Phe

Phe
  • 文章类型: Journal Article
    脑出血(ICH)患者的一般指南建议包括血压-,温度和葡萄糖管理。这种“护理束”的治疗效果(降血压,血糖控制,和发热的治疗)对临床结果的影响日益确立。对于目前的研究,我们旨在调查严格捆绑治疗(BCT)与临床结局的相关性,并描述与血肿扩大(HE)和出血性水肿高峰(PHE)等关键结局效应因素的相关性.
    我们从前瞻性UKER-ICH队列研究中筛选了连续的ICH患者(n=1,322)。BCT被定义为达到并维持收缩压的治疗范围(110-160mmHg),葡萄糖(80-180mg/dL),和体温(35.5-37.5°C)在前72小时。主要结果是12个月时的功能结果(改良的Rankin量表(mRS)0-3)。次要结果包括12个月时的死亡率,血肿扩大的发生,以及出血性周围水肿高峰的发展。通过计算绝对治疗效果(ATE)和计算e值的双重稳健方法解决了混淆问题。
    共有681名患者待分析,182例患者符合所有三项BCT标准,并与499例对照组进行比较.BCT达到主要结局的ATE为9.3%,95%CI(1.7至16.9),p<0.001;e值:3.1,CI(1.8)。12个月时的死亡率通过BCT显着降低[ATE:-12.8%,95%CI(-19.8至-5.7),p<0.001;e值:3.8,CI(2.2)],未观察到HE或PHE峰值的相关性。BCT对主要结局影响的重要驱动因素是收缩压控制(ATE:15.9%)和维持正常体温(ATE:10.9%)。
    ICH患者在急性住院期间的最初72小时内严格遵守此“护理捆绑”与改善的功能长期结局独立相关。由收缩压控制和维持正常体温驱动。我们的发现强烈保证了前瞻性验证,以确定其普遍性,尤其是在西方国家。临床试验注册:ClinicalTrials.gov,标识符[ID:NCT03183167]。
    UNASSIGNED: General guideline recommendations in patients with intracerebral hemorrhage (ICH) include blood pressure-, temperature- and glucose management. The therapeutic effect of such a \"care bundle\" (blood pressure lowering, glycemic control, and treatment of pyrexia) on clinical outcomes becomes increasingly established. For the present study, we aimed to investigate associations of strict bundled care treatment (BCT) with clinical outcomes and characterize associations with key outcome effectors such as hematoma enlargement (HE) and peak perihemorrhagic edema (PHE).
    UNASSIGNED: We screened consecutive ICH patients (n = 1,322) from the prospective UKER-ICH cohort study. BCT was defined as achieving and maintaining therapeutic ranges for systolic blood pressure (110-160 mmHg), glucose (80-180 mg/dL), and body temperature (35.5-37.5°C) over the first 72 h. The primary outcome was the functional outcome at 12 months (modified Rankin Scale (mRS) 0-3). Secondary outcomes included mortality at 12 months, the occurrence of hematoma enlargement, and the development of peak perihemorrhagic edema. Confounding was addressed by a doubly robust methodology to calculate the absolute treatment effect (ATE) and by calculating e-values.
    UNASSIGNED: A total of 681 patients remained for analysis, and 182 patients fulfilled all three BCT criteria and were compared to 499 controls. The ATE of BCT to achieve the primary outcome was 9.3%, 95% CI (1.7 to 16.9), p < 0.001; e-value: 3.1, CI (1.8). Mortality at 12 months was significantly reduced by BCT [ATE: -12.8%, 95% CI (-19.8 to -5.7), p < 0.001; e-value: 3.8, CI (2.2)], and no association was observed for HE or peak PHE. Significant drivers of BCT effect on the primary outcome were systolic blood pressure control (ATE: 15.9%) and maintenance of normothermia (ATE: 10.9%).
    UNASSIGNED: Strict adherence to this \"care bundle\" over the first 72 h during acute hospital care in patients with ICH was independently associated with improved functional long-term outcome, driven by systolic blood pressure control and maintenance of normothermia. Our findings strongly warrant prospective validation to determine the generalizability especially in Western countries.Clinical trial registration:ClinicalTrials.gov, identifier [ID: NCT03183167].
