Chemotherapy drugs derived nanoparticles encapsulating mRNA encoding tumor suppressor proteins to treat triple-negative breast cancer

Triple-negative breast cancer (TNBC) is one type of the most aggressive breast cancers with poor prognosis. It is of great urgency to develop new therapeutics for treating TNBC. Based on current treatment guideline and genetic information of TNBC, a combinational therapy platform integrating chemotherapy drugs and mRNA encoding tumor suppressor proteins may become an efficacious strategy. In this study, we developed paclitaxel amino lipid (PAL) derived nanoparticles (NPs) to incorporate both chemotherapy drugs and P53 mRNA. The PAL P53 mRNA NPs showed superior properties compared to Abraxane^® and Lipusu^® used in the clinic including high paclitaxel loading capacity (24 wt.%, calculated by paclitaxel in PAL), PAL encapsulation efficiency (94.7% ± 6.8%) and mRNA encapsulation efficiency (88.7% ± 0.7%). Meanwhile, these NPs displayed synergetic cytotoxicity of paclitaxel and P53 mRNA in cultured TNBC cells. More importantly, we demonstrated in vivo anti-tumor efficacy of PAL P53 mRNA NPs in an orthotopic TNBC mouse model. Overall, these chemotherapy drugs derived mRNA NPs provide a new platform to integrate chemotherapy and personalized medicine using tumor genetic information, and therefore represent a promising approach for TNBC treatment.

     

流量替代渗透率评价破碎性储层工作流体伤害程度

若地层岩石整体强度偏低,在力学环境改变后岩石易破碎成不规则破裂体,则储存油气资源的此类破碎地层被称为破碎性储层。由于破碎性储层在纵向上存在着较强的非均质性,通过测试单个柱塞岩样在工作流体伤害前后的渗透率变化难以体现工作流体对储层的整体伤害程度。为此,利用达西定律先从理论上探讨用流量替代渗透率定量表征储层伤害程度的可行性,再开展单层开采、双层及三层并采的流量测试实验,评价工作流体对单层、多层储层的整体伤害程度,并将流量损害率与渗透率损害率进行对比以求证流量替代渗透率的可行性。研究结果表明:①单层开采时,流量损害率与渗透率损害率基本一致,渗透率损害率是流量损害率的一种特殊形式;②双层及三层并采时,单层各自稳定流量损害率与渗透率损害率接近,且流量损害率可以定量表征并采储层的整体伤害程度,而渗透率损害率则无法定量表证;③稳定流量损害率较累积流量损害率更接近渗透率损害率。结论认为,测定稳定流量可以替代测定渗透率评价工作流体对破碎性储层的伤害程度,从而为优选工程技术与评价工作流体的适应性提供了方法依据。     

Compilation of Modern Technologies To Map Genome-Wide Cytosine Modifications in DNA

Over the past few decades, various DNA modification detection methods have been developed; many of the high-resolution methods are based on bisulfite treatment, which leads to DNA degradation, to a degree. Thus, novel bisulfite-free approaches have been developed in recent years and shown to be useful for epigenome analysis in otherwise difficult-to-handle, but important, DNA samples, such as hmC-seal and hmC-CATCH. Herein, an overview of advances in the development of epigenome sequencing methods for these important DNA modifications is provided.     

Confined Transformation of UiO‐66 Nanocrystals to Yttria‐Stabilized Zirconia with Hierarchical Pore Structures for Catalytic Applications

Solid acids as a substitution for hazardous liquid acids (e.g., HF and H₂SO₄) can promote many important reactions in the industry, such as carbon cracking, to proceed in a more sustainable way. Starting from a zirconium‐based metal‐organic framework (UiO‐66 nanocrystals), herein a transformative method is reported to prepare micro/mesoporous yttria‐stabilized zirconia (YSZ) encapsulated inside a mesoporous silica shell. It is then further demonstrated that the resultant reactor‐like catalysts can be used for a wide range of catalytic reactions. The acidity of the YSZ phase is found with rich accessible Lewis acid and Brønsted acid sites and they display superior performances for esterification (acetic acid and ethanol) and Friedel‐Crafts alkylation (benzylation of toluene). After being loaded with different noble metals, furthermore, hydrogenation of CO₂ and a one‐pot cascade reaction (nitrobenzene and benzaldehyde to N‐benzylaniline) are used as model reactions to prove the versatility and stability of catalysts. Based on the findings of this work, it is believed that this class of reactor‐like catalysts can meet future challenges in the development of new catalyst technology for greener heterogeneous catalysis.     

