Latest ArticlesThe A2A adenosine receptor (A2AAR) has attracted attention as an emerging immunotherapeutic target with several antagonists being evaluated in clinical trials. However, A2AAR antagonists show limited efficacy as monotherapies. Herein, we communicate our design and synthesis of a novel series of A2AAR/histone deacetylase (HDAC) bifunctional inhibitors, based on the core structure of the A2AAR antagonist PBF-509. The new compounds were designed using a pharmacophore-merging strategy and features a tri-substituted pyrimidine core. The binding affinity for A2AAR and inhibitory activity against HDACs of all the new compounds were tested. A number of compounds exhibited nanomolar or subnanomolar activity against both targets and some showed equally potent antiproliferative activity against MC38, CT26 and HCT116 colon cancer lines compared to HDAC inhibitors SAHA and MGCD-0103 in vitro. The binding poses of compound 5a in both A2AAR and HDAC1 were predicted by molecular docking studies. Collectively, these results suggest these tri-substituted pyrimidine derivatives are promising leads for developing A2AAR/HDAC dual-acting compounds as novel antitumor agents.
Photothermal effect has been widely employed in the H2 evolution process at the advantage of using clean energy sources to produce another one of higher benefits. The solar-to-heat conversion have various forms and heat can facilitate reactions in a variety of dimensions. Hence, summarizing the sources and destinations of heat is important for constructing hydrogen production systems of higher efficiency. This view mainly focuses on the recent state-of-art progress of hydrogen evolution reaction (HER) based on photothermal effect. First, we introduce the main pathways of photothermal conversions applied in H2 evolution. Then, the functions of the photothermal effect are clearly summarized. Furthermore, we go beyond the catalytic reaction and introduce a method to improve the catalytic system by changing the catalytic bulk phase through thermal means. In the end, we sort out the challenges and outlook to offer some noble insights for this promising area.
Nucleophilic phosphine and amine catalyst-switched chemodivergent [4 + 1] and [3 + 3] annulations of allenyl imides and β,γ-enones have been developed, furnishing highly substituted 2-cyclopentenone and 2-pyranone derivatives in moderate to excellent yields. Two plausible reaction mechanisms involving two different ketene intermediates have been proposed to explain the observed chemoselectivity. Moreover, by virtue of the α,β-enone substructure of the [4 + 1] adducts, 1,3-dipolar cycloaddition of nitrile imines has been studied in one-pot to provide various fused pyrazoline derivatives.
Increasing environmental pollution and shortage of conventional fossil fuels have made it urgent to develop renewable and clean energy sources. Electrocatalytic water splitting, with its abundant raw materials, simple process, and zero carbon emission, is considered one of the most promising processes for producing carbon-neutral hydrogen which has excellent energy conversion efficiency and high gravimetric energy density. Among them, oxygen evolution reaction (OER) electrocatalysts and hydrogen evolution reaction (HER) electrocatalysts are critical to decreasing the intrinsic reaction energy barrier and boosting the hydrogen evolution efficiency. Therefore, it is imperative to develop and design low-cost, highly active, and stable OER and HER electrocatalysts to lower the overpotential and drive the electrocatalytic reactions. Transition metal sulfides, especially iron-based sulfides, have attracted extensive exploration by researchers as a result of its high abundance in the Earth's crust and near-metallic conductivity. Consequently, in this review, we systematically and comprehensively summarize the progress in the application of iron-based sulfides and their composites as OER and HER electrocatalysts in electrocatalysis. Detailed descriptions and illustrations of the special relationships among their composition, structure, and electrocatalytic performance are presented. Finally, this review points out the challenges and future prospects of iron-based sulfides in practical applications for designing and fabricating more promising iron-based sulfide OER and HER electrocatalysts. We believe that iron-based sulfide materials will have a wide range of application prospects as OER and HER electrocatalysts in the future.
Atomization energy (AE) is an important indicator for measuring material stability and reactivity, which refers to the energy change when a polyatomic molecule decomposes into its constituent atoms. Predicting AE based on the structural information of molecules has been a focus of researchers, but existing methods have limitations such as being time-consuming or requiring complex preprocessing and large amounts of training data. Deep learning (DL), a new branch of machine learning (ML), has shown promise in learning internal rules and hierarchical representations of sample data, making it a potential solution for AE prediction. To address this problem, we propose a natural-parameter network (NPN) approach for AE prediction. This method establishes a clearer statistical interpretation of the relationship between the network's output and the given data. We use the Coulomb matrix (CM) method to represent each compound as a structural information matrix. Furthermore, we also designed an end-to-end predictive model. Experimental results demonstrate that our method achieves excellent performance on the QM7 and BC2P datasets, and the mean absolute error (MAE) obtained on the QM7 test set ranges from 0.2 kcal/mol to 3 kcal/mol. The optimal result of our method is approximately an order of magnitude higher than the accuracy of 3 kcal/mol in published works. Additionally, our approach significantly accelerates the prediction time. Overall, this study presents a promising approach to accelerate the process of predicting structures using DL, and provides a valuable contribution to the field of chemical energy prediction.
