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靶向信号通路杀伤结直肠癌干细胞的新型药物

癌症 2023年第4期42卷 169-212页

在全球范围内,结直肠癌(colorectal cancer,CRC)是第三大最常见的癌症,也是第二大致死的癌症。目前癌症生物学认为,癌是由一小群肿瘤干细胞(cancer stem cells,CSCs)形成,CSCs具有多潜能和自我更新的特性。CSCs被认为是与肿瘤发展、复... 详细信息

在全球范围内,结直肠癌(colorectal cancer,CRC)是第三大最常见的癌症,也是第二大致死的癌症。目前癌症生物学认为,癌是由一小群肿瘤干细胞(cancer stem cells,CSCs)形成,CSCs具有多潜能和自我更新的特性。CSCs被认为是与肿瘤发展、复发和耐药性有关。有趣的是,一些细胞信号通路参与维持CRC的存活、增殖和自我更新的特性,其中大多数信号通路在CSCs中被异常调控,这些通路包括Wnt(Wingless)/β-catenin、Notch、Hedgehog、NF-κb(nuclear factor kappa b)、JAK/STAT(Janus kinase/signal transducer and activator of transcription)、PPAR(peroxisome proliferator-activated receptor)、PI3K/Akt/mTOR(phosphatidyl-inositol-3-kinase/Akt/mechanistic target of rapamycin)和TGF-β(transforming growth factor-β)/Smad信号通路。在本综述中,我们总结了当前通过调控使这些异常信号通路来杀伤CRC干细胞的策略,这将有可能探索出联合常规药物和CSCs靶向药物的治疗方案,并将有助于提高CRC的治愈率。

关键词：结直肠肿瘤干细胞细胞信号通路 Wnt/β-catenin信号通路 Notch Hedgehog NF-κb JAK/STAT信号通路 PI3K/Akt/mTOR信号通路靶向治疗

Study on the tunnel shape and soil-lining interaction influencing the lining behavior under seismic loading

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Earthquake Engineering and Engineering Vibration 2024年第4期23卷 845-862页

作者： Van Vi Pham Ngoc Anh Do Piotr Osinski Ngoc Thai Do Daniel dias Sustainable Development in Underground Engineering Research Team Hanoi University of Mining and GeologyHanoiVietnam Department of Underground and Mining Construction Faculty of Civil EngineeringHanoi University of Mining and GeologyHanoiVietnam Department of Geotechnical Engineering Institute of Civil EngineeringWarsaw University of Life Sciences-SGGWWarszawaPoland Laboratory 3SR Grenoble Alpes UniversityGrenoble 38400France

The response of tunnels subjected to seismic loading is a complex mechanism and depends not only on the seismic nature but also on tunnel structure and surrounding soil *** individual behavior of circular,rectangular,and sub-rectangular tunnels subjected to seismic loadings has already been studied in the *** the present research,two case scenarios of circular,rectangular tunnels and four sub-rectangular shaped tunnels,with similar cross-section areas,were adopted to perform a comprehensive numerical *** purpose of the study was to determine the mechanical behavior of tunnels of different shapes,depending upon seismic *** were performed by considering the influence of soil-lining interaction,soil parameters,and lining thickness,as well as lining *** were performed for no-slip and full-slip *** results indicate that the tunnel shape design is of great importance when regarding the mechanical behavior of the surrounding *** concerns no-slip as well as full-slip soil-lining interaction,especially when the lining is subjected to seismic ***,it is shown that changes in incremental bending moments for circular,rectangular and sub-rectangular tunnels that depend upon the soil-lining interaction conditions differ significantly.

关键词： tunnel shape soil-lining interaction seismic loading internal forces numerical analysis

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

Clinical implications of single cell sequencing for bladder cancer

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Oncology Research 2024年第4期32卷 597-605页

作者： REZA YADOLLAHVANDMIANDOAb MEHRSA JALALIZADEH FRANCIELE APARECIDA VECHIA DIONATO KEINI bUOSI PATRÍCIA A.F.LEME LUCIANA S.b.DAL COL CRISTIANE F.GIACOMELLI ALEX dias ASSIS NASIM bASHIRICHELKASARI LEONARDO OLIVEIRA REIS UroScience School of Medical SciencesUniversity of CampinasUNICAMPCampinasSao Paulo13083-872Brazil ImmunOncology Pontifical Catholic University of CampinasPUC-CampinasCampinasSao Paulo13087-571Brazil

