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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
    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
    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
    聚丙烯(PP),聚苯乙烯(PS),和聚乙烯(PE)塑料通常用于家用物品,例如电子外壳,食品包装,瓶子,袋子,玩具,和屋顶膜。在COVID-19大流行封锁限制期间,许多人在室内呆了很长时间,室内空气中可吸入微塑料的存在已经成为一个令人担忧的话题,然而,对呼吸系统的毒性作用没有得到正确理解。我们检查了PP的毒性,PS,C57BL/6小鼠肺系统中的PE微塑料碎片。14天,小鼠气管内滴注5mg/kgPP,PS,每天体育。巨噬细胞等炎症细胞的数量,中性粒细胞,PS滴注小鼠的支气管肺泡灌洗液(BALF)中的嗜酸性粒细胞显着高于载体对照(VC)。与VC相比,PS滴注小鼠的BALF中炎性细胞因子和趋化因子的水平增加。然而,PP和PE刺激小鼠的炎症反应与VC组无显著差异.我们观察到与VC相比,PP滴注小鼠肺组织中Toll样受体(TLR)2的蛋白水平升高,PS滴注小鼠肺组织中TLR4的蛋白水平升高,而TLR1、TLR5和TLR6蛋白水平保持不变。与VC相比,PS滴注小鼠的核因子κB(NF-κB)和IB-α的磷酸化显着增加。此外,核苷酸结合寡聚化结构域样受体家族pyrin结构域包含3(NLRP3)炎性体成分,包括NLRP3,凋亡相关斑点样蛋白,含有caspase募集结构域(ASC),与VC相比,PS滴注小鼠肺组织中的Caspase-1增加,但不是在PP和PE滴注的小鼠中。这些结果表明,PS微塑料片段刺激可通过TLR4途径引起NFB和NLRP3炎性体活化引起肺部炎症。
    在线版本包含补充材料,可在10.1007/s43188-023-00224-x获得。
    Polypropylene (PP), polystyrene (PS), and polyethylene (PE) plastics are commonly used in household items such as electronic housings, food packaging, bottles, bags, toys, and roofing membranes. The presence of inhalable microplastics in indoor air has become a topic of concern as many people spent extended periods of time indoors during the COVID-19 pandemic lockdown restrictions, however, the toxic effects on the respiratory system are not properly understood. We examined the toxicity of PP, PS, and PE microplastic fragments in the pulmonary system of C57BL/6 mice. For 14 days, mice were intratracheally instilled 5 mg/kg PP, PS, and PE daily. The number of inflammatory cells such as macrophages, neutrophils, and eosinophils in the bronchoalveolar lavage fluid (BALF) of PS-instilled mice was significantly higher than that in the vehicle control (VC). The levels of inflammatory cytokines and chemokines in BALF of PS-instilled mice increased compared to the VC. However, the inflammatory responses in PP- and PE-stimulated mice were not significantly different from those in the VC group. We observed elevated protein levels of toll-like receptor (TLR) 2 in the lung tissue of PP-instilled mice and TLR4 in the lung tissue of PS-instilled mice compared with those to the VC, while TLR1, TLR5, and TLR6 protein levels remained unchanged. Phosphorylation of nuclear factor kappa B (NF-κB) and IĸB-α increased significantly in PS-instilled mice compared with that in VC. Furthermore, Nucleotide‑binding oligomerization domain‑like receptor family pyrin domain‑containing 3 (NLRP3) inflammasome components including NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and Caspase-1 in the lung tissue of PS-instilled mice increased compared with that in the VC, but not in PP- and PE-instilled mice. These results suggest that PS microplastic fragment stimulation induces pulmonary inflammation due to NF-ĸB and NLRP3 inflammasome activation by the TLR4 pathway.
    UNASSIGNED: The online version contains supplementary material available at 10.1007/s43188-023-00224-x.
