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培美曲塞加铂类联合或不联合帕博利珠单抗对初治转移性非鳞状NsCLC患者的疗效与安全性分析：KEYNOTE-189研究方案指定的最终分析

中国肺癌杂志 2022年第6期25卷 443-456页

作者：周彩存 Delvys RODRíGUEZ-ABREU s.F.POWELL M.J.HOCHMAIR s.gad geel E.EsTEBAN E.FELIP G.sPERANZA F.De ANGELIs M.DóMINE s.Y.CHENG H.G.BIsCHOFF N.PELED M.RECK R.HUI E.B.GARON M.BOYER T.KURATA J.YANG M.C.PIETANZA F.sOUZA M.C.GARAssINO 同济大学附属上海市肺科医院肿瘤科 Medical Oncology Complejo Hospitalario Universitario Insular Materno-Infantil de Gran CanariaUniversidad de Las Palmas de Gran Canaria Oncology Sanford Health 4. Department of Respiratory and Critical Care MedicineKarl Landsteiner Institute of Lung Research and Pulmonary Oncology Thoracic Oncology Karmanos Cancer InstituteWayne State University Department of Medical Oncology Hospital Universitario Central de Asturias Medical Oncology Department Vall d'Hebron UniversityVall d'Hebron Institute of Oncology (VHIO) 8. Centre Integre de Cancerologie de la MontérégieH?pital Charles-Le Moyne 9. Medical Oncology DepartmentHospital Universitario Fundacidn Jiménez DiazIIS-FJD sunnybrook Health sciences Centre Thoraxklinik Heidelberg Department of Oncology Shaare Zedek Medical Center LungenClinic Airway Research Center NorthGerman Center for Lung Research Department of Medical Oncology Westmead Hospital and University of Sydney Department of Medicine David Geffen School of Medicine at UCLA Department of Medical Oncology Chris O'Brien Lifehouse Department of Thoracic Oncology Kansai Medical University Hospital Merck & Co. Inc. Fondazione IRCCs Istituto Nazionale dei Tumori University of Chicago Medicine & Biological sciences Knapp Center for Biomedical Discovery

背景在KEYNOTE-189此项Ⅲ期研究(NCT02578680)中,与安慰剂联合培美曲塞加铂类相比,帕博利珠单抗联合培美曲塞加铂类化疗(培美曲塞-铂类)显著改善了初治转移性非鳞状非小细胞肺癌(non-small cell lung cancer,NsCLC)患者的总生存期(over... 详细信息

背景在KEYNOTE-189此项Ⅲ期研究(NCT02578680)中,与安慰剂联合培美曲塞加铂类相比,帕博利珠单抗联合培美曲塞加铂类化疗(培美曲塞-铂类)显著改善了初治转移性非鳞状非小细胞肺癌(non-small cell lung cancer,NsCLC)患者的总生存期(overall survival,Os)和无进展生存期(progression-free survival,PFs)。本研究报告了研究方案指定的最终分析的疗效结局,包括从培美曲塞-铂类交叉至帕博利珠单抗治疗的患者,以及完成35个周期(约2年)帕博利珠单抗治疗组的疗效。方法符合条件的患者以2:1随机分配至帕博利珠单抗,每3周一次,200 mg (n=410)或安慰剂(n=206)(共35周期,约2年),加上4个周期的培美曲塞(500 mg/m~2)和由研究者选择的每3周顺铂(75 mg/m~2)或卡铂(曲线下面积5 mg/min/mL)治疗,随后使用培美曲塞直至疾病进展。若符合纳入标准,分配至安慰剂联合培美曲塞加铂类治疗的患者可在疾病进展时转向帕博利珠单抗治疗。主要研究终点为Os和PFs。结果中位随访31.0个月,无论PD-L1的表达水平如何,与安慰剂联合培美曲塞-铂类治疗相比,帕博利珠单抗联合培美曲塞-铂类治疗可使患者的Os[风险比(hazard ratio,HR)为0.56;95%可信区间(confidence interval,CI) 0.46-0.69]和PFs (HR=0.49;95%CI:0.41-0.59)显著获益。接受帕博利珠单抗联合培美曲塞-铂类治疗的患者客观缓解率(objective response rate,ORR)(48.3%vs 19.9%)和第二次/后续无进展生存期(PFs2;HR=0.50;95%CI:0.41-0.61)均得到改善。安慰剂联合培美曲塞-铂类组的84例患者(40.8%)交叉至帕博利珠单抗治疗组。72.1%的接受帕博利珠单抗联合培美曲塞-铂类的患者和66.8%的接受安慰剂联合培美曲塞-铂类的患者发生了3级-5级不良事件。56例患者完成了35个周期(约2年)的帕博利珠单抗治疗;ORR为85.7%,53例(94.6%)患者存活至数据截止时间。结论与安慰剂联合培美曲塞-铂类治疗相比,帕博利珠单抗联合培美曲塞-铂类可持续提高疗效,且安全性可控。该研究结果支持将帕博利珠单抗联合培美曲塞-铂类作为初治转移性非鳞状NsCLC患者的一线治疗方案。