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  • 文章类型: Journal Article
    细胞外pH值改变与各种病理状况之间的相关性,包括癌症,炎症和代谢紊乱,是众所周知的。整体pH测量不能报告细胞表面的细胞外pH值。然而,有有限数量的合适的工具来测量细胞的细胞外pH具有高空间分辨率,它们都不常用于世界各地的实验室。在这项研究中,开发了一种用于测量细胞外pH的通用比率纳米传感器。纳米传感器由装载有pH惰性参考染料尼罗红的生物相容性聚苯乙烯纳米颗粒组成,并用pH响应性荧光素染料进行表面官能化。配有靶向部分,纳米传感器可以粘附在细胞膜上,允许直接测量细胞表面的细胞外pH。纳米传感器表现出在5.5-9.0范围内的灵敏比例pH响应,计算的pKa为7.47。该范围最佳地涵盖了大多数健康细胞和pHe异常的细胞的细胞外pH(pHe)。如癌细胞。结合纳米传感器靶向细胞膜的能力,它的高鲁棒性,可逆性及其生物相容性,phe纳米传感器被证明非常适合细胞外pH的原位测量,即使在延长的时间内。这种pH纳米传感器有可能通过提高我们对细胞微环境的理解来推进生物医学研究,其中细胞外pH起着重要作用。
    The correlation between altered extracellular pH and various pathological conditions, including cancer, inflammation and metabolic disorders, is well known. Bulk pH measurements cannot report the extracellular pH value at the cell surface. However, there is a limited number of suitable tools for measuring the extracellular pH of cells with high spatial resolution, and none of them are commonly used in laboratories around the world. In this study, a versatile ratiometric nanosensor for the measurement of extracellular pH was developed. The nanosensor consists of biocompatible polystyrene nanoparticles loaded with the pH-inert reference dye Nile red and is surface functionalized with a pH-responsive fluorescein dye. Equipped with a targeting moiety, the nanosensor can adhere to cell membranes, allowing direct measurement of extracellular pH at the cell surface. The nanosensor exhibits a sensitive ratiometric pH response within the range of 5.5-9.0, with a calculated pKa of 7.47. This range optimally covers the extracellular pH (pHe) of most healthy cells and cells in which the pHe is abnormal, such as cancer cells. In combination with the nanosensors ability to target cell membranes, its high robustness, reversibility and its biocompatibility, the pHe nanosensor proves to be well suited for in-situ measurement of extracellular pH, even over extended time periods. This pH nanosensor has the potential to advance biomedical research by improving our understanding of cellular microenvironments, where extracellular pH plays an important role.
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  • 文章类型: Journal Article
    这项工作致力于氧化镁(MgO)纳米颗粒(NPs)作为骨植入物的添加剂。从四种不同的广泛使用的植物中提取,包括芦荟,Echeveriaelegans,三层膜,和景天,评估了它们促进MgO纳米颗粒“绿色合成”的能力。通过热重分析(TGA)分析了MgONPs的热稳定性和分解行为。通过X射线衍射(XRD)进行结构表征,能量色散X射线光谱(EDS),紫外可见光谱(UV-Vis),动态光散射(DLS),和拉曼散射光谱(RS)。通过扫描电子显微镜(SEM)研究了形态学。利用紫外-可见光谱技术对甲基橙(MeO)的降解研究了MgO纳米粒子的光催化活性。利用表面增强拉曼光谱(SERS)监测L-苯丙氨酸(L-Phe)在MgONPs表面的吸附。对于MgO,计算的增强因子(EF)高达102个数量级。这是显示固定在MgO纳米颗粒表面上的化合物的SERS光谱的第一项工作。
    This work is devoted to magnesium oxide (MgO) nanoparticles (NPs) for their use as additives for bone implants. Extracts from four different widely used plants, including Aloe vera, Echeveria elegans, Sansevieria trifasciata, and Sedum morganianum, were evaluated for their ability to facilitate the \"green synthesis\" of MgO nanoparticles. The thermal stability and decomposition behavior of the MgONPs were analyzed by thermogravimetric analysis (TGA). Structure characterization was performed by X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDS), ultraviolet-visible spectroscopy (UV-Vis), dynamic light scattering (DLS), and Raman scattering spectroscopy (RS). Morphology was studied by scanning electron microscopy (SEM). The photocatalytic activity of MgO nanoparticles was investigated based on the degradation of methyl orange (MeO) using UV-Vis spectroscopy. Surface-enhanced Raman scattering spectroscopy (SERS) was used to monitor the adsorption of L-phenylalanine (L-Phe) on the surface of MgONPs. The calculated enhancement factor (EF) is up to 102 orders of magnitude for MgO. This is the first work showing the SERS spectra of a chemical compound immobilized on the surface of MgO nanoparticles.
