心肌缺血再灌注（MI/R）损伤是与心肌梗死再灌注治疗相关的一种重要并发症。富含亮氨酸重复序列蛋白8A（LRRC8A）是一种参与细胞内稳态的容积调节性阴离子通道蛋白，已被证明与心血管事件的进展有关，但其在MI/R中的作用仍未得到研究。在此，我们旨在明确LRRC8A在MI/R损伤中的作用，并揭示其潜在机制。通过结扎左冠状动脉前降支45分钟，随后再灌注4小时，建立大鼠MI/R模型，以评估心肌中LRRC8A表达的变化。结果显示，MI/R损伤后大鼠心脏中LRRC8A表达上调。为了沉默LRRC8A的表达，我们在缺血手术前3天将编码LRRC8A shRNA的腺病毒注射到MI/R大鼠的心肌中。我们观察到，在MI/R后大鼠中沉默LRRC8A可减少心肌梗死面积，抑制心肌细胞凋亡并增强心脏功能。此外，将大鼠H9c2细胞进行氧糖剥夺/复氧（OGD/R）以模拟体内MI/R损伤，结果表明，沉默LRRC8A可减少OGD/R诱导的心肌细胞凋亡，而其上调则产生相反的效果，如Bcl-2表达、Tunel染色所示。机制上，LRRC8A可与含三联基序蛋白21（TRIM21）相互作用，随后抑制粘着斑激酶（FAK）/核因子κB（NF-κB）通路，从而促进心肌细胞凋亡。敲低TRIM21可消除LRRC8A的促凋亡作用，并降低LRRC8A对MI/R大鼠以及OGD/R处理的心肌细胞中FAK/NF-κB通路的抑制作用。
先前的研究表明，暴露于碲化镉量子点会降低ND7/23细胞活性，并以时间依赖性方式诱导细胞凋亡。线粒体途径参与了碲化镉量子点诱导的ND7/23细胞凋亡。碲化镉量子点暴露后ND7/23细胞亚细胞水平的毒性作用仍不清楚。内质网应激和钙离子失衡这两种经典机制是否参与了碲化镉量子点诱导的ND7/23细胞亚细胞结构和功能障碍，以及Ca -钙蛋白酶2途径在碲化镉量子点诱导的ND7/23细胞凋亡中是否起重要作用仍有待验证。因此，本研究聚焦于碲化镉量子点暴露诱导的ND7/23细胞内质网应激、细胞器损伤和钙稳态失衡的研究。还研究了钙蛋白酶2和内质网应激介导的凋亡信号通路。结果表明，暴露于10μM碲化镉量子点0-24小时会导致细胞内和线粒体钙浓度增加，同时伴有内质网和线粒体肿胀以及线粒体嵴丢失。碲化镉量子点暴露还导致内质网应激相关Bip蛋白表达增加。碲化镉量子点暴露还引发了ND7/23细胞中钙蛋白酶2和裂解的半胱天冬酶7蛋白表达上调，以及半胱天冬酶12和PARP蛋白的裂解。添加钙螯合剂BAPTA-AM和钙蛋白酶2抑制剂钙肽素可显著抑制碲化镉量子点诱导的凋亡，并逆转这些蛋白的表达。本研究证实，暴露于碲化镉量子点会引发ND7/23细胞内质网应激，同时激活钙蛋白酶2-半胱天冬酶12信号通路，导致非线粒体依赖性凋亡。
本研究旨在评估瘤胃保护性甜菜碱（RPB）和瘤胃保护性胆碱（RPC）对敖湖羊胴体性状、氨基酸组成和脂肪酸组成的影响。总共96只绵羊被随机分为四组。试验持续105天，包括15天的适应期，随后是90天的试验期。试验日粮包括2.5克/天的RPB、0.25%/千克的RPC，以及2.5克/天的RPB与0.25%/千克的RPC的组合。与对照组（饲喂不添加RPB和RPC的基础日粮的绵羊）相比，所有试验组的胸最长肌（LT）中粗脂肪（CF）和总氨基酸（TAA）均显著增加。值得注意的是，RPB×RPC组在屠宰率（DP）和粗蛋白含量（CP）方面表现出显著的交互作用（P<0.05）。此外，所有处理组的LT肌肉中饱和脂肪酸（SFA）显著降低，而单不饱和脂肪酸（MUFA）和多不饱和脂肪酸（PUFA）增加（P<0.05）。RPB和RPC的组合对LT肌肉中的总氨基酸、SFA、PUFA和MUFA也有显著的交互作用。因此，补充RPB或RPC均可改善胴体性状，降低剪切力，提高鲜味氨基酸、必需氨基酸和总氨基酸的含量，并降低不饱和脂肪酸的比例。结果，肉的嫩度和营养价值均得到提高，从而使肉质总体得到改善。RPB和RPC联合补充的效果最为显著。
早期非小细胞肺癌（NSCLC）来源的外泌体中微小RNA-21（miRNA-21）表达升高对早期诊断具有重要意义。然而，由于外泌体miRNA-21丰度低，检测仍具有挑战性。在此，我们开发了一种集成3D DNA步行器和滚环扩增（RCA）的电化学发光（ECL）生物传感器，用于超灵敏检测miRNA-21。金银纳米簇（AuAgNCs，Au:Ag = 4:1）作为ECL发光体，而二茂铁修饰的DNA（Fc-DNA）淬灭信号（“信号关闭”）。靶标miRNA-21激活3D DNA步行器，产生用于RCA的引物。RCA产物取代Fc-DNA，恢复ECL（“信号开启”）。该生物传感器实现了1 fM-1 nM的宽线性范围，检测限为0.14 fM。至关重要的是，它在临床血清样本中能够将NSCLC患者（n = 10）与健康对照（n = 10）和慢性阻塞性肺疾病（COPD）患者（n = 10）区分开来，具有统计学意义（P < 0.001）。出色的稳定性（25天后信号保留84%）和重现性（RSD = 3.95%）进一步支持了其在早期肺癌筛查中的实用性。
这篇综述文章深入探讨了源自生物质的氮掺杂多孔碳（NPC）的合成及其多种应用。特别关注的是通过添加三聚氰胺作为氮源合成的那些NPC。由于需要用于从能量存储到环境修复等各种应用的环境可接受且可持续的材料，近年来对源自生物质的碳材料的研究加速了。一种改变最终产物结构和化学特性的新方法是使用三聚氰胺作为氮富集前体，从生物质中合成NPC。本综述涵盖了关于合成技术的详细报告。特别强调了三聚氰胺在获得高比表面积、优异导电性和所需氮掺杂方面所起的关键作用，所有这些都提高了碳材料的电化学和吸附能力。这些NPC在能量存储领域有广泛应用，即电池和超级电容器，其特殊的组成和结构可提高性能。此外，还研究了它们在环境修复方面的适用性，包括污染物吸附和染料降解。这篇综述的目的是通过全面研究这些材料的合成过程和不同应用，指导未来的研究计划、创新以及具有广泛功能的先进材料的可持续发展。
醛类因其气味和潜在致癌性而受到越来越多的关注。由于醛类在氧化过程（如臭氧化和氯化）中形成，且容易穿透反渗透（RO）膜，它们是用于饮用水回用的RO渗透液中的主要有机物质。在本研究中，过二硫酸盐（PDS）与VUV/UV（185/254 nm）辐照（VUV/UV/PDS）相结合，以产生多种活性物种，包括·OH和SO，用于消除乙醛（CH₃CHO）和有机物矿化。在0.05和0.5 mmol/L PDS的VUV/UV/PDS条件下，分别在6分钟和1.5分钟内消除了99%的CH₃CHO，这比单独的VUV/UV效率分别提高了约2倍和7倍。此外，在0.05和0.5 mmol/L PDS的VUV/UV/PDS条件下，总有机碳矿化的比例分别为90.7%和93.7%。与VUV/UV相比，VUV/UV/PDS能快速矿化CH₃CHO，且没有明显的乙酸盐或草酸盐积累。计算毒性评估表明，VUV/UV/PDS过程中产生的有机物质对各种生物的潜在风险低于VUV/UV过程中产生的有机物质。此外，VUV/UV/PDS的能量效率高于VUV/UV。本研究表明，VUV/UV/PDS是一种有前景的替代处理方法，用于消除用于饮用水回用的RO渗透液中的醛类。
全球塑料危机需要创新的解决方案来回收聚对苯二甲酸乙二酯（PET），这种化学性质稳定的聚合物占每年塑料垃圾的23%。本研究展示了利用工程化嗜盐单胞菌Y3在PET升级循环利用方面取得的重大进展，该嗜盐细菌特别适合工业生物处理。我们通过系统的代谢工程解决了PET增值过程中的关键挑战，即其解聚单体对苯二甲酸（TPA）和乙二醇（EG）的同化效率低下问题。首先，通过整合异源tph操纵子和转运蛋白实现了TPA分解代谢，TPA降解率达到1.39 mmol/L·h，比食酸丛毛单胞菌E6的0.95 mmol/L·h高出46%。同时，通过过表达glcDEFG和优化乙醛酸途径，EG利用率比野生型嗜盐单胞菌Y3（1.32 mmol/L·h）提高了6.3倍（8.34 mmol/L·h）。为了克服单菌株系统中的代谢干扰，我们开创了一种合成微生物群落（PET_co），它由两种特殊的嗜盐单胞菌菌株组成：一种代谢EG，另一种代谢TPA。该群落能够在36小时内完全共同利用混合的PET水解产物，产生7.99 g/L的聚羟基脂肪酸酯（PHA），比单培养对照（PET03、PET07、PET09）高出2.4倍，且无需补充碳源。值得注意的是，该菌株的耐盐性和嗜碱性使其能够直接与碱性PET解聚过程整合，绕过了成本高昂的灭菌步骤。通过将化学和生物过程协同作用，这项工作将嗜盐单胞菌Y3确立为工业规模塑料升级循环利用的强大平台，推动了循环经济战略以减轻塑料污染。
