百年中国儿童文学跨学科拓展的依据、路径与反思

在中国儿童文学领域“重提”跨学科实践,旨在于文学发展的内源性和时代演进的外源性同构的基石上,从学科界分的角度重审其概念的本体意涵,探寻跨学科拓展的知识学依据。中国儿童文学不仅是一个描述性的概念,还是一个结构与关系的概念。这种概念与学科的特殊性内在地驱动了学科互涉的转向。总体而言,中国儿童文学的跨学科拓展路径包含了内部“贯通”与外部“联动”两个层级。在世界儿童文学与百年中国文学的整体格局中,将这种跨学科实践纳入系统论的视野,超越“纯文学本质主义”与“非文学工具主义”的理论偏狭,在坚守学科本位的同时有效地开启学科间的对话交流,促进学科知识的整合,进而推动百年中国儿童文学向纵深方向发展。     

Nano-Based Co-Delivery System for Treatment of Rheumatoid Arthritis

A systemic autoimmune condition known as rheumatoid arthritis (RA) has a significant impact on patients’ quality of life. Given the complexity of RA’s biology, no single treatment can totally block the disease’s progression. The combined use of co-delivery regimens integrating various diverse mechanisms has been widely acknowledged as a way to make up for the drawbacks of single therapy. These days, co-delivery systems have been frequently utilized for co-treatment, getting over drug limitations, imaging of inflammatory areas, and inducing reactions. Various small molecules, nucleic acid drugs, and enzyme-like agents intended for co-delivery are frequently capable of producing the ability to require positive outcomes. In addition, the excellent response effect of phototherapeutic agents has led to their frequent use for delivery together with chemotherapeutics. In this review, we discuss different types of nano-based co-delivery systems and their advantages, limitations, and future directions. In addition, we review the prospects and predicted challenges for the combining of phototherapeutic agents with conventional drugs, hoping to provide some theoretical support for future in-depth studies of nano-based co-delivery systems and phototherapeutic agents.     

布里渊散射谱拟合的混合优化算法

基于布里渊光时域分析仪的全分布式光纤传感系统中,光纤沿途的探测信号含有噪声导致被测量的温度或应变信息难以识别,光谱拟合的精确度对传感信息的识别非常重要。在传感系统低信噪比的情况下,提出了一种提取高精度布里渊散射谱特征的拟合方法,利用小波去噪结合莱文伯-马奈特（LM）算法调节权值后向传输(BP)网络对布里渊散射谱进行特征提取。克服了传统BP神经网络易陷入局部极值的缺点,保证求解的精度。数值仿真表明,该方法适合不同权重比、不同线宽和低信噪比以及大测量范围的情况进行光谱拟合,并且在信噪比为10 dB的情况下得到拟合度均超过0.96。实验结果表明,该方法适用于多种泵浦功率情况下的布里渊散射谱的特征提取,优于传统BP神经网络算法且具有较高的拟合精度。     

Markov State Models and Molecular Dynamics Simulations Provide Understanding of the Nucleotide-Dependent Dimerization-Based Activation of LRRK2 ROC Domain

Mutations in leucine-rich repeat kinase 2 (LRRK2) are recognized as the most frequent cause of Parkinson’s disease (PD). As a multidomain ROCO protein, LRRK2 is characterized by the presence of both a Ras-of-complex (ROC) GTPase domain and a kinase domain connected through the C-terminal of an ROC domain (COR). The bienzymatic ROC–COR–kinase catalytic triad indicated the potential role of GTPase domain in regulating kinase activity. However, as a functional GTPase, the detailed intrinsic regulation of the ROC activation cycle remains poorly understood. Here, combining extensive molecular dynamics simulations and Markov state models, we disclosed the dynamic structural rearrangement of ROC’s homodimer during nucleotide turnover. Our study revealed the coupling between dimerization extent and nucleotide-binding state, indicating a nucleotide-dependent dimerization-based activation scheme adopted by ROC GTPase. Furthermore, inspired by the well-known R1441C/G/H PD-relevant mutations within the ROC domain, we illuminated the potential allosteric molecular mechanism for its pathogenetic effects through enabling faster interconversion between inactive and active states, thus trapping ROC in a prolonged activated state, while the implicated allostery could provide further guidance for identification of regulatory allosteric pockets on the ROC complex. Our investigations illuminated the thermodynamics and kinetics of ROC homodimer during nucleotide-dependent activation for the first time and provided guidance for further exploiting ROC as therapeutic targets for controlling LRRK2 functionality in PD treatment.     

