甲基莲心碱通过p62抑制肺腺癌A549细胞侵袭、转移的机制

目的 阐明甲基莲心碱（Nef）抑制肺腺癌A549细胞侵袭和转移的可能机制,为今后临床应用Nef防治肺腺癌转移提供理论基础。方法 常规培养肺腺癌A549细胞,加入不同浓度的Nef进行干预,CCK-8检测细胞活力;将A549细胞分为三组：空白组不做任何处理,TGF-β组采用TGF-β1干预,TGF-β+Nef组采用TGF-β1和Nef干预,显微镜下观察细胞形态;Transwell和Wound healing法检测各组细胞的侵袭和迁移能力; PCR、Western blotting检测各组细胞上皮间质转化（EMT）相关基因和蛋白的表达,电镜下验证细胞自噬,p62基因沉默进一步明确作用机制。结果 Nef可明显抑制TGF-β1诱导的A549细胞EMT,并可能通过抑制Twist1自噬降解抑制A549细胞的侵袭和迁移。结论 Nef可抑制肺腺癌A549细胞的侵袭和转移,其机制可能与促进p62介导的Twist1选择性自噬降解有关。     

Size-Dependent Persistent Luminescence of YAGG:Cr3+ Nanophosphors

In the current work, YAGG:Cr³⁺ nanophosphors were synthesized by the Pechini method and then annealed at different temperatures in the range 800–1300 °C. The structure and morphology of the samples were characterized by X-ray Powder Diffraction (XRPD). The lattice parameters and average crystalline sizes as site occupation by Al³⁺ and Ga³⁺ ions were calculated from the Rietveld refinement data. To investigate the effect of crystalline size of the materials on their optical properties: excitation and emission spectra were recorded and analyzed. Finally, the effect of crystalline size on the probability of carrier recombination leading to PersL was determined experimentally with thermoluminescence analyses. The T_max-T_stop method was applied to determine the trap type and particle size (calcination temperature) effect on their redistribution. A correlation between structural changes and trap redistribution was found. In particular, the extinction of high-temperature TL maximum with increasing annealing temperatures is observed, while low-temperature TL maximum increases and reaches a maximum when the lattice parameter reaches saturation.     

Investigation of the Thermodynamic Transformation and Rare Earth Microalloying of a Medium Carbon-Medium Alloy Steel for Large Ball Mill Liners

The medium carbon-medium alloy steel was developed for the manufacture of large ball mill liners and sports equipment. In this study, the continuous cooling transformation curve of a novel type of medium carbon-medium alloy steel was measured with a thermal simulation machine; based on this curve, the hardening and tempering processes were optimized. The steel was then complex modified with alkaline earth and rare earth alloys. The mechanical properties of the treated steel were tested. The microstructure of the steel was analyzed by metallographic microscopy, X-ray diffraction, scanning electron microscopy and transmission electron microscopy, and the wear surface of the steel was analyzed by a three-dimensional morphometer. After high-temperature tempering, the microstructure transformed into tempered sorbite, which possesses good mechanical properties and can adapt to working conditions that require high strength and toughness. Rare earth or alkaline earth modification of the medium carbon-medium alloy steel promoted microstructural uniformity and grain refinement and improved the mechanical and anti-wear properties.     

Effect of H2S Corrosion on the Fracture Toughness of the X80 Pipeline Steel Welded Joint

To analyze the causes and mechanisms affecting the fracture toughness of X80 pipeline steel welded joints against H₂S, the fracture toughness of different zones of X80 pipeline steel welded joints in both air and saturated H₂S solution was investigated. The fracture toughness of welded joints degraded significantly in the saturated H₂S solution, where the crack tip opening displacement (CTOD) characteristic value in the coarse grain heat-affected zone (CGHAZ) and weld metal (WM) was only 8% and 12% of that in air, respectively. However, the sub-critical grain heat-affected zone (SCHAZ) showed better resistance to H₂S corrosion, with the CTOD characteristic value reaching 42% of that in air. The resistance of the welded joint to H₂S corrosion was sensitive to microstructures. The grain boundary ferrite (GBF) presented in WM, and the angle of grain boundary orientation in CGHAZ was not conducive to hindering crack propagation. Moreover, the formation of the resultant hydrogen cracks owing to the H₂S corrosion also reduced the fracture toughness of the welded joint.     

Melatonin inhibits EMT and PD‐L1 expression through the ERK1/2/FOSL1 pathway and regulates anti‐tumor immunity in HNSCC

Melatonin is an endogenous hormone with various biological functions and possesses anti‐tumor properties in multiple malignancies. Immune evasion is one of the most important hallmarks of head and neck squamous cell carcinoma (HNSCC) and is closely related to tumor progression. However, as an immune modulator under physiological conditions, the roles of melatonin in tumor immunity in HNSCC remains unclear. In this study, we found that the endogenous melatonin levels in patients with HNSCC were lower than those in patients with benign tumors in head and neck. Importantly, lower melatonin levels were related to lymph node metastasis among patients with HNSCC. Moreover, melatonin significantly suppressed programmed death‐ligand 1 (PD‐L1) expression and inhibited epithelial–mesenchymal transition (EMT) of HNSCC through the ERK1/2/FOSL1 pathway in vitro and in vivo. In SCC7/C3H syngeneic mouse models, anti‐programmed death‐1 (PD‐1) antibody combined with melatonin significantly inhibited tumor growth and modulated anti‐tumor immunity by increasing CD8⁺ T cell infiltration and decreasing the regulatory T cell (Treg) proportion in the tumor microenvironment. Taken together, melatonin inhibited EMT and downregulated PD‐L1 expression in HNSCC through the ERK1/2/FOSL1 pathway and exerted synergistic effects with anti‐PD‐1 antibody in vivo, which could provide promising strategies for HNSCC treatment.     