关键词：帕博利珠单抗化疗非鳞状非小细胞肺癌

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suppression of NLRP3 inflammasome by ivermectin ameliorates bleomycin-induced pulmonary fibrosis

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Journal of Zhejiang University-science B(Biomedicine & Biotechnology) 2023年第8期24卷 723-733页

作者： Mai A.ABD-ELMAWLA Heba R.GHAIAD Enas s.gad Kawkab A.AHMED Maha ABDELMONEM Department of Biochemistry Faculty of PharmacyCairo UniversityCairo 11562Egypt Department of Pharmaceutical sciences Faculty of PharmacyKing Faisal UniversityAl-Ahsa 31982Saudi Arabia Department of Pharmacology and Toxicology Faculty of PharmacySinai UniversityIsmailia 45511Egypt Department of Pathology Faculty of Veterinary MedicineCairo UniversityCairo 12211Egypt

Ivermectin is a Us Food and Drug Administration(FDA)-approved antiparasitic agent with antiviral and anti-inflammatory *** recent studies reported the possible anti-inflammatory activity of ivermectin in respiratory injuries,its potential therapeutic effect on pulmonary fibrosis(PF)has not been *** study aimed to explore the ability of ivermectin(0.6 mg/kg)to alleviate bleomycin-induced biochemical derangements and histological changes in an experimental PF rat *** can provide the means to validate the clinical utility of ivermectin as a treatment option for idiopathic *** results showed that ivermectin mitigated the bleomycin-evoked pulmonary injury,as manifested by the reduced infiltration of inflammatory cells,as well as decreased the inflammation and fibrosis ***,ivermectin decreased collagen fiber deposition and suppressed transforming growth factor-β1(TGF-β1)and fibronectin protein expression,highlighting its anti-fibrotic *** study revealed for the first time that ivermectin can suppress the nucleotide-binding oligomerization domain(NOD)-like receptor family pyrin domain-containing protein 3(NLRP3)inflammasome,as manifested by the reduced gene expression of NLRP3 and the apoptosis-associated speck-like protein containing a caspase recruitment domain(AsC),with a subsequent decline in the interleukin-1β(IL-1β)*** addition,ivermectin inhibited the expression of intracellular nuclear factor-κB(NF-κB)and hypoxia‑inducible factor‑1α(HIF-1α)proteins along with lowering the oxidative stress and apoptotic ***,this study revealed that ivermectin could ameliorate pulmonary inflammation and fibrosis induced by *** beneficial effects were mediated,at least partly,via the downregulation of TGF-β1 and fibronectin,as well as the suppression of NLRP3 inflammasome through modulating the expression of HIF‑1αand NF-κB.

