChina department of Thoracic surgery Huadong Hospital Affiliated to Fudan UniversityShanghaiChina department of Thoracic surgery Changhai HospitalNaval Medical UniversityShanghaiChina department of Thoracic-Cardiovascular surgery Tongji HospitalTongji University School of MedicineShanghaiChina Central Laboratory Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina Experimental animal Center Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina department of Oncology Shanghai Pulmonary HospitalTongji University School of MedicineShanghaiChina department of Thoracic surgery Shanghai East HospitalTongji University School of MedicineShanghaiChina

This multicentre,two-arm,phase 2 study aimed to explore the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy or apatinib in patients with initially unresectable stage II–III non-small-cell lung cancer(NSCLC).Eligible patients regardless of PD-L1 expression received neoadjuvant camrelizumab 200 mg and platinum-doublet chemotherapy every 3 weeks(arm A)or those with PD-L1-positive tumors received neoadjuvant camrelizumab and apatinib 250 mg once daily(arm B),for 2–4 cycles,followed by *** primary endpoint was major pathological response(MPR)*** patients in arm A and 21 in arm B were *** rates were 50.0%(15/30)in arm A and 42.9%(9/21)in arm B,with all patients achieving R0 *** these patients,the MPR and pathological complete response rates were both 20.0%(95%CI 4.3–48.1)in arm A and were 55.6%(95%CI 21.2–86.3)and 11.1%(95%CI 0.3–48.2)in arm B,*** corresponding objective response rates were 33.3%(95%CI 11.8–61.6)and 55.6%(95%CI 21.2–86.3).With a median follow-up of 22.4 months(95%CI 19.0–26.0),the median event-free survival was not reached(NR;95%CI 13.6-NR)in arm A and 16.8 months(95%CI 8.6-NR)in arm *** 3 or above treatment-related adverse events occurred in eight(26.7%)patients in arm A and three(14.3%)in arm *** analysis showed baseline TYROBP expression was predictive of treatment response in arm *** camrelizumab plus chemotherapy or apatinib exhibits preliminary efficacy and manageable toxicity in patients with initially unresectable stage II–III NSCLC.

关键词： surgery chemotherapy treatment

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Effects of improved amino acid balance diet on lysine mammary utilization, whole body protein turnover and muscle protein breakdown on lactating sows

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Journal of animal Science and Biotechnology 2024年第5期15卷 2031-2043页

作者： Sai Zhang Juan C.Marini Vengai Mavangira Andrew Claude Julie Moore Mahmoud A.Mohammad Nathalie L.Trottier department of animal Science Michigan State UniversityEast Lansing 48824USA State Key Laboratory of Swine and Poultry Breeding Industry Key Laboratory of Animal Nutrition and Feed Science in South ChinaMinistry of Agriculture and Rural AffairsGuangdong Provincial Key Laboratory of Animal Breeding and NutritionInstitute of Animal ScienceGuangdong Academy of Agricultural SciencesGuangzhou 510640PR China USDA/ARS Children’s Nutrition Research Center and Pediatric Critical Care medicine Department of PediatricsBaylor College of MedicineHoustonTX 77030USA department of large animal Clinical Sciences Michigan State UniversityEast LansingMI 48824USA Present address:department of animal Science Cornell UniversityFrank Morrison Hall507 Tower RoadIthacaNY 14853‑4801USA

Background The study objective was to test the hypothesis that low crude protein(CP)diet with crystalline amino acids(CAA)supplementation improves Lys utilization efficiency for milk production and reduces protein turnover and muscle protein *** lactating multiparous Yorkshire sows were allotted to 1 of 2 isocaloric diets(10.80 MJ/kg net energy):control(CON;19.24%CP)and reduced CP with“optimal”AA profile(OPT;14.00%CP).Sow body weight and backfat were recorded on d 1 and 21 of lactation and piglets were weighed on d 1,14,18,and 21 of *** d 14 and 18,a subset of 9 sows(CON=4,OPT=5)was infused with a mixed solution of 3-[methyl-2H3]histidine(bolus injection)and[13C]bicarbonate(priming dose)first,then a constant 2-h[13C]bicarbonate infusion followed by a 6-h primed constant[1-13C]lysine *** blood and milk sampling were performed to determine plasma and milk Lys enrichment,Lys oxidation rate,whole body protein turnover,and muscle protein *** Over the 21-d lactation period,compared to CON,sows fed OPT had greater litter growth rate(P<0.05).Compared to CON,sows fed OPT had greater efficiency of Lys(P<0.05),Lys mammary flux(P<0.01)and whole-body protein turnover efficiency(P<0.05).Compared to CON,sows fed OPT tended to have lower whole body protein breakdown rate(P=0.069).Muscle protein breakdown rate did not differ between OPT and CON(P=0.197).Conclusion Feeding an improved AA balance diet increased efficiency of Lys and reduced whole-body protein turnover and protein *** results imply that the lower maternal N retention observed in lactating sows fed improved AA balance diets in previous studies may be a result of greater partitioning of AA towards milk rather than greater body protein breakdown.

