Research Progress on Targets and Selective Inhibitors of Polo-like Kinase-1(PLK-1)

In this paper,the biological function of PLK-1,the correlation between PLK-1 and tumors,and the latest research progress on PLK-1 inhibitors under study are reviewed,in order to provide references for the research and development of PLK-1 inhibitors.

Burnup analysis for the pebble-bed fluoride-salt-cooled high-temperature reactor based on the energy-dependent elastic scattering cross-sectional model

To carry out accurate burnup calculations for a pebble-bed fluoride-salt-cooled high-temperature reactor,the energy-dependent cross-sectional model based on the Doppler broadening rejection correction method has been proposed to develop the energy-dependent elastic scattering cross-sectional model. In this study, the Monte Carlo continuous energy code PSG2/Serpent was used to examine the difference between the constant cross-sectional model and the energy-dependent cross-sectional model during burnup. For the cases analyzed in this study,numerical simulations show that the multiplication coefficient was improved by hundreds pcm and ^(239)Pu concentration was improved by approximately 1–2% during burnup when the energy-dependent elastic scattering crosssectional model is considered.

黏着斑激酶抑制剂TAE226对人口腔鳞状细胞癌细胞上皮间质转化的影响

目的探究黏着斑激酶抑制剂TAE226对人口腔鳞状细胞癌细胞上皮间质转化(EMT)过程的影响。方法不同浓度(0、1、5、10μmol·L-1)的TAE226作用于人口腔鳞状细胞癌HSC-3和HSC-4细胞24、48、72 h后,实时定量聚合酶链反应检测EMT标志物E-钙黏蛋白(E-cadherin)、波形蛋白(Vimentin)的mRNA表达;蛋白质印迹法检测E-cadherin、Vimentin在TAE226作用48 h后的蛋白表达。结果实时定量聚合酶链反应检测表明,随着TAE226作用时间和浓度的增加,E-cadherin mRNA的表达增加,Vimentin mRNA的表达降低(P<0.05)。蛋白质印迹法检测表明,随着TAE226浓度的增加,E-cadherin蛋白的表达增加,Vimentin蛋白的表达降低(P<0.05)。结论TAE226能有效抑制人口腔鳞状细胞癌细胞株的EMT进程,有望成为治疗口腔鳞状细胞癌的有效药物之一。

6005A FSW接头金属运动行为研究

采用搅拌摩擦焊对6005A进行焊接,并对垂直、平行焊接方向接头不同区域的组织进行研究。结果表明:搅拌摩擦焊接头前进侧金属运动迹象大于后退侧,前进侧"匙孔"边缘底部基本保留了搅拌针形貌;在垂直焊缝方向,前进侧晶粒呈明暗带状分布的"洋葱环"结构,距离焊缝中心越远越明显,后退侧组织致密且过渡平缓;在平行焊缝方向,前进侧边缘塑性金属运动痕迹强烈,为连续锯齿状形貌,该形貌向焊缝中心逐渐减弱并消失于后退侧。

基于威布尔分布的APU二级涡轮叶片可靠性分析

收集并统计某型APU的二级涡轮叶片部分故障数据作为样本,并分别导入至MINITAB、M ATLAB中,通过比较分布、概率图分析出适合样本数据的寿命分布函数。在分布函数线性化基础上利用最小二乘法并借助于MATLAB编程对样本数据进行拟合,计算分布函数相关参数并进行分布拟合精度检验,绘制其对应的概率分布函数、概率密度函数、可靠度函数等。基于分布函数模型评估二级涡轮叶片在一定使用寿命下的累积失效概率、可靠度并为APU维修提供参考。

Photoacoustic nanoprobe forβ-galactosidase activity detection and imaging in vivo

Detection and visualization ofβ-galactosidase(β-gal)is essential to reffect its physiological and pathological effects on human health and disease,but it is still challenging to precisely trackβ-gal in vivo owing to the limitation of current analytical methods.In our work,we reported a photoacoustic(PA)nanoprobe for selective imaging of the endogenousβ-gal in vivo.Our nanoprobe Cy7-β-gal-LP was constructed by encapsulation of a near-infra red(NIR)dye Cy7-β-gal within a liposome(LP,DSPE-PEG2000-COOH).The dye Cy7-β-gal was synthesized based on a dye Cy-OH where the hydroxyl group was replaced by aβ-D-galactopyranoside residue,which can be recognized byβ-gal as an enzyme hydrolytic site.With the addition ofβ-gal,the absorbance of Cy7-β-gal exhibited a significant red shift with the absorption peak moved from 600 nm to 680 nm,which should generate a switch-on PA signal at 680 nm in the presence ofβ-gal.In addition,as theffuorescence of the dye was totally quenched due to aggregation within the liposome,Cy7-β-gal-LP exhibited high PA conversion efficiency.With the nanoprobe,we achieved the selective PA detection and imaging ofβ-gal in the tumor-bearing mice.

