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  • 文章类型: Case Reports
    文献显示,关于枪伤(GSW)患者从脊柱中去除弹道碎片的结果,发现相互矛盾。需要在该领域进行进一步的研究,以更好地理解GSW患者从脊柱中去除弹道碎片的风险和益处的细微差别。在这个案例报告中,我们讨论了晚发性颈椎前脓肿,该脓肿是在最初GSW后11年之前嵌入的子弹碎片迁移到咽后间隙时发展的。
    2011年,一名29岁的男性面部遭受枪伤。他通过后C3-C6侧块器械和融合而稳定下来。没有试图移除子弹碎片。2023年,患者因颈部疼痛恶化而返回。成像显示咽后脓肿,弹道碎片间隔旋转90°。在颈椎前方发现脓肿,其中有可自由移动的弹道碎片。
    此案例突出了几个问题:对保留的硬件进行射线照相监视的标准是什么?如果有记录的移动,这是否会引发进一步调查?可能会发生哪些并发症需要小心移除?
    UNASSIGNED: Literature showcases conflicting findings regarding the outcomes of ballistic fragment removal from the spine in gunshot wounds (GSW) patients. Further research in this area is needed to better comprehend the nuances of risks and benefits surrounding ballistic fragment removal from the spine in GSW patients. In this case report, we discuss the late-onset cervical prevertebral abscess which developed when a previously embedded bullet fragment migrated into the retropharyngeal space 11 years after an initial GSW.
    UNASSIGNED: A 29-year-old male sustained a gunshot wound to the face in 2011. He was stabilized with a posterior C3-C6 lateral mass instrumentation and fusion. There were no attempts to remove the bullet fragments. In 2023, the patient returned with worsening neck pain. Imaging demonstrated a retropharyngeal abscess with interval rotation of the ballistic fragment by 90°. An abscess was noted anterior to the cervical vertebrae with a freely mobile ballistic fragment within.
    UNASSIGNED: This case highlights several questions: What is the criteria for radiographic surveillance of retained hardware? If there is documented movement, should this trigger further investigation? What complications can occur that warrant careful removal?
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  • 文章类型: Journal Article
    细胞内tau聚集需要局部蛋白质浓度增加,称为“液滴”。然而,液滴形成的细胞机制知之甚少。这里,我们表达了OptoTau,与CRY2olig融合的P301L突变体tau,可以形成同型寡聚体的光敏蛋白。在蓝光照射下,OptoTau增加了tau磷酸化,并被隔离在侵入体中。通过nocodazole抑制侵袭性形成,在细胞质中形成tau颗粒簇。颗粒簇通过停止蓝光照射或1,6-己二醇处理而消失,这表明细胞内tau液滴的形成需要微管塌陷。表示OptoTau-ΔN,在阿尔茨海默病大脑中观察到的一种N末端切割的tau,在蓝光刺激下,在细胞质中形成1,6-己二醇和耐去污剂的tau簇。这些细胞内稳定的tau簇在体外充当tau原纤维的种子。这些结果表明,tau液滴的形成和N端裂解对于神经退行性疾病中神经原纤维缠结的形成是必需的。
    Intracellular tau aggregation requires a local protein concentration increase, referred to as \"droplets\". However, the cellular mechanism for droplet formation is poorly understood. Here, we expressed OptoTau, a P301L mutant tau fused with CRY2olig, a light-sensitive protein that can form homo-oligomers. Under blue light exposure, OptoTau increased tau phosphorylation and was sequestered in aggresomes. Suppressing aggresome formation by nocodazole formed tau granular clusters in the cytoplasm. The granular clusters disappeared by discontinuing blue light exposure or 1,6-hexanediol treatment suggesting that intracellular tau droplet formation requires microtubule collapse. Expressing OptoTau-ΔN, a species of N-terminal cleaved tau observed in the Alzheimer\'s disease brain, formed 1,6-hexanediol and detergent-resistant tau clusters in the cytoplasm with blue light stimulation. These intracellular stable tau clusters acted as a seed for tau fibrils in vitro. These results suggest that tau droplet formation and N-terminal cleavage are necessary for neurofibrillary tangles formation in neurodegenerative diseases.
