Latest ArticlesInflammatory bowel disease (IBD) is a chronic condition that severely affects the gastrointestinal tract. Current treatments often have limited efficacy and significant side effects. Iron oxide nanoparticles (Fe2O3 NPs) have emerged as promising candidates for IBD therapy due to their biocompatibility and stability. This study investigates how different surface modifications influence the therapeutic efficacy of Fe2O3 NPs in IBD management. We developed four different types of modified Fe2O3 NPs, including unmodified γ-Fe2O3 NPs, amine-functionalized Fe2O3 NPs (APTS-Fe2O3 NPs), poly-L-lysine-coated Fe2O3 NPs (PLL-Fe2O3 NPs), and dimercaptosuccinic acid-coated Fe2O3 NPs (DMSA-Fe2O3 NPs). Our results demonstrate that all types of Fe2O3 NPs can adsorb proteins to form the protein corona. However, the composition of the protein corona varies, leading to different therapeutic effects of the NPs on IBD. Among them, APTS-Fe2O3 NPs showed reduced therapeutic efficacy compared to the other surface-modified NPs. This was attributed to their adsorption of higher levels of protective and translocation-related proteins, as well as enhanced permeability across intestinal epithelial cells. These findings underscore the importance of carefully tailoring nanoparticle surface properties. Overall, this study highlights the significance of understanding nanoparticle-protein interactions in designing more effective nanoparticle-based therapies for IBD.
The Src homology 2 domain-containing phosphatase 2 (SHP2) plays a pivotal role in cellular processes and is associated with various diseases. Activation of SHP2 has been shown to be effective in inflammation-related diseases such as colitis, atherosclerosis and Parkinson's disease. Although SHP2 inhibitors have been extensively studied in recent years, especially allosteric inhibitors, only a small number of SHP2 activators exhibiting weak activation effects have been reported. Herein, we developed a facile approach to the total synthesis of plasiatine, which was extracted from the seeds of Plantago asiatica as a direct SHP2 activator. Iterative study on the structure-activity relationship identified a potent SHP2 activator, compound C8, with median effective concentration (EC50) = 0.11 µmol/L and Emax = 3.75-fold. Surface plasmon resonance experiment revealed a robust binding affinity between C8 and the SHP2 catalytic domain, with a dissociation constant (Kd) of 70.4 nmol/L. In vivo study showed that C8 significantly reduced atherosclerotic plaques and increased anti-inflammatory factors, highlighting its potential as an effective anti-atherosclerotic agent.
Exosome-based therapies stand at the forefront of precision medicine, offering tailored solutions for disease-specific drug delivery and personalized treatment strategies. Addressing challenges such as the non-specific targeting of exosomes in brain diseases is crucial for optimizing therapeutic efficacy. Chemical modification of exosomes enables specific targeting of brain diseases via precise chemical reactions to conjugate brain disease-targeting ligands, functional molecules, or responsive moieties. The modification efficiency and outcomes are inherently contingent upon varying chemical reaction conditions, while the modification process itself exerts profound influences on the stability, biological activity, and functional expression of exosomes. Advanced chemical modification strategies have been demonstrated to effectively cross the blood-brain barrier (BBB), enabling spatiotemporally precise targeting of intracerebral lesion sites while maintaining their optimal biological activity and structural stability. By integrating the latest research achievements, this study reveals the unique advantages and mechanistic pathways of chemical modification in constructing highly specific targeted delivery systems for brain diseases, providing a precisely controllable novel approach for the precision therapy of brain diseases. Despite existing challenges, these advancements in chemically modified exosome research hold promise for ushering in safer, highly precise, and personalized therapies, thereby propelling the further advancement of exosomes in the therapeutic landscape of brain diseases.
Polymer lamellar single crystals (PLSCs), the fundamental crystalline units of semicrystalline polymers, are ideal model systems to probe intrinsic structure-property relationships of polymer dielectrics. However, the reliable preparation and characterization of PLSCs remain challenging. Here, using a controlled solvent evaporation method, large-area isotactic poly(1-butene) (iPB-1) single crystals with lateral dimension spanning several hundred micrometers were directly grown on conductive substrates. This, in turn, enables straightforward fabrication of metal–insulator–metal (MIM) capacitors, and facilitates the subsequent determination of the dielectric constant for form Ⅲ iPB-1 single crystals with a remarkably low value of 1.82 ± 0.05. This low value is attributed to suppressed chain-segmental motion and low molecular packing density of form Ⅲ crystal phase. This study provides a model framework for quantifying the intrinsic dielectric performance of crystalline phase in semicrystalline polymer systems and highlighting the importance of crystal structure in determining the macroscopic behavior of polymeric dielectrics.
Transdermal drug delivery provides a non-invasive route to circumvent gastrointestinal irritation and first-pass metabolism. This review presents a unique framework by categorizing delivery strategies into biological, chemical, and physical domains, a synthesis complemented by an original analysis of U.S. Food and Drug Administration approved drugs and over 1100 clinical trials. We systematically evaluate representative delivery strategy including microneedles, peptides, and liposomes highlighting their developmental trajectories, advantages, limitations, and clinical adoption status. Furthermore, the review focuses on three paradigmatic drugs (insulin, donepezil, and cannabinoids) to assess their cutting-edge transdermal research and commercialization progress. The insights gathered herein not only summarize the current state but also identify key challenges and opportunities, offering valuable guidance for accelerating the translation of novel transdermal systems.