解读公羊或母羊的繁殖潜力对于确保高繁殖性能和最大化生产成果至关重要。本研究验证了一个绵羊生育力模型的准确性，该模型用于预测腹腔镜人工授精（AI）后怀孕的可能性，并提出了体外精液标准以改善怀孕结果。在3个繁殖季节（2021 - 2023年），将美利奴种公羊（N = 26）的精液授精到同步发情的美利奴母羊（N = 1269）体内。在人工授精时对母羊的子宫张力和腹内脂肪进行评分，同时在解冻后（6小时；37°C）评估所授精液的冷冻浓度、异常精子、顶体活力（6小时）以及计算机辅助精子分析（CASA）运动性和速度特征（0小时）。使用判别和校准测试将怀孕预测结果与人工授精后约55天经超声确认的怀孕情况进行比较，以正确评估其区分怀孕和未怀孕母羊的能力。该模型显示出较高的准确率（77%）、精确率（96%）和召回率（76%），但特异性较低（33%）。其F1分数为0.85，曲线下面积（AUC）为0.62。尽管误差值为26%，但预测和实际怀孕结果之间无统计学差异（P = 0.184）。一个切点将每个体外精液预测指标的数据进行划分，并计算该点上下的平均怀孕率。选择怀孕率差异最大的切点作为精液阈值。将这些阈值输入模型后，得到的累积怀孕概率为64.3%。这些标准可用于在人工授精前筛选精液，减少该行业腹腔镜人工授精程序的变异性。
用天然动物肠衣或人造胶原蛋白肠衣包装的散装香肠极易受到微生物污染。在本研究中，监测了用动物肠衣包装的香肠的质量变化，并通过结合传统细菌培养方法和16S rDNA测序，分析了在4℃下储存30天期间肠衣表面的细菌群落动态。在评估已鉴定的优势细菌群落的腐败能力后，确定了三种特定腐败菌（SSO）：热杀索丝菌、伦德假单胞菌和绿色魏斯氏菌。对于这三种SSO，单独或组合选择了三种天然抗菌剂：乳酸链球菌素、苯乳酸（PLA）和曲酸（KA），以提高香肠的储存稳定性。原位实验表明，乳酸链球菌素（15mg/mL）和PLA（2mg/mL）的组合最有效地抑制了香肠上的细菌生长。这些结果有望为延长散装香肠的保质期提供理论参考。
引言：我们旨在研究妇科肿瘤病例术前营养状况与术后白细胞介素-10（IL-10）和新蝶呤之间的关系。 材料与方法：这项前瞻性研究纳入了在我们诊所住院的病例。术前病例根据营养风险评分（NSR-2002）分为低风险和高风险两组。记录人口统计学和临床特征以及包括NSR-2002表格在内的问卷。术后1周分析IL-10和新蝶呤水平。 结果：评估了45例低风险病例和43例高风险病例。病例的平均年龄分别为56.7±7.8岁和57.2±14.3岁，两者之间无显著差异（P = 0.854）。两组在上臂围（P = 0.043）、肱三头肌皮褶厚度（P = 0.010）、伤口愈合时间较短（P = 0.009）、新蝶呤（P = 0.037）、IL-10（P = 0.043）、术前铁蛋白（P = 0.001）、血红蛋白（P = 0.026）、白蛋白（P = 0.047）、术后铁蛋白（P = 0.015）、血红蛋白（P = 0.044）和白蛋白（P = 0.042）水平方面存在统计学显著差异，低风险组更具优势。在这些显著因素中，只有伤口愈合时间呈正相关（P = 0.006，r = +0.290）。 结论：营养状况与术后病例恢复密切相关。营养指数低的病例术后白细胞介素-10和新蝶呤水平升高表明营养在术后阶段的重要性。
许多病理状况统称为淀粉样变性，与在应激的物理化学条件下错误折叠蛋白的聚集有关。能够调节蛋白聚集或拆解预先形成的纤维的天然化合物有望成为治疗聚集相关疾病的潜在候选药物。在本研究中，我们旨在使用各种光谱学、化学信息学和成像技术，研究哌啶生物碱洛贝林（Lobeline，Lob）在预防酸变性溶菌酶（Lysozyme，Lyz）淀粉样蛋白形成中的结合相互作用和有效性。稳态和时间分辨荧光测量证实Lyz和Lob之间存在直接相互作用，结合常数约为10 M，结合化学计量比为1:1。已发现该结合是自发的，由涉及非静电相互作用的熵驱动。分子对接显示Lob通过疏水和亲水相互作用稳定Lyz。通过一系列体外技术评估Lob在Lyz淀粉样纤维中的抗淀粉样特性，包括浊度测量、动态光散射（DLS）、硫黄素T（ThT）荧光、圆二色性研究和场发射扫描电子显微镜（FESEM）成像。这些研究表明，Lob通过为氢键形成以及与形成寡聚体和纤维所需的关键氨基酸残基的其他弱相互作用提供替代途径，在成核阶段阻止酸处理的Lyz的纤维化。
Thyroid hormones (THs) are essential for fish development, metabolism, and reproduction. Disruptions in TH balance caused by exposure to TH-disrupting chemicals (THDCs) can lead to serious physiological problems. While adverse outcome pathways (AOPs) for THDCs have been described in zebrafish and fathead minnows, similar pathways in Japanese medaka (Oryzias latipes) are still not well understood. In this study, we explored how methimazole (MMI), a thyroid peroxidase (TPO) inhibitor, affects the development of Japanese medaka, focusing on growth, swim bladder inflation, thyroid hormone (T4 and T3) levels, and gene expression patterns in this species. The results obtained indicated that MMI exposure suppressed T4 levels in a dose-dependent manner, but did not show any dose-dependent effects on the thyroid hormone-related genes expression levels or growth and the growth-related genes expression. Although the incidence of swim bladder inflation failure showed statistically significant differences, it was not dose-dependent; the inflation rate remained approximately 90 % across all exposure concentrations, suggesting no biologically meaningful effect. This observed disruption of T4 levels aligned with key events in established AOPs for THDCs. Furthermore, our findings provide valuable insights into the taxonomic domain of applicability for these AOPs.
