Uncoupling tumor necrosis factor-α and interleukin-10 at tumor immune microenvironment of breast cancer through miR-17-5p/MALAT-1/H19 circuit

Triple Negative Breast Cancer (TNBC) immunotherapy has recently shown promising approach. However, some TNBC patients presented with resistance. One of the reasons was attributed to the excessive release of cytokines at the tumor microenvironment (TME) such as Tumor necrosis factor alpha (TNF-α) and Interleukin-10 (IL-10). Fine regulation of these cytokines’ levels via non-coding RNAs (ncRNAs) might alleviate the immune quiescent nature of TME at TNBC tumors. However, the extrapolation of ncRNAs as therapeutic tools is highly challenging. Therefore, disentanglement the nature for the isolation of natural compounds that could modulate the ncRNAs and their respective targets is an applicable translational therapeutic approach. Hence, this study aimed to targeting the chief immune suppressive cytokines at the TME (TNF-α and IL-10) via ncRNAs and to examine the effects of Rosemary aerial parts extract on the expression levels of these ncRNAs in TNBC. Results revealed miR-17-5p as a dual regulator of TNF-α and IL-10. Moreover, an intricate interaction has been shown between miR-17-5p and the oncogenic lncRNAs: MALAT1 and H19. Knocking down of MALAT1 and/or H19 caused an induction in miR-17-5p and reduction in TNF-α and IL-10 expression levels. miR-17-5p was found to be down-regulated, while TNF-α, IL-10, MALAT1 and H19 were up-regulated in BC patients. Forced expression of miR-17-5p in MDA-MB-231 cells reduced TNF-α, IL-10, MALAT1 and H19 expression levels, as well as several BC hallmarks. In a translational approach, ursolic acid (UA) isolated from rosemary induced the expression of miR-17-5p, MALAT1 and decreased H19 expression levels. In conclusion, this study suggests miR-17-5p as a tumor suppressor and an immune-activator miRNA in BC through tuning up the immunological targets TNF-α, IL-10 at the TME and the oncological mediators MALAT1 and H19 lncRNAs.     

Towards efficient device-to-device multicast content delivery with social awareness

Frequent content retrieval leads to significant energy consumption in cellular networks. Thereby, device-to-device (D2D) communication is used for proximal content delivery. Be aware that social friends may have common content interests, D2D content delivery is further improved by considering social network. However, how to implement efficient D2D multicast with the aid of social relationship needs further consideration. In this paper, with a proposed architecture on combined networks, the cooperation range of content sharing is investigated for D2D multicast to minimize the average energy consumption of serving a content request. Based on combined networks, a cooperation group formation scheme is proposed. Simulation results verify our analyzes and the advantage of proposed scheme.     

5CrNiMoV钢马氏体相变塑性和应力对其相变动力学的影响

利用DIL-805ADT动态相变膨胀仪测定了5CrNiMoV钢在低于奥氏体屈服强度的应力下的马氏体相变膨胀曲线,根据膨胀曲线分析并计算出了不同应力下Greenwood-Johnson相变塑性机制中的相变塑性系数k值和Koistinen-Marburger马氏体相变动力学模型中α和Ms的值,并且将Greenwood-Johnson模型和Leblond模型计算结果与实际试验值对比。结果显示:k值随应力的变化有所波动,但趋近于一个定值;通过对比,Leblond模型更符合试验结果;Ms点随着应力的增大呈现微小的上升趋势,说明小于或等于80 MPa 的应力对Ms点的影响不显著;拉应力下α值普遍大于无应力下的α值,压应力下α值普遍小于无应力下的α值,说明拉应力对相变有一定的促进作用,压应力对相变有一定的阻碍作用。     

