MicroRNA-mediated suppression of P-glycoprotein by quantum dots in lung cancer cells

The interactions between adenosine triphosphate-binding cassette (ABC) transporters and nano-sized materials are attracting increasing attention, due to their great potential in overcoming the multidrug resistance (MDR) phenomena in cancer treatment. However, the inner mechanisms involved in the interactions are largely unknown. In this study, two commercial quantum dots (QDs), CdSe/ZnS-MPA and CdSe/ZnS-GSH, were tested for their interactions with P-glycoprotein (P-gp), as well as the relating mechanisms in lung cancer (A549) cells. Both QDs significantly suppressed the gene and protein expressions of P-gp in A549 cells. To explain this, the gene expressions of nine relating microRNAs (miRNAs) were evaluated. The results indicated a shared up-regulation of miR-34b and miR-185 by both QDs. Furthermore, mimics and inhibitors of miR-34b and miR-185 significantly enhanced and suppressed the gene and protein expressions of P-gp, respectively, confirming the modulatory function of these two miRNAs on P-gp. Interestingly, expressions of both miRNAs were suppressed during treatment with Cd²⁺ and doxorubicin, which induced the expression of P-gp, indicating the universality of these miRNAs-related mechanisms. Thus, as miR-34b and miR-185 participated in the suppression of P-gp functions in A549 cells they could be interesting targets for the treatment of lung cancer.     

Tryptophan 387 and 390 residues in ADAMTS13 are crucial to the ability of vascular tube formation and cell migration of endothelial cells

A disintegrin and metalloproteinase with thrombospondin motifs 13 (ADAMTS13) was mainly generated and secreted from endothelial cells (ECs). Our previous study showed that tryptophan (Trp) residues at 387 and 390 in ADAMTS13 are required for its secretion and enzymatic activity. However, the effects on its host cell as well as the potential mechanism have not been clear. The aim of the study was to examine the effects of Trp residues 387 and 390 of ADAMTS13 on the biological processes of ECs. Herein, Trp was substituted with alanine in ADAMTS13 to generate ADAMTS13 mutants at 387 (W387A), 390 (W390A), and double mutants at 387 and 390 (2WA), respectively. We found that substitution mutation impaired vascular endothelial growth factor (VEGF) secretion and the downstream JAK1/STAT3 activation, the binding ability to Von Willebrand factor, cell proliferation, migration, and vascular tube formation. Overall, our study concluded that Trp³⁸⁷ and Trp³⁹⁰ of ADAMTS13 play vital roles in the biological function of ECs.     

Discovery of 2,4-diaminopyrimidine derivatives targeting p21-activated kinase 4: Biological evaluation and docking studies

In this study, novel 2,4-diaminopyrimidine derivatives targeting p21-activated kinase 4 (PAK4) were discovered and evaluated for their biological activity against PAK4. Among the derivatives studied, promising compounds A2 , B6 , and B8 displayed the highest inhibitory activities against PAK4 (IC₅₀ = 18.4, 5.9, and 20.4 nM, respectively). From the cellular assay, compound B6 exhibited the highest potency with an IC₅₀ value of 2.533 μM against A549 cells. Some compounds were selected for computational ADME (absorption, distribution, metabolism, and elimination) properties and molecular docking studies against PAK4. The detailed structure–activity relationship based on the biochemical activities and molecular docking studies were explored. According to the docking studies, compound B6 had the lowest docking score (docking energy: −7.593 kcal/mol). The molecular docking simulation indicated the binding mode between compound B6 and PAK4. All these results suggest compound B6 as a useful candidate for the development of a PAK4 inhibitor.     