In the present study the shielding efficiencies of gamma and neutron radiations for fabricated composites using high-density polyethylene (HDPE) via the sol-gel method were investigated. These lightweight, low-cost, and ductile materials incorporate xBiO nanoparticles (x = 4.0 %, 12.0 %, 20.0 %, 30.0 %, and 40 %) as a non-toxic nanofiller. The study employed X-ray diffraction (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDX) to characterize the BiO/HDPE nanocomposites. The effectiveness of these composites in attenuating gamma-ray was assessed by using an HPGe detector. Measurements were conducted across various gamma-ray energies (121, 244, 334, 444, 778, 963, 1112, and 1408 keV) emitted by a standard Eu-152 point source. The relationship between mass attenuation coefficients (μ) and the BiO loading was investigated at each energy level experimentally and theoretically. Using other shielding parameters, such as half-value layer (HVL) and mean free path (MFP), were also calculated. Total macroscopic neutron cross-section (ΣT) of the composites was also determined using an Am241-Be (α, n) neutron source. It was observed that gamma and neutron shielding properties were improved due to increasing amount of BiO nanoparticles in the composite.
Pest infestations have been posing a serious and persistent threat to agricultural production. Traditional insecticides are currently confronted with a multitude of problems. The discovery of novel insecticide targets and the screening of active molecules can offer an entirely new direction for surmounting the limitations of traditional insecticides and lay a solid foundation for the development of highly effective insecticides with distinctive mechanisms of action. In this study, the Na,K-ATPase of Drosophila melanogaster has been selected as the target. Its three-dimensional structure has been constructed via homology modeling, and the evaluation has indicated that its quality is reliable. Subsequently, techniques including virtual screening, molecular docking, and molecular dynamics simulation have been employed to screen compounds and investigate their mechanisms of action. The analysis of binding modes has demonstrated that hydrogen bonding and hydrophobic interactions have played a crucial role in the binding of ligands. Molecular dynamics simulations and calculations of binding free energies have shown that Compound 1 and Compound 2 have exhibited similar or even stronger affinities in comparison to known inhibitors. Residue decomposition free energy reveals the types of key amino acid residues involved in the interaction between these compounds and NKA. Preliminary bioactivity assays have verified the bioactivities of these compounds. Ouabain, Compound 1, Compound 2, and Compound 4 have shown significant delayed toxic effects, with Compound 4 having a more pronounced delayed effect. Our study has provided certain valuable ideas and insights for the development of new insecticide molecules targeting the Na,K-ATPase of Drosophila melanogaster.
MYB transcription factors (TFs) play a critical role in plant immunity; however, their involvement in chaperone-mediated defense mechanisms remains unclear. Here, we demonstrated that MYB48 negatively regulates rice blast resistance by directly activating the heat shock protein gene HSP71.1. CRISPR/Cas9-generated MYB48 knockout lines exhibited enhanced resistance, with reduced lesion numbers and sizes, while overexpression lines displayed increased susceptibility. Nuclear-localized MYB48 directly binds to the HSP71.1 promoter to activate its transcription. Furthermore, knockout of HSP71.1 enhanced blast resistance. Notably, MYB48 knockout did not compromise agronomic traits, highlighting its potential for breeding applications. This study uncovers a novel MYB48-HSP71.1 regulatory module, linking MYB TFs to chaperone-mediated immunity, and provides dual targets for engineering blast-resistant rice.
The ABA receptor PYL/RCAR plays a crucial role in initiating ABA sensing and signal transduction, which is essential for plant stress resistance. However, the role of OsPYL2 in rice drought and blast tolerance remains largely unexplored. In this study, we investigated the function of OsPYL2 in drought and rice blast. Overexpression of OsPYL2 resulted in stronger drought tolerance by increasing photosynthetic pigment content, water-holding capacity in rice leaves, while significantly decreasing MDA content. Additionally, overexpression of OsPYL2 could also increase the resistance to rice blast by promoting the accumulation of HO. In contrast, loss of OsPYL2 function resulted in the opposite effects. And, PYL2 also regulates hormone content by affecting the expression of ABA and JA signaling pathway genes in response to stress environment. Results of yeast two-hybrid assay, bimolecular fluorescence complementation and firefly luciferase complementation revealed that OsPYL2 could interact with PP2C proteins, VQ24 protein and JAZ proteins. These results illustrated that OsPYL2 can integrate dual stress tolerance responses by synergistically regulating ABA and JA signaling pathways. This study provides valuable insights underlying drought and blast tolerance in rice.
BACKGROUND: The prevalence of comorbid psychopathological disorders and associated problems is high among patients with substance use disorder (SUD). The Symptom Checklist 90-R (SCL-90-R) is one of the most widely used self-report instruments to assess psychopathology. This study examined the psychometric properties of the SCL-90-R and its short-form versions for patients with SUD. METHOD: The values of the short versions were calculated a posteriori based on the SCL-90-R scores. Confirmatory factor analysis (CFA) was conducted using the diagonally weighted least squares estimator to assess construct validity. Reliability was assessed via the ordinal alpha coefficient, McDonald's omega coefficient and intraclass correlation coefficient (ICC). RESULTS: The SCL-90-R showed acceptable model fit (χ/df = 1.916, CFI = 0.940, TLI = 0.938, RMSEA = 0.035). Among the short versions, the BSI-53, SA-45, SCL-27, HSCL-25, and BSI-18 demonstrated good to excellent fit. The depression scale showed the highest reliability across the versions. Pearson correlations and ICCs revealed strong associations between the SCL-90-R and its short forms, although the agreement declined with shorter versions. Despite the excellent fit of the SCL-6, it had lower reliability. CONCLUSION: These results provide evidence of the psychometric robustness of short versions of the SCL-90-R and support their use to assess comorbid psychopathology in people with SUD.
