Latest ArticlesCentral nervous system diseases (CNSDs), such as Parkinson's disease (PD) and depression, have attracted considerable attention due to their high morbidity and mortality rates. Neuronal damage in CNSDs is primarily driven by inflammation and oxidative stress induced by activated astrocytes and microglia. Thus, new therapeutic strategies are urgently needed that not only enable effective drug delivery across the blood-brain barrier (BBB), but also specifically target lesions while exerting antioxidant and anti-inflammatory effects on glial cells. To address this challenge, we developed an exosome-liposome hybrid system targeting glial cells co-loaded with fisetin (FIS) and pioglitazone (PIO) (RMP7-EL-FIS-PIO). This hybrid system crosses the BBB through the B2 bradykinin receptor-mediated opening and takes advantage of the homing properties of exosomes to accumulate at the site of brain lesions in murine models of PD and of depression. Through receptor-ligand binding and phagocytosis, the hybrid system targets glial cells to deliver drugs that inhibit their activation, thus protecting neurons. Our study demonstrates the great potential of the developed exosome-liposome hybrid system for the targeted treatment of CNSDs.
Given the widespread use of pyriproxyfen (PPF) in public health and agricultural pest management, accurate residue monitoring is critical to ensuring food safety, preserving ecological equilibrium, and protecting human health. While fluorescent sensing techniques represent promising paradigm for PPF detection, existing probes often lack rapid response and high specificity. To address this issue, we present the development of a novel FA1-targeting albumin-based supramolecular probe (DOCD@ALB) for the ratiometric detection of PPF. The strategy design minimizes competitive interference from DS1-binding compounds (e.g., epicatechin), thereby significantly improving its detection accuracy and specificity. When integrated with a smartphone-assisted portable sensing device, the DOCD@ALB system enables on-site PPF quantification in tea matrices, demonstrating its clear translational potential. These findings highlight the pivotal role of binding site selection in modulating the sensing performance of the supramolecular probe system, offering a robust analytical tool with implications for food safety surveillance and environmental protection.
Solid additives have emerged as effective tools for morphology regulation in organic photovoltaics (OPVs), yet simultaneous control over donor and acceptor domains remains challenging. Here, we report a dual-functional solid additive, NSA2, designed to optimize vertical phase distribution and suppress energy loss in PM6:Y6 systems. Compared to the control device with a power conversion efficiency (PCE) of 16.28%, NSA2-incorporated devices achieve a PCE of 18.51%, and up to 19.31% using a layer-by-layer structure with co-additive (DIB). Detailed characterization reveals improved π-π stacking, prolonged crystallization, reduced trap-assisted and bimolecular recombination, and enhanced charge transport. Notably, the non-radiative energy loss (ΔE3) is reduced from 0.214 eV to 0.204 eV, contributing to higher open-circuit voltage. The additive also improves device stability and shows broad compatibility, across other acceptor systems (BTP-eC9-based binary device), achieving PCE of 19.68%. This work demonstrates a general and scalable strategy for designing multifunctional solid additives to boost efficiency and stability in high-performance OPVs.
Paper and ink serve as important media for cultural inheritance and information transmission. With the development of civilization, the research on functional paper and ink has gradually gained attention. Carbon dots (CDs) have attracted widespread interest due to their excellent photoluminescence (PL) properties, strong ultraviolet (UV) absorption, electrical characteristics, and stability. This review summarizes the functionalization applications of CDs in ink and paper, and their applications progress in paper-based cultural relics conservation. To begin, the preparation methods of CDs are introduced. Subsequently, the PL, light absorption mechanisms, and electrical properties of CDs are discussed from the perspective of structure and classification. Then, we discuss the functional applications of CDs with unique optical or electrical properties in paper and ink, and also present the research progress of CDs in the field of paper conservation. Finally, the research development and potential challenges of CDs are presented. It is believed that in the near future, more properties of CDs will be developed, paving the way for the protection, development, and commercialization of paper and ink materials.
MicroRNA (miRNA)-based therapeutics hold great promise for the treatment of ocular fundus diseases. However, naked miRNAs exhibit poor stability in vivo, are readily degraded by nucleases in body fluids, and their negative charge hinders efficient uptake by target cells. Therefore, a safe and effective nucleic acid delivery system is essential. In this study, we developed an efficient and safe polycationic nucleic acid carrier by modifying polyethyleneimine (PEI) with p-toluenesulfonyl chloride (i.e., PEI-T3). The introduction of tosyl groups onto PEI enhanced the hydrophobic interactions between polymer and cell membrane, and contributed to the cellular uptake of miRNA. Intravitreal injection of PEI-T3/miRNA complexes caused negligible effects on retinal structure and function and did not induce neurotoxicity. Using microRNA-578 (miR-578) as the therapeutic gene, PEI-T3/miR-578 treatment effectively downregulated the levels of vascular endothelial growth factor A (VEGF-A) and vascular cell adhesion molecule 1 (VCAM-1), suppressed the proliferation, migration, and tube formation of vascular endothelial cells. In a choroidal neovascularization (CNV) model, a single dose of PEI-T3/miR-578 significantly relieved the disease progression and showed an excellent in vivo safety profile. This study provides a valuable reference for the in vivo delivery of miRNAs using polymeric carriers for the treatment of ocular fundus diseases.