关键词： Intra-tracheal instillation Immunohistochemistry Transforming growth factor-β1(TGF-β1) Nuclear factor-κB(NF-κB) Lung fibrosis

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Geochemistry of the High Dam Lake sediments,south Egypt:implications for environmental significance

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International Journal of sediment Research 2013年第4期28卷 544-559页

作者： Mohamed Abdallah gad DARWIsH Geology department Faculty of ScienceAswan University

The goal of the present work is to perform a geochemical assessment of High Dam Lake bottom sediments for determining the fate,dispersion and levels of trace elements causing environmental pollution,and provided an access to their probable *** sediment samples were analyzed using ICP-Ms for 20 elements;Ag,Ba,Cr,Cu,Ga,Hf,Mn,Pb,Rb,sc,sc,sn,sr,Ta Th Ti,T1,U,V and Zr,and their obtained data were treated using statistical,graphical and mapping *** results showed the data set of all analyzed elements affected by outliers and extreme values that caused deviation away from *** Wallis test revealed that median of some trace clement levels in Lake sediments,was not significantly different and other elements rejected the Null *** analyzed elements had high values of median and mean in sediments of Lake Nubia rather than Lake Nasser and their normalization gave the same results of calculated environment ***,Lake Nubia sediments possessed high combined EF levels of Th,sc,sn,Ag,Zr,Hf,Ta,sr,U,Ti,V,Cr,and Mn,causing significant contamination,which was great potentially related to industrial,agricultural,urbanization and mining ***,combined EF of se,Cu,Ga,Pb,Ba,Rb,and Tl,which are highly elevated in southern Lake Nasser sediments owing to their source are great possibly derived from Lake Nubia and geogenic *** decreasing distance towards the High Dam body,the contaminant elements were diminished due to reduction in the environmental factors and sudanese pollution sources leading to the northern Lake Nasser considered to be less ***,the present study is an environmental alert for contaminated sediments that carried contaminants and considered the secondary source of pollution impact on ecosystem,and subsequently,their environmental risk on Human health.

关键词： Geochemistry High Dam Lake sediments Environmental significance south Egypt

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Impact of different nano additives on performance, combustion, emissions and exergetic analysis of a diesel engine using waste cooking oil biodiesel

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Propulsion and Power Research 2022年第2期11卷 209-223页

作者： M.s.gad Mostafa M.Abdel Aziz Hatem Kayed Mechanical Engineering Department Faculty of EngineeringFayoum UniversityEgypt Mechanical Engineering Department Institute of Aviation Engineering and TechnologyGizaEgypt Mechanical Power Engineering Department Faculty of EngineeringCairo University12613Egypt

Biodiesel is derived from waste cooking oil (WCO) by transesterification. Methylester was prepared by mixing diesel and biodiesel oils as 20% by volume. Nano particles asTiO2, Al2O3 and CNTs were blended with biodiesel blend at different concentrations of 25,50, and 100 mg/l to enhance the physicochemical fuel characteristics to obtain clean and effi-cient combustion performance. An experimental setup was incorporated into a diesel engine toinvestigate the influence of these nano-materials on engine performance, exergy analysis, combustion characteristics and emissions using WCO biodiesel-diesel mixture. Enriching methylester mixture with 100 ppm titanium, alumina and CNTs (B20T100, B20A100 andB20C100) increased the thermal efficiency by 4%, 6% and 11.5%, respectively compared toB20. Biodiesel blending with nano additives B20T100, B20A100 and B20C100 decreasedthe emissions of CO (11%, 24% and 30%, respectively), HC (8%, 17% and 25%, respectively)and smoke (10%, 13% and 19%, respectively) compared to B20. However, the noticeable increase of NOx was estimated by 5%, 12% and 27% for B20T100, B20A100 and B20C100,respectively. Finally, the results showed the rise in peak cylinder pressure by 5%, 9% and 11% and increase in heat release rate by 4%, 8% and 13% for B20T100, B20A100 andB20C100, respectively. The fuel exergy of B20T100, B20A100 and B20C100 are lower thanbiodiesel blend B20 by 6.5%, 16% and 23% but the exergetic efficiency are increased by 7%,19% and 30% at full load about B20.