心理资本在新入职护士转型冲击与职场适应间的中介效应

目的:了解新入职护士转型冲击、心理资本与职场适应现状,分析三者之间的相关关系及心理资本在转型冲击与职场适应间的作用机制。方法:便利选取郑州市4所三级甲等医院2020年437名新入职护士作为研究对象,采用积极心理资本量表、新入职护士转型冲击评价量表及护士职场适应度量表进行调查。结果:437名新入职护士心理资本得分(81.65±19.49)分、转型冲击得分(98.80±16.54)分、职场适应得分(47.98±12.10)分。转型冲击与职场适应呈负相关(r=-0.604,P<0.01),与心理资本呈负相关(r=-0.585,P<0.01),心理资本与职场适应呈正相关(r=0.514,P<0.01)。心理资本在转型冲击与职场适应间的中介效应为0.231,占总效应的34.4%。结论:心理资本是新入职护士转型冲击与职场适应间的中介变量,临床管理者应关注并评估新入职护士心理资本,以便采取干预措施减少其转型冲击,进一步提高其职场适应水平。     

TGF-β1诱导的肝癌细胞SMMC-7721上皮间质转化对细胞Wnt/β-catenin表达的影响

目的探讨TGF-β1诱导的肝癌细胞SMMC-7721上皮间质转化对细胞信号通路蛋白Wnt/β-catenin表达的影响。方法采用5μg·mL-1 TGF-β1诱导SMMC-7721发生上皮间质转化,分别采用RT-PCR和Western blot法检测细胞中Wnt1、β-catenin、Vimentin mRNA和总蛋白的表达。结果 TGF-β1能显著诱导肝癌细胞SMMC-7721发生上皮间质转化,细胞中Wnt1、β-catenin、Vimentin mRNA和相应总蛋白的表达均显著增加(P<0.05)。结论 TGF-β1诱导肝癌细胞SMMC-7721上皮间质转化时可促进细胞Wnt/β-catenin的表达。     

B7-H3沉默对乳腺癌MDA-MB-231细胞上皮间质转化及生物学功能的影响

目的:探讨B7-H3沉默对人乳腺癌MDA-MB-231细胞上皮间质转化及生物学行为的影响.方法:通过脂质体LipofectamineTM2000转染B7-H3 siRNA干涉载体pSilencer4.1-CMV neo/B7-H3到乳腺癌MDA-MB-231细胞,经G418筛选后获得B7-H3沉默细胞株MDA-MB-2...     

Mechanisms of hepatotoxicity.

This review addresses recent advances in specific mechanisms of hepatotoxicity. Because of its unique metabolism and relationship to the gastrointestinal tract, the liver is an important target of the toxicity of drugs, xenobiotics, and oxidative stress. In cholestatic disease, endogenously generated bile acids produce hepatocellular apoptosis by stimulating Fas translocation from the cytoplasm to the plasma membrane where self-aggregation occurs to trigger apoptosis. Kupffer cell activation and neutrophil infiltration extend toxic injury. Kupffer cells release reactive oxygen species (ROS), cytokines, and chemokines, which induce neutrophil extravasation and activation. The liver expresses many cytochrome P450 isoforms, including ethanol-induced CYP2E1. CYP2E1 generates ROS, activates many toxicologically important substrates, and may be the central pathway by which ethanol causes oxidative stress. In acetaminophen toxicity, nitric oxide (NO) scavenges superoxide to produce peroxynitrite, which then causes protein nitration and tissue injury. In inducible nitric oxide synthase (iNOS) knockout mice, nitration is prevented, but unscavenged superoxide production then causes toxic lipid peroxidation to occur instead. Microvesicular steatosis, nonalcoholic steatohepatitis (NASH), and cytolytic hepatitis involve mitochondrial dysfunction, including impairment of mitochondrial fatty acid beta-oxidation, inhibition of mitochondrial respiration, and damage to mitochondrial DNA. Induction of the mitochondrial permeability transition (MPT) is another mechanism causing mitochondrial failure, which can lead to necrosis from ATP depletion or caspase-dependent apoptosis if ATP depletion does not occur fully. Because of such diverse mechanisms, hepatotoxicity remains a major reason for drug withdrawal from pharmaceutical development and clinical use.     

肝内肌成纤维细胞的来源及其在肝纤维化中作用的研究

肝脏慢性损伤,包括病毒性肝炎、酗酒、药物作用、代谢性疾病等各种致病因子导致肝内结缔组织异常增生,肝内细胞外基质过度沉淀形成肝纤维化,在此过程中分泌胶原能力更强且具有收缩能力的肌成纤维细胞的大量生成被认为是肝纤维化发生与发展的关键环节。目前对于肝纤维化时肌成纤维细胞来源的认识尚没有完全明了,在肝纤维化发生时肝星状细胞活化为肌成纤维细胞的主要来源;而骨髓间充质干细胞、上皮细胞经上皮间质转化及一些仍具有分化能力的外周血细胞在一定条件下也可转变为肌成纤维细胞并发挥作用。该文就近年来此方面的研究作一综述。