Aptamer/Peptide-Functionalized Genome-Editing System for Effective Immune Restoration through Reversal of PD-L1-Mediated Cancer Immunosuppression

Effective reversal of tumor immunosuppression is of critical importance in cancer therapy. A multifunctional delivery vector that can effectively deliver CRISPR-Cas9 plasmid for β-catenin knockout to reverse tumor immunosuppression is constructed. The multi-functionalized delivery vector is decorated with aptamer-conjugated hyaluronic acid and peptide-conjugated hyaluronic acid to combine the tumor cell/nuclear targeting function of AS1411 with the cell penetrating/nuclear translocation function of TAT-NLS. Due to the significantly enhanced plasmid enrichment in malignant cell nuclei, the genome editing system can induce effective β-catenin knockout and suppress Wnt/β-catenin pathway, resulting in notably downregulated proteins involved in tumor progression and immunosuppression. Programmed death-ligand 1 (PD-L1) downregulation in edited tumor cells not only releases the PD-1/PD-L1 brake to improve the cancer killing capability of CD8⁺ T cells, but also enhances antitumor immune responses of immune cells. This provides a facile strategy to reverse tumor immunosuppression and to restore immunosurveillance and activate anti-tumor immunity.     

基于CFD方法的铅铋冷却燃料棒束的热工水力特性分析

铅铋冷却快堆作为第4代反应堆候选之一具有安全性高等特点，研究其在正常工况下的热工水力特性具有重要意义。本文基于商用计算流体力学（CFD）软件STAR-CCM+，使用流固耦合的方法对带有绕丝结构的19棒束铅铋组件进行数值分析，探究了质量流量、功率等边界条件对组件内部流动传热特性的影响。模拟计算结果表明：CFD方法在子通道中心温度和壁面温度预测上与实验结果取得了较好的一致。同时，绕丝结构的存在使得子通道之间存在周期性的横向交混，并使得棒束表面温度呈现震荡。随质量流量的增加，子通道间横向交混增大。功率变化对通道间的横向交混速度的影响较小，冷却剂温度的横向分布无明显差异。     

Three-dimensional immersed finite-element method for anisotropic magnetostatic/electrostatic interface problems with nonhomogeneous flux jump

Anisotropic diffusion is important to many different types of common materials and media. Based on structured Cartesian meshes, we develop a three-dimensional (3D) nonhomogeneous immersed finite-element (IFE) method for the interface problem of anisotropic diffusion, which is characterized by an anisotropic elliptic equation with discontinuous tensor coefficient and nonhomogeneous flux jump. We first construct the 3D linear IFE space for the anisotropic nonhomogeneous jump conditions. Then we present the IFE Galerkin method for the anisotropic elliptic equation. Since this method can efficiently solve interface problems on structured Cartesian meshes, it provides a promising tool to solve the physical models with complex geometries of different materials, hence can serve as an efficient field solver in a simulation on Cartesian meshes for related problems, such as the particle-in-cell simulation. Numerical examples are provided to demonstrate the features of the proposed method.     

pazopanib血药浓度个体差异与细胞色素P450 3A4基因多态性的关系初探

目的：分析健康受试者口服pazopanib片后体内药代动力学（PK）规律，初步探讨pazopanib片PK个体差异的遗传学机制。方法：14例健康男性受试者分别在给药当天单次口服pazopanib片（200 mg）后，采集基线至96 h血液样本，用LC-MS/MS法测定服药后各时间点血药浓度，用WinNonlin 6.3软件计算药代动力学相关参数，采用SNapShot法测定细胞色素P450 3A4（CYP3A4）基因多态性。结果：Cmax变化范围（7 361.65-26 081.00） ng/mL，平均值±标准差（15 410.72±6 366.21） ng/mL ；tmax变化范围（1.50-4.00） h、平均值±标准差（2.50±0.83） h；AUC0-t变化范围（228 013.55-775 231.63）ng·mL-1·h，平均值±标准差（516 279.90±175 688.41）ng·mL-1·h。个体间Cmax、AUC相差达3倍以上，tmax可相差2倍以上；14例受试者CYP3A4（RS35599367）位点皆为野生型。结论：pazopanib片在中国健康男性志愿者中个体差异较大，未观察到CYP3A4（rs35599367）位点单核苷酸多态性，pazopanib个体间PK差异可能与其他药物代谢相关基因多态性有关。     