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  • 文章类型: Journal Article
    胃癌是世界上第五大常见疾病和第四大最常见的死亡原因。它是通过食管胃十二指肠镜检查和活检诊断的;然而,早期发现病变存在局限性.最近,已经积极进行了使用液体活检来诊断各种癌症的研究,包括胃癌.来自癌症的各种物质反映在血液中。通过分析这些物质,预计不仅可以诊断癌症的存在或不存在,而且可以诊断癌症的类型。然而,这些物质的量非常小,甚至这些变量取决于个体的特征或癌症的特征。为了克服这些,我们使用MeDIP收集甲基化DNA片段,并将其与正常血浆进行比较,以确定胃癌组织或患者血浆的特征.我们试图利用通过癌组织和患者血浆反映在血液中的癌症特征来诊断胃癌。因此,我们证实了组织和血浆之间常见甲基化片段的一致性约为41.2%,我们发现通过SFR和5'端基序分析,使用片段的特征诊断和表征癌症的可能性.
    Gastric cancer is the fifth most common disease in the world and the fourth most common cause of death. It is diagnosed through esophagogastroduodenoscopy with biopsy; however, there are limitations in finding lesions in the early stages. Recently, research has been actively conducted to use liquid biopsy to diagnose various cancers, including gastric cancer. Various substances derived from cancer are reflected in the blood. By analyzing these substances, it was expected that not only the presence or absence of cancer but also the type of cancer can be diagnosed. However, the amount of these substances is extremely small, and even these have various variables depending on the characteristics of the individual or the characteristics of the cancer. To overcome these, we collected methylated DNA fragments using MeDIP and compared them with normal plasma to characterize gastric cancer tissue or patients\' plasma. We attempted to diagnose gastric cancer using the characteristics of cancer reflected in the blood through the cancer tissue and patients\' plasma. As a result, we confirmed that the consistency of common methylated fragments between tissue and plasma was approximately 41.2% and we found the possibility of diagnosing and characterizing cancer using the characteristics of the fragments through SFR and 5\'end-motif analysis.
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  • 文章类型: Journal Article
    分离的功效受到胶体颗粒对激光束辐射的自发吸收的显着影响。通过收集波长为1064nm和532nm的激光脉冲的组合来调节碎裂处理期间银纳米颗粒的分类。
    本研究对植物提取物与补充银纳米颗粒结合的功效进行了研究,以及使用激光破碎产生较小尺寸的银纳米颗粒。然后测量血液的毒性。
    在绿茶AgNP上使用脉冲激光碎裂合成Ag纳米颗粒。合成过程涉及使用波长为1064nm和532nm的Q开关Nd:YAG激光器,能量范围从200到1000mJ。最初,通过在各种能级下使用532nm的二次谐波产生将Ag靶碎裂的过程合成了银纳米胶体。确定所选波长内的最佳能量以便于最终比较。透射电子显微镜(TEM)用于确定表面形貌和平均粒径,而分光光度计用于分析紫外光的光谱特性。测量集中在表面等离子体共振(SPR)现象上。银纳米颗粒的吸收光谱在405nm和415nm的波长处表现出明显的峰。发现银纳米颗粒的平均直径为16nm和20nm,对应于1064nm和532nm的波长,分别。
    因此,颗粒尺寸的范围减小,平均尺寸减小到较低的幅度,产生非常稳定的胶体。这种特定的方法已经证明在生产具有预期颗粒尺寸的胶体悬浮液中相当有效。此外,通过分析人体血液中的纳米颗粒,没有看到血液成分的明显变化,表明其无毒性质。
    UNASSIGNED: The efficacy of fractionation is significantly impacted by the colloidal particles\' spontaneous absorption of laser beam radiation. The classification of silver nanoparticles during fragmentation processing is regulated through the collection of a combination of laser pulses with wavelengths of 1064 nm and 532 nm.
    UNASSIGNED: This study presents an investigation of the efficacy of a plant extract in conjunction with the incorporation of supplementary silver nanoparticles, as well as the generation of smaller-sized silver nanoparticles using laser fragmentation.and then measure thier toxity on the blood.
    UNASSIGNED: Ag nanoparticles were synthesized using pulsed laser fragmentation on green tea AgNPs. The synthesis process involved the utilization of a Q-switch Nd:YAG laser with wavelengths of 1064 nm and 532 nm, with energy ranging from 200 to 1000 mJ. Initially, a silver nano colloid was synthesized through the process of fragmented of the Ag target using the second harmonic generation of 532 nm at various energy levels. The optimal energy within the selected wavelengths was determined in order to facilitate the ultimate comparison. Transmission electron microscopy (TEM) was used to determine surface morphology and average particle size, while a spectrophotometer was used to analyses UV light\'s spectrum characteristics. The measurements focused on the surface plasmon resonance (SPR) phenomenon. The absorption spectra of silver nanoparticles exhibit distinct and prominent peaks at wavelengths of 405 nm and 415 nm. The mean diameter of the silver nanoparticles was found to be 16 nm and 20 nm, corresponding to wavelengths of 1064 nm and 532 nm, respectively.