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  • 文章类型: Journal Article
    光催化析氢(PHE)通常受到光利用不足和光生电子-空穴对的快速结合速率的限制。此外,传统的PHE工艺通常通过添加牺牲试剂来消耗光诱导的空穴,这使得这种方法在经济上不利。在这里,我们设计了一种空间分离的双功能助催化剂装饰中空结构CdS(HCdS)@ZnIn2S4(ZIS)的Z方案异质结,它是通过牺牲硬模板法制备的,然后是光沉积。因此,PdOx@HCdS@ZIS@Pt表现出高效的PHE(86.38mmol·g-1·h-1)和苄胺(BA)氧化偶联(164.75mmol·g-1·h-1),选择性高(97.34%)。这项工作中独特的中空核壳形态和双功能助催化剂负载为设计和合成双功能Z方案光催化剂提供了巨大的潜力。
    Photocatalytic hydrogen evolution (PHE) is frequently constrained by inadequate light utilization and the rapid combination rate of the photogenerated electron-hole pairs. Additionally, conventional PHE processes are often facilitated by the addition of sacrificial reagents to consume photo-induced holes, which makes this approach economically unfavorable. Herein, we designed a spatially separated bifunctional cocatalyst decorated Z-scheme heterojunction of hollow structured CdS (HCdS) @ZnIn2S4 (ZIS), which was prepared by a sacrificial hard template method followed by photo-deposition. Consequently, PdOx@HCdS@ZIS@Pt exhibited efficient PHE (86.38 mmol·g-1·h-1) and benzylamine (BA) oxidation coupling (164.75 mmol·g-1·h-1) with high selectivity (97.34 %). The unique hollow core-shelled morphology and bifunctional cocatalyst loading in this work hold great potential for the design and synthesis of bifunctional Z-scheme photocatalysts.
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  • 文章类型: Journal Article
    背景:我们的目的是检验脑出血(ICH)患者血肿体积与长期(>72h)水肿扩展距离(EED)演变之间的关系,以及峰值EED与早期EED增加与3个月时功能结局之间的关系。
    方法:本回顾性队列研究纳入了2006年1月至2014年1月自发性幕上ICH患者。EED,定义为血肿边界和外部水肿边界之间的距离的水肿度量,使用绝对血肿和水肿体积计算。我们使用多变量逻辑回归分析年龄,ICH卷,以及位置和接收器操作特性分析,用于评估与功能结果和EED演变相关的措施。3个月后的功能结果通过使用改良的Rankin量表进行评估(0-3=有利,4-6=不利)。为了确定与峰值EED相关的特性,进行了多变量线性和逻辑回归分析。
    结果:共纳入292例患者。中位年龄为70岁(四分位间距[IQR]62-78),入院时ICH中位体积17.7mL(IQR7.9-40.2),出血性水肿(PHE)的中位数峰值为37.5mL(IQR19.1-60.6),中位EED峰值为0.67cm(IQR0.51-0.84),早期EED在72h内增加(EED72-0)0.06cm(-0.02~0.15).发现峰值EED与ICH体积无关(R2=0.001,p=0.6)。在多变量分析中,峰值EED(比值比0.224,95%置信区间[CI][0.071-0.705])和峰值PHE体积(比值比0.984[95%CI0.973-0.994])与3个月时有利的功能结局呈负相关.受试者工作特征分析确定PHE的峰值体积为26.8mL(曲线下面积0.695[95%CI0.632-0.759];p≤0.001),EED的峰值为0.58cm(曲线下面积0.608[95%CI0.540-0.676];p=0.002)作为结果区分的最佳预测值。
    结论:与绝对峰值PHE体积相比,峰值EED代表了ICH患者的一种有前景的水肿指标,该指标在很大程度上与血肿体积无关,但与功能结局相关.