Radiation damage can cause a series of gastrointestinal (GI) tract diseases. The development of safe and effective GI tract radioprotectants still remains a great challenge clinically. Here, we firstly report an oral radioprotectant Gel@GYY that integrates a porous gelatin-based (Gel) hydrogel and a pH-responsive hydrogen sulfide (H2S) donor GYY4137 (morpholin-4-ium 4 methoxyphenyl(morpholino) phosphinodithioate). Gel@GYY has a remarkable adhesion ability and long retention time, which not only enables responsive release of low-dose H2S in stomach and subsequently sustained release of H2S in the whole intestinal tract especially in the colon, but also ensures a close contact between H2S and GI tract. The released H2S can effectively scavenge free radicals induced by X-ray radiation, reduce lipid peroxidation level, repair DNA damage and recover vital superoxide dismutase and glutathione peroxidase activities. Meanwhile, the released H2S inhibits radiation-induced activation of nuclear factor κB (NF-κB), thus reducing inflammatory cytokines levels in GI tract. After treatment, Gel@GYY displays efficient excretion from mice body due to its biodegradability. This work provides a new insight for therapeutic application of intelligent H2S-releasing oral delivery system and potential alternative to clinical GI physical damage protectant.
DNA circuits are powerful tools in various applications such as logical computation, molecular diagnosis and synthetic biology. Leakage is a major problem in constructing complex DNA circuits. It directly affects the output signal and harms the circuit's performance significantly. In the traditional DNA circuits, the gate complex is a duplex structure. There are insufficient energy barriers to prevent spontaneous detachment of strands, resulting in a leak prone. Herein, we have developed triplex-structure based DNA circuit with ultra-low leakage and high signal-to-noise ratio (SNR). The triplex structure improves the stability in the absence of input. At the same time, the driving force of the strand displacement cascades reduces the influence of the triplex structure on the desired reaction. The SNR of the DNA circuit was increased to 695, while the desired reaction rate remained 90% of the conventional translator circuit. The triplex-structure mediated leakage prevention strategy was further tested at different temperatures and in DNA translator and seesaw circuits. We also constructed modular basic logic gates with a high efficiency and low leakage. On this basis, we further constructed triplex-structure based tertiary DNA logic circuits, and the SNR reached 295, which, to the best of our knowledge, was among the highest of the field. We believe that our scheme provides a novel, valid, and general tool for reducing leakages, and we anticipate that it will be widely adopted in DNA nanotechnology.
Alcohol consumption is one of the leading causes of death worldwide. Adolescence is a critical period of structural and functional maturation of the brain. Adolescent alcohol use can alter epigenetic modifications. However, little is known on the long-term effects of alcohol consumption during adolescence on RNA epigenetic modifications in brain. Herein, we systematically explored the long-term effects of alcohol exposure during adolescence on small RNA modifications in adult rat brain tissues by comprehensive liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) analysis. We totally detected 26 modifications in small RNA of brain tissues. Notably, we observed most of these modifications were decreased in brain tissues. These results suggest that alcohol exposure during adolescence may impose a long-lasting impact on RNA modifications in brain tissues. This is the first report that alcohol use during adolescence can alter RNA modifications in adult brain. Collectively, this study suggests a long-term adverse effects of alcohol consumption on brain from RNA epigenetics angle by comprehensive mass spectrometry analysis.
A new strategy to induce vesicle fusion has been developed by employing pillar[5]arene derivatives that were channel-like and were prepared by appending side chains onto pillar[5]arenes backbones. The channels feature with hydrophilic negatively and positively charged groups at both ends and hydrophobic Trp residues at the outer surface, which endows the channels with amphiphilicity. The zwitterionic amphiphilic channels could spontaneously incorporate into the bilayer membranes of lipid vesicles to induce vesicle fusion driven by the electrostatic interactions between negatively charged and positively charged groups.
Molecular doping has become a widely used method to modulate the electric performance of organic semiconductors (OSC). Highly effective charge transfer during molecular doping is desired to achieve ideal electrical conductivity. Two types of charge transfer mechanisms are widely accepted in molecular doping process: integer charge transfer (ICT) and charge transfer complex (CTC). In this review, fundamental principles of two mechanisms are revisited and the characterization methods are depicted. The key points for the formation of two mechanisms are highlighted from aspects of molecular structure and process engineering. Then, the strategies to improve the proportion of ICT are discussed. Finally, the challenges and perspectives for future developments in the molecular doping of polymer semiconductors are provided.
No. 86 Xueyuan South Road, Haidian District, Beijing
010-62199257
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