bladder cancer(bC)is the 10th most common cancer worldwide,with about 0.5 million reported new cases and about 0.2 million deaths per *** this scoping review,we summarize the current evidence regarding the clinical implications of single-cell sequencing for bladder cancer based on PRISMA *** searched PubMed,CENTRAL,Embase,and supplemented with manual searches through the Scopus,and Web of Science for published studies until February *** included original studies that used at least one single-cell technology to study bladder ***-one publications were included in the ***-nine studies showed that this technology can identify cell subtypes in the tumor microenvironment that may predict prognosis or response to immune checkpoint inhibition *** studies were able to diagnose bC by identifying neoplastic cells through single-cell sequencing urine *** remaining studies were mainly a preclinical exploration of tumor microenvironment at single cell ***-cell sequencing technology can discriminate heterogeneity in bladder tumor cells and determine the key molecular properties that can lead to the discovery of novel perspectives on cancer *** nascent tool can advance the early diagnosis,prognosis judgment,and targeted therapy of bladder cancer.

关键词： bladder cancer Urothelial carcinoma Transitional cell carcinoma Single-cell sequencing Tumor heterogeneity Immunotherapy Scoping review Tumor microenvironment

Utilizing semantic-level computer vision for fracture trace characterization of hard rock pillars in underground space

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Geoscience Frontiers 2024年第2期15卷 366-391页

作者： Chuanqi Li Jian Zhou Daniel dias Laboratory 3SR CNRS UMR 5521Grenoble Alpes UniversityGrenoble 38000France School of Resources and Safety Engineering Central South UniversityChangsha 410083China

This study utilizes a semantic-level computer vision-based detection to characterize fracture traces of hard rock pillars in underground *** trace images captured by photogrammetry are used to establish the database for training two convolutional neural network(CNN)-based models,i.e.,U-Net(University of Freiburg,Germany)and DeepLabV3+(Google,USA)*** code technology,polyline approximation algorithm,and the circular window scanning approach are combined to quantify the main characteristics of fracture traces on flat and uneven surfaces,including trace length,dip angle,density,and *** extraction results indicate that the CNN-based models have better performances than the edge detection methods-based Canny and Sobel operators for extracting the trace and reducing noise,especially the DeepLabV3+***,the quantization results further prove the reliability of extracting the fracture *** a result,a case study with two types of traces(i.e.,on flat and uneven surfaces)demonstrates that the applied semantic-level computer vision detection is an accurate and efficient approach for characterizing the fracture trace of hard rock pillars.

关键词： Fracture trace Hard rock pillar Semantic-level computer vision Convolutional neural network(CNN) Underground space

Driving factors behind multiple populations

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Science China(Physics,Mechanics & Astronomy) 2024年第5期67卷 172-181页

作者： Ruoyun Huang baitian Tang Chengyuan Li Doug Geisler Mario Mateo Ying-Yi Song Holger baumgardt Julio A.Carballo-bello Yue Wang Jundan Nie bruno dias JoséG.Fernández-Trincado School of Physics and Astronomy Sun Yat-sen UniversityZhuhai 519082China CSST Science Center for the Guangdong-Hong Kong-Macao Greater bay Area Zhuhai 519082China Departamento de Astronomía Universidad de ConcepcionConcepcionChile Instituto de Investigación Multidisciplinario en Ciencia y Tecnología Universidad de La SerenaLa SerenaChile Departamento de Astronomía Facultad de CienciasUniversidad de La SerenaChile Department of Astronomy University of MichiganAnn Arbor 48109USA David A.Dunlap Department of Astronomy&Astrophysics University of TorontoToronto ON M5S 3H4Canada Dunlap Institute for Astronomy&Astrophysics University of TorontoToronto ON M5S 3H4Canada School of Mathematics and Physics The University of QueenslandSt.Lucia QLD 4072Australia Instituto de Alta Investigación Universidad de TarapacáAricaChile CAS Key Laboratory of Optical Astronomy National Astronomical ObservatoriesChinese Academy of SciencesBeijing 100101China Instituto de Astrofísica Departamento de Ciencias FísicasFacultad de Ciencias ExactasUniversidad Andres BelloSantiagoChile Instituto de Astronomía Universidad Católica del NorteAntofagastaChile

Star clusters were historically considered simple stellar populations,with all stars sharing the same age and initial chemical ***,the presence of chemical anomalies in globular clusters(GCs),called multiple stellar populations(MPs),has challenged star formation theories in dense *** studies show that mass,metallicity,and age are likely controlling parameters for the manifestation of *** the limit between clusters with/without MPs in physical parameter space is crucial to reveal the driving mechanism behind their *** this study,we look for MP signals in Whiting 1,which is traditionally considered a young *** the Magellan telescope,we obtained low-resolution spectra withinλλ=3850-5500?for eight giants of Whiting *** measured the C and N abundances from the CN and CH spectral indices.C and N abundances have variations comparable with their measurement errors(~0.1 dex),suggesting that MPs are absent from Whiting *** these findings with literature studies,we propose a limit in the metallicity *** compactness index parameter space,which relatively clearly separates star clusters with/without MPs(GCs/open clusters).This limit is physically *** a larger scale,the galactic environment determines cluster compactness and metallicity,leading to metal-rich,diffuse,old clusters formed ex *** proposed limit also impacts our understanding of the formation of the Sagittarius dwarf galaxy:star clusters formed after the first starburst(age≤8-10 Gyr).These clusters are simple stellar populations because the enriched galactic environment is no longer suitable for MP formation.