    BACKGROUND: Our objective was to test the association between hematoma volume and long-term (> 72 h) edema extension distance (EED) evolution and the association between peak EED and early EED increase with functional outcome at 3 months in patients with intracerebral hemorrhage (ICH).
    METHODS: This retrospective cohort study included patients with spontaneous supratentorial ICH between January 2006 and January 2014. EED, an edema measure defined as the distance between the hematoma border and the outer edema border, was calculated by using absolute hematoma and edema volumes. We used multivariable logistic regression accounting for age, ICH volume, and location and receiver operating characteristic analysis for assessing measures associated with functional outcome and EED evolution. Functional outcome after 3 months was assessed by using the modified Rankin Scale (0-3 = favorable, 4-6 = unfavorable). To identify properties associated with peak EED multivariable linear and logistic regression analyses were conducted.
    RESULTS: A total of 292 patients were included. Median age was 70 years (interquartile range [IQR] 62-78), median ICH volume on admission 17.7 mL (IQR 7.9-40.2), median peak perihemorrhagic edema (PHE) volume was 37.5 mL (IQR 19.1-60.6), median peak EED was 0.67 cm (IQR 0.51-0.84) with an early EED increase up to 72 h (EED72-0) of 0.06 cm (- 0.02 to 0.15). Peak EED was found to be independent of ICH volume (R2 = 0.001, p = 0.6). In multivariable analyses, peak EED (odds ratio 0.224, 95% confidence interval [CI] [0.071-0.705]) and peak PHE volume (odds ratio 0.984 [95% CI 0.973-0.994]) were inversely associated with favorable functional outcome at 3 months. Receiver operating characteristic analysis identified a peak PHE volume of 26.8 mL (area under the curve 0.695 [95% CI 0.632-0.759]; p ≤ 0.001) and a peak EED of 0.58 cm (area under the curve 0.608 [95% CI 0.540-0.676]; p = 0.002) as best predictive values for outcome discrimination.
    CONCLUSIONS: Compared with absolute peak PHE volume, peak EED represents a promising edema measure in patients with ICH that is largely hematoma volume-independent and nevertheless associated with functional outcome.
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  • 文章类型: Journal Article
    远程医疗在为初级保健提供医疗保健方面发挥了重要作用,慢性病患者,和那些患有实体器官恶性肿瘤的人。然而,它在血液系统恶性肿瘤等亚专科的应用,造血细胞移植(HCT),或嵌合抗原受体T细胞(CAR-T)疗法并不普遍,因为体格检查是提供护理的重要组成部分。在COVID-19大流行期间,我们广泛使用远程医疗,因为保护我们的免疫功能低下的患者成为我们的首要任务。HCT和CAR-T疗法在高风险血液系统恶性肿瘤中的应用持续增长,特别是老年和体弱的患者,他们必须访问专业中心进行治疗。一般来说,HCT和CAR-T治疗是非常复杂的,需要患者的承诺,看护者,和专业学术中心的多学科团队。在COVID-19公共卫生紧急情况(PHE)期间,所有医疗保健系统都适应了危机,并实施了快速变化。远程医疗,在服务不足的地区提供医疗保健的重要方式,经历了快速扩张,无论地理区域如何,在COVID-19PHE期间。PHE期间实施的实践中出现的数据正在推动远程医疗领域向前发展,特别是对于具有复杂医学治疗的专业,如HCT和CAR-T疗法。在这次审查中,我们检查了HCT远程医疗和细胞治疗护理模式的最新数据,用于患者的急性和长期护理.