Preparation and thermal decomposition studies of l-tyrosine intercalated MgAl, NiAl and ZnAl layered double hydroxides

l-Tyrosine (represented as l-Tyr) intercalated MgAl, NiAl and ZnAl layered double hydroxides (LDHs) have been obtained by the method of coprecipitation. In situ FT-IR, in situ HT-XRD and TG-DTA measurements allow a detailed understanding of the thermal decomposition process for the three intercalated composites. In situ HT-XRD reveals that the layered structure of l-Tyr/MgAl-LDH collapses completely at 450 °C with the first appearance of reflections of a cubic MgO phase, while the corresponding temperature for l-Tyr/NiAl-LDH is some 50 °C lower. In contrast, there is a major structural change in l-Tyr/ZnAl-LDH at 250 °C as shown by the disappearance of its (0 0 6) and (0 0 9) reflections at this temperature accompanied by the appearance of reflections of ZnO. In situ FT-IR experiments give information about the decomposition of the interlayer -Tyr ions. The decomposition temperature of l-Tyr in the ZnAl host is about 50 °C lower than the corresponding values for the MgAl and NiAl hosts. TG-DTA curves show a significant weight loss step (170-260 °C) in l-Tyr/ZnAl-LDH which is due to the dehydroxylation of the host layers, with a corresponding weak endothermic peak at 252 °C. This temperature range is much lower than that observed for MgAl and NiAl hosts, indicating that the ZnAl-LDH layers are relatively unstable. The data indicate that the order of thermal stability of the three intercalates is: l-Tyr/MgAl-LDH > l-Tyr/NiAl-LDH > l-Tyr/ZnAl-LDH.     

The first enantiospecific synthesis of (−)-koumidine via the intramolecular palladium-catalyzed enolate driven cross coupling reaction. The stereospecific introduction of the 19-(Z) ethylidene side chain

The stereospecific synthesis of (−)-koumidine was realized by replacement of triphenylphosphine with tricyclohexylphosphine in the enolate driven palladium-catalyzed cross coupling process.     

Topological minimal sets and existence results

In this article we introduce a definition of topological minimal sets, which is a generalization of that of Mumford-Shah-minimal sets. We prove some general properties as well as two existence theorems for topological minimal sets.     

A Divergent Synthetic Route to the Vallesamidine and Schizozygine Alkaloids: Total Synthesis of (+)‐Vallesamidine and (+)‐14,15‐Dehydrostrempeliopine

The total synthesis of representative members of the schizozygine alkaloids, (+)‐vallesamidine and (+)‐14,15‐dehydrostrempeliopine, were completed from a late‐stage divergent intermediate. The synthesis took advantage of efficient nitro‐group reactions with the A/B/C ring skeleton constructed concisely on a gram scale through an asymmetric Michael addition, nitro‐Mannich/lactamisation, Tsuji–Trost allylation, and intramolecular C?N coupling reaction. Other key features of the synthesis are a novel [1,4] hydride transfer/Mannich‐type cyclisation to build ring E and a diastereoselective ring‐closing metathesis reaction to construct ring D. This approach gave access to a late‐stage C14,C15 alkene divergent intermediate that could be simply transformed into (+)‐vallesamidine, (+)‐14,15‐dehydrostrempeliopine, and potentially other schizozygine alkaloids and unnatural derivatives.     

Isolation and Characterization of PHA-Producing Bacteria from Propylene Oxide Saponification Wastewater Residual Sludge

Single-chain variable fragment (scFv) antibodies as therapeutic agents have the potential to reduce the production cost and immunogenicity relative to monoclonal antibodies, but their monovalency and lack of a fragment crystallizable region can lead to reduced function. Multimerization is one strategy for recovering the function; however, their application is limited by the production of multimeric proteins. In our previous study, an anti-lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) scFv showed potential use in diagnosis and therapy of atherosclerotic diseases, but is limited by its inherent low antigen-binding activity. In this study, to improve the efficacy of the anti-LOX-1 scFv, we constructed the anti-LOX-1 scFv multimers by modifying the linker length between the variable domains of the scFv or by fusing the scFv with self-merization domains and expressed these scFv multimers in Brevibacillus choshinensis hosts. After optimization, all of the scFv multimers obtained efficient secretion expression. Compared with the scFv monomer, the multimers that are successfully fractionated displayed increased neutralization activity and showed elevated antigen-binding avidity, especially the tetramer, which improved the antigen avidity by two orders of magnitude. Moreover, the scFv dimer and the tetramer both displayed better stability and longer half-life in serum, which can be attractive candidates for the next-generation anti-LOX-1 therapeutic antibody.