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Extracellular vesicles-coupled miRNAs from oviduct and uterus modulate signaling pathways related to lipid metabolism and bovine early embryo development

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Journal of Animal Science and Biotechnology 2024年第4期15卷 1528-1549页

作者： Rosane Mazzarella Karina canon‑Beltran Yulia N.cajas Meriem Hamdi Encina M.Gonzalez Juliano C.da Silveira Claudia L.V.Leal D.Rizos Department of Animal Reproduction INIA-CSICMadridSpain Department of Biochemistry and Molecular Biology Veterinary FacultyComplutense University of Madrid(UCM)MadridSpain Department Agrarian Production Technical University of MadridUPMMadridSpain Departamento de Ciencias Biologicas Universidad Tecnica Particular de LojaUTPLLojaEcuador Department of Anatomy and Embryology FV-UCMMadridSpain Department of Veterinary Medicine FZEA-USPPirassunungaBrazil

Background Extracellular vesicles(EVs) present in oviductal(OF) and uterine fluid(UF) have been shown to enhance bovine embryo quality during in vitro culture by reducing lipid contents and modulating lipid metabolism-related genes(LMGs), while also influencing cell proliferation, suggesting their involvement on the regulation of different biological pathways. The regulation of signaling pathways related to cell differentiation, proliferation, and metabo-lism is crucial for early embryo development and can determine the success or failure of the pregnancy. Bioactive molecules within EVs in maternal reproductive fluids, such as micro RNAs(miRNAs), may contribute to this regulatory process as they modulate gene expression through post-transcriptional *** This study evaluated miRNA cargo in OF-EVs from the early luteal phase and UF-EVs from the mid-luteal phase, coinciding with embryo transit within oviduct and uterus in vivo, and its possible influence on LMGs and sign-aling pathways crucial for early embryo development. A total of 333 miRNAs were detected, with 11 exclusive to OF, 59 to UF, and 263 were common between both groups. From the 20 differentially expressed miRNAs, 19 up-regulated in UF-EVs(bta-miR-134, bta-miR-151-3p, bta-miR-155, bta-miR-188, bta-miR-181b, bta-miR-181d, bta-miR-224, bta-miR-23b-3p, bta-miR-24-3p, bta-miR-27a-3p, bta-miR-29a, bta-miR-324, bta-miR-326, bta-miR-345-3p, bta-miR-410, bta-miR-652, bta-miR-677, bta-miR-873 and bta-miR-708) and one(bta-miR-148b) in OF-EVs. These miRNAs were predicted to modulate several pathways such as Wnt, Hippo, MAPK, and lipid metabolism and degradation. Differ-ences in miRNAs found in OF-EVs from the early luteal phase and UF-EVs from mid-luteal phase may reflect differ-ent environments to meet the changing needs of the embryo. Additionally, miRNAs may be involved, particularly in the uterus, in the regulation of embryo lipid metabolism, immune system, and *** Our study su

关键词： Embryo-maternal interaction Epigenetic Exosomes Mammalian Preimplantation Reproductive fluids

Mineralogical properties and co-sintering characteristics of fluxed iron ore with magnetite concentrates

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Journal of Iron and Steel Research International 2024年第2期31卷 318-328页

作者： Le-le Niu Zheng-jian Liu Jian-liang Zhang Yao-zu Wang Zhen-xing Yang Si-da Li Chang-dong Shan Ben Feng School of Metallurgical and Ecological Engineering University of Science and Technology BeijingBeijing100083China Institute of Artificial Intelligence University of Science and Technology BeijingBeijing100083China Xinxing casting Pipe Xinjiang Co. Bayingol841300XinjiangChina