    UNASSIGNED: As a consequence, there is a decrease in the range of particle sizes and a decrease in the mean size to lower magnitudes, resulting in a very stable colloid. This particular methodology has demonstrated considerable efficacy in the production of colloidal suspensions with the intended particle dimensions. Moreover, by the analysis of nanoparticles in human blood, no discernible alterations in the blood constituents were seen, indicating their non-toxic nature.
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  • 文章类型: Journal Article
    微塑料(MPs)与新兴污染物有关。这里,四种不同营养水平的可食用水生物种中的MPs(在2-4之间),包括鱼类Esoxlucius(Esocidae:Esocinae);鲤鱼(Cyprinidae:Cyprininae);和Luciobarbuscaspius(Cyprinidae:Barbinae);和天鹅贻贝Anodontacygnea(Unionidae),在Anzali淡水生态系统中进行了评估。这是蒙特勒记录中列出的湿地。MPs从胃肠道(GI)中提取,ill,肌肉,和皮肤。所有研究的鱼和贻贝(n=33)都有MP。MP纤维,在每个检查的GI中都检测到碎片和床单,然而,纤维是皮肤中唯一的国会议员,肌肉和ill是最丰富的MP。在鱼类和贻贝中发现的MP主要由尼龙制成(占MP总数的35%),聚丙烯-低密度聚乙烯(30%),和聚碳酸酯(25%)。在每个鱼标本中发现的国会议员的平均数量,表示为每湿体重,与条件因子(K)呈中度负相关(MP/g-K:皮尔逊相关r=-0.413,p=0.049),与生长因子(b)没有显着关系(r=-0.376;p=0.068)。重要的是,Luciobarbuscaspius(营养级2.7-2.8)生物积累了MPs,其MP污染与年龄之间存在很强的相关性(r=0.916p<0.05)。较大的g质量(或相关因素)在MP的积累中起着重要作用,Esoxlucius和Ceprinuscarpio的这些因素之间存在很强的相关性(r=0.876;r=0.846;p<0.05)。最高的MP/gg(1.91±2.65)位于底栖区的滤嘴喂食器Anodontacygnea中。埃索克斯·卢修斯(食肉,营养级4.1)是总体上污染最严重的物种(8个个体中共有83个MPs,0.92MPs/g鱼),以及国会议员主要积累的g。鲤鱼是污染最严重的标本(标本中的MPs),而每质量单位的MP数量随着营养水平的增加而增加。它们在水生生境中的摄食和生态行为影响了积累水平。这项工作包括MPs在水生生物中易位的证据。
    Microplastics (MPs) are concerning emerging pollutants. Here, MPs in four edible aquatic species of different trophic levels (between ∼2 and 4), including fish species Esox lucius (Esocidae: Esocinae); Cyprinus carpio (Cyprinidae: Cyprininae); and Luciobarbus caspius (Cyprinidae: Barbinae); and the swan mussel Anodonta cygnea (Unionidae), were assessed in the Anzali freshwater ecosystem. It is a listed wetland in the Montreux record. MPs were extracted from gastrointestinal tracts (GI), gills, muscles, and skin. All the studied fish and mussels (n = 33) had MPs. MP fibres, fragments and sheets were detected in every GI examined, however, fibres were the only type of MPs in skins, muscles and gills and were the most abundant MP. The MPs found in the fish and mussels were mainly made of nylon (35% of the total MPs), polypropylene-low density polyethylene (30%), and polycarbonate (25%). The average numbers of MPs found in every fish specimen, expressed per wet body mass, had a moderate negative correlation with the condition factor (K) (MP/g - K: Pearson correlation r = -0.413, p = 0.049), and there was no significant relation with the growth factor (b) (r = -0.376; p = 0.068). Importantly, Luciobarbus caspius (with trophic level 2.7-2.8) bioaccumulated MPs and presented a strong correlation between their MP contamination and age (r = 0.916 p < 0.05). Greater gill mass (or related factors) played an important role in the accumulation of MPs, and there was a strong correlation between these factors for Esox lucius and Cyprinus carpio (r = 0.876; r = 0.846; p < 0.05 respectively). The highest MP/g gills (1.91 ± 2.65) were in the filter feeder Anodonta cygnea inhabiting the benthic zone. Esox lucius (piscivorous, trophic level 4.1) was the most contaminated species overall (a total of 83 MPs in 8 individuals, with 0.92 MP/g fish), and their gills where MPs mainly accumulated. Cyprinus carpio was the most contaminated specimen (MPs in specimens), while the number of MPs per mass unit increased with the trophic level. Their feeding and ecological behavior in the aquatic habitat affected the level of accumulation. This work includes evidence of translocation of MPs within the aquatic organisms.