    Telemedicine has played an important role in delivering healthcare for primary care, chronic disease patients, and those with solid organ malignancies. However, its application in subspecialties such as hematologic malignancies, hematopoietic cell transplantation (HCT), or chimeric antigen receptor-T cell (CAR-T) therapy is not widespread since physical examination is a vital component in delivering care. During the COVID-19 pandemic, we widely used telemedicine, since protecting our immunocompromised patients became our top priority. The employment of HCT and CAR-T therapies continues to grow for high-risk hematologic malignancies, particularly in older and frail patients who must visit specialty centers for treatment access. Generally, HCT and CAR-T therapy care is highly complex, necessitating commitment from patients, caregivers, and a multidisciplinary team at specialty academic centers. All healthcare systems adapted to the crisis and implemented rapid changes during the COVID-19 public health emergency (PHE). Telemedicine, a vital modality for delivering healthcare in underserved areas, experienced rapid expansion, regardless of the geographic region, during the COVID-19 PHE. The data emerging from practices implemented during the PHE are propelling the field of telemedicine forward, particularly for specialties with complex medical treatments such as HCT and CAR-T therapy. In this review, we examine the current data on telemedicine in HCT and cellular therapy care models for the acute and long-term care of our patients.
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  • 文章类型: Journal Article
    全球变暖和气候变化是造成许多灾难的原因。洪水带来了严重的风险,需要立即管理和策略以获得最佳响应时间。技术可以通过提供信息来代替人类在紧急情况下做出反应。作为这些新兴的人工智能(AI)技术之一,无人机在其修改的系统中由无人驾驶飞行器(UAV)控制。在这项研究中,我们提出了一种安全的方法,在沙特阿拉伯使用洪水检测安全系统(FDSS),基于深度主动学习(DeepAL)的分类模型在联邦学习中,以最小化通信成本和最大限度地提高全局学习的准确性。我们使用基于区块链的联邦学习和部分同态加密(PHE)进行隐私保护和随机梯度下降(SGD)来共享最佳解决方案。InterPlanetary文件系统(IPFS)解决了块存储有限的问题以及区块链中传输的高信息梯度带来的问题。除了提高安全性,FDSS可以防止恶意用户泄露或更改数据。利用图像和物联网数据,FDSS可以训练检测和监控洪水的本地模型。采用同态加密技术对每个局部训练的模型和梯度进行加密,实现密文级模型聚合和模型过滤,这确保了本地模型可以在保持隐私的同时进行验证。拟议的FDSS使我们能够估计洪水泛滥的地区,并跟踪大坝水位的快速变化,以衡量洪水威胁。所提出的方法很简单,容易适应,并为沙特阿拉伯决策者和地方管理人员提供建议,以解决日益严重的洪水危险。本研究最后讨论了使用人工智能和区块链技术管理偏远地区洪水的方法及其挑战。
    Global warming and climate change are responsible for many disasters. Floods pose a serious risk and require immediate management and strategies for optimal response times. Technology can respond in place of humans in emergencies by providing information. As one of these emerging artificial intelligence (AI) technologies, drones are controlled in their amended systems by unmanned aerial vehicles (UAVs). In this study, we propose a secure method of flood detection in Saudi Arabia using a Flood Detection Secure System (FDSS) based on deep active learning (DeepAL) based classification model in federated learning to minimize communication costs and maximize global learning accuracy. We use blockchain-based federated learning and partially homomorphic encryption (PHE) for privacy protection and stochastic gradient descent (SGD) to share optimal solutions. InterPlanetary File System (IPFS) addresses issues with limited block storage and issues posed by high gradients of information transmitted in blockchains. In addition to enhancing security, FDSS can prevent malicious users from compromising or altering data. Utilizing images and IoT data, FDSS can train local models that detect and monitor floods. A homomorphic encryption technique is used to encrypt each locally trained model and gradient to achieve ciphertext-level model aggregation and model filtering, which ensures that the local models can be verified while maintaining privacy. The proposed FDSS enabled us to estimate the flooded areas and track the rapid changes in dam water levels to gauge the flood threat. The proposed methodology is straightforward, easily adaptable, and offers recommendations for Saudi Arabian decision-makers and local administrators to address the growing danger of flooding. This study concludes with a discussion of the proposed method and its challenges in managing floods in remote regions using artificial intelligence and blockchain technology.
