水产品及养殖水中丁香酚类化合物风险研究

目的 检测水产品及养殖水中丁香酚类化合物。方法 应用食品补充检验方法BJS 201908《水产品及水中丁香酚类化合物的测定》，以海水鱼、淡水鱼、海水虾、淡水虾及养殖水作为基质，测定6种丁香酚类化合物的含量。结果 通过对实际样品测定后发现，在水产品中检出了丁香酚类化合物，主要为丁香酚，检出率为28.9%，其中海水鱼相对突出。结论 本研究为丁香酚作为渔用麻醉剂提供了方法论，为丁香酚类化合物在水产运输的合理使用提供理论依据。     

典型废玻璃回收厂区空气颗粒物及噪声分布特征研究

以某典型废玻璃回收厂区作为研究对象, 监测和分析了车间及厂区内部的噪声强度、空气颗粒物(PM_2.5、PM₁₀) 浓度等环境指标, 点位布设涵盖了车间入口、人工分拣、物料筛分、破碎、干法清洗等关键工艺环节; 其次, 解析了空气颗粒物的组分及形貌特征, 并对其在厂区及车间内部的时空分布特征进行了研究; 此外, 利用噪声控制模型模拟并分析了隔声罩对噪声的控制作用。结果表明, 生产车间中工作态的空气颗粒物浓度显著高于非工作态, 其中干法清洗区浓度最高, 其PM_2.5 浓度为3.725 mg/m³, PM₁₀浓度为4.055 mg/m³; 噪声监测结果显示生产车间内噪声强度较高, 达到99.5 dB, 而引入隔声罩后噪声强度可降至67 dB, 结果表明, 隔声罩可有效控制频率为125~1 000 Hz 的噪声。该研究可为废玻璃的绿色、高效回收处置提供理论基础和实践经验。     

Opportunities and Challenges in Tunneling Nanotubes Research: How Far from Clinical Application?

Tunneling nanotubes (TNTs) are recognized long membrane nanotubes connecting distance cells. In the last decade, growing evidence has shown that these subcellular structures mediate the specific transfer of cellular materials, pathogens, and electrical signals between cells. As intercellular bridges, they play a unique role in embryonic development, collective cell migration, injured cell recovery, cancer treatment resistance, and pathogen propagation. Although TNTs have been considered as potential drug targets for treatment, there is still a long way to go to translate the research findings into clinical practice. Herein, we emphasize the heterogeneous nature of TNTs by systemically summarizing the current knowledge on their morphology, structure, and biogenesis in different types of cells. Furthermore, we address the communication efficiency and biological outcomes of TNT-dependent transport related to diseases. Finally, we discuss the opportunities and challenges of TNTs as an exciting therapeutic approach by focusing on the development of efficient and safe drugs targeting TNTs.     

Two Methods,One Goal: Structural Differences between Cocrystallization and Crystal Soaking to Discover Ligand Binding Poses

In lead optimization, protein crystallography is an indispensable tool to analyze drug binding. Binding modes and non-covalent interaction inventories are essential to design follow-up synthesis candidates. Two protocols are commonly applied to produce protein–ligand complexes: cocrystallization and soaking. Because of its time and cost effectiveness, soaking is the more popular method. Taking eight ligand hinge binders of protein kinase A, we demonstrate that cocrystallization is superior. Particularly for flexible proteins, such as kinases, and larger ligands cocrystallization captures more reliable the correct binding pose and induced protein adaptations. The geometrical discrepancies between soaking and cocrystallization appear smaller for fragment-sized ligands. For larger flexible ligands that trigger conformational changes of the protein, soaking can be misleading and underestimates the number of possible polar interactions due to inadequate, highly impaired positions of protein amino-acid side and main chain atoms. Thus, if applicable cocrystallization should be the gold standard to study protein–ligand complexes.     

Design,Synthesis, and in vitro Evaluation of Tubulin-Targeting Dibenzothiazines with Antiproliferative Activity as a Novel Heterocycle Building Block

We prepared a series of free NH and N-substituted dibenzonthiazines with potential anti-tumor activity from N-aryl-benzenesulfonamides. A biological test of synthesized compounds (59 samples) was performed in vitro measuring their antiproliferative activity against a panel of six human solid tumor cell lines and its tubulin inhibitory activity. We identified 6-(phenylsulfonyl)-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide and 6-tosyl-6H-dibenzo[c,e][1,2]thiazine 5,5-dioxide as the best compounds with promising values of activity (overall range of 2–5.4 μM). Herein, we report the dibenzothiazine core as a novel building block with antiproliferative activity, targeting tubulin dynamics.     