Waste biomass is an ideal material for electrode modification of low-cost and high-performance microbial fuel cell (MFC). MFC is mainly committed to effectively improve the power generation performance and degradation performance through anode modification. In this study, a biomass-derived N-rich 3D macroporous MFC anode (PPy-DSC/CF) with high conductivity, superhydrophilicity, and biocompatibility was successfully prepared by in-situ polymerization of pyrrole on the surface of carbonized durian shell (DS) using carbon mats as the substrate material. PPy successfully increased the pyrrole-N content of the DSC, and the more graphitized structure could improve the conductivity of the biochar. High electrical conductivity of biochar catalyzes the RhB degradation by electron transfer. Meanwhile, the rich macroporous structure of 3D PPy-DSC/CF electrode material is crucial for the attachment, growth, biofilm formation and electron transfer of electroactive bacteria. It achieved the highest power density output of 5184 mW/m and 91.26 % COD removal efficiency. The RhB degradation efficiency reached 96.36 %. This study provides a new strategy for biomass-derived porous carbon electrodes for energy utilization and MFC electrochemical systems to achieve environmental sustainability.
许多食草昆虫以不均衡的食物为食，并依靠细菌内共生体来满足其所有营养需求。豌豆蚜（Acyrthosiphon pisum）就是这样，它是一种植物害虫，仅靠其唯一的营养来源——植物韧皮部汁液，无法维持其显著的生长和繁殖能力，而是依靠与细胞内细菌蚜虫内共生菌（Buchnera aphidicola）维持了数百万年的共生关系来进行氨基酸和维生素的生物合成。利用原始实验数据和代谢重建，我们构建了蚜虫内共生菌的定量基因组规模代谢模型，并利用它来量化该细菌与其宿主之间的氨基酸交换。我们发现了能够重新连接代谢途径的代谢物，这些代谢物影响着自私行为（以生长为重点）和互利行为（氨基酸合成）之间的平衡。在蚜虫内共生菌合成的产物中，苯丙氨酸、酪氨酸和亮氨酸是主要的物质汇，消耗了超过60%的输入葡萄糖和丝氨酸。最后，我们将预测的细菌氨基酸供应与豌豆蚜的需求进行了比较。我们发现，豌豆蚜可能会根据其代谢需求有效地调节其共生体种群密度，但胚胎在数量上无法自我维持，胚胎期细菌的供应比需求短缺50%。总体而言，我们的研究突出了一些候选化合物和代谢途径，可作为破坏这种共生关系或预测其对环境或营养扰动恢复力的靶点。
黄褐斑是一种难治性色素沉着障碍，需要非侵入性工具进行准确的病理评估。本研究比较了双光子显微镜（TPM）和反射式共聚焦显微镜（RCM）对黄褐斑病理的体内特征分析。在这项横断面研究中，对130例黄褐斑患者的TPM和RCM特征及成像清晰度进行了评估。对TPM定量的表皮黑色素、黑色素指数（MI）和个体分型角（ITA）进行了Spearman相关性分析。还比较了疾病活动期和稳定期的特征。TPM和RCM在检测表皮黑色素增加（κ = 0.651）、真皮-表皮交界处（DEJ）的活化黑素细胞（κ = 0.711）和平坦的 rete 嵴（κ = 0.691）方面显示出高度一致性（所有p < 0.001）。TPM在可视化细胞内黑色素分布、DEJ下方的悬垂黑素细胞和日光性弹力纤维变性方面表现出色，而RCM能更好地识别DEJ处的活化黑素细胞。TPM定量的表皮黑色素含量与MI呈正相关，与ITA呈负相关。RCM检测到的真皮炎症细胞在活动期黄褐斑中比稳定期更普遍。总之，TPM和RCM协同捕捉黄褐斑的关键特征，TPM通过表皮黑色素定量评估疾病严重程度，而RCM通过检测炎症细胞反映疾病活动。这为临床医生提供了用于精准管理的定制成像工具。
甲状腺内胸腺癌（ITTC）是一种罕见的甲状腺恶性肿瘤，类似于胸腺上皮相关肿瘤。在此，我们报告一例经细针穿刺细胞学检查（FNA）确诊的ITTC病例。一名55岁男性患者出现颈部肿块，且肿块逐渐增大。颈部超声检查发现一个不规则肿块，大小为3.7×2.5×2.1cm。进行了FNA检查。细胞学检查结果显示肿瘤细胞丰富，肿瘤细胞呈胰岛样簇状排列，并伴有淋巴细胞。肿瘤细胞的核质比高。细胞核呈圆形至卵圆形或梭形。梭形肿瘤细胞呈规则的流线状排列，类似于鳞状细胞癌。免疫细胞化学检查显示，肿瘤细胞CD5和c-KIT呈阳性。对切除的甲状腺标本进行病理检查，发现上皮样细胞和梭形细胞融合成巢状，整个肿瘤有明显的淋巴细胞和浆细胞浸润。免疫组织化学检查显示，肿瘤细胞细胞角蛋白、CD5、c-KIT和p63呈阳性，甲状腺转录因子-1（TTF-1）和甲状腺球蛋白呈阴性。因此，该肿瘤被诊断为ITTC。尽管ITTC罕见，但在鉴别诊断甲状腺下极出现的、表现为大的紧密胰岛样簇状且有大量淋巴细胞以及具有类似鳞状细胞癌特征的肿块时，应考虑到该病。
钓放式钓鱼（C&R）是一种保护策略，该策略假定被放生的鱼类能够存活并对种群数量有所贡献。然而，钓放应激，尤其是在产卵期间，可能会影响处于繁殖期的雌鱼及其后代，比如母代对子代的投资变化。在此，我们研究了母代应激对湖鳟（Salvelinus namaycush，一种被大量钓放的鱼类）及其后代的影响。将雌鱼钓获、采集血液样本，然后一部分雌鱼被放置48小时（袋装组），或者放置48小时且每隔12小时进行空气暴露以模拟反复的钓放事件（气曝+袋装组）。第三组鱼（对照组）仅在捕获后不做放置并立即采样（对照组）。袋装处理组的雌鱼在48小时后再次采集血液样本以确定应激指标（皮质醇、葡萄糖和乳酸）。处理后，对鱼实施安乐死并收集鱼卵，受精后孵化69天（DPF）。对鱼卵和幼体进行定时分析，检测皮质醇、大分子物质含量（糖原、蛋白质、水分和脂质）以及形态指标（湿重、干重和体长）。袋装处理组中母代皮质醇水平升高，表明应激反应出现偏差。同样，在这些处理组中，鱼卵皮质醇在3 DPF和12 DPF时升高，幼体皮质醇在69 DPF时升高。虽然各处理组之间大分子物质含量变化有限，但气曝+袋装处理组的鱼卵和幼体质量增加，且在69 DPF时幼体体长更长。这些发现表明母代应激会影响湖鳟后代的应激轴和形态发育。然而，幼体应激反应和生长变化对湖鳟种群的长期影响仍不明确，这是未来发展可持续休闲渔业工作的一个关键领域。
纳米气泡（NBs）是液体中直径小于1微米的气泡，在纳米尺度上形成球形气液界面；同时，其制备技术和检测方法已得到广泛研究。值得注意的是，纳米气泡具有超高的比表面积、独特的电荷分布以及增强的传质和传热特性，使其与界面处的物质具有高度的相互作用。这些独特的界面相互作用使其在环境、农业食品和医学领域具有巨大的应用潜力。深入了解这些界面机制对于有效指导和优化其实际应用至关重要。因此，本综述重点关注纳米气泡的气液界面特性，如卓越的稳定性和出色的气体传输效率。此外，还探讨了它们与周围物质的相互作用，重点阐述了纳米气泡诱导聚集和自组装、调节传热和传质、引发化学反应以及造成机械损伤的机制。此外，本综述还汇总了纳米气泡在可持续食品加工和人类健康方面的潜在应用，包括优化食品加工效率、降低能源消耗和污染、提高产品感官和营养品质以及增强人体消化吸收能力。建议未来的研究阐明它们与复杂食品系统中各种成分的相互作用机制，并进一步完善安全问题和工艺优化。这些努力将有利于人类发展的长期可持续性。