考虑流固耦合的Spar型浮式风力机涡激运动特性研究

对弹性支撑单圆柱在均匀流作用下的涡激运动特性进行数值模拟,捕捉到"锁定区"、"拍"、"频率变换"等现象。柱体周围流场采用Fluent求解,将4阶Runge-Kutta方法代码写入用户自定义函数(UDF)求解运动微分方程,运用动网格技术更新流场,实现圆柱与流场的非线性耦合作用。发现随着折合速度的增大,涡激运动响应可分为锁定前支、锁定区、锁定后支3个阶段,在进入锁定区前(折合速度Ur=3)横向运动响应发生拍现象,当跨过锁定区后(折合速度Ur=10)发生频率变换现象。结果表明,横向涡激运动有较大范围的频率锁定现象,频率解锁前后圆柱涡激运动轨迹由"右8字"形变换为"左8字"形。     

Facile synthesis of a castor oil-based hyperbranched acrylate oligomer and its application in UV-curable coatings

Fabrication and performance of the castor oil (CO)-based hyperbranched acrylate (C20AA) UV-curable coatings are highlighted in this work. Herein, C20AA was obtained through a facile reaction of a castor oil-based hyperbranched polyol (C20) with acrylic acid. FT-IR and ¹H NMR spectra confirmed the synthesis of the target C20AA. Subsequently, the as-prepared C20AA was employed for crosslinking a commercialized linear polyurethane acrylate (PUA) UV-curable oligomer. Specifically, by varying the content of C20AA over the range of 0, 20, 40, and 60 wt%, a series of UV-curable coatings were prepared and coded as C20AA-0, C20AA-20, C20AA-40, and C20AA-60, respectively, which were further cured under UV irradiation. The effect of C20AA loadings on the UV-curing efficiency and final polymer performance were investigated. Consequently, the tensile strength, Shore D hardness, pencil hardness, gel content, water resistance, and glass-transition temperature of the UV-cured coatings were greatly improved upon the addition of C20AA. Impressively, with the incorporation of 40 wt% C20AA, the resultant UV-cured coating exhibited highest double bond conversion, superior chemical resistance, and good flexibility. Additionally, all of the coatings showed outstanding transparency and good surface microstructures.     

节镍型奥氏体不锈钢的组织性能对比

针对200系J5A、J5两种牌号节镍型奥氏体不锈钢冷轧压延性能的差异,对比分析J5A、J5钢成分设计、组织、力学性能和马氏体含量,研究冷加工性能差异产生的机理。结果表明:由于J5A钢成分设计不合理,镍当量较低,奥氏体稳定性较差,马氏体转变点M_d(30/50)高,在轧制过程中产生大量冷加工变形诱变马氏体,加工硬化程度严重,压延性能差。     

基于互信息和PID神经网络的SCR脱硝扰动补偿控制

针对火电厂选择性催化还原(Selective Catalytic Reduction，SCR)烟气脱硝系统机理复杂，工况变化时呈现的不确定性、强扰动等特点，提出了一种基于互信息和PID神经网络的SCR烟气脱硝扰动补偿控制方法。利用PID前向神经网络的学习性能逼近被控对象的逆构成扰动观测器对系统进行反馈补偿，以达到超前消除系统扰动的目的。选取观测扰动和系统扰动的互信息为目标函数，采用改进的帝国竞争算法实现PID神经网络权值的优化调整。设计鲁棒PID控制器来进一步克服被控对象存在的不确定性。仿真实验表明，该方法具有突出的抗干扰能力和较好的鲁棒性，控制品质优于常规的PID控制。     

Quantitative Relationship Between the Nucleation Undercooling of Liquid Iron and Its Liquid Structure: Investigated by In Situ Synchrotron Radiation

Metallurgical and Materials Transactions A - The nucleation behavior of liquid iron with various iron oxides was investigated through an in situ synchrotron radiation analysis and undercooling...     

Improvement of polyamide/thermoplastic polyurethane blends with polyamide 6-polyurethane copolymer prepared via suspension polymerization as compatibilizer

The polyamide 6-polyurethane copolymer (PA6-b-PU-b-PA6) was synthesized through anionic suspension polymerization and then mixed with polyamide 6/thermoplastic polyurethane (PA6/TPU) and polyamide 6, 6/thermoplastic polyurethane (PA66/TPU) blends using as the compatibilizer. The results show that the PA6-b-PU-b-PA6 copolymers powders several can be obtained through suspension polymerization using dimethicone as disperse medium. The average diameter of PA6-b-PU-b-PA6 copolymer powders decreased with the increasing of PU content. With the addition of PA6-b-PU-b-PA6, the TPU phase dispersed more uniformly in PA6 or PA66 matrix, and the size of TPU dispersed phase decreased obviously. The PA6-b-PU-b-PA6 copolymer with higher PU content shows better compatibilizing effect. Addition of PA6-b-PU-b-PA6 can improve both strength and toughness of the PA/TPU blends. When the amount of PA6-PU25% copolymer was 5 phr, the tensile strength and notched impact strength of PA6/TPU/PA6-PU25% blends increased 29 and 159.4%, respectively, compared to the PA6/TPU blend without compatibilizer.