To investigate the feasibility of co-sintering of fluxed iron ore with magnetite concentrates, the mineralogical properties of a novel fluxed iron ore were studied using particle size analysis, microscopic morphology characterization, and X-ray diffraction Rietveld analysis. Following that, the experiments for granulation performance and basic sintering characteristics were designed under seven different fluxed iron ore ratios, and the integrated ranking of different fluxed iron ore ratios was determined using gray relation analysis. Finally, the results of the industrial trails were combined with the feasibility analysis. Test and experimental results show that the fraction of the fluxed iron ore particles larger than 0.5 mm can account for more than 48%, and the particles have two morphologies: spherical-rough and flaky-smooth. ca elements are found in the form of calcite (caCO3) and dolomite (caMg(CO3)2). The average particle size of granules and powder removal rate can be improved from 2.50 to 3.16 mm and 39.60% to 24.20%, respectively, with the increase in the fluxed iron ore ratio. Furthermore, the fluxed iron ore can improve assimilability and liquid fluidity of magnetite concentrates. In terms of overall granulation performance and sintering characteristics, the fluxed iron ore ratios are graded from best to worst as follows: 12%, 15%, 9%, 18%, 21%, 6% and 3%. The industrial trails show that when the fluxed iron ore ratio is increased, the beneficial effect of the superior sintering characteristics of the fluxed iron ore itself is ideally balanced with the negative effect of the lower amount of additional caO at 12% ratio, and thus, it is feasible to bring the fluxed iron ore into production at a level of roughly 12%.

关键词： Fluxed iron ore Magnetite concentrate Granulation performance Sintering characteristics Gray relation analysis

Assessment of programmed death-ligand 1 expression in primary tumors and paired lymph node metastases of gastric adenocarcinoma

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 883-893页

作者： Brendha cação Coimbra Marina Alessandra Pereira Leonardo cardili Venancio Avancini Ferreira Alves Evandro Sobroza de Mello Ulysses Ribeiro Jr Marcus Fernando Kodama Pertille Ramos Department of Gastroenterology Instituto do CancerHospital das Clínicas da Faculdade de Medicina da Universidade de São PauloFaculdade de MedicinaUniversidade de São PauloSão Paulo 01246000Brazil Department of Pathology Instituto do CancerHospital das Clínicas da Faculdade de Medicina da Universidade de São PauloSão Paulo 01246000Brazil

BACKGROUND Anti-programmed death-1/programmed death-ligand 1(PD-1/PD-L1)immuno-therapy has demonstrated promising results on gastric cancer(GC).However,PD-L1 can express differently between metastatic sites and primary tumors(PT).AIM To compare PD-L1 status in PT and matched lymph node metastases(LNM)of GC patients and to determine the correlation between the PD-L1 status and clinicopathological *** We retrospectively reviewed 284 GC patients who underwent ***-L1 was evaluated by immunohistochemistry(clone SP142)using the com-bined positive *** PD-L1+PT staged as pN+were also tested for PD-L1 expression in their ***-L1(-)GC with pN+served as the comparison *** Among 284 GC patients included,45 had PD-L1+PT and 24 of them had pN+.For comparison,44 PD-L1(-)cases with pN+were included(sample loss of 4 cases).Of the PD-L1+PT,54.2%(13/24 cases)were also PD-L1+in the *** PD-L1(-)PT,9.1%(4/44)had PD-L1+in the *** agreement between PT and LNM had a kappa value of *** tumor size and moderate/severe peritumoral inflammatory response were associated with PD-L1 positivity in both *** was no statistical difference in overall survival for PT and LNM according to the PD-L1 status(P=0.166 and P=0.837,respectively).CONCLUSION Intra-patient heterogeneity in PD-L1 expression was observed between the PT and matched *** disagreement in PD-L1 status may emphasize the importance of considering different tumor sites for analyses to select patients for immunotherapy.

关键词： Gastric cancer Lymph node Programmed death ligand 1 Stomach neoplasms Immunohistochemistry Metastasis

Cocktail effect of ionic patch driven by triboelectric nanogenerator for diabetic wound healing

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Chinese Chemical Letters 2024年第8期35卷 460-465页

作者： Yixia Zhang caili Xue Yunpeng Zhang Qi Zhang Kai Zhang Yulin Liu Zhaohui Shan Wu Qiu Gang Chen Na Li Hulin Zhang Jiang Zhao da-Peng Yang College of Biomedical Engineering Taiyuan University of TechnologyTaiyuan 030024China College of Electronic Information and Optical Engineering Taiyuan University of TechnologyTaiyuan 030024China Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering Taiyuan 030024China College of Integrated Circuit Science and Engineering Nanjing University of Posts and TelecommunicationsNanjing 210023China School of Rehabilitation Science and Engineering University of Health and Rehabilitation SciencesQingdao 266024China School of Materials and Chemical Engineering Quanzhou Normal UniversityQuanzhou 362000China