Effect of low protein diet combined with drug therapy on renal function and oxidation - anti-oxidation balance in patients with diabetic nephropathy

Objective:To study the effect of low protein diet combined with drug therapy on renal function and oxidation - anti-oxidation balance in patients with diabetic nephropathy.Methods: Patients with diabetic nephropathy who were treated in the Second People's Hospital of Deyang City between July 2014 and March 2017 were collected, retrospectively analyzed and then divided into two groups according to the application of low protein diet intervention or not, observation group received low protein diet combined with drug therapy, and control group accepted routine drug therapy. The contents of renal function indexes, oxidative products and antioxidant indexes in serum as well as the expression of podocyte injury markers in urine were measured before treatment and 3 months after treatment.Results: 3 months after treatment, BUN, Scr, CysC, Hcy, MDA and AOPP contents in serum as well asα-actinin-4, ZO-1, nephrin and podocinde mRNA expression in urine of both groups were lower than those before treatment whereas CAT, SOD and T-AOC contents in serum were higher than those before treatment, and BUN, Scr, CysC, Hcy, MDA and AOPP contents in serum as well asα-actinin-4, ZO-1, nephrin and podocinde mRNA expression in urine of observation group were lower than those of control group whereas CAT, SOD and T-AOC contents in serum were higher than those of control group.Conclusion:Low protein diet combined with drug therapy can improve the renal function and the oxidation - anti-oxidation balance in patients with diabetic nephropathy.

Single-nucleus RNA sequencing reveals heterogeneity among multiple white adipose tissue depots

Regardless of its anatomical site,adipose tissue shares a common energy-storage role but exhibits distinctive properties.Exploring the cellular and molecular heterogeneity of white adipose tissue(WAT)is crucial for comprehending its function and properties.However,existing single-nucleus RNA sequencing(snRNA-seq)studies of adipose tissue heterogeneity have examined only one or two depots.In this study,we employed snRNA-seq to test five representative depots including inguinal,epididymal,mesenteric,perirenal,and pericardial adipose tissues in mice under physiological conditions.By analyzing the contents of main cell catego-ries and gene profiles of various depots,we identified their distinctive physiological properties.Immune cells and fibro-adipogenic progenitor cells(FAPs)showed dramatic differences among WAT depots,while adipocytes seemed to be conserved.The heightened presence of regulatory macrophages and B cells in pericardial adipose tissues implied their potential contribution to the preservation of coronary vascular function.Moreover,the selective aggregation of pericytes within mesenteric adipose tissue was likely associated with the maintenance of intestinal barrier homeostasis.Using a combination of RNA sequencing and snRNA-seq analysis,the major subpopulations of FAPs derived from these depots determined the site characteristics of FAPs to a certain extent.Our work estab-lishes a systematic and reliable foundation for investigating the heterogeneity of WAT depots and elucidating the unique roles these depots play in coordinating the function of adjacent organs.

基于深度学习的区域背光亮度提取方法

在分析现有算法的优缺点的基础上,尽可能考虑各种类型的图像,基于发光二极管-液晶显示器直下式图像视频显示原理样机,提出了一种可靠有效的基于区域背光亮度提取的数据测量方法,并提出了一种高效实用的基于深度学习的背光亮度提取方法。该方法基于采用多层下采样结构的神经网络,综合提取图像特征,获得最优的背光。实验结果表明,该方法可以提高图像显示质量和扩大图像的动态范围,而网络结构中有无旁路的对比实验结果验证了所提方法的优越性和有效性。

Efficacy of probiotics or synbiotics for critically ill adult patients:a systematic review and meta-analysis of randomized controlled trials