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  • 文章类型: Journal Article
    生物炭是在500°C的温度下从Eucheuma(EBC)衍生的,并且使用NaOH对所得的生物炭进行改性,KOH,KOHNaOH+KOH和HNO3+HCl。这项研究调查了这些修饰对生物炭特性的影响及其从水溶液中吸附菲(Phe)的有效性。结果表明,表面粗糙度增加,导致比表面积的增加,复杂孔隙结构的发展,导致通过KOH和HNO3HCl(EBC-K和EBC-H)的混合物改性的生物炭的极性降低和疏水性增加。EBC-K和EBC-H样品表现出优异的表面积(272.76和289.60m2g-1)和对Phe的吸附能力(去除率分别为99.8%和99.4%)。伪一阶,伪二阶和颗粒内扩散动力学模型表明,吸附过程由物理化学和颗粒内扩散决定。Langmuir模型很好地描述了吸附过程。与原始生物炭相比,EBC-K和EBC-H的最大吸附容量增加了约2.4倍。批量吸附实验表明,去除率随投加量的增加而增加。此外,从正己烷再生的EBC-H除去了85.52%的Phe溶液。
    Biochar was derived from Eucheuma (EBC) at a temperature of 500 °C and the resulting biochar was modified using NaOH, KOH, NaOH + KOH and HNO3 + HCl. This study investigated the impact of these modifications on the characteristics of the biochar and its effectiveness in adsorbing phenanthrene (Phe) from an aqueous solution. The results indicated that the surface roughness increased, leading to an increase in the specific surface area, and the development of complex pore structure, leading to a decrease in the polarity and increase in hydrophobicity of biochar modified by a mixture of KOH and HNO3 + HCl (EBC-K and EBC-H). The EBC-K and EBC-H samples exhibited superior surface areas (272.76 and 289.60 m2 g-1) and adsorption capabilities for Phe (removal rates of 99.8% and 99.4%). The pseudo-first order, pseudo-second order and intraparticle diffusion Kinetic model demonstrated that the adsorption process is determined by both physicochemical and intra-particle diffusion. The adsorption process was well described by the Langmuir model. The maximum adsorption capacity of EBC-K and EBC-H was increased by approximately 2.4 times compared with the original biochar. Batch adsorption experiments indicated that the removal rate increases with the increase of dosage. Additionally, EBC-H regenerated from n-hexane removed 85.52% of the Phe solution.
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  • 文章类型: Journal Article
    背景:体外获能在辅助生殖技术(ART)中对于胚胎产生至关重要。最近,精氨酸已被证明可增强哺乳动物精子的获能。然而,精氨酸的详细作用机制仍然难以捉摸。
    目的:本研究研究了精氨酸诱导的获能和运动性增强对山羊精子RNA(spRNA)群体的影响。
    方法:用精氨酸处理山羊精子长达6小时,并与未处理或PHE(青霉胺,亚牛磺酸,和肾上腺素)以不同的间隔(0、1、2、4和6小时)处理的精子。精子参数,包括生存能力,个体运动性,获能,顶体反应,和ROS生产,进行了评估。通过短读RNA测序(RNA-seq)分析spRNA群体。
    结果:在精氨酸处理中,获能(73.21±4.22%)和顶体反应(18.35±0.56%)的精子的百分比最高,而PHE处理显示在孵育0至4小时内活动精子的百分比最高(79.82±4.31%)。与对照相比,RNA-seq分析在精氨酸处理的精子中鉴定了1,321个差异表达基因(DEG)。PGK2,RNASE10,ODF1和ROPN1L基因参与精子运动和ACR,参与获能过程的DKKL1,KCNJ11和PRND基因在精氨酸处理的精子中上调。DEGs调节精子获能相关的cAMP-PKA,PI3-Akt,钙,和MAPK信号通路。
    结论:精氨酸诱导的获能和精子运动性增强与一些参与精子运动性和获能途径的基因上调有关。比较研究还表明,精氨酸可以代替PHE用于增强山羊精子的运动性和体外获能。
    BACKGROUND: In vitro capacitation is essential in assisted reproductive technologies (ART) for embryo production. Recently, arginine has been proven to enhance capacitation in mammalian spermatozoa. However, the detailed mechanism of action of arginine remains elusive.