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  • 文章类型: Journal Article
    制备了包含金属骨架和聚脲弹性体互穿相的复合结构,实验研究了其对低速大质量碎片的抗侵彻性能。基于穿透阻力测量,比较了三种聚脲的保护能力。结果表明,由于其背面支撑效应和相变效应,背面的聚脲涂层提高了聚脲填充的球形孔多孔铝(SCPA)板的性能,伴随着大量的能量吸收。正面涂覆的聚脲层无法剪切,并且对互穿相复合板的抗穿透性具有非常有限的增强作用。SCPA中的填充聚脲增加了损伤面积,并形成了背面涂层的压缩锥,导致显著的应力扩散效应。互穿相复合材料的堵块效应和PU涂层的背面支撑效应协同提高了抗渗透性能。与SCPA相比,复合材料板的初始冲击破坏强度和平均阻力分别提高了120-200%和108-274%,分别。
    A composite structure containing a metallic skeleton and polyurea elastomer interpenetrating phase was fabricated, and its anti-penetration performance for low-velocity large mass fragments was experimentally studied. The protection capacity of three polyurea was compared based on the penetration resistance force measurement. Results show that the polyurea coating layer at the backside improves the performance of the polyurea-filled spherical cell porous aluminum (SCPA) plate due to its backside support effect and phase transition effect, which are accompanied by a large amount of energy absorption. The frontal-side-coated polyurea layer failed to shear and provided a very limited strengthening effect on the penetration resistance of the interpenetrating phase composite panel. The filling polyurea in SCPA increased the damage area and formed a compression cone for the backside coating layer, leading to a significant stress diffusion effect. The anti-penetration performance was synergistically improved by the plug block effect of the interpenetrating phase composite and the backside support effect of the PU coating layer. Compared with SCPA, the initial impact failure strength and the average resistance force of the composite plate were improved by 120-200% and 108-274%, respectively.
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  • 文章类型: Journal Article
    有效抑制剂的鉴定是药物开发中的重要起始步骤。不幸的是,许多问题,如蛋白质结合位点的表征,筛选库,用于化验的材料,等。,使药物筛选成为一个困难的命题。随着筛选文库规模的增加,更多的资源将被低效消耗。因此,需要新的策略来预处理筛选文库,并将其集中于靶向蛋白.在这里,我们报告了集成机器学习(ML)模型,以生成以CDK8为中心的筛查库.集成模型由针对CDK8抑制剂分类优化的六种不同算法组成。使用CDK8特异性片段文库以及含有CDK8活性的分子训练模型。优化的集成模型处理了含有160万个分子的商业文库。这导致了一个包含1,672个分子的CDK8集中的筛选文库,减少超过99.90%。然后对CDK8聚焦文库进行分子对接,选择25个候选化合物。酶分析证实了六种CDK8抑制剂,一种化合物的IC50值≤100nM。集成ML模型的分析揭示了CDK8片段库在训练期间的作用。分子的结构分析揭示了命中化合物是结构新颖的CDK8抑制剂。一起,结果突出显示了为特定蛋白质靶标策划聚焦文库的管道,例如CDK8。
    The identification of an effective inhibitor is an important starting step in drug development. Unfortunately, many issues such as the characterization of protein binding sites, the screening library, materials for assays, etc., make drug screening a difficult proposition. As the size of screening libraries increases, more resources will be inefficiently consumed. Thus, new strategies are needed to preprocess and focus a screening library towards a targeted protein. Herein, we report an ensemble machine learning (ML) model to generate a CDK8-focused screening library. The ensemble model consists of six different algorithms optimized for CDK8 inhibitor classification. The models were trained using a CDK8-specific fragment library along with molecules containing CDK8 activity. The optimized ensemble model processed a commercial library containing 1.6 million molecules. This resulted in a CDK8-focused screening library containing 1,672 molecules, a reduction of more than 99.90%. The CDK8-focused library was then subjected to molecular docking, and 25 candidate compounds were selected. Enzymatic assays confirmed six CDK8 inhibitors, with one compound producing an IC50 value of ≤100 nM. Analysis of the ensemble ML model reveals the role of the CDK8 fragment library during training. Structural analysis of molecules reveals the hit compounds to be structurally novel CDK8 inhibitors. Together, the results highlight a pipeline for curating a focused library for a specific protein target, such as CDK8.
