Low Reynolds number turbulence modeling of blood flow in arterial stenoses.

Moderate and severe arterial stenoses can produce highly disturbed flow regions with transitional and or turbulent flow characteristics. Neither laminar flow modeling nor standard two-equation models such as the kappa-epsilon turbulence ones are suitable for this kind of blood flow. In order to analyze the transitional or turbulent flow distal to an arterial stenosis, authors of this study have used the Wilcox low-Re turbulence model. Flow simulations were carried out on stenoses with 50, 75 and 86% reductions in cross-sectional area over a range of physiologically relevant Reynolds numbers. The results obtained with this low-Re turbulence model were compared with experimental measurements and with the results obtained by the standard kappa-epsilon model in terms of velocity profile, vortex length, wall shear stress, wall static pressure, and turbulence intensity. The comparisons show that results predicted by the low-Re model are in good agreement with the experimental measurements. This model accurately predicts the critical Reynolds number at which blood flow becomes transitional or turbulent distal an arterial stenosis. Most interestingly, over the Re range of laminar flow, the vortex length calculated with the low-Re model also closely matches the vortex length predicted by laminar flow modeling. In conclusion, the study strongly suggests that the proposed model is suitable for blood flow studies in certain areas of the arterial tree where both laminar and transitional/turbulent flows coexist.     

Targeting LSD1 suppresses stem cell-like properties and sensitizes head and neck squamous cell carcinoma to PD-1 blockade

Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive tumor with poor clinical outcomes due to recurrence, metastasis, and treatment resistance. Cancer stem cells (CSCs), a small population among tumor cells, are proposed to be responsible for tumor initiation, progression, metastasis, drug resistance, and recurrence. Here we show that high LSD1 expression was a predictor of poor prognosis for HNSCC patients. We found that high expression of LSD1 is essential for the maintenance of the CSC properties by regulating Bmi-1 expression. Moreover, tumor LSD1 ablation suppresses CSC-like characteristics in vitro and inhibits tumorigenicity in vivo in immune-deficient xenografts. However, this deletion induces the upregulation of PDL1 levels, which compromises antitumor immunity and reduces antitumor efficacy in an immune-competent mouse model. Functionally, the combination of LSD1 inhibitor and anti-PD-1 monoclonal antibody can overcome tumor immune evasion and greatly inhibit tumor growth, which was associated with reduced Ki-67 level and augmented CD8⁺ T cell infiltration in immunocompetent tumor-bearing mouse models. In summary, these findings provide a novel and promising combined strategy for the treatment of HNSCC using a combination of LSD1 inhibition and PD-1 blockade.Subject terms: Oral cancer, Stem-cell research     

Solvation-Driven Grain Boundary Passivation Improving the Performance of Perovskite Solar Cells

The efficiency of perovskite solar cells (PSCs) is hindered by substantial defects within the grain boundaries (GBs) of polycrystalline perovskite films. Conventional post-treatment strategies struggle to precisely repair these defects at GBs. Here, a targeted grain boundary passivation strategy through solvent effects by incorporating symmetrical biphenyl molecules is proposed, 4,4′-diaminodiphenyl sulfone (DDS) and 4,4′-sulfodiphenol (SDP), aiming to mitigate defects at GBs and optimize energy level arrangements through their electric dipole effects. Compared to the pristine device, the SDP-modified device exhibits significant improvements, including a champion efficiency of 24.39% and an impressive fill factor, along with excellent operation stability. This work provides an effective and straightforward solution for improving the performance of PSCs.     