关键词： Waste cooking oil(WCO) Nano additives Engine performance Exergy Combustion characteristics Emissions

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Whole-Plant Live Imaging of Reactive Oxygen species

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Molecular Plant 2019年第9期12卷 1203-1210页

作者： Yosef Fichman gad Miller Ron Mittler The Division of Plant sciences and Interdisciplinary Plant Group College of AgricultureFood and Natural ResourcesChristopher S.Bond Life Sciences Center University of Missouri1201 Rollins StreetColumbiaMO 65201USA The Mina and Everard Goodman Faculty of Life sciences Bar-llan UniversityThe Gonda Medical Diagnostic Research Building(204)Room 211Ramat-Gan 52900Israel Department of surgery University of Missouri School of Medicine1 Hospital DriveColumbiaMO 65212USA

Reactive oxygen species(ROs)are key regulators of numerous subcellular,cellular,and systemic *** function in plants as an integral part of many different hormonal,physiological,and developmental pathways,as well as play a critical role in defense and acclimation responses to different biotic and abiotic *** many ROs imaging techniques have been developed and utilized in plants,a wholeplant imaging platform for the dynamic detection of ROs in mature plants is *** we report a robust and straightforward method for the whole-plant live imaging of ROs in mature plants grown in *** new method could be used to study local and systemic ROs signals in different genetic variants,conduct phenotyping studies to identify new pathways for ROs signaling,monitor the stress level of different plants and mutants,and unravel novel routes of ROs integration into stress,growth regulation,and development in *** demonstrate the utility of this new method for studying systemic ROs signals in different A rabidopsis mutants and wound responses in cereals such as wheat and corn.

关键词： live imaging ROs stress systemic signaling whole plant

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Performance,emissions and exergy analyses of adding CNTs to various biodiesel feedstocks

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Propulsion and Power Research 2022年第4期11卷 511-526页

Extraction of biodiesel from waste cooking oil,jatropha,and corn oils is done by *** and biodiesel were blended at 20%volume ratio to make methyl *** doses of 25,50,and 100 mg/l,carbon nanotubes(CNTs)was mixed with biodiesel *** objective of the present research is to examine experimentally a diesel engine performance,combustion characteristics,exergy and emissions analyses with inclusion of nano additive to various methyl ester *** ester blend is enriched with CNTs as JB20C100,WB20C100 and CB20C100 where the improvements in thermal efficiency are raised about biodiesel mixture by 9%,13%and 15%,*** of 100 ppm of CNTs to biodiesel blends achieves the greatest reductions in CO(14%,22%and 30%),HC(16%,20%and 25%),and smoke emissions(15%,19%and 23%)for JB20C100,WB20C100 and CB20C100,*** comparing with B20,blending 100 ppm CNTs with JB20,CB20,and WB20 obtained the highest increases in cylinder pressure of 3%,5%,and 10%,as well as the highest increases in heat release of 4%,7%,and 11%,*** downside of CNTs addition achieves a rise in NOx emissions by 10%,17%,and 22%for JB20C100,WB20C100,and CB20C100,*** efficiency increases by 8%,19%,and 24%for B20T100,B20A100,and B20C100,*** index improvements achieve 1.5%,5%and 6.5%,for B20T100,B20A100,and B20C100,***20 with CNTs of 100 ppm is highly recommended for improving engine performance,combustion,and exergy characteristics with considerable emissions reduction.

关键词： Biodiesel Carbon nanotubes(CNTs) Engine performance Exergy Combustion characteristics Emissions

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伊维菌素抑制NLRP3炎症小体可改善博来霉素诱导的肺纤维化（英文）

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Journal of Zhejiang University-science B(Biomedicine & Biotechnology) 2023年第8期 723-737页

作者： Mai A.ABD-ELMAWLA Heba R.GHAIAD Enas s.gad Kawkab A.AHMED Maha ABDELMONEM 埃及开罗大学药学院生物化学系费萨尔国王大学药学院药学系埃及西奈大学药学院药理毒理学系埃及开罗大学兽医学院病理学系

伊维菌素是美国食品药品监督管理局（FDA）批准的抗寄生虫剂，具有抗病毒和抗炎特性。尽管最近有研究表明伊维菌素在呼吸系统损伤中可能具有抗炎活性，但其对肺纤维化（PF）的潜在影响尚未得到验证。本研究旨在探讨伊维菌素（0.6 mg/kg... 详细信息