There is increasing evidence shows that either electrical stimulation(ES)or metal ion is an effective way to accelerate ulcerative wound ***,less attention is paid to investigating the synergistic effect between ***,we explore the combined effects of ES and multiple metal ions on dia-betic wound healing assisted by a triboelectric nanogenerator(TENG).Firstly,the novel Eggshell@CuFe_(2)O_(4)nanocomposites(NCs)are prepared,which show unique structure and intrinsic antimicrobial ***,the as-prepared nanocomposites are embedded in oxidized starch hydrogel to form a mul-tifunctional composite gel,which is further assembled into a wearable ionic triboelectric nanogenerator(iTENG)patch with polydimethylsiloxane(PDMS).It can convert the mechanical energy produced by a human body motion to electric energy and mediate the sequential release of metal ions(Fe^(2+)/ca^(2+)/Cu^(2+)),thereby resulting in the“cocktail effect”on impaired *** their effects,a satisfying healing re-sult in diabetic mouse is identified,which can effectively accelerate wound healing process by relieving inflammation,promoting angiogenesis and collagen *** work puts forward the cocktail effect of electric simulation coupled with the multiple metal ions,and opens up a new perspective in designing iTENG patch towards repair of hard-to-heal wounds.

关键词： iTENG Cocktail effect CuFe_(2)O_(4) Eggshell Diabetic wound

Detection of Novel BEST1 Variations in Autosomal Recessive Bestrophinopathy Using Third-generation Sequencing

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Current Medical Science 2024年第2期44卷 419-425页

作者： Jia-xun LI Ling-rui MENG Bao-ke HOU Xiao-lu HAO da-jiang WANG Ling-hui QU Zhao-hui LI Lei ZHANG Xin JIN Department of Senior Ophthalmology the Third Medical Center of PLA General HospitalBeijing 100853China Department of Ophthalmology the 74th Army Group HospitalGuangzhou 510318China

Objective:Autosomal recessive bestrophinopathy(ARB),a retinal degenerative disease,is characterized by central visual loss,yellowish multifocal diffuse subretinal deposits,and a dramatic decrease in the light peak on *** potential pathogenic mechanism involves mutations in the BEST1 gene,which encodes ca2+-activated Cl−channels in the retinal pigment epithelium(RPE),resulting in degeneration of RPE and *** this study,the complete clinical characteristics of two Chinese ARB families were ***:Pacific Biosciences(PacBio)single-molecule real-time(SMRT)sequencing was performed on the probands to screen for disease-causing gene mutations,and Sanger sequencing was applied to validate variants in the patients and their family ***:Two novel mutations,c.202T>C(chr11:61722628,p.Y68H)and c.867+97G>A,in the BEST1 gene were identified in the two Chinese ARB *** novel missense mutation BEST1 c.202T>C(p.Y68H)resulted in the substitution of tyrosine with histidine in the N-terminal region of transmembrane domain 2 of *** novel variant,BEST1 c.867+97G>A(chr11:61725867),located in intron 7,might be considered a regulatory variant that changes allele-specific binding affinity based on motifs of important transcriptional ***:Our findings represent the first use of third-generation sequencing(TGS)to identify novel BEST1 mutations in patients with ARB,indicating that TGS can be a more accurate and efficient tool for identifying mutations in specific *** novel variants identified further broaden the mutation spectrum of BEST1 in the Chinese population.

关键词： autosomal recessive bestrophinopathy BEST1 gene third-generation sequencing mutation

Seasonal variation and host sex affect bat–bat fly interaction networks in the Amazonian savannahs

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Integrative Zoology 2024年第3期19卷 400-416页

作者： Paulo MEJIA Gustavo Lima URBIETA Bruna da Silva XAVIER IsaíJorge de caSTRO JoséJúlio DE TOLEDO Gustavo GRACIOLLI Lucio AndréVIANA DIAS William Douglas caRVALHO Programa de Pós-Graduação em Biodiversidade Tropical Universidade Federal do Amapá(UNIFAP)MacapáAPBrazil Programa de Pós-Graduação em Ecologia Instituto de BiologiaCentro de Ciências da SaúdeUniversidade Federal do Rio de Janeiro(UFRJ)Rio de JaneiroRJBrazil Laboratório de Mamíferos Instituto de Pesquisas Científicas e Tecnológicas do Estado do Amapá(IEPA)MacapáAPBrazil Programa de Pós-Graduação em Biologia Animal Laboratório de SistemáticaEcologia e Evolução(LSEE)Instituto de BiociênciasUniversidade Federal de Mato Grosso do Sul(UFMS)Campo GrandeMTBrazil Terrestrial Ecology Group(TEG-UAM) Departamento de EcologíaFacultad de CienciasUniversidad Autónoma de MadridMadridSpain Centro de Investigación en Biodiversidad y cambio Global(CIBC-UAM) Universidad Autónoma de MadridMadridSpain

