Enzyme-Activated Prodrug-Based Smart Liposomes Specifically Enhance Tumor Hemoperfusion with Efficient Drug Delivery to Pancreatic Cancer Cells and Stellate Cells

Tumor-specific enhanced delivery of chemotherapeutics and modulators to tumor cells and activated pancreatic stellate cells (aPSCs), respectively, represents safer and more effective therapy for pancreatic cancer. Herein, a membrane type 1-matrix metalloproteinase (MT1-MMP)-cleavable spacer is used to assemble low-density cRGDfK onto thermosensitive liposomes loaded with phosphorylated calcipotriol (PCAL) and doxorubicin (DOX), yielding MR-T-PD. The liposome-linked cRGDfK prodrug on MR-T-PD surface is first activated by MT1-MMP, which is selectively expressed on tumor endothelial cells, to release cRGDfK. The free cRGDfK specifically promotes tumor angiogenesis, leading to 3.4-fold higher accumulation and a wider distribution of MR-T-PD in tumors. Furthermore, MR-T-PD rapidly releases PCAL and DOX into the interstitium under heat treatment. The released DOX enters tumor cells to induce apoptosis, whereas the PCAL prodrug is converted to CAL by alkaline phosphatase on the surface of aPSCs; CAL can then enter aPSCs to induce quiescence and promote the antitumor effect of DOX. Finally, by enhancing the exposure of DOX and CAL to tumor cells and aPSCs, respectively, in a tumor-specific manner, MR-T-PD exerts superior efficacy (a 5.9-fold decrease in tumor weight) without causing additional side effects. Overall, this prodrug-based smart liposome system represents a promising paradigm for pancreatic cancer therapy.     

An Artificial Skyrmion Platform with Robust Tunability in Synthetic Antiferromagnetic Multilayers

Magnetic skyrmions are topologically nontrivial spin structures, and their existence in ferromagnetically coupled multilayers has been widely reported with a disordered arrangement. Here, a nucleation scenario of ordered skyrmions in nanostructured synthetic antiferromagnetic (SAF) multilayers is proposed and experimentally demonstrated using direct magnetization imaging, indirect magnetometer and magnetoresistance measurement, and micromagnetic simulation. Instead of relying on Dzyaloshinskii–Moriya interaction, the antiferromagnetic interlayer exchange coupling in the SAF multilayers fulfills the role of nucleation and stabilization of skyrmions. The robustness of the proposed skyrmion nucleation scenario is examined against temperature from 4.5 to 300 K and device size from 400 to 1200 nm. Interestingly, these synthetic skyrmions still behave well with a size less than 100 nm. The higher stability than generic magnetic domains can be attributed to topological protection. The results thus provide an artificial skyrmion platform to meet the functional needs of high density and designable arrangement in magnonic and spintronic applications.     

Allosteric p97 Inhibitors Can Overcome Resistance to ATP-Competitive p97 Inhibitors for Potential Anticancer Therapy

Abstract : A major challenge of targeted cancer therapy is the selection for drug-resistant mutations in tumor cells leading to loss of treatment effectiveness. p97/VCP is central regulator of protein homeostasis and a promising anticancer target because of its vital role in cell growth and survival. One ATP-competitive p97 inhibitor, CB-5083, has entered clinical trials. Selective pressure on HCT116 cells dosed with CB-5083 identified five different resistant mutants. Identification of p97 inhibitors with different mechanisms of action would offer the potential to overcome this class of resistance mutations. Our results demonstrate that two CB-5083 resistant p97 mutants, N660 K and T688 A, were also resistant to several other ATP-competitive p97 inhibitors, whereas inhibition by two allosteric p97 inhibitors NMS-873 and UPCDC-30245 were unaffected by these mutations. We also established a CB-5083 resistant cell line that harbors a new p97 double mutation (D649 A/T688 A). While CB-5083, NMS-873, and UPCDC-30245 all effectively inhibited proliferation of the parental HCT116 cell line, NMS-873 and UPCDC-30245 were 30-fold more potent in inhibiting the CB-5083 resistant D649 A/T688 A double mutant than CB-5083. Our results suggest that allosteric p97 inhibitors are promising alternatives when resistance to ATP-competitive p97 inhibitors arises during anticancer treatment.     

垂直轴风力机两种翼型气动性能比较研究

叶片是风力机最重要的组成部分,在不同的风能资源情况下,翼型的选择对垂直轴风力机气动特性有着重要的影响。文章分别以NACA0018翼型(对称翼型)和NACA4418翼型(非对称翼型)建立3叶片H型垂直轴风力机二维仿真模型。应用数值模拟的研究方法,从功率系数、单个叶片切向力系数等方面比较两种风力机模型在不同叶尖速比下的气动特性,并采用风洞实验数据验证了流场计算的准确性。CFD计算结果表明:在低叶尖速比下,NACA4418翼型风力机气动特性优于NACA0018翼型风力机,适用于低风速区域;在高叶尖速比下,NACA0018翼型风力机气动特性较好,适用于高风速地区。而且在高叶尖速比时,NACA0018翼型在上风区时,切向力系数平均值要高于NACA4418翼型,在下风区时,NACA418翼型切向力系数平均值高。该研究可为小型垂直轴风力机翼型的选择提供参考。     

五跨双塔自锚式悬索桥空间结构静力特性分析与研究

本文以五跨双塔自锚式悬索桥——成都云龙湾大桥为工程背景,通过建立有限元模型,对该桥空间结构静力特性进行了分析与研究.根据设计需求,分析并讨论了恒载、活载、温度等效应对结构受力的影响,并进行了荷载效应组合下结构受力性能检算,为桥梁设计、施工和运营提供理论依据,同时也为同类型桥梁的设计研究提供参考.     