背景：对于数字病理学在细胞学中的应用，诸如局部精度和数据量等挑战依然存在。本验证研究的目的是比较在液基宫颈细胞学（LBC）中使用Z-stack扫描（z-WSI）的数字玻片与传统玻璃玻片之间的诊断准确性、筛查时间、注释数量以及观察者间和观察者内的一致性。 方法：我们收集了91份LBC样本，非典型鳞状细胞意义不明确（NILM）、低度鳞状上皮内病变（LSIL）、高度鳞状上皮内病变（HSIL）和鳞状细胞癌（SCC）病例数量相等。四名细胞技术人员分别使用玻璃玻片和z-WSI评估病例。他们在两种不同的模式下对病例进行分类：（1）“筛查-2-分类”：NILM（正常）与其他病变（非典型鳞状细胞不除外高级别鳞状上皮内病变及以上）；（2）“形态学-3-分类”：NILM与LSIL（轻度发育异常）与非典型鳞状细胞不除外高级别鳞状上皮内病变及更高级别（中度发育异常至鳞状细胞癌），以反映病变严重程度和治疗意义。 结果：对于“筛查-2-分类”，玻璃玻片的观察者间一致性为0.685，z-WSI为0.637，观察者内一致性范围为82.4%至95.6%。对于“形态学-3-分类”，玻璃玻片的观察者间一致性为0.700，z-WSI为0.598，表明z-WSI的一致性降低。“筛查-2-分类”的准确率玻璃玻片为91.2%，z-WSI为87.1%；“形态学-3-分类”的准确率分别为86.5%和81.0%，无显著差异。在两种模式下，细胞技术人员倾向于在真阳性病例中应用更多注释，而在假阴性病例中应用较少。所有细胞技术人员使用z-WSI的筛查时间平均长2 - 5分钟。 结论：z-WSI与玻璃玻片并不完全等同，但它有潜力用作细胞学筛查工具。专门为WSI设计的培训有望提高诊断准确性并改善工作流程效率。
汗腺圆柱瘤是一种罕见的良性附属器肿瘤，具有汗腺腺瘤和圆柱瘤的特征，最常见于头皮和面部。它们被认为起源于退化的附属器原始组织的多能细胞。细针穿刺细胞学检查以及细胞块检查可为诊断提供线索。最终诊断依靠组织病理学，其显示同一肿瘤中既有圆柱瘤又有汗腺腺瘤的特征。多发性汗腺圆柱瘤可与布鲁克-施皮格勒综合征相关，也有恶变的报道。我们报告一例50岁男性手臂的汗腺圆柱瘤病例，并描述其临床、细胞学、细胞块及组织病理学特征。
通过超声支气管镜引导下细针穿刺抽吸术（FNA）或粗针活检常用于评估可疑肺结节。在这些标本中常见肺泡巨噬细胞。当遇到含有大量肺泡巨噬细胞聚集的细胞丰富标本时，尤其是当它们表现出上皮样形态、空泡状细胞质和明显的细胞学异型性，包括显著的核大小不均和胞质内包涵体时，在快速现场评估（ROSE）过程中它们可能会被错误地解释为“病变细胞”，从而过早终止超声支气管镜检查程序。重要的是要记住，上皮样肺泡巨噬细胞可能会模仿肺神经内分泌肿瘤（NET）、肺腺癌，甚至转移过程。细胞质色素沉着和免疫组织化学分析对于防止恶性肿瘤的误诊非常有用。
背景：新冠疫情扰乱了全球医疗系统，包括非紧急护理的推迟以及资源向新冠患者的重新分配。本研究旨在评估荷兰首次新冠封锁对新药镇痛处方开具的影响。 方法：本研究分析了来自1890家荷兰药店的配药数据，覆盖约96%的人口（546万患者）。比较了2019年和2020年上半年首次开具的处方镇痛药（解剖学治疗学化学分类系统第二级N02类，如阿片类、酰苯胺类）数量。首次使用者定义为前一年未使用过该药物的患者。数据按年龄组（儿童、青少年、成年人、老年人）、性别和时间段分层：第1 - 11周（2020年封锁前）、第12 - 19周（封锁期）和第20 - 26周（封锁后）。 结果：2020年首次配药的镇痛药总数（367,094）显著低于2019年（388,973，p = 0.021），在封锁期间出现显著下降（p = 0.003）。在封锁期间，青少年和成年人中首次配药的镇痛药数量显著下降（p < 0.001），尤其是女性。相比之下，儿童和老年人中未发现显著变化。两年间封锁前和封锁后时期首次配药的镇痛药数量相当。 结论：封锁期间医疗保健的延迟与首次配药的镇痛药数量减少有关，尤其是在青少年和成年人中。这可能表明在此期间疼痛未得到治疗或对非处方替代药物的依赖增加。 意义声明：这项荷兰全国性研究表明，在新冠疫情首次封锁期间，首次配药的镇痛药数量显著下降，尤其是在青少年和成年人中。这可能表明由于医疗保健延迟导致疼痛未得到治疗，或在此期间对非处方替代药物的依赖增加。
肾脏是陆生脊椎动物主要的渗透压调节器官，依靠保水来维持生存。在除哺乳动物以外的脊椎动物中，只有鸟类能够浓缩尿液，以此适应陆地环境。集合管上皮细胞的水流入由水通道蛋白2（AQP2）以及沿皮质和髓质集合管表达的一种对精氨酸血管加压素（AVT）敏感的水通道控制。本研究旨在检查两种鸟类肾脏的解剖学、组织学、组织化学和超微结构变化：海鸟绿头鸭（Anas platyrhynchos）和陆禽家鸡（Gallus gallus domesticus）。此外，利用系统发育关系将这两个物种的AQP2基因组序列与哺乳动物脊椎动物的序列进行比较。在组织学上，所研究的两个物种的肾脏结构没有差异。在绿头鸭中，肾小叶相对地分为细长的髓质（30%）和皮质（70%），并且有更丰富的皮质型爬行动物肾单位。然而，家鸡的肾小叶皮质区域（85%）比髓质区域（15%）更大，并且有更多的哺乳动物肾单位。近端曲管的刷状缘和肾单位衬里细胞的基底膜对PAS染色呈阳性，但对AB染色呈阴性，而集合管和远端曲管的管腔表面对AB染色呈阳性。与绿头鸭相比，家鸡的肾小球和近端曲管更易与溴酚蓝染色发生反应。透射电镜显示，绿头鸭近端、远端和集合肾小管以及集合管的衬里细胞含有活跃且肥大的线粒体，因此绿头鸭的肾脏比家鸡的更活跃。多序列比对和系统发育树分析表明，AQP2的预期基因组序列在鸟类物种中相对保守。总之，对肾单位的研究已经确定了鸟类物种间的相似性和种内差异。
尽管双侧睾丸不对称对雄性生育能力具有潜在重要意义，但脊椎动物中这一现象仍未得到充分了解。波动不对称性（FA）作为随机发育变异的指标，是表型变异的一个关键但常被忽视的方面。虽然FA通常在形态特征中进行检测，但由于方法上的限制，此前尚未对功能性睾丸特征进行测量。我们使用计算机辅助精子分析（CASA），分析了来自野生种群的生殖成熟雄性林姬鼠（Clethrionomys glareolus，n = 61）附睾精子活力（曲线速度，VCL）和精子浓度（SEC）中的FA。同时对“软”（睾丸和肾脏质量）和“硬”（下颌尺寸）形态特征进行平行测量以作比较。CASA显示出可靠的可重复性（VCL：0.89；SEC：0.73），能够准确量化FA，并确认不存在方向不对称或反不对称。功能特征表现出非常高的FA值：VCL为平均特征值的12%，SEC为30%，这比形态特征高一个数量级。FA占总变异的四分之一（VCL）到二分之一（SEC），是形态特征相应比例的两到三倍。这些升高的FA水平表明个体内左右差异可能超过个体间差异。我们的研究结果强调了（1）进行重复双侧测量以准确量化睾丸功能中的FA，以及（2）使用来自两个睾丸的平均数据进行种群水平分析的重要性。这些发现对使用啮齿动物模型的生理和生态毒理学研究具有重要的实际意义，在这些研究中附睾精子分析是标准做法，突出了考虑功能不对称以防止得出有偏差结论的必要性。
据报道，黑猩猩和倭黑猩猩的肌肉具有“超强力量”，有人认为这归因于它们肌肉更大的比张力和比功率。为了对此进行研究，我们比较了85条人类和49条倭黑猩猩（Pan paniscus）去皮纤维在15℃时的力-速度关系。通过凝胶电泳将纤维分为I型或II型。在两个物种中，II型纤维的最大缩短速度（Vmax）更高，力-速度关系的曲率更低（a/Po更高），比I型纤维（p < 0.001）。虽然两种类型的倭黑猩猩纤维都比人类纤维更大，产生的力也更多，但它们的比张力和Vmax更低（p < 0.001）。倭黑猩猩纤维的a/Po更高（p < 0.001）。综合起来，力-速度关系参数的这些差异导致倭黑猩猩和人类纤维具有相似的比功率。力-速度关系较小的曲率抵消了较低的比张力和Vmax对倭黑猩猩肌肉纤维比功率的负面影响。倭黑猩猩的“超强力量”不能用肌肉纤维收缩特性的差异来解释，而可能反映出其II型纤维的比例比人类肌肉更高。
Colorectal cancer (CRC) is a major global health burden, ranking among the leading causes of cancer-related deaths. Despite improvements in screening and treatment, challenges such as late-stage diagnosis, high recurrence rates, and therapy resistance continue to impede optimal outcomes. Liquid biopsy, a minimally invasive technique that analyzes tumor-derived components in bodily fluids-including circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and extracellular vesicles (EVs)-is emerging as a powerful tool to transform CRC management across the disease continuum. This review provides a comprehensive overview of liquid biopsy's current and