Latest ArticlesThree discrete tetrahedral metallo-supramolecular cages were designed and constructed using truxene-pended base ligands. Owing to the synergistic rigidifying effect of unsymmetric cyano-substituted oligo(p-phenylene-vinylene) (u-COPV) suspended by the truxene skeleton, the resulting supramolecular cages were confirmed to exhibit significant aggregation-induced emission (AIE) accompanied by an interesting solvatochromic fluorescent behavior as well as a porous honeycomb-like state during aggregation. In particular, the anti-counterfeiting performance and emission behaviors of the cages in the solid state under external hydrostatic pressure were investigated.
As a strong oxidizer, hypochlorite (ClO–) are widely employed as bleaching agents and disinfectants. Determination of ClO– is required to ensure bactericidal effects and avoid hazards caused by excessive residual chlorine. Herein, the derivative bicyclic 2-pyridone, namely DHIP-Py, was prepared successfully to establish a new ClO–-quantitative method. The probe exhibits excellent ClO– selectivity over other ROS and anions/cations, high sensitivity (LOD = 1.32 µmol/L), fast response (<5 s), and wide-pH tolerance (pH 4~10). Benefit from its good water solubility, DHIP-Py is well suited for water sample analysis and has been successfully applied to detect ClO– in real-world food and environmental samples, including tap water, bottled water and river water. The detection results were essentially identical to that of obtained from traditional DPD method. Moreover, visual detection of ClO– via filter paper-based solid sensor and imaging of ClO– in Escherichia coli were also achieved by DHIP-Py. These satisfactory results demonstrate that this bicyclic 2-pyridone-based hypochlorite probe is a promising free chlorine chemosensor with great potential for analytical applications.
The abnormal activation of BRD4 accelerates the progression of acute myeloid leukemia (AML), developing more precise therapeutics to intervene BRD4 promise to be an excellent opportunity to avoid current limitations of chemotherapy in clinic. Herein, a range of small-molecule PROTACs with the privileged 8-methyl-pyrrolo[1,2-a]pyrazin-1(2H)-one scaffold were rationally designed, which harbored different carbon or ethylenedioxy chains to degrade BRD4 mediated by the E3 ubiquitin ligase CRBN. Among them, the most potential B24 exhibited remarkable BRD4 degradation and excellent anti-proliferative activities in MV4-11 cells, with values of DC50 and IC50 for 0.75 nmol/L and 0.4 nmol/L, respectively, which were better than the BRD4 inhibitor (+)-JQ-1. Notably, this compound could time-dependently degrade the target protein in the BRD4-, CRBN-, and proteasome-dependent manner. Besides, B24 dramatically decreased the level of proto-oncogene c-Myc, and induced cell apoptosis by arresting the cell cycle in G0/G1 phase, down-regulating Bcl-2 and up-regulating Bax to amplify apoptotic effectors. This proof-of-concept study also highlighted the feasibility of BRD4-based PROTACs as a more powerful strategy against AML.
Ibrutinib is a first-line treatment drug for B-cell malignancies. However, resistance to ibrutinib has been reported due to BTKC481S mutation. Although PROTAC strategy is expected to overcome this clinical resistance, it has limitations such as large molecular weight and moderate bioactivity, which restrict its potential clinical application. Herein, we report a new type of potent BTKC481S-targeting PROTAC degrader. Through design, computer-assisted optimization and SAR studies, we have developed a representative BTKC481S degrader L6 with a much smaller molecular weight and improved solubility. Notably, L6 demonstrates better BTK degrading activity and lower IC50 value in ibrutinib-resistant cell line than the first-generation BTK degrader P13I. Optimization strategy of L6 provides a general approach in the development of PROTACs targeting BTK and other proteins for future study.
As the main target cells of immune regulation, macrophages play an important role in the bone regeneration process. Macrophages can be polarized into the M1 and M2 types under the stimulation of different factors. They have proinflammatory and anti-inflammatory effects, respectively, and play key roles in different stages of bone regeneration. The ratio of M1 to M2 macrophages can be regulated by immunomodulatory biomaterials to promote bone repair and regeneration. In this paper, we review the recent literature on the chemical, physical and biological properties of biomaterials and the regulation of macrophage polarization under the influence of other factors. We also cover new methods for preparing immunomodulatory biomaterials for bone regeneration. This paper will provide new design ideas for the development of biomaterials with immunological properties and will support the clinical translation of bone-related medical biomaterials.