伊维菌素是美国食品药品监督管理局（FDA）批准的抗寄生虫剂，具有抗病毒和抗炎特性。尽管最近有研究表明伊维菌素在呼吸系统损伤中可能具有抗炎活性，但其对肺纤维化（PF）的潜在影响尚未得到验证。本研究旨在探讨伊维菌素（0.6 mg/kg）在PF大鼠模型中减轻博来霉素诱导的生化紊乱和组织学变化的效果。这可用于验证伊维菌素作为治疗特发性PF在临床上的效用。在本研究中，伊维菌素减轻了博来霉素诱发的肺损伤，表现为炎症细胞浸润减少以及炎症和纤维化评分降低。值得注意的是，伊维菌素减少了胶原纤维的沉积并抑制了转化生长因子-β1(TGF-β1)和纤连蛋白的表达，突显了其抗纤维化活性。本研究首次揭示伊维菌素可以抑制NOD样受体家族含吡啶结构域蛋白3(NLRP3)炎症小体，表现为NLRP3和含有半胱天冬酶募集结构域的凋亡相关斑点样蛋白（AsC）基因的表达减少，以及白细胞介素-1β(IL-1β)水平的下降。此外，伊维菌素抑制细胞内核因子-κB(NF-κB)和缺氧诱导因子-1α(HIF-1α)蛋白的表达，同时降低氧化应激和凋亡标志物的水平。本研究表明，伊维菌素可以改善博来霉素引起的肺部炎症和纤维化，并且部分功能是通过下调TGF-β1和纤连蛋白以及通过调节HIF-1α和NF-κB的表达抑制NLRP3炎性小体来介导的。

关键词：气管内滴注免疫组化转化生长因子-β1(TGF-β1) 核转录因子-κB(NF-κB) 肺纤维化

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The Fibrillar Matrix:Novel Avenues for Breast Cancer Detection and Treatment

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Engineering 2021年第10期7卷 1375-1380页

作者： Rasha Rezk Raquel Marín-García Annica K.B.gad Weston Park Cancer Centre Department of Oncology and MetabolismThe Medical SchoolThe University of SheffieldSheffield S102RXUnited Kingdom Department of Engineering University of CambridgeCambridge CB21PZUnited Kingdom Madeira Chemistry Research Center University of MadeiraFunchal 9020105Portugal

Breast cancer is marked by large increases in the protein fibers around tumor *** fibers increase the mechanical stiffness of the tissue,which has long been used for tumor diagnosis by manual *** research in bioengineering has led to the development of novel biomaterials that model the mechanical and architectural properties of the tumor microenvironment and can be used to understand how these cues regulate the growth and spread of breast ***,we provide an overview of how the mechanical properties of breast tumor tissues differ from those of normal breast tissue and noncancerous *** also describe how biomaterial models make it possible to understand how the stiffness and viscosity of the extracellular environment regulate cell migration and breast cancer *** highlight the need for biomaterial models that allow independent analysis of the individual and different mechanical properties of the tumor microenvironment and that use cells derived from different regions within *** models will guide the development of novel mechano-based therapies against breast cancer metastasis.

关键词： Breast cancer Tissue stiffness Cancer metastasis Cell migration Bioengineered scaffold Viscosity

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Assessing the impact of non-governmental organization’s extension programs on sustainable cocoa production and household income in Ghana

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Journal of Integrative Agriculture 2021年第10期20卷 2820-2836页

作者： sonny gad ATTIPOE CAO Jian-min Yaa OPOKU-KWANOWAA Frank OHENE-sEFA College of Economics and Management Jilin Agricultural UniversityChangchun 130118P.R.China Ministry of Food and Agriculture Department of EconomicsAccra 183Ghana College of Resources and Environment sciences Jilin Agricultural UniversityChangchun 130118P.R.China Ghana Cocoa Board Warehousing and Port OperationsAccra 1017Ghana

