The Potential Toxic Side Effects of Flavonoids

Flavonoids are a class of phytochemical molecules abundant in many plants, fruits, vegetables, and leaves. Flavonoids possess a series of significant biological activities, including anticancer, antioxidant, antiviral, and antiinflammatory properties. They become an important source of dietary supplements and natural health products. Though many studies confirmed the safety of flavonoids, the potential toxicity of flavonoids is still a remarkable field of research to be explored. The enthusiasm for flavonoids expressed by the public has sometimes overlooked their toxicity and also consumed the flavonoids exceeding the body requirements. The current review focused on the potential toxicity of flavonoids to make the public consume flavonoids with caution. This review summarizes the current toxicity which has been reported in vivo and in vitro experiments. The toxicity involves carcinogenicity and mutation, liver and kidney toxicity, and the influence on the thyroid and reproductive function and intestinal flora disorders. The mechanism of toxicity is fully complicated, and current evidence indicates that natural flavonoid glycosides act on different targets with different doses in vivo and in vitro experiments. Though most kinds of flavonoids are considered safe, flavonoids proposed as food supplements need to be assessed their tolerable upper intake level as there have been reports of toxic flavonoids.     

miR-181b promotes the oncogenesis of renal cell carcinoma by targeting TIMP3

Renal cell carcinoma (RCC) has a poor prognosis due to limited diagnosis and treatment. Thus, it is necessary to find novel prognostic biomarkers and therapeutic targets. The aberrant expression of microRNAs plays an important role in RCC oncogenesis. Tissue inhibitors of metalloproteinase 3 (TIMP3) acts as a downstream target of miR-181b. The aim of this study was to understand the role and molecular mechanism of miR-181b in RCC oncogenesis. The results showed that miR-181b expression was significantly higher in RCC tumour tissues, especially in those with significant invasion or metastasis. miR-181b overexpression promoted proliferation and migration of the RCC cell line 786-O, while miR-181b knockdown had the opposite effect. In addition, miR-181b was inversely correlated with TIMP3 expression in RCC tumour tissues. miR-181b overexpression reduced TIMP3 expression in RCC cell line 786-O or OS-RC-2, while miR-181b knockdown had the inverse effect. Mechanistically, a luciferase reporter assay confirmed the binding sites of miR-181b on the 3’-UTR of TIMP3, confirming the targeting effect of miR-181b on TIMP3. Overall, miR-181b promotes the development and progression of RCC by targeting TIMP3 expression, indicating the potential use of miR-181b in the diagnosis and treatment of RCC.     

An integrated bioinformatics analysis and experimental study identified key biomarkers CD300A or CXCL1, pathways and immune infiltration in diabetic nephropathy mice

Diabetic nephropathy (DN) is a common microvascular complication that easily leads to end-stage renal disease. It is important to explore the key biomarkers and molecular mechanisms relevant to diabetic nephropathy (DN). We used highthroughput RNA sequencing to obtain the genes related to DN glomerular tissues and healthy glomerular tissues of mice. Then we used LIMMA to analyze differentially expressed genes (DEGs) between DN and non-diabetic glomerular samples. And we performed KEGG, gene ontology functional (GO) enrichment, and gene set enrichment analysis to reveal the signaling pathway of the disease. The CIBERSORT algorithm based on support vector machine was used to determine the immune infiltration score. Random forest algorithm and Cytoscape obtained hub genes. Finally, we applied co-staining, immunohistochemical staining, RT-qPCR and western blotting to validate the protein and mRNA expression of both hub genes. We obtained 913 DEGs mainly related to inflammatory factors and immunity. GSEA results showed that differential genes were mainly enriched in IL-17 signaling pathway, lipid and atherosclerosis, rheumatoid arthritis, TNF signaling pathway, neutrophil extracellular trap formation, Staphylococcus aureus infection and other pathways. The intersection of the random forest algorithm and Cytoscape revealed both hub genes of CD300A and CXCL1. Experiments have shown that the both key genes of CD300A and CXCL1 shown increased expression in glomerular podocytes, and are related to the inflammation of diabetic nephropathy. And immunohistochemical staining and RT-qPCR further confirmed that the protein and mRNA expression level of CD300A or CXCL1 in glomeruli tissue in DN mice were increased. The expression levels of CD300A and CXCL1 increased significantly under HG (high glucose) stimulation, further confirming that diabetes can lead to increased levels of CD300A and CXCL1 at the cellular level. Through bioinformatics analysis, machine learning algorithms, and experimental research, CD300A and CXCL1 are confirmed as both potential biomarkers in diabetic nephropathy. And we further revealed the main pathways of differential genes and the differentially distributed immune infiltrating cells in diabetic nephropathy.     