Bats are the second-most diverse group of mammals in the world,and bat flies are their main ***,significant knowledge gaps remain regarding these antagonistic interactions,especially since diverse factors such as seasonality and host sex can affect their network ***,we explore the influence of such factors by comparing species richness and composition of bat flies on host bats,as well as specialization and modularity of bat–bat fly interaction networks between seasons and adult host *** captured bats and collected their ectoparasitic flies at 10 sampling sites in the savannahs of AmapáState,northeastern region of the Brazilian *** female bats being more parasitized and recording greater bat fly species richness in the wet season,neither relationship was statistically *** pooled network could be divided into 15 compartments with 54 links,and all subnetworks comprised>12 *** total number of links ranged from 27 to 48(for the dry and wet seasons,respectively),and female and male subnetworks had 44 and 41 links,*** values were very low for the pooled network and for all *** results revealed higher bat fly species richness and abundance in the wet season,whereas specialization and modularity were higher in the dry ***,the subnetwork for female bats displayed higher specialization and modularity than the male ***,both seasonality and host sex contribute in different ways to bat–bat fly network *** studies should consider these factors when evaluating bat–bat fly interaction networks.

关键词： Amapá Amazon biome bat flies bats interaction networks

Low-frequency Stimulation at the Subiculum Prevents Extensive Secondary Epileptogenesis in Temporal Lobe Epilepsy

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Neuroscience Bulletin 2024年第5期40卷 564-576页

作者： Yujia Shen Yiwei Gong Xiaoli da Shajing Gao Shuo Zhang Minjuan Sun Yuanzhi Yang Xiaoyun Qiu Menghan Li Yang Zheng Fan Fei Yi Wang Zhong Chen Cenglin Xu Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province School of Pharmaceutical ScienceZhejiang Chinese Medical UniversityHangzhou310053China Institute of Pharmacology and Toxicology NHC and CAMS Key Laboratory of Medical NeurobiologyCollege of Pharmaceutical SciencesZhejiang UniversityHangzhou310058China Department of Neurology First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou310003China Department of Pharmacy The First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou310003China

Secondary epileptogenesis is characterized by increased epileptic susceptibility and a tendency to generate epileptiform activities outside the primary *** is one of the major resultants of pharmacoresistance and failure of surgical outcomes in epilepsy,but still lacks effective ***,we aimed to test the effects of low-frequency stimulation(LFS)at the subiculum for secondary epileptogenesis in a mouse ***,secondary epileptogenesis was simulated at regions both contralateral and ipsilateral to the primary focus by applying successive kindling *** kindled at the right ca3 showed higher seizure susceptibilities at both the contralateral ca3 and the ipsilateral entorhinal cortex and had accelerated kindling processes compared with naive *** at the ipsilateral subiculum during the primary kindling progress at the right ca3 effectively prevented secondary epileptogenesis at both the contralateral ca3 and the ipsilateral entorhinal cortex,characterized by decreased seizure susceptibilities and a retarded kindling process at those secondary *** application along with the primary epileptogenesis was ***,the effects of LFS on secondary epileptogenesis were associated with its inhibitory effect at the secondary focus through interfering with the enhancement of synaptic connections between the primary and secondary *** results imply that LFS at the subiculum is an effective preventive strategy for extensive secondary epileptogenesis in temporal lobe epilepsy and present the subiculum as a target with potential translational importance.

关键词： Secondary epileptogenesis Low-frequency stimulation Subiculum Temporal lobe epilepsy

PCDH17 restricts dendritic spine morphogenesis by regulating ROCK2-dependent control of the actin cytoskeleton,modulating emotional behavior

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Zoological Research 2024年第3期45卷 535-550页