High-entropy ferroelastic rare-earth tantalite ceramic: (Y0.2Ce0.2Sm0.2Gd0.2Dy0.2)TaO4

In this study, high-entropy rare-earth tantalate ceramics (Y_0.2Ce_0.2Sm_0.2Gd_0.2Dy_0.2)TaO₄ ((5RE_0.2)TaO₄) have been successfully fabricated. The possibility of formation of (5RE_0.2)TaO₄ was verified via first-principles calculations. In addition, the phase structure, ferroelastic toughening mechanism, thermophysical, and mechanical properties were systematically investigated. The (5RE_0.2)TaO₄ ceramics have lower phonon thermal conductivity (1.2–2.6 W·m^–1·K^–1) in the entire temperature range than that of RETaO₄ and YSZ. (5RE_0.2)TaO₄ has a higher fracture toughness and lower brittleness index than YSZ. The thermal expansion coefficients of (5RE_0.2)TaO₄ are as high as 10.3 × 10^-6 K^–1 at 1200°C and Young's modulus is 66–189 GPa, and thus, (5RE_0.2)TaO₄ possesses great potential for application in thermal barrier coatings (TBCs).     

Structure and crystallization behavior of complex mold flux glasses in the system CaO-Na2O-Li2O-CaF2-B2O3-SiO2: A multi-nuclear NMR spectroscopic study

The structure of mold flux glasses in the system CaO-(Na,Li)₂O-SiO₂-CaF₂ with unusually high modifier contents, stabilized by the addition of ∼4 mol% B₂O₃, is studied using ⁷Li, ²³Na, ¹⁹F, ¹¹B, and ²⁹Si magic-angle-spinning (MAS), and ⁷Li{¹⁹F} and ²³Na{¹⁹F} rotational echo double-resonance (REDOR) nuclear magnetic resonance (NMR) spectroscopy. When taken together, the spectroscopic results indicate that the structure of these glasses consists primarily of dimeric [Si₂O₇]⁻⁶ units that are linked to the (Ca,Na,Li)-O coordination polyhedra, and are interspersed with chains of corner-shared BO₃ units. The F atoms in the structure are exclusively bonded to Ca atoms, forming Ca(O,F)_n coordination polyhedra. This structural scenario is shown to be consistent with the crystallization of cuspidine (3CaO·2SiO₂·CaF₂) from the parent melts on slow supercooling. The progressive addition of Li to a Na-containing base composition results in a corresponding increase in the undercooling required for the nucleation of cuspidine in the melt, which is attributed to the frustrated local structure caused by the mixing of alkali ions.     

An efficient procedure for optimization design of anti-seepage curtains: a case study

Bulletin of Engineering Geology and the Environment - In large-scale hydropower projects, the anti-seepage curtain is an important measure to reduce the leakage of reservoirs and ensure the...     

Synthesis and photocatalytic performance of MoS2/Polycrystalline black phosphorus heterojunction composite

As a promising catalyst for solar hydrogen production, black phosphorus (BP) has received widespread attention due to variable band gaps, high carrier mobility, and strong light absorption performance. Herein, we use MoS₂ as a cocatalyst to synthesize BP/MoS₂ catalyst with polycrystalline BP to improve photocatalytic performance under visible light irradiation. A small amount of MoS₂ can reduce the recombination of electron-hole pairs in the composite, increase carrier transport efficiency, and then improve photocatalytic performance. As expected, the 10/0.5 ratio of BP/MoS₂ catalyst exhibits the highest photocatalytic hydrogen evolution performance with a hydrogen evolution rate of 575.4 μmol h^?1 g^?1, which is 2.5 times of pure BP. Based on the results above, a simple method is provided to synthesize low-cost black phosphorus-based photocatalysts.     

南美白对虾进食前后发声信号特点分析

为了探索南美白对虾进食前后发声信号特点和规律,首先进行了养殖虾塘环境下的实验,利用水听器与采集器采集信号;然后利用Matlab软件对信号进行频谱分析和时频分析,得到南美白对虾的发声信号规律。实验证明,在淡水养殖环境下,南美白对虾产生的声信号具有一定的规律,一般情况单个脉冲信号时长为0.005 s,主峰频率在2～10 kHz之间,投饵后主峰频率有所扩大,约在5～15 kHz之间。投饵后南美白对虾随着咀嚼活动的展开产生的信号增多,并且时频域特征明显与投饵前不同。该实验结果为利用南美白对虾产生的信号来控制投饵机实现按需投饵提供了可能。