Engineering Nanorobots for Tumor-Targeting Drug Delivery: From Dynamic Control to Stimuli-Responsive Strategy

Nanotechnology has been widely applied to the fabrication of drug delivery systems in the past decades. Recently, with the progress made in microfabrication approaches, nanorobots are steadily becoming a promising means for tumor-targeting drug delivery. In general, nanorobots can be divided into two categories: nanomotors and stimuli-responsive nanorobots. Nanomotors are nanoscale systems with the ability to convert surrounding energies into mechanical motion, whereas stimuli-responsive nanorobots are featured with activatable capacity in response to various endogenous and exogenous stimulations. In this minireview, the dynamic control of nanomotors and the rational design of stimuli-responsive nanorobots are overviewed, with particular emphasis on their contribution to tumor-targeting therapy. Moreover, challenges and perspectives associated with the future development of nanorobots are presented.     

Fabrication of ultrafast temperature-responsive nanofibrous hydrogel with superelasticity and its 'on–off' switchable drug releasing capacity

The temperature-responsive bulky hydrogel with fast response rate and satisfactory mechanical property has fascinating application potential in many aspects, such as the implantable macroscale controlled drug release carrier for post-surgical therapy; however, creating such a smart hydrogel was proven extremely challenging. Here a novel type of temperature-responsive bulky hydrogel with ultrafast response rate and super compressible elasticity was fabricated by the fibrous freeze-shaping technique using shortened temperature-responsive polymer based electrospun hollow nanofibers as building blocks, followed by heat treatment for endowing the hydrogel with high stability in water. Because the hydrogel has hierarchical porous structure and its constituent nanofibers have hollow structure, which are beneficial to diffusion of its embodied water during temperature-induced volume phase transition, its temperature-response time is less than 30 s. In addition, the hierarchical porous structure benefits dissipation of the compression stress exerted on the hydrogel. Fluorescein isothiocyanate (FITC)-dextran as a model biomacromolecular drug, was loaded into the shells of the hollow nanofibers during coaxial electrospinning, and the ultimately obtained nanofibrous hydrogel can release its loaded FITC-dextran in a 'on–off' switchable fashion in response to temperature alternation between 15 and 47°C. Cell cytotoxicity test results demonstrate that the temperature-responsive nanofibrous hydrogel is biocompatible.     

Design,Synthesis, and Biological Evaluation of Lysine Demethylase 5 C Degraders

Lysine demethylase 5 C (KDM5C) controls epigenetic gene expression and is attracting great interest in the field of chemical epigenetics. KDM5C has emerged as a therapeutic target for anti-prostate cancer agents, and recently we identified triazole 1 as an inhibitor of KDM5C. Compound 1 exhibited highly potent KDM5C-inhibitory activity in in vitro enzyme assays, but did not show strong anticancer effects. Therefore, a different approach is needed for the development of anticancer agents targeting KDM5C. Here, we attempted to identify KDM5C degraders by focusing on a protein-knockdown strategy. Compound 3 b , which was designed based on compound 1 , degraded KDM5C and inhibited the growth of prostate cancer PC-3 cells more strongly than compound 1 . These findings suggest that KDM5C degraders are more effective as anticancer agents than compounds that only inhibit the catalytic activity of KDM5C.     

Steerable Microinvasive Probes for Localized Drug Delivery to Deep Tissue

Enhanced understanding of neuropathologies has created a need for more advanced tools. Current neural implants result in extensive glial scarring and are not able to highly localize drug delivery due to their size. Smaller implants reduce surgical trauma and improve spatial resolution, but such a reduction requires improvements in device design to enable accurate and chronic implantation in subcortical structures. Flexible needle steering techniques offer improved control over implant placement, but often require complex closed‐loop control for accurate implantation. This study reports the development of steerable microinvasive neural implants (S‐MINIs) constructed from borosilicate capillaries (OD = 60 µm, ID = 20 µm) that do not require closed‐loop guidance or guide tubes. S‐MINIs reduce glial scarring 3.5‐fold compared to prior implants. Bevel steered needles are utilized for open‐loop targeting of deep‐brain structures. This study demonstrates a sinusoidal relationship between implant bevel angle and the trajectory radius of curvature both in vitro and ex vivo. This relationship allows for bevel‐tipped capillaries to be steered to a target with an average error of 0.23 mm ± 0.19 without closed‐loop control. Polished microcapillaries present a new microinvasive tool for chronic, predictable targeting of pathophysiological structures without the need for closed‐loop feedback and complex imaging.