Latest ArticlesCombining cytotoxic drugs with tumor microenvironment (TME) modulator agents is an effective strategy to enhance anti-tumor effects. In this study, two natural anti-tumor active ingredients celastrol (CEL) and glycyrrhetinic acid (GA) were combined for tumor treatment. In order to ensure the precise co-delivery and controllable synchronous release of combined drugs to tumors, it is necessary to construct a suitable nano-drug delivery platform. Based on this, we coupled hyaluronic acid (HA) with CEL by amide reaction to obtain an amphiphilic polymer prodrug HA-SS-CEL, and GA was spontaneously loaded into polymer micelles by self-assembly to obtain G/HSSC-M. G/HSSC-M has ideal size distribution, redox-responsive synchronous drug release, enhanced tumor cell internalization and in vivo tumor targeting. Compared with free drugs, the construction of multifunctional polymer micelles makes G/HSSC-M show better anticancer effect at the same concentration, and can significantly inhibit the proliferation and migration of HepG2 and 4T1 cells. In the in vivo experiments, G/HSSC-M achieved a tumor inhibition rate as high as 75.12% in H22 tumor-bearing mice. The mechanism included regulation of M1/M2 macrophage polarization, inhibition of Janus kinase 1/signal transducer and activator of transcription 3 (JAK1/STAT3) signaling pathway, and remodeling of tumor blood vessels. Therefore, the development of prodrug micelles co-loaded with CEL and GA provides a promising drug co-delivery strategy for combined cancer therapy.
Self-assembled prodrug nanomedicine has emerged as an advanced platform for antitumor therapy, mainly comprise drug modules, response modules and modification modules. However, existing studies usually compare the differences between single types of modification modules, neglecting the impact of steric-hindrance effect caused by chemical structure. Herein, single-tailed modification module with low-steric-hindrance effect and two-tailed modification module with high-steric-hindrance effect were selected to construct paclitaxel prodrugs (P-LAC18 and P-BAC18), and the in-depth insights of the steric-hindrance effect on prodrug nanoassemblies were explored. Notably, the size stability of the two-tailed prodrugs was enhanced due to improved intermolecular interactions and steric hindrance. Single-tailed prodrug nanoassemblies were more susceptible to attack by redox agents, showing faster drug release and stronger antitumor efficacy, but with poorer safety. In contrast, two-tailed prodrug nanoassemblies exhibited significant advantages in terms of pharmacokinetics, tumor accumulation and safety due to the good size stability, thus ensuring equivalent antitumor efficacy at tolerance dose. These findings highlighted the critical role of steric-hindrance effect of the modification module in regulating the structure-activity relationship of prodrug nanoassemblies and proposed new perspectives into the precise design of self-assembled prodrugs for high-performance cancer therapeutics.
The chemo-, regio-, and enantio-controlled synthesis of P-chiral phosphines in a general and efficient manner remains a significant synthetic challenge. In this study, a Pd-catalyzed hydrofunctionalization is developed for the highly selective synthesis of P-stereogenic alkenylphosphinates and alkenylphosphine oxides via conjugate addition of enynes. Notably, this methodology is suitable for both phosphine oxide and phosphinate nucleophiles, providing a versatile approach for the construction of diverse P-chiral organophosphosphorus compound.
Traditional electrospray ionization tandem mass spectrometry (ESI-MSn) has been a powerful tool in diverse research areas, however, it faces great limitations in the study of protein-small molecule interactions. In this article, the state-of-the-art temperature-controlled electrospray ionization tandem mass spectrometry (TC-ESI-MSn) is applied to investigate interactions between ubiquitin and two flavonol molecules, respectively. The combination of collision-induced dissociation (CID) and MS solution-melting experiments facilitates the understanding of flavonol-protein interactions in a new dimension across varying temperature ranges. While structural changes of proteins disturbed by small molecules are unseen in ESI-MSn, TC-ESI-MSn allows a simultaneous assessment of the stability of the complex in both gas and liquid phases under various temperature conditions, meanwhile investigating the impact on the protein’s structure and tracking changes in thermodynamic data, and the characteristics of structural intermediates.
Neutrophil extracellular traps (NETs) formation (NETosis), is a crucial immune system mechanism mediated by neutrophils, measuring the capacity to induce NETosis is proposed as a clinical biomarker indicating the severity of COVID-19 and long COVID. Azvudine (FNC), has shown efficacy in treating SARS-CoV-2 infection and potential for alleviating inflammation. However, the molecular mechanism underlying its anti-inflammatory effects has not been extensively investigated. Therefore, a series of experiments were conducted on SARS-CoV-2 infected rhesus macaques (RMs) to investigate the anti-inflammatory effects of FNC. The experiments involved HE staining, mass spectrometry-based proteomics, validation experiments conducted in vivo using RMs tissues and in vitro differentiation of HL-60 cells. Additionally, interaction investigations were carried out utilizing LiP-MS, CETSA, Co-IP along with molecular docking. The results demonstrated that FNC treatment effectively alleviated neutrophil infiltration and attenuated inflammatory injury following infection. In addition to exhibiting antiviral effects, FNC treatment exhibited a reduction in inflammation-associated proteins and pathways such as myeloperoxidase (MPO) and the formation of NETs, respectively. Validation experiments confirmed the impact of FNC on regulating NETs formation, interaction experiments suggested that MPO may serves as a therapeutic target. The multifaceted properties of FNC, including its antiviral and anti-inflammatory characteristics, highlight the therapeutic potential in diseases associated with NETosis, particularly those involving concurrent SARS-CoV-2 infection, providing insights for drug development targeting MPO and NETosis-associated diseases.