关键词： stellar galactic galaxy

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

Impact of microbial self-induced anaerobiosis fermentation(SIAF)on coffee quality

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Food bioscience 2022年第3期47卷 421-430页

作者： Marcela Caroline batista da Mota Nádia Nara batista Disney Ribeiro dias rosane Freitas Schwan Department of biology Federal University of LavrasLavrasMGBrazil Food Science Department Federal University of LavrasLavrasMGBrazil

The fermentation of natural(NC)and pulped coffee(PC)was performed with a conventional method(platform)and under self-induced anaerobic fermentation(SIAF).Of the 12 samples analyzed during the fermentation process,the highest temperature was obtained by the SIAF method(30.5℃ for NC and 29.67℃ for PC)with 87 h of *** compounds(36 samples)were evaluated by high-performance liquid *** in the SIAF method contributed to the maximum amount of citric acid(2.534 mg/g)in pulped coffee and acetic acid(6.04 mg/g)and lactic acid(2.533 mg/g)in *** was the primary chemical class detected,followed by ketones and *** coffees(12 samples)were evaluated five times and classified as specialty coffees(>80 points)following Specialty Coffee Association(SCA)*** pulped coffee processed by the SIAF method showed a 2.83-point increase in the sensory score compared to the conventional ***,the SIAF method is accessible to producers,contributes to coffees with differentiated sensory profiles,and increases beverage quality.

关键词： bioreactor Fermentative process Specialty coffee Anaerobic conditions Natural processing

黄花菜醇提物对斑马鱼抑郁样行为的改善作用研究

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中国比较医学杂志 2024年第4期34卷 20-27页

作者：郑涵文王梓航刘昕玥于佳玮 Alberto Carlos Pires dias 王凤忠王琼西南医科大学附属中医医院中葡中医药国际合作中心四川泸州646000 中国农业科学院农产品加工研究所北京100193 中国农业大学食品科学与营养工程学院北京100083 葡萄牙米尼奥大学生物系中葡药食植物资源研究中心葡萄牙布拉加4710-057

目的探究黄花菜醇提物(Hemerocallis citrina baroni,HCE)在利血平(reserpine)诱导的斑马鱼幼鱼(Danio rerio)模型中对抑郁行为的改善作用。方法将斑马鱼幼鱼分为对照(Con)组、利血平组、氟西汀组、黄花菜低剂量组(1.5 mg/L)、黄花菜... 详细信息

目的探究黄花菜醇提物(Hemerocallis citrina baroni,HCE)在利血平(reserpine)诱导的斑马鱼幼鱼(Danio rerio)模型中对抑郁行为的改善作用。方法将斑马鱼幼鱼分为对照(Con)组、利血平组、氟西汀组、黄花菜低剂量组(1.5 mg/L)、黄花菜中剂量组(3 mg/L)、黄花菜高剂量组(4.5 mg/L)。采用斑马鱼声音刺激和光刺激进行抑郁样行为学分析。利用RT-qPCR研究黄花菜醇提物对抑郁症有关的星状胶质细胞标志物及其衍生物基因(GFAP、C3、C4b、EMP-1和S100α-10)以及神经营养因子(bDNF)及其自身受体转录基因(P75、Trkb)的调节功能。结果与对照组相比,模型组在440 Hz声音刺激与8000 Lux光照刺激下运动距离缩短、运动时间减少(PbDNF、P75、Trkb下调(PbDNF、P75、Trkb表达显著上调(P<0.01,P<0.0001)。表明黄花菜醇提物抑制了星形胶质细胞激活诱发的炎症表现,同时促进了神经营养因子及其受体基因的生成,对抑郁起到了改善作用。结论黄花菜醇提物可以改善利血平诱导的斑马鱼幼鱼的抑郁样行为变化,斑马鱼脑中星形胶质细胞标志物的表达量减少,同时促进神经营养因子及其受体基因的生成,起到抗抑郁作用。

关键词：黄花菜抑郁症利血平斑马鱼