Background:Microbial dysbiosis in critically ill patients is a leading cause of mortality and septic complications.Probiotics and synbiotics have emerged as novel therapy on gut microbiota to prevent septic complications.However,current evidence on their effects is conflicting.This work aims to systematically review the impact of probiotics or synbiotics in critically ill adult patients.Methods:A comprehensive search of the PubMed,CBM,Embase,CENTRAL,ISI,and CNKI databases was performed to identify randomized controlled trials that evaluate probiotics or synbiotics in critically ill patients.The quality assessment was based on the modified Jadad’s score scale and the Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1.The major outcome measure was mortality.Secondary outcomes included incidence of septic complications,sepsis incidence,length of intensive care unit(ICU)stay,incidence of non-septic complication,and ventilator day.Data synthesis was conduct by Review Manager 5.4.Results:A total of 25 randomized controlled trials reporting on 5049 critically ill patients were included.In the intervention group,2520 participants received probiotics or synbiotics,whereas 2529 participants received standard care or placebo.Pooling data from randomized controlled trials demonstrated a significant reduction in the incidence of ventilator-associated pneumonia(VAP)in the treatment group[(risk ratio(RR)0.86;95%confidence interval(CI):0.78-0.95;p<0.003,I^(2)=85%)].However,in the subgroup analysis,the reduction of incidence of VAP was only significant in patients receiving synbiotics(RR=0.61,95%CI:0.47-0.80,p=0.0004,I^(2)=40%)and not significant in those receiving only probiotics(RR=0.91,95%CI:0.82-1.01,p=0.07,I^(2)=65%).Moreover,sepsis incidence of critically ill patients was only significantly reduced by the addition of synbiotics(RR=0.41;95%CI:0.22-0.72,p=0.005,I^(2)=0%).The incidence of ICU-acquired infections was significantly reduced by the synbiotics therapy(RR=0.72;95%CI:0.58-0.89,p=0.0007,I^(2)=79%).There was no significant difference in mortality,diarrhea,or length of ICU stay between the treatment and control groups.Conclusions:Synbiotics is an effective and safe nutrition therapy in reducing septic complications in critically ill patients.However,in such patients,administration of probiotics alone compared with placebo resulted in no difference in the septic complications.

Light-responsive charge-reversal nanovector for high-efficiency in vivo CRISPR/Cas9 gene editing with controllable location and time

Controllably and efficaciously localized CRISPR/Cas9 plasmids transfection plays an essential role in genetic editing associated with various key human diseases.We employed near-infrared(NIR)light-responsive CRISPR/Cas9 plasmids delivery via a charge-reversal nanovector to achieve highly efficient and site-specific gene editing.The nanovector with abundant positive charges was fabricated on the basis of an ultraviolet-sensitive conjugated polyelectrolyte coated on an upconversion nanomaterial(UCNP-UVP-P),which can convert into negative charges upon 980 nm light irradiation.Using the as-prepared nanovector,we demonstrated the plasmids could be efficiency transfected into tumor cells(~63%±4%)in a time-contolled manner,and that functional CRISPR/Cas9 proteins could be successfully expressed in a selected NIR-irradiated region.Particularly,this strategy was successfully applied to the delivery of CRISPR/Cas9 gene to tumor cells in vivo,inducing high efficiency editing of the target gene PLK-1 under photolrradiation.Therefore,this precisely controlled gene regulation strategy has the potential to serve as a new paradigm for gene engineering in complex biological systems.

空心铝挤压型材焊合扩口试验失效分析

通过成分检测、金相测试、横向拉伸测试及扫描电镜观察,对铝合金地板空心挤压型材焊合扩口试验失效的原因进行分析。根据分析结果得出:空心铝挤压型材焊合扩口试验失效的主要原因为焊合位置存在粘结界面,粘结界面与铝合金基体组织不连续。在扩口试验的外力作用下,在粘结界面与铝合金型材组织观察不连续处萌发裂纹,引发扩口试验失效。扩口试验的失效位置与正常位置处的横向拉伸试验的结果表明,抗拉强度、屈服强度下降明显,伸长率降低至2.3%,低于要求值8%;拉伸试样的断口齐平,为典型的脆性断裂。扩口试验失效处横向拉伸断口的宏观形貌表现出层状、不连续现象,通过SEM观察可知,焊合扩口试验失效处无韧窝特征,存在明显的裂纹及空腔。

The morphology of hydroxyapatite nanoparticles regulates clathrinmediated endocytosis in melanoma cells and resultant anti-tumor efficiency

Clathrin-mediated endocytosis plays a critical role for hydroxyapatite nanoparticles(HANPs)to enter tumor cells,induce mitochondrial apoptosis,and inhibit tumor growth.This study was aimed to investigate how the morphology of HANPs impacts the endocytosis of the particles in melanoma cells,and their anti-tumor effect by using in vitro cell experiments and in vivo tumor animal model.Three shapes of HANPs,including granular HANPs(G-HANPs),rod-like HANPs(R-HANPs),and needle-like HANPs(N-HANPs),were successfully prepared by wet chemical method.All the three HANPs could be internalized into A375 melanoma cells as indicated by cellular transmission electron microscopy images.Among these HANPs,only G-HANPs induced morphological change of mitochondria and loss of mitochondrial membrane potential(Δψm),and exhibited the greatest intracellular internalization efficiency in the tumor cells.Furthermore,the results of immunofluorescence staining and western blotting indicated that the level of adaptin-2(AP2)protein was up-regulated by all the HANPs,and highest in G-HANPs treated A375 cells.Moreover,in the tumor-bearing mouse model,we found that tumor growth was delayed by all the three HANPs,of which,G-HANPs delayed tumor growth most efficiently and presented a highest expression level of AP2 protein in tumor tissues.Therefore,this study suggested that the morphology of HANPs regulated their endocytosis efficiency and their effect to inhibit tumor growth.This work facilitates to direct the rational design of nano-materials for tumor therapy.