风机主轴锻件锻后热处理工艺优化

通过对42CrMo4风机主轴结构尺寸、性能要求、材质特点等方面进行分析,对原有锻后热处理工艺进行优化,制定出既能达到锻后热处理效果又经济节能的工艺参数。     

One-pot foam-gelcasting/nitridation synthesis of high porosity nano-whiskers based 3D Si3N4 porous ceramics

Nano-whiskers based 3D Si₃N₄ porous ceramics (3D-NWSNPC) with high-porosity (about 91–93 %), low density (0.17–0.25 g/cm³), low thermal conductivity, and a certain degree of recoverability under cyclic compressive loading and reasonably strengths were prepared at 1423–1523 K via a one-pot foam-gelcasting/nitridation route using inexpensive commercial Si powders as starting materials and hexadecyl trimethyl ammonium bromide as foaming agent. After nitridation at 1523 K, the sample with an original solid loading of 12.5 wt% exhibited the highest compressive strength of 1.9 MPa, even though its density was lowered to 0.25 g/cm³. The sample nitrided at 1473 K had a relative density of 7.3 %. Its compressive and specific strength were respectively 1.1 MPa and 5.5 MPa·cm³ g^?1, and its thermal conductivity was as low as 0.074 W/(m K) (measured at 323 K). These outstanding properties would make the as-prepared 3D-NWSNPC a promising candidate for applications in catalysis, filtration, thermal insulation and many other important areas.     

Defect Engineering in Ambipolar Layered Materials for Mode-Regulable Nociceptor

Defect engineering represents a significant approach for atomically thick 2D semiconductor material development to explore the unique material properties and functions. Doping-induced conversion of conductive polarity is particularly beneficial for optimizing the integration of layered electronics. Here, controllable doping behavior in palladium diselenide (PdSe₂) transistor is demonstrated by manipulating its adatom-vacancy groups. The underlying mechanisms, which originate from reversible adsorption/desorption of oxygen clusters near selenide vacancy defects, are investigated systematically via their dynamic charge transfer characteristics and scanning tunneling microscope analysis. The modulated doping effect allows the PdSe₂ transistor to emulate the essential characteristics of photo nociceptor on a device level, including firing signal threshold and sensitization. Interestingly, electrostatic gating, acting as a neuromodulator, can regulate the adaptive modes in nociceptor to improve its adaptability and perceptibility to handle different danger levels. An integrated artificial nociceptor array is also designed to execute unique image processing functions, which suggests a new perspective for extension of the promise of defect engineered 2D electronics in simplified sensory systems toward use in advanced humanoid robots and artificial visual sensors.     

东北地区传统发酵食品中两株植物乳杆菌的安全性评价

针对已分离的植物乳杆菌L12和L20通过体外和体内两种方法进行安全性评价。通过体外实验测定乳酸水解活性抗生素敏感性，胆盐水解酶活性，D-乳酸含量，γ溶血等指标；体内实验是对小鼠进行短期口服毒性的研究，口服0.2 mL（109 CFU/mL）的实验性细菌溶液30 d。结果表明，体外实验中，两株菌株均具有良好的抗氧化活性，对抗生素敏感性高，胆盐水解酶活性高，D-乳酸含量低，γ溶血；体内实验中灌胃给药对治疗小鼠的生长、行为、摄食量、器官重量或组织病理学分析均无不良影响。与对照组相比，益生菌组小鼠血清MDA浓度和肝脏GSH含量差异有统计学意义(P<0.05)。这些结果表明，菌株L12和L20是非致病性的，人直接食用是安全的。     

Position-varying surface roughness prediction method considering compensated acceleration in milling of thin-walled workpiece

Machined surface roughness will affect parts’ service performance. Thus, predicting it in the machining is important to avoid rejects. Surface roughness will be affected by system position dependent vibration even under constant parameter with certain toolpath processing in the finishing. Aiming at surface roughness prediction in the machining process, this paper proposes a position-varying surface roughness prediction method based on compensated acceleration by using regression analysis. To reduce the stochastic error of measuring the machined surface profile height, the surface area is repeatedly measured three times, and Pauta criterion is adopted to eliminate abnormal points. The actual vibration state at any processing position is obtained through the single-point monitoring acceleration compensation model. Seven acceleration features are extracted, and valley, which has the highest R-square proving the effectiveness of the filtering features, is selected as the input of the prediction model by mutual information coefficients. Finally, by comparing the measured and predicted surface roughness curves, they have the same trends, with the average error of 16.28% and the minimum error of 0.16%. Moreover, the prediction curve matches and agrees well with the actual surface state, which verifies the accuracy and reliability of the model.