emerging applications in CRC. We examine its role in early detection, where sensitive ctDNA-based assays and epigenetic biomarkers have demonstrated the ability to identify CRC at asymptomatic or early stages, potentially improving screening uptake and compliance. Furthermore, we explore how liquid biopsy enables dynamic monitoring of treatment response and clonal evolution, facilitating the timely identification of resistance mutations and supporting personalized therapy adjustments. Innovations in multi-omics integration, artificial intelligence, and ultra-sensitive sequencing technologies are also discussed as pivotal advancements that enhance the clinical utility of liquid biopsy. Despite significant progress, the widespread adoption of liquid biopsy faces several hurdles, including assay standardization, sensitivity for low-shedding tumors, regulatory approval, and cost-effectiveness. Continued research, validation in large prospective trials, and harmonization of testing protocols are essential to overcome these challenges. Ultimately, liquid biopsy holds the potential to become a cornerstone of precision oncology in CRC, enabling earlier intervention, more tailored treatment strategies, and improved patient outcomes.
与骨髓瘤性积液相比，专门针对血液淋巴样浆细胞性积液（HPEs）的研究较少。我们进行了一项为期15年的回顾性研究，以调查HPEs的患病率、细胞学模式、潜在的解读陷阱以及临床关联。浆细胞样细胞和浆细胞占积液细胞10%以上的浆液性积液被归类为HPEs。我们提取了每位患者的相关临床、实验室和随访数据。我们发现6例患者[年龄范围：60 - 88岁，平均年龄：73岁，男女比例1:1]患有HPEs，占浆液性积液的0.2%。相关临床病史促使我们考虑HPEs，并在细胞块切片中纳入浆细胞免疫标志物。在没有流式细胞术检测积液的情况下，轻链受限的浆细胞浸润证实了细胞学诊断。我们识别出三种细胞形态学模式：单纯浆细胞浸润、淋巴浆细胞浸润以及浆细胞与其他细胞成分混合。4例患者患有多发性骨髓瘤（2例为单纯高级别大的多形性骨髓瘤细胞，2例为成熟浆细胞与炎性细胞混合），1例患者患有边缘区淋巴瘤，另1例患者患有淋巴浆细胞淋巴瘤。这些患者具有相似的临床特征，κ链（3例）和λ链（3例）分布均衡。HPEs是罕见的恶性积液，发生于患有多发性骨髓瘤和低级别B细胞淋巴瘤的老年患者中。高级别骨髓瘤细胞可能与血液淋巴样和非血液淋巴样恶性肿瘤混淆，而多发性骨髓瘤和低级别淋巴瘤中的成熟浆细胞可能被误诊为反应性浆细胞增多症。细胞块免疫细胞化学是一种有价值的诊断工具。
目的：探讨与高危型人乳头瘤病毒（HR-HPV）基因型单一感染和合并感染模式相关的高级别鳞状上皮内病变或更严重病变（HSIL+）的差异风险。 方法：在这项回顾性队列研究中，纳入了10570例在武汉儿童医院（2021年5月至2023年5月）接受阴道镜引导下宫颈活检的薄层液基细胞学检查结果异常和/或HR-HPV感染的患者。组织病理学诊断作为金标准。采用多因素逻辑回归分析HPV感染模式下的HSIL+风险，并对年龄和病毒载量进行校正。 结果：HPV31、HPV33或HPV58单一感染的HSIL+阳性率与HPV16单一感染相当。校正混杂因素后，逻辑回归显示，与HPV16单一感染相比，HPV16与低危型HPV基因型合并感染降低了进展为HSIL+的风险（p<0.05）。同样，涉及HPV33或HPV58的合并感染（无论高危/低危伴侣）与较低的HSIL+风险相关（所有p<0.05）。相比之下，无论合并感染状态如何，HPV31的HSIL+风险一致。 结论：在筛查和管理方案中，HPV16、HPV31、HPV33或HPV58需要同等的临床警惕。低危型HPV基因型合并感染可降低HPV16感染个体的HSIL+风险，HPV33/58合并感染（与任何基因型）具有保护作用。我们的研究表明，HPV31相关风险可能不受合并感染的影响，提示存在基因型特异性的生物学相互作用。这些发现凸显了基因分型指导的风险分层在宫颈癌筛查中的重要性。
Cell-cultured meat is an essential alternative source of animal meat. In in vitro cell culture, extracellular matrix (ECM) proteins are commonly used for cell adhesion and proliferation. However, using pure ECM proteins is challenging regarding cost-effectiveness and quality control. Gelatin has great potential to replace ECM proteins, but optimizing its performance to better mimic the real meat's structure and taste remains unclear. This review explores the potential application of cell-cultured meat using gelatin-based biomaterial instead of traditional ECM proteins. Functionalization strategies are employed to modulate the physical and biological properties of gelatin, enabling it to better match the structural and functional requirements of the ECM. In addition, the cell-cultured meat biomanufacturing process based on functionalized gelatin-based materials is reviewed, including module assembly, 3D or 4D bioprinting technologies. The positive effects of functional scaffolds on the quality changes in cultured meat are also briefly described. Gelatin-based scaffolds with excellent physical and biological properties provide sufficient mechanical support and create biomimetic environments, closely mimicking natural tissues. This makes them suitable for designing high-quality cultured meat. By addressing future challenges and promoting advanced technologies, the full potential of gelatin-based biomaterials can be realized and propelled to the forefront of innovative applications in cellular agriculture.