水稻糯性相关基因的全基因组关联分析

利用1 090 071个SNP标记, 对419份广西地方稻种资源核心种质的糯性进行全基因组关联分析。结果表明, 运用混合线性模型, 在P<4.72×10^-8 (4.72E-8)水平下, 检测到45个与糯性显著关联的SNP位点, 均位于第6号染色体上。通过筛选显著关联位点上、下游各150 kb区域内的基因, 共找到305个候选基因, 其中包含2个与淀粉合成酶相关的Wx和SSIIa基因; 同时在第6号染色体5.69-5.89 Mb区域发现4个与糯性显著关联的SNP位点, 该区域可能是影响水稻(Oryza sativa)糯性的重要候选区域。     

Rapid and reliable detection of 11 food-borne pathogens using thin-film biosensor chips

Traditional methods for identifying food-borne pathogens are time-consuming and laborious, so it is necessary to develop innovative methods for the rapid identification of food-borne pathogens. Here, we report the development of silicon-based optical thin-film biosensor chips for sensitive detection of 11 food-borne pathogens. Briefly, aldehyde-labeled probes were arrayed and covalently attached to a hydrazine-derivatized chip surface, and then, biotinylated polymerase chain reaction (PCR) amplicons were hybridized with the probes. After washing and brief incubation with an antibiotin immunoglobulin G–horseradish peroxidase conjugate and a precipitable horseradish peroxidase substrate, biotinylated chains bound to the probes were visualized as a color change on the chip surface (gold to blue/purple). Highly sensitive and accurate examination of PCR fragment targets can be completed within 30 min. This assay is extremely robust, sensitive, specific, and economical and can be adapted to different throughputs. Thus, a rapid, sensitive, and reliable technique for detecting 11 food-borne pathogens was successfully developed.     

Novel urushiol derivatives as HDAC8 inhibitors: rational design,virtual screening,molecular docking and molecular dynamics studies

Three series of novel urushiol derivatives were designed by introducing a hydroxamic acid moiety into the tail of an alkyl side chain and substituents with differing electronic properties or steric bulk onto the benzene ring and alkyl side chain. The compounds’ binding affinity toward HDAC8 was screened by Glide docking. The highest-scoring compounds were processed further with molecular docking, MD simulations, and binding free energy studies to analyze the binding modes and mechanisms. Ten compounds had Glide scores of ?8.2 to ?10.2, which revealed that introducing hydroxy, carbonyl, amino, or methyl ether groups into the alkyl side chain or addition of –F, –Cl, sulfonamide, benzamido, amino, or hydroxy substituents on the benzene ring could significantly increase binding affinity. Molecular docking studies revealed that zinc ion coordination, hydrogen bonding, and hydrophobic interactions contributed to the high calculated binding affinities of these compounds toward HDAC8. MD simulations and binding free energy studies showed that all complexes possessed good stability, as characterized by low RMSDs, low RMSFs of residues, moderate hydrogen bonding and zinc ion coordination and low values of binding free energies. Hie147, Tyr121, Phe175, Hip110, Phe119, Tyr273, Lys21, Gly118, Gln230, Leu122, Gly269, and Gly107 contributed favorably to the binding; and Van der Waals and electrostatic interactions provided major contributions to the stability of these complexes. These results show the potential of urushiol derivatives as HDAC8 binding lead compounds, which have great therapeutic potential in the treatment of various malignancies, neurological disorders, and human parasitic diseases.     

EB病毒潜伏膜蛋白1诱导人鼻咽上皮细胞端粒酶的表达

Telomerase activation has been linked to cell immortalization in vitro and tumorigenicity in vivo. In this study, for the first, we reported that Epstein-Barr virus activated the telomerase activity of human nasopharyngeal epithelial cells in the early stage of immortalization as tested by the PCR-ELISA. The telomerase activity in nasopharyngeal epithelial cells was only observed in presenescent cells. It was implicated that Epstein-Barr virus induced the escape of nasopharyngeal epithelial cells from senescence via the activation of telomerase. We further showed that telomerase activation in infected cells was dependent on the protein level of latent membrane protein 1 (LMP1) encoded by Epstein-Barr virus using a Tetracycline regulatory cell line expressing LMP1, pTet-on-LMP1-HNE2. The activity of telomerase in nasopharyngeal cells was decreased when the protein level of LMP1 was blocked by antisense LMP1 plasmid DNA. And the activity of telmerase was also related to the carboxyl terminus of LMP1. It was implicated that the ability of Epstein-Barr virus to suppress senescence is associated with telomerase activation by LMP1.