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  • 文章类型: Journal Article
    牙外伤是临床实践中遇到的最普遍的问题之一。涉及前牙骨折的创伤性损伤是儿童和青少年中最常见的问题之一。由于外伤性牙齿损伤(TDI)对患者的生活质量有身体和社会影响。儿童和青少年经常出现冠骨折,需要立即干预。临床医生需要了解TDI的各种治疗方式,并且必须立即解决这些损伤。由于粘合剂技术的进步,当片段可用并且保存良好时,片段再连接是选择的治疗方法。本文的目的是涵盖用于重新附着断裂碎片的各种技术以及用于此目的的粘合剂系统的最新发展。
    Dental trauma is one of the most prevalent problems encountered in clinical practice. Traumatic injuries involving fractures of the anterior tooth are one of the most common problems among children and adolescents. There is a physical and social impact on patients\' quality of life due to traumatic dental injuries (TDIs). Children and adolescents frequently present with a crown fracture that necessitates immediate intervention. Clinicians need to be aware of various treatment modalities for TDIs and have to address these injuries immediately. Due to advances in adhesive technologies, fragment reattachment is the treatment of choice when the fragment is available and well stored. The purpose of this article is to cover various techniques for reattaching fractured fragments and the most current developments in adhesive systems for this purpose.
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  • 文章类型: Journal Article
    肝细胞癌(HCC)是癌症相关死亡的主要原因。FGFR4与HCC进展有关,使其成为有希望的治疗目标。我们介绍了一种通过向普通弹头单元顺序添加片段来鉴定新型FGFR4抑制剂的方法。这种策略导致发现了一种有效的抑制剂,4c,在FGFR家族成员中具有33nM的IC50和高选择性。尽管需要进一步优化,我们的方法证明了发现有效的FGFR4抑制剂用于HCC治疗的潜力,并提供了从小碎片中获得命中化合物的有用方法。
    Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. FGFR4 has been implicated in HCC progression, making it a promising therapeutic target. We introduce an approach for identifying novel FGFR4 inhibitors by sequentially adding fragments to a common warhead unit. This strategy resulted in the discovery of a potent inhibitor, 4c, with an IC50 of 33 nM and high selectivity among members of the FGFR family. Although further optimisation is required, our approach demonstrated the potential for discovering potent FGFR4 inhibitors for HCC treatment, and provides a useful method for obtaining hit compounds from small fragments.
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  • 文章类型: Journal Article
    识别和评估新的靶标对于对抗HIV/AIDS治疗中的耐药性至关重要。HIV衣壳(HIV-CA),蛋白质在病毒生命周期的早期和晚期都起着重要作用,已经成为一个重要的目标。我们已经应用了NMR片段筛选平台,并鉴定了在靠近C端结构域(CTD)界面的位点与HIV-CA的N端结构域(NTD)结合的分子。用X射线晶体学,我们已经能够获得晶体结构,以确定这些化合物的结合模式。这使得最初的进展迅速,弱结合,片段起始指向化合物37和38,其19F-pKi值分别为5.3和5.4。
    Identification and assessment of novel targets is essential to combat drug resistance in the treatment of HIV/AIDS. HIV Capsid (HIV-CA), the protein playing a major role in both the early and late stages of the viral life cycle, has emerged as an important target. We have applied an NMR fragment screening platform and identified molecules that bind to the N-terminal domain (NTD) of HIV-CA at a site close to the interface with the C-terminal domain (CTD). Using X-ray crystallography, we have been able to obtain crystal structures to identify the binding mode of these compounds. This allowed for rapid progression of the initial, weak binding, fragment starting points to compounds 37 and 38, which have 19F-pKi values of 5.3 and 5.4 respectively.
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