Three novel β-carboline alkaloid dimers, pecanthines A–C (1−3), featuring unprecedented 6/5/6/6–5/6 and 6/5/6/6/5/6 polycyclic frameworks, were isolated from the seeds of Peganum harmala. Their structures were elucidated by spectroscopic analyses and X-ray diffraction. Notably, compounds 1 and 2 represent the first heterodimeric alkaloids merging canthin-6-one and melatonin-type scaffolds, with 1 additionally displaying neuroprotective activity. In addition, a gram-scale synthesis of 3 was achieved in six steps, leveraging a key acyl-ketene imine condensation and Suzuki coupling. Biological evaluation revealed that 3 acts as a new topoisomerase Ⅰ (Topo Ⅰ) inhibitor, exhibiting remarkable antiproliferative activity. Mechanistic studies demonstrated that 3 induces DNA damage, triggering apoptosis and cell cycle arrest in cancer cells. The discovery and gram-scale synthesis of 3 provide a promising lead compound and a novel molecular scaffold for anticancer drug development.
Aqueous zinc batteries tend to be safe, low-cost, and environmentally friendly. An aqueous cell coupling zinc metal anode and polyanion cathode provides high voltage. However, water-induced side reactions on zinc electrodes, as well as the decomposition of polyanionic cathode, limit the stability of the system. The application of water-in-salt (WiS) electrolytes offers a viable alternative. However, the solubility of conventional zinc salts with weak acidity is low. Herein, we increased the concentration of Zn(OTf)2 to 10 m (mol/kgwater) by introducing saturated betaine (BT) as a cosolvent. In the 10 m Zn(OTf)2/13 m BT electrolyte, the high salt concentration and the interactions between betaine and water effectively lower water activity. Moreover, betaine participates in the solvation structure of zinc ions, facilitating the formation of protective interphases on both the zinc anode and the Li3V2(PO4)3 cathode, thereby suppressing side reactions and cathode decomposition. As a result, the electrolyte enables reversible Zn plating/stripping over 2900 h. The Li3V2(PO4)3 cathode also maintains two pairs of redox reactions at high voltage of 1.8 V/1.7 V and 1.4 V/1.3 V, demonstrating excellent rate capability and stable cycling performance.
The development of unnatural α-amino esters as key building blocks for peptide drug discovery remains a significant challenge due to the inherent limitations of natural amino acids and scarcity of unnatural amino acids. By leveraging the dual reactivity of α-diazo sulfonium salts, this study reports the efficient synthesis of unnatural α-amino esters via a rhodium-catalyzed three-component tandem strategy. This method undergoes the sequential N–H insertion and nucleophilic substitution (SN1) reactions, avoiding the tedious and complex reaction operations. In addition, tandem C–H functionalization-SN1 processes for the facile construction of 1,1-di(hetero)aryl compounds were also achieved. The utility of this methodology was demonstrated by its application in the concise synthesis of the bioactive natural products Streptindole and Arsindoline B, as well as its successful scalability to gram-scale quantities. Furthermore, the mechanistic insights obtained from DFT (density functional theory) calculations provide a rational explanation of the reaction pathway, highlighting the pivotal role of rhodium-carbynoid intermediates.
The emissive layer of stretchable optoelectronic devices currently incorporates luminescent units through physical blending or co-polymerization. However, these methods often compromise material performance due to interference from the introduced functional groups, and a significant portion of the luminescent components embedded within the material is wasted. In this work, we propose an innovative "click chemistry" strategy for integrating luminescent functional groups onto the surface of polyaniline (PANI) through a simple stirring process. After proton doping, the functionalized PANI exhibited a 29-fold increase in electrical conductivity compared to pristine PANI. This improvement originates from the extended conjugation of the anthracene moiety and enhanced proton-doping efficiency, making it promising for advanced electronic devices.
The integration of mechanochemistry and piezocatalysis can open new strategies for driving redox reactions used in synthetic chemistry. However, due to the complex interplay between mechanical forces and surface charges, it remains challenging to design piezocatalysts based on a clear understanding of their catalytic mechanisms. Herein, by utilizing conventional BaTiO3 as a piezoelectric material, we explore the hydroacylation of dialkyl azodicarboxylates for the synthesis of acyl hydrazides to gain insights into the piezoelectric material-mediated conversion process. Control experiments and mechanistic studies revealed that the reaction follows a pathway where mechanical activation induces polarization in the piezoelectric material, promoting benzoyl radical generation, which subsequently undergoes radical addition to acylhydrazine derivatives, leading to the formation of acylhydrazides. The collaborative contributions of piezoelectric activation and mechanical milling in the reaction between aldehydes and dialkyl azodicarboxylates enable the synthesis of a broad range of acyl hydrazides with excellent yields. This efficient and sustainable strategy provides valuable insights for theoretical guidance in designing piezocatalysis for future applications.