关键词： Amino acid Efficiency Lactating sows Protein breakdown Protein turnover Reduced protein diet

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Boosting liver regeneration: kinase inhibitor as a new tool to prevent liver failure

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3145-3146页

作者： Anna Sichler Norbert Huser Klaus-Peter Janssen department of surgery School of Medicine and HealthTechnical University of MunichMunichGermany

In a recent manuscript in Cell,a first-in-class small molecule inhibitor of the kinase MKK4(mitogen-activated protein kinase kinase 4)was described that greatly enhances liver regeneration after partial hepatectomy in animal models,with an excellent safety profile in humans.1 The findings of Zwirner et *** promise to alter the clinical management of liver failure in critically ill patients.

关键词： liver al. clinical

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Chromatin condensation but not DNA integrity of pig sperm is greater in the sperm-rich fraction

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Journal of animal Science and Biotechnology 2024年第1期15卷 171-181页

作者： Estel Viñolas-Vergés Jordi Ribas-Maynou Isabel Barranco Camila Peres Rubio Sergi Bonet Jordi Roca Marc Yeste Unit of Cell Biology Department of BiologyFaculty of SciencesUniversity of GironaGironaSpain Biotechnology of animal and Human Reproduction(TechnoSperm) Institute of Food and Agricultural TechnologyUniversity of GironaGironaSpain department of medicine and animal surgery Faculty of Veterinary ScienceUniversity of MurciaMurciaSpain Catalan Institution for Research and Advanced Studies(ICREA) S08010 BarcelonaSpain

Background Protamination and condensation of sperm chromatin as well as DNA integrity play an essential role during fertilization and embryo *** some mammals,like pigs,ejaculates are emitted in three separate fractions:pre-sperm,sperm-rich(SRF)and post sperm-rich(PSRF).These fractions are known to vary in volume,sperm concentration and quality,as well as in the origin and composition of seminal plasma(SP),with differences being also observed within the SRF ***,whether disparities in the DNA integrity and chromatin condensation and pro-tamination of their sperm exist has not been *** This study determined chromatin protamination(Chromomycin A3 test,CMA_(3)),condensation(Dibromobi-mane test,DBB),and DNA integrity(Comet assay)in the pig sperm contained in the first 10 m L of the SRF(SRF-P1),the remaining portion of the sperm-rich fraction(SRF-P2),and the post sperm-rich fraction(PSRF).While chromatin protamination was found to be similar between the different ejaculate fractions(P>0.05),chromatin condensation was seen to be greater in SRF-P1 and SRF-P2 than in the PSRF(P=0.018 and P=0.004,respectively).Regarding DNA integrity,no differences between fractions were observed(P>0.05).As the SRF-P1 has the highest sperm concentra-tion and ejaculate fractions are known to differ in antioxidant composition,the oxidative stress index(OSi)in SP,calcu-lated as total oxidant activity divided by total antioxidant capacity,was tested and confirmed to be higher in the SRF-P1 than in SRF-P2 and PSRF(0.42±0.06 vs.0.23±0.09 and 0.08±0.00,respectively;P<0.01);this index,in addition,was observed to be correlated to the sperm concentration of each fraction(Rs=0.973;P<0.001).Conclusion While sperm DNA integrity was not found to differ between ejaculate fractions,SRF-P1 and SRF-P2 were observed to exhibit greater chromatin condensation than the *** could be related to the OSi of each fraction.