Hydroxyapatite nanoparticles drive the potency of Toll-like receptor 9 agonist for amplified innate and adaptive immune response

The potency of Toll-like receptor 9(TLR9)agonist to drive innate immune response was limited due to immune suppression or tolerance during TLR9 signaling activation in immune cells.Herein we addressed this problem by introducing hydroxyapatite nanoparticles(HANPs)to CpG ODN(CpG),a TLR9 agonist.The study revealed that HANPs concentration and durationdependently reprogramed the immune response by enhancing the secretion of immunostimulatory cytokines(tumor necrosis factorα(TNFα)or IL-6)while reducing the production of immunosuppressive cytokine(IL-10)in macrophages in response to CpG.Next,the enhanced immune response benefited from increased intracellular Ca2+in macrophage by the addition of HANPs.Further,we found exposure to HANPs impacted the mitochondrial function of macrophages in support of the synthesis of adenosine triphosphate(ATP),the production of nicotinamide adenine dinucleotide(NAD),and reactive oxygen species(ROS)in the presence or absence of CpG.In vaccinated mice model,only one vaccination with a mixture of CpG,HANPs,and OVA,a model antigen,allowed the development of a long-lasting balanced humoral immunity in mice without any histopathological change in the local injection site.Therefore,this study revealed that HANPs could modulate the intracellular calcium level,mitochondrial function,and immune response in immune cells,and suggested a potential combination adjuvant of HANPs and TLR9 agonist for vaccine development.

Aza-BODIPY-based phototheranostic nanoagent for tissue oxygen auto-adaptive photodynamic/photothermal complementary therapy

Tumor oxygen spatial heterogeneity is a critical challenge for the photodynamic inhibition of solid tumors.Development of an intelligent nanoagent to initiate optimal therapeutics according to the localized oxygen levels is an effective settlement.Herein,we report an activatable nanoagent(BDP-Oxide nanoparticles(NPs))to enable the oxygen auto-adaptive photodynamic/photothermal complementaly treatment.Upon the nanoagent accumulated in the tumor region,the low extracellular pH could trigger the disassociation of the nanoagent to release the phototheranostic agent,BDP-Oxide,which will subsequently afford the fluorescence imaging-guided photodynamic oxidation after it gets into the outer oxygen-rich tumors.Along with the penetration deepening in the solid tumor,furthermore,BDP-Oxide could be reduced into BDP by the cytochrome P450(CYP450)enzymes activated in the low oxygen tension regions of inner hypoxic tumors,which will switch on the photothermal and photoacoustic effects.Overall,the BDP-Oxide NPs-enabled photodynamic/photothermal complementary therapy significantly suppressed the solid tumor growth(inhibition rate of 94.8%).This work proposes an intelligent platform to address the oxygen partial pressure for the optimization of cancer phototherapeutics.

Novel photoelectrochemical immunosensor for MCF-7 cell detection based on n-p organic semiconductor heterojunction

In this work,we developed a novel photoelectrochemical(PEC)sensor based on n-p organic semiconductor heterojunction for sensitive detecting MCF-7 cancer cells.BTA-C4 Ph and PM6 were designed as photoactive materials to form n-p heterojunction,which greatly enhanced the photoelectric conversion efficiency.Antibody-modified magnetic nanoparticles were utilized to capture and separate MCF-7 cells from samples.Detection of MCF-7 is ascribed to the loading of MCF-7 onto BTA-C4 Ph-PM6 modified electrode that resulted in the decrease of photocurrent intensity.The PEC immunosensor displayed a linear concentration ranging from 50 cell/m L to 1×10^(4) cell/m L with a limit of detection(LOD)of 41 cell/m L(S/N=3)for MCF-7.Additionally,the senor also exhibited good stability,excellent selectivity and prominent reproducibility.Furthermore,the sensor was successfully applied to detect MCF-7 in whole blood.This work illustrates that n-p heterojunction of organic semiconductor may find wide applications for the preparation of different photoelectrochemical sensors.

Feasibility Study of Mixing Throat Swab Samples for Severe Acute Respiratory Syndrome Coronavirus-2 Screening

Dear Editor,The outbreak of coronavirus disease 2019(COVID-19)has been declared a pandemic by the World Health Organization(WHO)and has resulted in the worst public health crisis since World War II(Wang et al.2020).