辅助电流对Cu/Al大功率超声波焊接的影响

为获得更高质量的Cu/Al异质金属接头，开展了Cu/Al电流辅助大功率超声波焊接工艺试验，研究了辅助电流对Cu/Al超声波焊接的界面温度、材料塑性流动、界面中间相分布及接头力学性能的影响。结果表明，复合焊件成型良好，其接头抗拉剪力为3030 N，接头的断裂模式为韧性-脆性复合断裂。在同样的焊接时间0.2 s内，随着电流的增大，Cu/Al界面温度增加，金属塑性流动以及界面扩散也随之增强，这说明辅助电流能明显促进界面冶金；相比长时间0.4 s的超声波焊接，辅助电流能在保证界面温度、材料塑性变形的前提下，能明显减薄了界面IMC层的厚度，这是电流增强Cu/Al接头的主要物理机制。研究结果为优化Cu/Al复合焊接头强度提供了参考。     

真空热处理炉布料矩阵优化仿真分析

为了获得更高的加热效率和更好的温度均匀性,采用有限元软件建立了真空热处理炉加热过程仿真模型,并耦合PID算法用于温度控制。通过与实测温度对比,验证了仿真模型的准确性。借助该模型,模拟研究了布料矩阵对两种典型形状零件在真空热处理炉内加热特性的影响。模拟装炉时基于零件几何形状特征,对圆棒形工件采用顺排、叉排和环形排列3种形式,对圆盘形工件采用横排式和竖排式。研究结果表明:尽管零件形状和数量相同,但是随着布料矩阵的变化,加热效率和温度均匀性都会改变。对于圆棒形工件,采用环形排列不仅可以提高内部工件的加热速率,而且相较于叉排式可以将最大温差减小36 ℃;对于圆盘形工件,由水平式改为竖直式布料可以将最大温差由248 ℃减小至171 ℃。     

粗金粉中金的氯浸-控制电位还原精炼

某冶炼厂氰化金泥还原得到的粗金产品纯度较低，采用氯浸-还原工艺对粗金进行了精炼提纯。在生产工艺中采用盐酸+氯酸钠对粗金进行氯浸溶解，用焦亚硫酸钠控制电位选择性还原浸出液中的金。采用补水-冷却使银和铅从氯浸液充分沉淀析出，通过调整pH值、改变焦亚硫酸钠添加方式、精确控制还原电位等方法，产品金锭达到IC-Au99.99标准。两年的生产实践创造了明显的经济效益。     

PCBN材料的组织结构与力学性能

以CBN-TiN-Ti-Al₂O₃为初始原料，采用高温高压法在1500 ℃不同保温时间下制备PCBN材料，探讨其在不同保温时间下的物相组成、显微结构、力学性能和切削性能。结果表明:保温时间对PCBN材料物相组成无明显影响，但有助于提高其结晶度，实现其烧结均匀化和致密化；在保温时间为9.00 min时，能获得综合性能最佳的PCBN材料，其相对密度为99.1%，抗弯强度为910.9 MPa，磨耗比为7120，显微硬度为33.5 GPa；用此PCBN做成的刀具加工模具钢零件，最多可加工365个。      

海参废渣皂苷通过核苷酸结合寡聚化结构域样受体信号通路抵抗环磷酰胺诱导小鼠的免疫抑制

在我国海参是一种具有多种生物活性的传统滋补品。本实验系统性地研究了2.5、5.0、10.0 mg/（kg mb·d）海参废渣皂苷（saponins extracted from sea cucumber residues，SCRSS）对免疫抑制小鼠的调节作用。结果表明，与模型对照组相比，5.0 mg/（kg mb·d）SCRSS使小鼠的体质量、脾脏指数和胸腺指数分别增加了15.3%、23.8%和39.8%；5.0 mg/（kg mb·d）SCRSS也极显著增加了免疫抑制小鼠的吞噬指数（P＜0.01）。此外，与模型对照组相比，各剂量SCRSS均明显地增加了血清中细胞因子的水平，并促进了脾淋巴细胞和腹腔巨噬细胞的增殖活性。其中，中等剂量（5.0 mg/（kg mb·d））SCRSS可以更有效地上调免疫抑制小鼠核苷酸结合寡聚化结构域蛋白1、核苷酸结合寡聚化结构域蛋白2、受体相互作用蛋白-2和核因子-κB的表达。结论：SCRSS具有作为提高免疫力的功能性食品补充剂的潜力。     

杏鲍菇富硒蛋白的营养结构特性及对铅毒性的缓解作用

铅主要通过饮食进入人体并在体内积累，对人体免疫和代谢等系统造成损伤，补充硒可以显著改善铅暴露对机体的危害。本研究以杏鲍菇富硒蛋白（selenium-enriched protein from Pleurotus eryngii，SePEP）为原料，通过高效液相色谱-电感耦合等离子体质谱联用技术、傅里叶变换红外光谱等测定蛋白硒形态及结构。通过细胞实验探究蛋白体外模拟消化产物对Pb2＋引起的RAW264.7细胞毒性的缓解作用。结果表明，SePEP硒含量为（360.64±3.11）mg/kg，硒形态主要包括硒代蛋氨酸（SeMet，（48.04±0.64）%（相对含量，下同））、硒代胱氨酸（SeCys2，（31.91±0.51）%）和甲基硒代半胱氨酸（MeSeCys，（14.65±0.36）%）。硒的添加显著促进了氨基酸的生成，改变了蛋白质的结构，α-螺旋结构相对含量由（20.30±0.87）%增加至（25.00±1.60）%，无规卷曲结构相对含量由（20.38±0.84）%减少至（13.85±1.66）%，总巯基与二硫键含量及表面疏水性均显著增加（P＜0.05）。添加75 μg/mL SePEP消化产物后，Pb2＋处理的RAW264.7细胞存活率由接近50%显著升高至（76.95±6.95）%，细胞培养液中乳酸脱氢酶释放量降低57.45%，并且3 种促炎细胞因子白细胞介素（interleukin，IL）-6、IL-8和肿瘤坏死因子α的释放受到显著抑制（P＜0.05），说明SePEP消化产物对Pb2＋暴露引起的RAW264.7细胞损伤有缓解作用。本实验研究成果可为研发安全、有效的改善铅毒性的功能富硒蛋白食品提供参考。