Here we present a highly efficient protocol utilizing nickel-hydride hydrogen atom transfer catalysis for the regio- and enantioselective hydrofluorination of internal alkenes. This method efficiently assembles a wide array of enantioenriched β-fluoro amides with excellent regio- and enantioselectivity from internal unactivated alkenes. Mechanistic investigations suggest that this transformation proceeds via a NiH-hydrogen atom transfer to alkene, followed by a stereoselective fluorine atom transfer process. The weak coordination effect of the tethered amide group is identified as a crucial factor governing the observed regio- and enantioselectivity.
Nanoplastics exhibit greater environmental biotoxicity than microplastics and can be ingested by humans through major routes such as tap water, bottled water and other drinking water. Nanoplastics present a challenge for air flotation due to their minute particle size, negative surface potential, and similar density to water. This study employed dodecyltrimethylammonium chloride (DTAC) as a modifier to improve conventional air flotation, which significantly enhanced the removal of polystyrene nanoplastics (PSNPs). Conventional air flotation removed only 3.09% of PSNPs, while air flotation modified by dodecyltrimethylammonium chloride (DTAC-modified air flotation) increased the removal of PSNPs to 98.05%. The analysis of the DTAC-modified air flotation mechanism was conducted using a combination of instruments, including a zeta potential analyzer, contact angle meter, laser particle size meter, high definition camera, scanning electron microscope (SEM), energy dispersive spectrometer (EDS) and Fourier transform infrared spectrometer (FTIR). The results indicated that the incorporation of DTAC reversed the electrostatic repulsion between bubbles and PSNPs to electrostatic attraction, significantly enhancing the hydrophobic force in the system. This, in turn, improved the collision adhesion effect between bubbles and PSNPs. The experimental results indicated that even when the flotation time was reduced to 7 min, the DTAC-modified air flotation still achieved a high removal rate of 96.26%. Furthermore, changes in aeration, pH, and ionic strength did not significantly affect the performance of the modified air flotation for the removal of PSNPs. The removal rate of PSNPs in all three water bodies exceeded 95%. The DTAC-modified air flotation has excellent resistance to interference from complex conditions and shows great potential for practical application.
Hyperglycemia resulting from diabetes mellitus (DM) exacerbates osteoporosis and fractures, damaging bone regeneration due to impaired healing capacity. Stem cell therapy offers the potential for bone repair, accelerating the healing of bone defects by introducing stem cells with osteogenic differentiation ability. Dental follicle stem cells (DFSCs) are a newly emerging type of dental stem cells that not only have the potential for multipotent differentiation but also hold easy accessibility and can stand long-term storage. However, DM-associated oxidative stress and inflammation elevate the risk of DFSCs dysfunction and apoptosis, diminishing stem cell therapy efficacy. Recent nanomaterial advances, particularly in DNA nanostructures like tetrahedral framework nucleic acids (tFNAs), have been promising candidates for modulating cellular behaviors. Accumulating experiments have shown that tFNAs' cell proliferation and migration-promoting ability and induce osteogenic differentiation of stem cells. Meanwhile, tFNAs can scavenge reactive oxygen species (ROS) and downregulate the secretion of inflammatory factors by inhibiting various inflammation-related signaling pathways. Here, we applied tFNAs to modify DFSCs and observed enhanced osteogenic differentiation alongside ROS scavenging and anti-inflammatory effects mediated by suppressing the ROS/mitogen-activated protein kinases (MAPKs)/nuclear factor kappa-B (NF-κB) signaling pathway. This intervention reduced stem cell apoptosis, bolstering stem cell therapy efficacy in DM. Our study establishes a simple yet potent tFNAs-DFSCs system, offering potential as a bone repair agent for future DM treatment.
The asymmetric addition of aromatic organometallic compounds to the carbonyl group (C-3) of isatins, catalyzed by transition metals, has emerged as a remarkably efficient method for the synthesis of chiral 3-hydroxyoxindoles. Here, an exceptionally enantioselective approach was developed for the first time to achieve a catalytic NHK reaction of isatins with aromatic halides (both aryl and heteroaryl). Utilizing chiral cobalt complexes as catalysts, and the presence of a diboron reagent B2nep2 as both a reducing agent and determinant in enantiocontrol, has resulted in the triumphantly achieved synthesis of enantioenriched products. Compared to reported strategies, this approach exhibits remarkable compatibility with substrates bearing sensitive functional groups, such as halides and borate esters, while also eliminating the need for organometallic reagents as required in previous strategies. Through experimental investigations, the presence of aryl-cobalt species during the addition process was confirmed, rather than in-situ generation of an arylboron reagent. Furthermore, the successful attainment of the R absolute configuration through aryl addition was demonstrated.
Humic acid (HA), as a represent of natural organic matter widely existing in water body, dose harm to water quality and human health; however, it was commonly treated as an environmental background substance while not targeted contaminant in advanced oxidation processes (AOPs). Herein, we investigated the removal of HA in the alkali-activated biochar (KBC)/peroxymonosulfate (PMS) system. The modification of the original biochar (BC) resulted in an increased adsorption capacity and catalytic activity due to the introduction of more micropores, mesopores, and oxygen-containing functional groups, particularly carbonyl groups. Mechanistic insights indicated that HA is primarily chemically adsorbed on the KBC surface, while singlet oxygen (1O2) produced by the PMS decomposition served as the major reactive species for the degradation of HA. An underlying synergistic adsorption and oxidation mechanism involving a local high concentration reaction region around the KBC interface was then proposed. This work not only provides a cost-effective solution for the elimination of HA but also advances our understanding of the nonradical oxidation at the biochar interface.
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