评价Karl迭代重建技术对胸部CT图像质量的影响

目的 评价Karl迭代重建技术对胸部CT图像质量的影响。 方法 ①模体研究:以管电压120 kVp、管电流140 mAs扫描为常规剂量组;降低管电流50%,以管电压120 kVp、管电流70 mAs扫描为低剂量组,2组分别采用滤波反投影（FBP）和Karl迭代重建技术（重建等级1~9级）进行图像重建,采用噪声功率谱（NPS）和标准差对图像噪声进行测量。②临床研究:基于模体研究结果,选取行胸部CT的受检者120例,其中男性61例、女性59例,年龄35~75岁,BMI为（23.95±0.27） kg/m2。采用随机数字表法分成常规剂量组和低剂量组,每组分别为60例,扫描参数同模体研究,分别采用Karl 5级迭代重建技术和FBP法进行图像重建。比较2组CT容积剂量指数（CTDIvol）、剂量长度乘积（DLP）、有效辐射剂量（ED）及图像噪声、信噪比等客观指标和图像质量主观评分指标。客观指标的比较采用t检验;主观评分的比较采用χ2检验。 结果 ①模体研究:常规剂量组采用Karl迭代重建技术重建图像的平均噪声均低于FBP法重建图像噪声,且随着Karl迭代重建技术等级的升高而降低,差异均有统计学意义（t=5.14~47.50,均P<0.01）。通过NPS曲线对比,Karl 1~9级重建图像在降低图像噪声的同时,保持了与FBP法重建图像的噪声纹理特性,差异无统计学意义（t=2.49, P=0.42）。低剂量组Karl 5级迭代重建图像的噪声[（6.40±0.16） Hu]与常规剂量组FBP重建图像的噪声[（6.30±0.38） Hu]较其他Karl迭代重建技术等级更接近,差异无统计学意义（t=28.34,P=0.423）。②临床研究:低剂量组的CTDIvol[（5.56±0.01） mGy]、DLP[（170.74±18.40） mGy]均明显低于常规剂量组[（11.06±0.01） mGy、（348.93±26.16） mGy·cm],差异有统计学意义（t=4757.7,P=0.003;t=39.23,P=0.005）;ED[（2.58±0.16） mSv]较常规剂量组[（5.01±0.17） mSv]降低了51.5%,差异有统计学意义（t=37.94,P=0.004）。低剂量Karl 5级迭代重建技术重建图像与常规剂量FBP重建图像比较,噪声（升主动脉:t=0.24,P=0.38; 降主动脉:t=1.51,P=0.70）和信噪比（升主动脉:t=0.45,P=0.45; 降主动脉:t=0.08,P=0.72）的差异均无统计学意义;纵隔窗图像（χ2=2.32,P=0.317; χ2=1.38,P=0.268）和肺窗图像（χ2=0.97,P=0.614; χ2=0.59,P=0.760）的主观图像质量评分比较,差异均无统计学意义。 结论 Karl迭代重建技术可以不同程度地降低图像噪声。降低常规管电流的50%至70 mAs、采用Karl 5级迭代重建技术重建图像可获得与常规剂量FBP相同的图像质量。     

Massively parallel sequencing analysis of nondegraded and degraded DNA mixtures using the ForenSeq™ system in combination with EuroForMix software

Massively parallel sequencing (MPS) technologies enable the simultaneous analysis of short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs). MPS also enables the detection of alleles of the minor contributors in imbalanced DNA mixtures. In this study, 59 STRs (amelogenin, 27 autosomal STRs, 7 X-STRs, and 24 Y-STRs) and 94 identity-informative SNPs of 119 unrelated Taiwanese (50 men, 69 women) were sequenced using a commercial MPS kit. Forty-eight nondegraded and 44 highly degraded two-person artificial DNA mixtures with various minor to major ratios (1:9, 1:19, 1:29, 1:39, 1:79, and 1:99) were analyzed to examine the performance of this system for detecting the alleles of the minor contributors in DNA mixtures. Likelihood ratios based on continuous model were calculated using the EuroForMix for DNA mixture interpretation. The STR and SNP genotypes of these 119 Taiwanese were obtained. Several sequence variants of STRs were observed. Using EuroForMix software based on the sequence data of autosomal STRs and autosomal SNPs, 97.9% (47/48) and 97.7% (42/43) of minor donors were accurately inferred among the successfully analyzed nondegraded and degraded DNA mixtures, respectively. In conclusion, combined with EuroForMix software, this commercial kit is effective for assignment of the minor contributors in nondegraded and degraded DNA mixtures.