背景：子宫内膜癌的分子分类有助于预测预后。基因组检测使用福尔马林固定石蜡包埋（FFPE）组织进行；然而，我们之前报道过液基细胞学（LBC）标本可用于下一代测序（NGS）。在本研究中，我们评估了LBC标本长期保存对基于NGS的基因组分析的影响，包括基因突变、肿瘤突变负荷（TMB）和微卫星不稳定性（MSI）。 方法：使用四种LBC固定剂（CellPrep、ThinPrep、CytoRich Red和SurePath）从培养的子宫内膜样癌HEK - 251细胞制备NGS样本。用CytoRich Red固定12例子宫内膜样癌患者的子宫内膜LBC标本。在培养的HEK - 251细胞中储存1周、6个月和12个月后，分析TMB、MSI和基因突变。对储存15 - 45个月的配对子宫内膜样癌LBC和FFPE标本进行基于NGS的分析，并将其分子谱与初始诊断时的进行比较。 结果：在培养细胞中，任何一种LBC固定剂在储存期间TMB和MSI均无差异；除基因突变外，临床FFPE和LBC标本的初次和二次分析结果具有可比性。子宫内膜样癌亚型分类的综合诊断没有变化。 结论：LBC标本在长期保存后仍保留高质量基因组用于分子分类，可能是子宫内膜癌综合诊断的基因组检测的替代来源。
Polydatin is a bioactive compound extracted from the roots of Reynoutria japonica Houtt. It has demonstrated various protective effects on the cardiovascular system. However, the underlying molecular mechanisms through which polydatin exerts its effects in atherosclerosis (AS) remain largely unclear, particularly regarding the involvement of the ferroptosis pathway in its anti-atherosclerotic action. This study aims to investigate the anti-atherosclerotic effects of polydatin and its potential mechanisms, with a primary focus on the ferroptosis pathway. To this end, we employed an ApoE mouse model and endothelial cells exposed to oxidized low-density lipoprotein (ox-LDL). We analyzed atherosclerosis progression, endothelial function, and ferroptosis both in vitro and in vivo using various biological and biochemical techniques. To further explore the underlying mechanisms of polydatin's effects, Nrf2 expression was silenced using siRNA. Polydatin inhibited atherosclerosis in vivo and improved endothelial function in vitro. We evaluated ferroptosis-related markers, including ferrous iron, glutathione, malondialdehyde, lipid reactive oxygen species (ROS), GPX4, and SLC7A11, as well as overall ROS production, mitochondrial membrane potential, and mitochondrial ROS. The results indicated that polydatin suppressed ferroptosis both in vivo and in vitro. Moreover, the ferroptosis inducer erastin counteracted the endothelial cytoprotective effects of polydatin. Mechanistically, polydatin significantly enhanced Nrf2 nuclear translocation in both the aortic tissues of ApoE mice and ox-LDL-stimulated endothelial cells. Furthermore, silencing Nrf2 markedly abrogated the protective effects of polydatin on endothelial ferroptosis and impaired cellular function. Collectively, these findings demonstrate that modulating Nrf2-dependent ferroptosis contributes to the ability of polydatin to mitigate atherosclerosis and protect endothelial cells from injury.
This case report highlights cutaneous mucormycosis in a 99-year-old patient who was effectively treated with intravenous isavuconazole and local amphotericin B after wound debridement. The patient showed significant improvement within two weeks, highlighting the importance of diagnosis and treatment for this rare fungal infection. It underscores the need for early recognition and suggests that combining antifungal treatments with surgical intervention may be an optimal strategy, even in patients lacking typical risk factors.
In light of the global proliferation of antibiotics and the increasing resistance of pathogenic bacteria to antibiotics, antimicrobial peptides (AMPs), which are important immune effectors of invertebrate innate immune defense against pathogenic infections, are thought to have a high potential to replace antibiotics. Aside from antibacterial activity, AMPs also display antibiofilm, antifungal, antiviral, immune-regulatory, and other functions. Red swamp crayfish Procambarus clarkii, being a lower invertebrate with great commercial value, lacks adaptive immunity, hence unique AMPs have become a vital and key element of their defense mechanism. In this review, we summarize the research progress on AMPs related to invertebrate, especially in P. clarkii, as well as their structure feature, action mechanisms and future prospects in drug development, aiming to improve the understanding of P. clarkii innate immunity and provides guidance for the fight against antimicrobial resistance in P. clarkii culture.
INTRODUCTION: The rat sciatic nerve crush injury model is commonly employed to evaluate the efficacy of treatments aimed at promoting nerve regeneration. This review examines various crush techniques and the types of nerve injuries they are designed to produce. METHODS: A literature review was conducted using PubMed, Embase, Web of Science, and SCOPUS for studies published between 2010 and 2024. Studies were included if they involved surgical crush injuries on the rat sciatic nerve, performed at least one sensory functional evaluation, and compared outcomes with naive or sham controls. Crush techniques and the resulting nerve injuries were analyzed based on postoperative sensory evaluations. RESULTS: Of the 48 studies reviewed, 21 met the inclusion criteria. The crush techniques used included clamp (11 studies), forceps (5), clip (4), and others (1), all of which resulted in sensory impairments. Ten studies reported transient impairments with recovery to control levels, while 11 reported no recovery during the observation period (permanent). The transient group had significantly longer observation periods compared to the permanent group (57.7 vs. 17.4 days, p = 0.0009). ROC analysis determined 25 days as the optimal cutoff to distinguish transient from permanent injuries, with 90.0 % sensitivity and 81.8 % specificity. DISCUSSION: Regardless of the technique used, the induced nerve injury aligns with axonotmesis, characterized by spontaneous recovery over time. To accurately evaluate functional recovery, a minimum postoperative observation period of 4 weeks is recommended. This model is best suited for assessing rapid-acting agents, as spontaneous recovery may obscure the effects of slower-acting treatments.
Acute kidney injury (AKI) is a prevalent and severe condition characterized by sudden renal dysfunction. In this investigation, we explored the therapeutic potential of C5a receptor (C5aR) blockade in a murine model of lipopolysaccharide (LPS)-induced AKI. Our findings reveal that LPS administration disrupts renal morphology, while treatment with the C5aR antagonist W54011 effectively reverses these changes. Moreover, W54011 significantly reduces renal iron content, implying its possible involvement in ferroptosis. C5aR blockade not only attenuates LPS-induced AKI by lowering levels of N-acetyl-β-D-glucosaminidase (NAG) and proinflammatory cytokines but also modulates markers related to oxidative stress. Transmission electron microscopy analysis indicated the role of W5401 in safeguarding tubular epithelial cells from mitochondrial damage, underscoring its protective effects against ferroptosis-induced cellular structural deterioration. Further analyses via Western blot and immunofluorescence detection illustrate that C5aR blockade suppresses p38 phosphorylation, thus restoring the activity of the Nrf2/SLC7A11/GPX4 signaling pathway within the kidney. This restoration leads to heightened expression of antioxidant enzymes and cytoprotective proteins. In summary, our study underscores that W54011-mediated C5aR blocking alleviates LPS-induced AKI by modulating the p38/Nrf2/SLC7A11/GPX4 signaling axis. These findings accentuate the potential therapeutic significance of targeting the C5aR pathway to counteract ferroptosis in kidney-related ailments.