Globally,cocoa is famous for the production of chocolates and ***,it also serves as a source of raw material for the manufacturing of high-quality cosmetic and pharmaceutical products. Due to its high demand,cocoa is regarded as a major commodity for poverty alleviation in deprived cocoa farming communities. Government has therefore instigated relevant measures to address issues facing the sector by investing in extension programs. These programs act as information dissemination tools for teaching modern farming technologies and enhancing learning among farmers. This study highlighted the effects of the Cocoa Life Project (CLP) by Cooperative for Assistance and Relief Everywhere (CARE) International on farm productivity and income of 200 cocoa farmers in three districts of the Eastern Region,Ghana. Regression on covariates,Heckman’s treatment effects model,and propensity scores were used to test the robustness of the estimates. A positive association between extension program participation,farm productivity,and household income was discovered. specifically,after correcting for selection bias,the estimated results of the Heckman’s model showed that the extension program significantly increased participating farmers’ cocoa yield by 14.3%. The effects on total farm income showed a significant increase of 25.1 and 42.9%,respectively from regression on propensity scores and the Heckman’s model. Across all three models,program participation led to an increase in total household income by 46.1,31.7,and 69.3%,respectively. Other variables such as farming characteristics,institutional and demographic factors affected farmers’ income,depending on the estimation method used. This study reiterated the supporting role played by extension programs in enhancing cocoa production and increasing household income in Ghana. Conclusively,government and development partners should invest in extension programs by providing enough logistics,training qualified agents,and creat

关键词： cocoa extension Heckman’s model regression on propensity scores smallholders

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small-extracellular vesicles and their microRNA cargo from porcine follicular fluids:the potential association with oocyte quality

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Journal of Animal science and Biotechnology 2022年第6期13卷 1727-1742页

作者： Ahmed gad Matej Murin Alexandra Bartkova Veronika Kinterova Katerina Marcollova Jozef Laurincik Radek Prochazka Institute of Animal Physiology and Genetics Czech Academy of Sciences27721 LiběchovCzech Republic Department of Animal Production Faculty of AgricultureCairo UniversityGiza 12613Egypt Department of Botany and Genetics Faculty of Natural SciencesConstantine the Philosopher University in Nitra94901 NitraSlovakia.

Background: Ovarian follicular fluids(FFs) contain several kinds of regulatory factors that maintain a suitable micro-environment for oocyte development. Extracellular vesicles(EVs) are among the factors that play essential roles in regulating follicle and oocyte development through their cargo molecules that include microRNAs(miRNAs). This study aimed to investigate small-EV(s-EV) miRNAs in porcine FFs and their potential association with oocyte ***: Individual aspirated oocytes were stained with lissamine green B stain(LB), a vital stain for oocyte quality, and each oocyte was classified as high-quality(unstained;HQ) or low-quality(stained;LQ). FFs corresponding to oocytes were pooled together into HQ and LQ groups. small-EVs were isolated from FFs, characterized, and their miRNA cargo was identified using the Illumina Nova seq sequencing platform. Additionally, s-EVs from the HQ and LQ groups were utilized to investigate their effect on oocyte development after co-incubation during in vitro ***: A total of 19 miRNAs(including miR-125b, miR-193a-5p, and miR-320) were significantly upregulated, while 23(including miR-9, miR-206, and miR-6516) were downregulated in the HQ compared to the LQ group. Apoptosis, p53 signaling, and cAMP signaling were among the top pathways targeted by the elevated miRNAs in the HQ group while oocyte meiosis, gap junction, and TGF-beta signaling were among the top pathways targeted by the elevated miRNAs in the LQ group. The supplementation of small-EVs during maturation does not affect the oocyte developmental rates. However, LQ s-EVs increase the proportion of oocytes with homogeneous mitochondrial distribution and decrease the proportion of heterogeneous ***: Our findings indicated that FF-EVs contain different miRNA cargos associated with oocyte quality and could affect the mitochondrial distribution patterns during oocyte maturation.

关键词： Extracellular vesicles Follicular fuids MiRNA Oocyte quality Porcine

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