Extracellular vesicles (EVs) are cell-derived nanosized vesicles widely recognized for their critical roles in various pathophysiological processes. Molecular analysis of EVs is currently being considered an emerging tool for diseases diagnosis. However, the small size and heterogeneity of EVs has staggered the EVs research for diseases diagnosis. DNA nanotechnology enables self-assembly of versatile DNA nanostructures and has shown enormous potential in assisting EVs biosensing. In this review, we briefly introduce the recent advances in DNA nanotechnology approaches for EVs detection. The approaches were categorized based on the dimension of DNA nanostructures. We provide critical evaluation of these approaches, and summarize the pros and cons of specific methods. Further, we discuss the challenges and future perspectives in this field.
Proteolysis targeting chimeras (PROTACs) are bifunctional degrader molecules via hijacking the ubiquitin-proteasome system (UPS) to specifically eliminate targeted proteins. PROTACs have gained momentum as a new modality of attractive technologies in the drug discovery landscape, since it allows to degrade disease-related proteins effectively. Although some PROTACs drugs reached the clinical research, they are still facing some bottlenecks and challenges that should not be neglected, such as poor oral bioavailability and potential toxic side effects. To overcome these limitations, herein, we provide an overview of recent strategies for improving the durability of PROTACs by enhancing cell permeability and reducing toxic side effects. Meanwhile, the impact of these strategies on improving oral bioavailability as well as their advantages and drawbacks will also be discussed. This review will give a useful reference toolbox for PROTACs design and further promote its clinical application.
As a high-flux operation mode of thin film composite-forward osmosis (TFC-FO) membrane, active layer facing draw solution (AL-DS) mode suffers from the severe membrane fouling tendency, which is not addressed well. Here, we introduced a photocatalyst (Anatase titanium dioxide, A-TiO2) onto the support layer of TFC-FO membrane via the bonding of polydopamine (PDA) and polytetrafluoroethylene (PTFE), and prepared two photocatalytic membranes, A-TiO2/PDA@TFC and A-TiO2/PTFE@TFC. Compared with the pristine TFC-FO membrane, both A-TiO2/PDA @TFC and A-TiO2/PTFE@TFC had an improved water permeability (10.5 L m−2h−1 and 9.5 L m−2 h−1, respectively) and reduced reverse NaCl flux salt (0.8 g m−2 h−1 and 0.7 g m−2 h−1, respectively) in the AL-DS mode using 1 mol/L NaCl as draw solution and pure water as feed solution. Moreover, in the 16 h fouling experiment using 200 ppm bovine serum albumin (BSA) solution as a representative pollutant, the flux decline rate of both photocatalytic membranes was dramatically alleviated from 39.7% and 21.7% in the darkness to 8.5% and 9.7% under UV irradiation, respectively, indicating a significant anti-fouling capacity of photocatalytic effect. In all, the presence of A-TiO2 endowed membrane with high permeability, high rejection efficiency and excellent anti-fouling capacity under UV spotlight. As bonding agent, PTFE provided the modified membrane with a high photocatalytic effect and high self-cleaning capacity, while PDA increased the membrane permeability and protected membrane against photocatalytic damage. This work provides a simple and feasible method to improve the anti-fouling capacity of TFC-FO membrane in AL-DS mode.
Microscale zero valent iron (mFe0) is one of the most potential water pollution remediation materials, but the effective utilization ability of electrons released by mFe0 in the reduction of hexavalent chromium (Cr(Ⅵ)) is not satisfactory. Here, we find the microscale iron-copper (mFe/Cu) bimetals coated with copper on the surface of mFe0 can significantly improve the effective utilization of electrons released by mFe0. Electrochemical analysis displays that copper plating on the surface of mFe/Cu can promote the release the electrons from mFe0 and reduce the impedance of mFe0. Spin-polarized density functional theory (DFT) calculation reveals that Cu on the surface of mFe/Cu bimetals promotes the release of electrons from mFe0 and reduces the adsorption energy of Fe to Cr. As the electron transporter, moreover, Cu can always attract Cr to the hollow position near itself of the Fe surface, which could promote the effective utilization of electrons released by Fe. Effective utilization ability of electrons in mFe/Cu system is 12.5 times higher than that in mFe0 system. Our findings provide another basis for the efficient reduction of Cr(Ⅵ) by mFe/Cu bimetals, which could promote the application and popularization of mFe/Cu bimetals.
No. 86 Xueyuan South Road, Haidian District, Beijing
010-62662699(Operation and Technical Support)
qkjq@cast.org.cn
Copyright © 2025 China Association for Science and Technology. All rights reserved. For all open access content, the relevant licensing terms apply.
Sponsored by the Office of the Leading Group for Cybersecurity and Informatization of CAST, and supported by Science and Technology Review Publishing House