    OBJECTIVE: This study investigated the effect of arginine-induced capacitation and motility enhancement on the spermatozoal RNA (spRNA) population in goats.
    METHODS: Goat spermatozoa were treated with arginine for up to six hours and compared with non-treated or PHE (penicillamine, hypotaurine, and epinephrine)-treated spermatozoa at different intervals (0, 1, 2, 4, and 6 hours). Sperm parameters, including viability, individual motility, capacitation, acrosome reaction, and ROS production, were evaluated. The spRNA population was analyzed by short-read RNA sequencing (RNA-seq).
    RESULTS: The percentage of capacitated (73.21 ± 4.22%) and acrosome reacted (18.35 ± 0.56%) spermatozoa was highest in arginine treatment, while PHE treatment showed the highest percentage (79.82 ± 4.31%) of motile spermatozoa from 0 to 4 hours of incubation. RNA-seq analysis identified 1,321 differentially expressed genes (DEGs) in arginine-treated spermatozoa compared to the control. The PGK2, RNASE10, ODF1, and ROPN1L genes involved in sperm motility and ACR, DKKL1, KCNJ11, and PRND genes involved in the capacitation process were upregulated in arginine-treated spermatozoa. The DEGs regulate sperm capacitation-related cAMP-PKA, PI3-Akt, calcium, and MAPK signaling pathways.
    CONCLUSIONS: The arginine-induced capacitation and enhanced sperm motility were associated with the upregulation of several genes involved in sperm motility and capacitation pathways. The comparative study also suggests that arginine may be used in lieu of PHE for motility enhancement and in vitro capacitation of goat spermatozoa.
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  • 文章类型: Journal Article
    细胞外酸化已被证明是侵袭性肿瘤的重要特征,因为它促进入侵和迁移,但也抵抗治疗。靶向参与肿瘤pH调节的转运蛋白构成了一种有希望的抗肿瘤方法,因为它会破坏细胞pH稳态并对肿瘤生长产生负面影响。在这项研究中,我们评估了Syrosingopine的影响,MCT1和MCT4的抑制剂,在人乳腺癌(MDA-MB-231)和咽鳞状细胞癌(FaDu)细胞模型中作为肿瘤代谢和细胞外酸化的调节剂。在这两种体外模型中,我们观察到,暴露于syrosingopine导致细胞外酸化率降低,细胞内pH,葡萄糖消耗,乳酸分泌和肿瘤细胞增殖,晚期凋亡/坏死细胞数量增加。然而,使用MDA-MB-231模型的体内实验用每日注射的Syrosingopine治疗,没有发现细胞外pH(pHe)(使用CEST-MRI测量)或原发性肿瘤生长的任何显著变化.总的来说,我们的研究表明,靶向MCT可能导致肿瘤细胞代谢和增殖的深刻变化,它需要进一步的研究来确定没有脱靶效应的候选人。
    Extracellular acidification has been shown to be an important characteristic of invasive tumors, as it promotes invasion and migration but also resistance to treatments. Targeting transporters involved in the regulation of tumor pH constitutes a promising anti-tumor approach, as it would disrupt cellular pH homeostasis and negatively impact tumor growth. In this study, we evaluated the impact of syrosingopine, an inhibitor of MCT1 and MCT4, as a modulator of tumor metabolism and extracellular acidification in human breast cancer (MDA-MB-231) and pharyngeal squamous cell carcinoma (FaDu) cell models. In both models in vitro, we observed that exposure to syrosingopine led to a decrease in the extracellular acidification rate, intracellular pH, glucose consumption, lactate secretion and tumor cell proliferation with an increase in the number of late apoptotic/necrotic cells. However, in vivo experiments using the MDA-MB-231 model treated with a daily injection of syrosingopine did not reveal any significant change in extracellular pH (pHe) (as measured using CEST-MRI) or primary tumor growth. Overall, our study suggests that targeting MCT could lead to profound changes in tumor cell metabolism and proliferation, and it warrants further research to identify candidates without off-target effects.
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