DRD2和5-HTR2A基因多态性及其交互作用对奥氮平治疗精神分裂症疗效的影响

目的：探讨多巴胺D2受体（dopamine D2 receptor, DRD2）和5-羟色胺2A受体（5-hydroxytryptamine 2A receptor, 5-HTR2A）基因多态性及其交互作用与奥氮平治疗精神分裂症疗效的关系。方法：纳入147例接受单一奥氮平治疗的精神分裂症住院患者为研究对象，采用阳性与阴性症状量表（PANSS）评定药物疗效，按PANSS减分率≥50%和<50%，分为有效组和无效组。采用多重高温连接酶检测反应技术（iMLDR）检测DRD2（rs1799978、rs1800497）和5-HTR2A（rs6311、rs6313）基因多态性；采用多因素Logistic回归分析各基因型和奥氮平疗效的关联性，采用多因子降维法（MDR）分析基因-基因的交互作用。结果：有效组和无效组rs1799978、rs6313位点基因型和等位基因频率分布差异均有统计学意义（P<0.05），而两组rs1800497、rs6311位点基因型和等位基因频率分布差异均无统计学意义（P>0.05）；rs1799978位点GA和GG型患者奥氮平疗效较野生AA型好，其比值比（OR）及95%CI分别为5.101（1.118～23.267）、6.051（2.454～14.925）；rs6313位点CT和CC型患者奥氮平疗效较野生TT型好，其OR及95%CI分别为2.623（1.054～6.528）、3.412（1.180～9.869）；rs1799978、rs1800497和rs6313位点间存在交互作用，其交互模型为最优基因-基因交互作用模型（P<0.05），该模型检验样本准确度为0.727 3，交叉验证一致性为10/10。结论：DRD2（rs1799978）和5-HTR2A（rs6313）基因多态性可能与奥氮平治疗精神分裂症疗效相关，DRD2（rs1799978、rs1800497）和5-HTR2A（rs6313）对奥氮平疗效的影响存在交互作用。     

[学科发展]5D打印——生物功能组织的制造

生物制造是制造技术与生命科学技术交叉融合产生的新兴学科方向，这一学科方向的发展将为巨大的人体组织与器官市场提供新技术，同时也给制造技术变革带来新机遇。面向生物制造未来发展，提出5D打印制造概念，论述了5D打印的内涵，分析了其关键技术。结合生物制造技术的现有进展，介绍了研究团队在心肌组织支架的制造、类脑神经组织制造、爬行生命机械混合机器人方面取得的初步研究进展，为生物制造技术拓展新方向提供新思路。     

Mechanical and thermal properties of light weight boron-mullite Al5BO9

Al₅BO₉ is a promising thermal sealing material for hypersonic vehicles due to its low density, theoretically predicted low shear modulus, and low thermal conductivity. However, experimental investigations on the mechanical and thermal properties of bulk Al₅BO₉ have not been carried out. Herein, we report the mechanical and thermal properties of bulk Al₅BO₉ prepared by spark plasma sintering of solid-state reaction synthesized Al₅BO₉ powders. The bulk (B), shear (G), and Young's (E) moduli are 148 GPa, 85 GPa, and 214 GPa, respectively, which are close to the theoretical values. The Pugh's ratio G/B is 0.574, indicating its intrinsic damage tolerance, which is also revealed by Hertzian contact test. The Vickers hardness (H_v) is 10.8 GPa, being lower than mullite. The flexural strength, compressive strength, and fracture toughness are, respectively, 277 ± 35 MPa, 814 ± 75 MPa, and 2.4 ± 0.3 MPa·m^1/2, which are close to those of mullite. Al₅BO₉ has anisotropic coefficient of thermal expansion (CTE) in three crystallographic directions, ie α_a = (4.40 ± 0.21) × 10⁻⁶ K⁻¹, α_b = (7.11 ± 0.18) × 10⁻⁶ K⁻¹, α_c = (6.70 ± 0.29) × 10⁻⁶ K⁻¹ from Debye temperature to 1473 K, which are underpinned by its structural feature, ie lower α_a is resulted from the edge-shared AlO₆ octahedron chains along the [100] direction. The average CTE is (6.05 ± 0.06) × 10⁻⁶ K⁻¹. The thermal conductivity declines with temperature as κ = 1336.39/T + 1.97, consisting with predicted trend from Slack's model. The low thermal conductivity and low density guarantee Al₅BO₉ a promising candidate as ceramic wafer in the seal structure for hypersonic vehicles.     