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  • 文章类型: Journal Article
    在药物化学中特别寻求蛋白质-片段复合物结构以合理设计前导分子。这些结构通常是使用X射线晶体学得出的,但故障率是不可忽视的。NMR是计算弱相互作用复合物的可能替代方法。然而,耗时的蛋白质信号分配步骤仍然是其常规应用的障碍。NMR分子置换(NMR2)是一种通用且快速的方法,可以阐明蛋白质-配体复合物的结构。它已成功应用于肽,类似药物的分子,最近还有碎片。由于碎片尺寸小,ca<300Da,解决蛋白质-片段复合物的结构尤其具有挑战性。这里,我们介绍了NMR2应用于蛋白质片段复合物时的预期性能。NMR2方法已与SERAPhic片段文库进行了基准测试,以确定蛋白质片段NMR结构计算中的技术挑战。提出了一种简单的策略来进一步提高方法的成功率。所提出的工作证实NMR2是X射线晶体学的替代方法,用于解决蛋白质片段复合物结构。
    Protein-fragment complex structures are particularly sought after in medicinal chemistry to rationally design lead molecules. These structures are usually derived using X-ray crystallography, but the failure rate is non-neglectable. NMR is a possible alternative for the calculation of weakly interacting complexes. Nevertheless, the time-consuming protein signal assignment step remains a barrier to its routine application. NMR Molecular Replacement (NMR2) is a versatile and rapid method that enables the elucidation of a protein-ligand complex structure. It has been successfully applied to peptides, drug-like molecules, and more recently to fragments. Due to the small size of the fragments, ca < 300 Da, solving the structures of the protein-fragment complexes is particularly challenging. Here, we present the expected performances of NMR2 when applied to protein-fragment complexes. The NMR2 approach has been benchmarked with the SERAPhic fragment library to identify the technical challenges in protein-fragment NMR structure calculation. A straightforward strategy is proposed to increase the method\'s success rate further. The presented work confirms that NMR2 is an alternative method to X-ray crystallography for solving protein-fragment complex structures.
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  • 文章类型: Journal Article
    组蛋白复合物的结构是表观遗传学的关键。线性组蛋白肽尾通常通过弱相互作用与阅读蛋白的浅袋结合,使他们的结构确定具有挑战性。在本研究中,一个新的协议,PegGrow,是介绍的。PepGrow使用对接的组蛋白片段作为种子,并在阅读器结合袋中生长出完整的肽尾,产生组蛋白-阅读器复合物的原子分辨率结构。PepGrow能够处理组蛋白肽的灵活性,并且证明它比连接预对接的肽片段更有效。新协议结合了流行程序包的优点,并允许快速生成解决方案结构。AutoDock,基于力场的程序,用于提供用作结构种子的对接肽片段,并采用了Modeller的构建算法作为肽生长引擎进行了测试。将PepGrow的性能与其他十种对接方法进行了比较,结论是,从种子中原位生长配体是以原子分辨率生产组蛋白肽复杂结构的可行策略。
    The structures of histone complexes are master keys to epigenetics. Linear histone peptide tails often bind to shallow pockets of reader proteins via weak interactions, rendering their structure determination challenging. In the present study, a new protocol, PepGrow, is introduced. PepGrow uses docked histone fragments as seeds and grows the full peptide tails in the reader-binding pocket, producing atomic-resolution structures of histone-reader complexes. PepGrow is able to handle the flexibility of histone peptides, and it is demonstrated to be more efficient than linking pre-docked peptide fragments. The new protocol combines the advantages of popular program packages and allows fast generation of solution structures. AutoDock, a force-field-based program, is used to supply the docked peptide fragments used as structural seeds, and the building algorithm of Modeller is adopted and tested as a peptide growing engine. The performance of PepGrow is compared to ten other docking methods, and it is concluded that in situ growing of a ligand from a seed is a viable strategy for the production of complex structures of histone peptides at atomic resolution.
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