The study explored the nephroprotective potential of Rosa canina (dog rose) ethanolic fruit extract against carbon tetrachloride (CCl4)-induced nephrotoxicity in rats, while also analyzing its phytochemical composition using UPLC-ESI-MS/MS. Male Wistar rats were allocated into five groups: control, R. canina extract alone, CCl4-induced nephrotoxicity, CCl4 with R. canina extract and CCl4 with silymarin. UPLC-ESI-MS/MS revealed 15 compounds in R. canina extract, predominantly anthocyanins, flavonoids, and lycopene. Treatment with R. canina extract significantly ameliorated CCl4-induced kidney dysfunction, abating oxidative stress and inflammation. Enhanced expression of HO-1 (heme oxygenase-1) and Nrf2 (nuclear factor erythroid 2-related factor 2) mRNA in the kidney suggested their involvement in protective mechanisms. Inhibition of HO-1 attenuated R. canina's protective effect against CCl4-induced kidney injury, underscoring the significance of the Nrf2/HO-1 pathway. For further validation, high throughput molecular docking analysis were performed. The docking analysis revealed the interaction between HO-1 and Nrf2 against Pelarginidin, Malvidin and Petunidin. Among all the three compounds, pelargonidin showed the highest binding score of -9.3 kcal/mol and -7.7 kcal/mol against Nrf2 and HO-1 respectively. In conclusion, R. canina extract, rich in phenolics, exhibited nephroprotective effects via inflammation and oxidative stress attenuation, potentially mediated through Nrf2/HO-1 pathway modulation against CCl4-induced nephrotoxicity.
PURPOSE: Four-dimensional (4D) flow MRI enables comprehensive assessment of aortic hemodynamics, but normative values remain limited, especially for Asian populations. This study aimed to establish age- and sex-specific normative values for flow-related parameters in healthy Korean adults. METHODS: Seventy-seven healthy volunteers (aged 20-79 years) underwent 4D flow MRI. Hemodynamic parameters-velocity, viscous energy loss, normalized vorticity, and helicity-were quantified in the ascending aorta (AAo), aortic arch (AoA), and descending aorta (DAo). RESULTS: Significant sex differences were found for velocity in the AAo (p < 0.001) and viscous energy loss across all segments (p < 0.05), while normalized vorticity and helicity showed no sex-related differences. In viscous energy loss, males had higher values than females in the AAo (2.84 ± 1.05 vs 2.22 ± 0.60 mW, p = 0.017), AoA (0.74 ± 0.37 vs 0.42 ± 0.19 mW, p = 0.001), and DAo (4.78 ± 1.82 vs 3.32 ± 1.55 mW, p = 0.002). Most parameters demonstrated age-related declines, especially in the DAo. Strongest correlations with age were seen for velocity (r = -0.725, p < 0.001) and viscous energy loss (r = -0.745, p < 0.001). Positive helicity showed sex-specific aging trends, with the strongest correlations in the DAo for men and the AoA for women. Negative helicity showed the strongest correlation in the DAo in both sexes. CONCLUSIONS: This study established age- and sex-specific normative values for aortic hemodynamic parameters in healthy Korean adults using 4D flow MRI. While sex differences were limited, most flow parameters declined with age.
Carboxylated osteocalcin (cOC), produced during post-translational modification of osteocalcin (OC) in a vitamin K-dependent pathway, has a high affinity for calcium and hydroxyapatite. Despite the observed link between vitamin K deficiency and fracture risk, supplementation studies have not consistently demonstrated improvements in bone mineral density (BMD) or bone microarchitecture, though studies have reported improvement in cOC status. We hypothesise that these inconsistent findings are due to the lack of knowledge on the mechanisms by which cOC affects bone health. Hence, the aim of this study was to investigate the relationship between cOC and bone turnover markers, cortical and trabecular bone microarchitecture and strength. Forty-five patients who underwent hip arthroplasty for hip osteoarthritis were prospectively recruited. Patients with conditions or medications that could affect bone outcomes were excluded and intra-operative bloods and bone biopsies were collected. Cortical thickness and hip strength was measured with dual-energy X-ray absorptiometry and micro-computed tomography was used to determine trabecular bone microarchitecture. Cortical thickness, cross-sectional area, cross-sectional moment of inertia, femoral neck width and section modulus correlated positively with cOC (p < 0.05, all). There was no association between partially or fully un-carboxylated fractions and hip strength variables. Further, cOC was found to be an independent predictor of bone alkaline phosphastase while the partially or fully un-carboxylated OC predicted c-terminal telopeptide of type 1 collagen. In conclusion, higher cOC concentrations were associated with improved femoral bone strength, and the effect is possibly mediated through higher bone mineralisation, independent of age, parathyroid hormone, kidney function, BMD and physical activity.
Aquatic pollution caused by pesticides raises concerns about the effects on wildlife. While risk assessment protocols with invertebrates focus mainly on arthropods, the effects on gastropods are underexplored. In this way, the impact of exposure to imidacloprid, a neonicotinoid insecticide, and tebuconazole, an azole fungicide, on different life stages of the freshwater snail Physa acuta was investigated. Chronic tests with newly hatched (initial growth) and sexually mature adults (biomass and reproduction) were carried out, testing five environmentally relevant concentrations of imidacloprid (5 to 46 µg L) and tebuconazole (18 to 272 µg L). Besides, the displacement behavior was assessed in both stages. The exposure to insecticide did not alter the initial growth of the species; however, adults presented reduced reproduction marked by decreases in the number of egg clutches (20-40 %) and eggs (25-50 %). Besides, reductions in egg hatching reached 50 %. The fungicide caused more pronounced responses, marked by declines in initial growth by 10 to 90 % across all tested concentrations. To adults, the fungicide provoked reproductive losses of 45-60 % regarding the number of clutches and 40-70 % in egg counting. The egg hatchability was also reduced, and the effects were more pronounced when eggs were incubated in the contaminated medium, with inhibition reaching 100 %. Both life stages exposed to tebuconazole presented reduced displacement capability, while only adults were affected by imidacloprid, despite its neurotoxic character. The output observed in hatchlings and adults of P. acuta demonstrates that relevant concentrations of both pesticides endanger freshwater gastropods with cascade effects on freshwater environments.
Cultured meat is an emerging field in future food production, employing interdisciplinary strategies that integrate the food industry, tissue engineering, and biotechnology to meet global food needs. Cultivating meat from stem cells is an increasingly recognized solution to address concerns associated with animal husbandry in terms of environment, health, and ethics. Despite significant advances, substantial technical challenges persist. In this review, we focus on recent advances in cutting-edge engineering approaches and biomaterials for the production of cultured meat. Furthermore, perspectives on opportunities to enhance the development of cultured meat, especially through bioengineering, synthetic biology, and artificial intelligence, are also discussed. Finally, we discuss the future trends of cultured meat, with specific emphasis on nutritional optimization and safety assurance. This review comprehensively demonstrates the emerging technologies in cultured meat, providing a reference for accelerating the development of intelligent cell agriculture and realizing the production of customized meat products.