钽表面铜掺杂Ta2O5纳米棒的制备及抗菌性能研究

本实验采用两步水热法在钽基体表面制备出掺杂Cu_²⁺的Ta₂O₅纳米棒薄膜。采用XRD、SEM、XPS等方法分析了材料的物相和表面微观结构。用ICP检测了样品在生理盐水中离子析出浓度,最后通过平板计数法检验了不同含量铜掺杂Ta₂O₅薄膜的抗菌能力。结果表明,通过两步水热处理,在钽表面生成了简单斜方晶体结构的Ta₂O₅纳米棒阵列,Cu_²⁺的掺杂不会对纳米棒薄膜的微观形貌和物相造成显著影响。随时间的增加,掺铜薄膜的铜离子析出速率逐渐趋于平缓。平板计数法表明,Cu_²⁺ 的掺杂量达到2.68At%时,铜掺杂Ta₂O₅纳米棒薄膜的抗菌性能最好,抗菌率达99.2%。     

Effect of α phase morphology on fatigue crack growth behavior of Ti−5Al−5Mo−5V−1Cr−1Fe alloy

Taking a Ti−5Al−5Mo−5V−1Cr−1Fe alloy as exemplary case, the fatigue crack growth sensitivity and fracture features with various tailored α phase morphologies were thoroughly investigated using fatigue crack growth rate (FCGR) test, optical microscopy (OM) and scanning electron microscopy (SEM). The tailored microstructures by heat treatments include the fine and coarse secondary α phase, as well as the widmanstatten and basket weave features. The sample with coarse secondary α phase exhibits better comprehensive properties of good crack propagation resistance (with long Paris regime ranging from 15 to 60 MPa·m^1/2), high yield strength (1113 MPa) and ultimate strength (1150 MPa), and good elongation (11.6%). The good crack propagation resistance can be attributed to crack deflection, long secondary crack, and tortuous crack path induced by coarse secondary α phase.     

Comprehensive mutagenesis on yeast cytosine deaminase yields improvements in 5-fluorocytosine toxicity in HT1080 cells

Improved prodrug-activating enzymes have the potential to increase the therapeutic efficacy of gene-directed enzyme prodrug therapy (GDEPT). Yeast cytosine deaminase (yCD) is commonly used to convert the prodrug 5-fluorocytosine (5-FC) to the chemotherapeutic 5-fluorouracil for GDEPT. Mutagenesis studies on yCD aimed at improving its application in GDEPT have been limited to subsets of residues or have sought to improve a single property of the enzyme. We performed comprehensive site-saturation mutagenesis (CSM) on yCD designed to create all 2,983 possible unique protein mutants with a single amino acid substitution. We identified active variants through Escherichia coli genetic complementation and screened these mutants, and combinations thereof, for increased ability to sensitize E. coli and HT1080 fibrosarcoma cells to 5-FC. Several mutants identified in this study showed increased sensitization ability for both E. coli and HT1080 cells indicating that CSM is an effective directed evolution tool for identifying unexpectedly beneficial mutations.     

胡尖山地区长4+5层油气富集控制因素研究

胡尖山地区长4+5油层组储层非均质性强、物性差异较大,开展该区储层地质特征研究,尤其是针对胡尖山地区长4+5油层组的构造形态、储层特征、孔隙类型、油藏类型的研究,分析原油的分布特征,总结原油富集区的聚集特征、重点分析分布特征及控制因素,得到胡尖山地区长4+5层油气富集的规律,可加深对优质储层形成机理和分布规律的认识,为油藏勘探开发提供有利的方向。