作者： Laidong Yu Fangfang Zeng Mengshu Fan Kexuan Zhang Jingjing Duan Yalu Tan Panlin Liao Jin Wen Chenyu Wang Meilin Wang Jialong Yuan Xinxin Pang Yan Huang Yangzhou Zhang Jia-da Li Zhuohua Zhang Zhonghua Hu Hunan Key Laboratory of Molecular Precision Medicine Department of Critical Care MedicineXiangya HospitalCentral South UniversityChangshaHunan 410008China Center for Medical Genetics and Hunan Key Laboratory of Medical Genetics School of Life SciencesCentral South UniversityChangshaHunan 410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China Hunan Provincial Clinical Research Center for Critical care Medicine Xiangya HospitalCentral South UniversityChangshaHunan 410008China Hunan Key Laboratory of Animal Models for Human Diseases School of Life SciencesCentral South UniversityChangshaHunan 410008China MOE Key Lab of Rare Pediatric Diseases School of Life SciencesCentral South UniversityChangshaHunan 410008China Department of Neurosciences University of South China Medical SchoolHengyangHunan 421001China

Proper regulation of synapse formation and elimination is critical for establishing mature neuronal circuits and maintaining brain *** abnormalities,such as defects in the density and morphology of postsynaptic dendritic spines,underlie the pathology of various neuropsychiatric *** 17(PCDH17)is associated with major mood disorders,including bipolar disorder and ***,the molecular mechanisms by which PCDH17 regulates spine number,morphology,and behavior remain *** this study,we found that PCDH17 functions at postsynaptic sites,restricting the number and size of dendritic spines in excitatory *** overexpression of PCDH17 in the ventral hippocampal ca1 results in spine loss and anxiety-and depression-like behaviors in ***,PCDH17 interacts with actin-relevant proteins and regulates actin filament(F-actin)***,PCDH17 binds to ROCK2,increasing its expression and subsequently enhancing the activity of downstream targets such as LIMK1 and the phosphorylation of cofilin serine-3(Ser3).Inhibition of ROCK2 activity with belumosudil(KD025)ameliorates the defective F-actin organization and spine structure induced by PCDH17 overexpression,suggesting that ROCK2 mediates the effects of PCDH17 on F-actin content and spine ***,these findings reveal a novel mechanism by which PCDH17 regulates synapse development and behavior,providing pathological insights into the neurobiological basis of mood disorders.

关键词： Synapse development Dendritic spine Mood disorder Actin cytoskeleton Animal behavior

Serum bile acid and unsaturated fatty acid profiles of non-alcoholic fatty liver disease in type 2 diabetic patients

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World Journal of Diabetes 2024年第5期15卷 898-913页

作者： Su-Su Feng Si-Jing Wang Lin Guo Pan-Pan Ma Xiao-Long Ye Ming-Lin Pan Bo Hang Jian-Hua Mao Antoine M Snijders Yi-Bing Lu da-Fa Ding Department of Endocrinology The Second Affiliated Hospital of Nanjing Medical UniversityNanjing 210011Jiangsu ProvinceChina Biological Systems and Engineering Division Lawrence Berkeley National LaboratoryBerkeleyCA 94720United States

BACKGROUND The understanding of bile acid(BA)and unsaturated fatty acid(UFA)profiles,as well as their dysregulation,remains elusive in individuals with type 2 diabetes mellitus(T2DM)coexisting with non-alcoholic fatty liver disease(NAFLD).Investigating these metabolites could offer valuable insights into the pathophy-siology of NAFLD in *** To identify potential metabolite biomarkers capable of distinguishing between NAFLD and *** A training model was developed involving 399 participants,comprising 113 healthy controls(HCs),134 individuals with T2DM without NAFLD,and 152 individuals with T2DM and *** validation encompassed 172 *** patients were divided based on liver fibrosis *** analytical approach employed univariate testing,orthogonal partial least squares-discriminant analysis,logistic regression,receiver operating characteristic curve analysis,and decision curve analysis to pinpoint and assess the diagnostic value of serum *** Compared to HCs,both T2DM and NAFLD groups exhibited diminished levels of specific *** UFAs,particular acids exhibited a positive correlation with NAFLD risk in T2DM,while theω-6:ω-3 UFA ratio demonstrated a negative *** ofα-linolenic acid andγ-linolenic acid were linked to significant liver fibrosis in *** validation cohort substantiated the predictive efficacy of these biomarkers for assessing NAFLD risk in T2DM *** This study underscores the connection between altered BA and UFA profiles and the presence of NAFLD in individuals with T2DM,proposing their potential as biomarkers in the pathogenesis of NAFLD.

关键词： Bile acid Non-alcoholic fatty liver disease Type 2 diabetes mellitus Unsaturated fatty acid