关键词： Chromatin Condensation DNA integrity Ejaculate fractions Pig Protamination Sperm

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The incidence rate and histological characteristics of intimal hyperplasia in elastase-induced experimental abdominal aortic aneurysms in mice

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animal Models and Experimental medicine 2024年第3期7卷 388-395页

作者： Meng Li Panpan Wei Kexin Li Haole Liu Naqash Alam Haiwen Hou Jie Deng Baohui Xu Enqi Liu Sihai Zhao Yankui Li Laboratory animal Center Xi'an Jiaotong UniversityXi'anChina department of Vascular surgery The Second Hospital of Tianjin Medical UniversityTianjinChina department of Cardiology The Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina department of Vascular surgery Stanford University School of MedicineStanfordCaliforniaUSA

Intimal hyperplasia(IH)is a negative vascular remodeling after arterial *** occasionally occurs in elastase-induced abdominal aortic aneurysm(AAA)mouse *** study aims to clarify the incidence and histological characteristics of IH in aneurysmal mice.A retrospective study was conducted by including 42 male elastaseinduced mouse AAA *** IH incidence,aortic diameters with or without IH,and hyperplasia lesional features of mice were *** 42 elastase-induced AAA mouse models,10 mice developed mild IH(24%)and severe IH was found in only 2 mice(5%).The outer diameters of the AAA segments in mice with and without IH did not show significant *** mild and severe IH lesions show strong smooth muscle cell positive staining,but endothelial cells were occasionally observed in severe IH *** was obvious macrophage infiltration in the IH lesions of the AAA mouse models,especially in mice with severe ***,only a lower numbers of T cells and B cells were found in the IH *** cell-secreted matrix metalloproteinases(MMP)2 was highly expressed in all IH lesions,but MMP9 was only overexpressed in severe *** conclusion,this study is the first to demonstrate the occurrence of aneurysmal IH and its histological characteristics in an elastaseinduced mouse AAA *** will help researchers better understand this model,and optimize it for use in AAA-related research.

关键词： abdominal aortic aneurysms animal model histology intimal hyperplasia

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Clinical significance of surgical resection for hepatocellular carcinoma with portal vein invasion:a nationwide cohort study

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Hepatobiliary surgery and Nutrition 2024年第5期13卷 814-823,I0006-I0008页

作者： Hye-Sung Jo Pyoung-Jae Park Young-Dong Yu Yoo Jin Choi Se Hyeon Yu Dong-Sik Kim Korean Liver Cancer Association Division of HBP surgery and Liver Transplantation Department of SurgeryKorea University College of MedicineSeoulRepublic of Korea Division of Transplantation and Vascular surgery Department of SurgeryKorea University Guro HospitalKorea University College of MedicineSeoulRepublic of Korea

Background:Hepatocellular carcinoma(HCC)with portal vein invasion(PVI)is considered an advanced stage with a poor *** current guidelines recommend systemic treatment for HCC with PVI,surgical resection could produce acceptable outcomes in selected *** study aimed to identify the clinical significance of surgical resection for HCC with PVI patients using a large-scale nationwide ***:This retrospective,multicenter,observational cohort analyzed data from the Korean Primary Liver Cancer Registry.A total of 16,781 patients who were newly diagnosed with HCC between 2008 and 2018 were enrolled in this *** with worse Child-Turcotte-Pugh scores(≥7)or performance status(≥2)were *** them,998 patients who received treatment for HCC with PVI were included in the analysis and were divided into two groups:resection group of 151(15.1%)and palliative group of 847(84.9%)who received transarterial and systemic therapy according to the treatment *** matching the number and size of the tumors and model for end-stage liver disease(MELD)score between the groups,the final study cohort for analysis comprised 151(26.6%)patients in the resection group and 417(73.4%)in the palliative *** primary endpoints were overall survival(OS)and cancer-specific survival(CSS).Results:The number and maximum size of HCC did not differ between the resection and palliative groups after matching[1(range,1-5)vs.1(range,1-6),P=0.11 and 5.5(range,1.2-20.6)vs.6.0(range,1.0-20.5)cm,P=0.24,respectively].Tumor markers,including alpha-fetoprotein(AFP)and protein induced by vitamin K absence or antagonist-II(PIVKA-II),also did not differ between the groups(P=0.29 and P=0.36,respectively).The 5-year OS and CSS rates of the resection and palliative groups were 44.8%and 17.4%(P<0.001)and 47.7%and 18.6%(P<0.001),*** analysis showed that palliative treatment intent was the most significant risk factor for OS and CSS[odds ratio(OR