Probiotics encompass a diverse assortment of biological activities and are widely distributed in barrier organs, which enables them to dynamically modulate multiple physiological processes within the human body. Due to their diminished side effects, a spectrum of probiotic-centric functional formulations has been used as an alternative to traditional anti-inflammatory drugs. Nonetheless, probiotics are intrinsically sensitive to environmental fluctuations, which greatly limits their therapeutic effectiveness. The specific combination of probiotics with nanozymes opens up novel perspectives for resolving this issue. Nanozymes are nanomaterials that exhibit enzyme-like properties, showcasing exceptional catalytic prowess while retaining the distinctive attributes of nanomaterials. The alliance of nanozymes and probiotics demonstrates a significant synergistic effect in the treatment of diseases. On one hand, inherent targeting and metabolic properties of probiotics impart nanozymes with site-selectivity, alongside the capacity to fine-tune the catalytic microenvironment for optimized activity. On the other hand, nanozymes exhibit exceptional catalytic properties that can be leveraged to safeguard probiotics and concurrently bestow new bioactivities, thereby enhancing their therapeutic efficacy. This review underscores the therapeutic potential of nanozyme-enhanced probiotics in regulating reactive oxygen species for the synergetic therapy of various diseases, as well as the challenges associated with the biosafety of such biomimetic functional agents.
Lipid-based vaccines, such as liposomes, emulsions, and lipid nanoparticles, play a key role in the development of antiviral vaccines due to their unique immunomodulatory properties, capacity to serve as antigen depots, ability to protect antigens, and adjuvant effect. Among the various approved vaccines, the vast majority utilize lipid-based adjuvants and delivery systems, such as AS01, AS03, MF59, and BNT162b2. These formulations establish an inflammatory microenvironment at the injection site, recruit immune cells, and activate innate immune pathways, thereby enhancing the immunogenicity of the antigen. Concurrently, they protect antigens from enzymatic degradation and thereby maintain the stability of antigens. This review comprehensively summarizes approved lipid-based antiviral vaccines, encompassing their composition, structure, and underlying immunological mechanisms. Furthermore, it outlines emerging trends in the development of diverse lipid-based vaccine platforms, including strategies to enhance antigen loading capacity, achieve more precise targeting of antigen-presenting cells, and implement novel combinatorial approaches involving multi-platform and multi-pathway strategies. Finally, the review addresses the prevalent challenges, future development directions, industrial-scale manufacturing considerations, and quality control requirements for lipid-based vaccines, with the aim of advancing this promising field.
Ocular diseases are the main cause of vision loss and even blindness, with treatments including topical medications (such as eye drops), intravitreal injections, and surgery. However, the eye’s complex anatomical structure and physiological barriers significantly limit drug bioavailability, affecting therapeutic efficacy. Nanomaterials have shown promise in ophthalmic drug delivery due to their unique properties. Nanomaterials can effectively penetrate ocular barriers to enhance drug permeability and bioavailability. Their ocular penetration can be further optimized by regulating nanoparticle (NP) size and surface properties, thereby prolonging drug residence time on the ocular surface and reducing administration frequency. Additionally, as controlled-release carriers, they enable sustained drug release to extend therapeutic duration and improve treatment efficacy. In addition, some nanomaterials also possess biological activities such as antioxidant, antibacterial and anti-inflammatory, making them a promising therapeutic strategy. This review focuses on the advances in nanomaterials application for ocular diseases, summarizes the mechanisms underlying nanomaterial-based drug delivery, and discusses the current challenges and future research directions, with the aim of providing new insights into the clinical application and translation of nanomaterials in ophthalmology.
Inducing ferroptosis is a promising strategy for oral cancer therapy, but existing inducers often lack selectivity and possess poor drug-like properties. Our preliminary work identified 26a as a potent ferroptosis inducer targeting glutathione peroxidase 4 (GPX4), yet its selectivity and safety needed improvement. In this study, we designed a series of hybrid molecules by integrating the privileged fragment of 26a with the known GPX4 inhibitor ML210. Subsequent structural modifications led to the discovery of XW19, a novel structural scaffold exhibiting GPX4 inhibitory activity. XW19 demonstrated enhanced ferroptosis-inducing potency and highly selectivity (selectivity index (SI) = 1200) as well as inhibitory effects against oral cancer (half maximal inhibitory concentration (IC50) values ranging from 0.71 µmol/L to 2.39 µmol/L). Cellular thermal shift assay (CETSA) confirmed the strong binding affinity of XW19 with GPX4. Notably, XW19 exhibited significant tumor suppression and an improved safety profile in a nude mouse model bearing Cal27 ectopic xenografts, positioning XW19 as a promising therapeutic candidate for oral cancer treatment.
Bioassay- and molecular network-guided isolation of the extract from Hypericum monogynum led to the identification of five polycyclic polyprenylated acylphloroglucinol (PPAP) derivatives, including a previously unreported bis-seco compound, hypermonane A (HMA, 1). HMA possesses a unique 3/6-5/6/5 pentacyclic scaffold, characterized by C-1/C-2 and C-2/C-3 bond cleavage. In addition to HMA, four structurally related biosynthetic analogs (2–5) were also obtained. Its structure was elucidated using computer-assisted structure elucidation (CASE) software and gauge-independent atomic orbital (GIAO)-based nuclear magnetic resonance (NMR) calculations. The absolute configuration of 1 was determined through comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Biological investigations revealed that HMA potently inhibited aortic valve calcification by simultaneously suppressing osteogenic differentiation (runt-related transcription factor 2/alkaline phosphatase, RUNX2/ALP) and extracellular matrix remodeling (collagen type Ⅰ alpha 1 chain/a disintegrin and metalloproteinase with thrombospondin motif 4, COL1A1/ADAMTS4). Moreover, in a murine model of calcific aortic valve disease (CAVD), HMA significantly attenuated pathological aortic valve calcification. These findings highlight HMA as a promising lead compound for the development of anti-CAVD therapeutics.
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