Lighting the Path: Light Delivery Strategies to Activate Photoresponsive Biomaterials In Vivo

Photoresponsive biomaterials are experiencing a transition from in vitro models to in vivo demonstrations that point toward clinical translation. Dynamic hydrogels for cell encapsulation, light-responsive carriers for controlled drug delivery, and nanomaterials containing photosensitizers for photodynamic therapy are relevant examples. Nonetheless, the step to the clinic largely depends on their combination with technologies to bring light into the body. This review highlights the challenge of photoactivation in vivo, and presents strategies for light management that can be adopted for this purpose. The authors’ focus is on technologies that are materials-driven, particularly upconversion nanoparticles that assist in “direct path” light delivery through tissue, and optical waveguides that “clear the path” between external light source and in vivo target. The authors’ intention is to assist the photoresponsive biomaterials community transition toward medical technologies by presenting light delivery concepts that can be integrated with the photoresponsive targets. The authors also aim to stimulate further innovation in materials-based light delivery platforms by highlighting needs and opportunities for in vivo photoactivation of biomaterials.     

Oxidation State Modulation of Bismuth for Efficient Electrocatalytic Nitrogen Reduction to Ammonia

Electrocatalytic nitrogen reduction reaction (NRR) is a promising strategy for ammonia (NH₃) production under ambient conditions. However, it is severely impeded by the challenging activation of the NN bond and the competing hydrogen evolution reaction (HER), which makes it crucial to design electrocatalysts rationally for efficient NRR. Herein, the rational design of bismuth (Bi) nanoparticles with different oxidation states embedded in carbon nanosheets (Bi@C) as efficient NRR electrocatalysts is reported. The NRR performance of Bi@C improves with the increase of Bi⁰/Bi³⁺ atomic ratios, indicating that the oxidation state of Bi plays a significant role in electrochemical ammonia synthesis. As a result, the Bi@C nanosheets annealed at 900  ° C with the optimal oxidation state of Bi demonstrate the best NRR performance with a high NH₃ yield rate and remarkable Faradaic efficiency of 15.10  ± 0.43% at − 0.4 V versus RHE. Density functional theory calculations reveal that the effective modulation of the oxidation state of Bi can tune the p-filling of active Bi sites and strengthen adsorption of *NNH, which boost the potential-determining step and facilitate the electrocatalytic NRR under ambient conditions. This work may offer valuable insights into the rational material design by modulating oxidation states for efficient electrocatalysis.     

Improving Strategies in the Development of Protein-Downregulation-Based Antiandrogens

The androgen receptor (AR) plays a crucial role in the occurrence and development of prostate cancer (PCa), and its signaling pathway remains active in castration-resistant prostate cancer (CRPC) patients. The resistance against antiandrogen drugs in current clinical use is a major challenge for the treatment of PCa, and thus the development of new generations of antiandrogens is under high demand. Recently, strategies for downregulating the AR have attracted significant attention, given its potential in the discovery and development of new antiandrogens, including G-quadruplex stabilizers, ROR-γ inhibitors, AR-targeting proteolysis targeting chimeras (PROTACs), and other selective AR degraders (SARDs), which are able to overcome current resistance mechanisms such as acquired AR mutations, the expression of AR variable splices, or overexpression of AR. This review summarizes the various strategies for downregulating the AR protein, at either the mRNA or protein level, thus providing new ideas for the development of promising antiandrogen drugs.     

GM-CSF及CBS在肝损伤中的研究进展

肝损伤(liver injury)是指基因遗传或外部原因诱发的肝脏功能异常性疾病.临床表现为食欲不振、乏力、恶心、黄疸、疲乏等,严重者将出现肝功能衰竭,致死风险极高.在交通肇事、暴力犯罪及意外事件中,肝由于体积大、位置固定、质地脆弱、血运丰富等原因,往往是最容易发生损伤的器官之一,肝损伤后的死亡率可高达10.5％～25％[1].随着时间的变化,肝损伤的程度、病理改变、GM-CSF等相关细胞因子及CBS等相关酶的表达水平也会进一步变化.肝损伤后,由于肝内部环境稳态的破坏,器官的状态、结构、各种蛋白的转录水平、蛋白及细胞因子的表达变化水平也会发生一定程度的改变.因此定性定量地分析这些变化,找到时间相关性强的特异性指标,对于指导法医学的实践具有重要的作用.因此在法医学鉴定中,通过肝脏损伤及病变程度的改变,明确肝损伤病变与死亡时间的关系有利于判断事件或案件性质,并有助于进一步对责任方的认定.     

振动环境下液压胶管疲劳寿命分析

在硬岩掘进机(TBM)掘进过程中,液压胶管长期处于振动环境会引起胶管的疲劳破坏,因此液压胶管的选型对TBM设计及施工具有重要意义.运用经典层合板理论建立缠绕式和编织式两种液压胶管在振动载荷和油压载荷下的数学模型.仿真试验研究得到了油压及振动参数对胶管疲劳寿命的影响,结果表明:(1)在无基础振动环境下,缠绕式胶管疲劳寿命优于编织式胶管;在有基础振动条件下,编织液压胶管疲劳寿命优于缠绕液压胶管;(2)当胶管发生疲劳破坏后,胶管疲劳寿命与振幅呈近似线性关系,振动频率越靠近胶管共振频率,胶管寿命越低;可知在同等基础振动条件下,编织式液压胶管的疲劳寿命均高于缠绕式液压胶管的疲劳寿命.