关键词： Hepatocellular carcinoma(HCC) portal vein invasion(PVI) overall survival(OS) cancer-specific survival(CSS) surgical resection

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Evaluation of mitral chordae tendineae length using four-dimensional computed

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World Journal of Cardiology 2024年第5期16卷 274-281页

作者： Takuya Mori Satoshi Matsushita Terumasa Morita Abulaiti Abudurezake Junji Mochizuki Atsushi Amano department of Cardiovascular surgery Juntendo University Faculty of MedicineTokyo 113-8421Japan department of Cardiovascular surgery JACCT Japan Animal Cardiovascular Care TeamOsaka 533-0033Japan department of Radiology Minamino Cardiovascular HospitalTokyo 192-0918Japan

BACKGROUND Mitral valvuloplasty using artificial chordae tendineae represents an effective surgical approach for treating mitral *** precise measurements of artificial chordae tendineae length(CL)is an important factor in the procedure;however,no objective index currently exists to facilitate this ***,preoperative assessment of CL is critical for surgical planning and ***-dimensional x-ray micro-computed tomography(4D-CT)may be useful for accurate CL measurement considering that it allows for dynamic three-dimensional(3D)evaluation compared to that with transthoracic echocardiography,a conventional inspection *** To investigate the behavior and length of mitral chordae tendineae during systole using *** Eleven adults aged>70 years without mitral valve disease were evaluated.A 64-slice CT scanner was used to capture 20 phases in the cardiac cycle in electrocardiographic *** length of the primary chordae tendineae was measured from early systole to early diastole using the 3D *** primary chordae tendineae originating from the anterior papillary muscle and attached to the A1-2 region and those from the posterior papillary muscle and attached to the A2-3 region were designated as cA and cP,*** behavior and maximum lengths[cA(ma),cP(max)]were compared,and the correlation with body surface area(BSA)was *** In all cases,the mitral anterior leaflet chordae tendineae could be *** most cases,the cA and cP chordae tendineae could be measured *** mean cA(max)and cP(max)were 20.2 mm±1.95 mm and 23.5 mm±4.06 mm,***(max)was significantly *** correlation coefficients(r)with BSA were 0.60 and 0.78 for cA(max)and cP(max),*** cA and cP exhibited constant variation in CL during systole,with a maximum 1.16-fold increase in cA and a 1.23-fold increase in cP from early to *** cP,CL reached a plateau at 15%and remaine

关键词： Mitral valve Chordae tendineae Computed tomography Four-dimensional Cardiac cycle

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Knockdown of neuronal DAF-15/Raptor promotes healthy aging in ***

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Journal of Genetics and Genomics 2024年第5期51卷 507-516页

作者： Xiao Zang Qi Wang Hanxin Zhang Yiyan Zhang Zi Wang Zixing Wu Di Chen Model animal Research Center of Medical School Nanjing UniversityNanjingJiangsu 210061China Zhejiang University-University of Edinburgh Institute School of MedicineZhejiang UniversityHainingZhejiang 314400China department of Colorectal surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310058China

The highly conserved target of rapamycin(TOR)pathway plays an important role in aging across *** studies have established that inhibition of the TOR complex 1(TORC1)significantly extends lifespan in Caenorhabditis ***,it has not been clear whether TORC1 perturbation affects aging in a spatiotemporal ***,we apply the auxin-inducible degradation tool to knock down endogenous DAF-15,the *** ortholog of regulatory associated protein of TOR(Raptor),to characterize its roles in *** or tissue-specific inhibition of DAF-15 during development results in various growth defects,whereas neuron-specific knockdown of DAF-15 during adulthood significantly extends lifespan and *** neuronal DAF-15 deficiency-induced longevity requires the intestinal activities of DAF-16/FOXO and PHA-4/FOXA transcription factors,as well as the AAK-2/AMP-activated protein kinaseαcatalytic *** profiling reveals that the neuronal DAF-15 knockdown promotes the expression of genes involved in *** findings define the tissue-specific roles of TORC1 in healthy aging and highlight the importance of neuronal modulation of aging.

关键词： Aging targetof rapamycin DAF-15 DAF-16 C.elegans

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