Latest ArticlesCu-Zn solid solutions are investigated as advanced current collector materials for anode-free Li metal batteries (AFLMBs), addressing the limited lithiophilicity and slow Li+ diffusion kinetics inherent to conventional Cu foil. Benefiting from the uniform distribution of lithiophilic Zn, Cu-Zn solid solutions demonstrated enhanced lithiophilicity and accelerated Li+ diffusion, which effectively facilitated uniform and reversible lithium deposition. First-principles calculations confirmed that Cu-Zn solid solutions, particularly Cu62Zn38, exhibited stronger Li adsorption and reduced diffusion barriers compared to Cu. Unlike alloy-prone metal coatings (e.g., Cu@Zn and thermally processed Cu@Zn) that sacrifice interfacial stability for lithiophilicity, Cu-Zn solid solution maintains robust electrode-electrolyte interfaces due to its alloying inertness. Ex-situ SEM and COMSOL simulations revealed dendrite-suppressed and homogeneous Li deposition on Cu62Zn38. In anode-free full cells, Cu62Zn38 achieves a capacity retention of 55.1% after 150 cycles, far exceeding Cu foil (13.8%). This work establishes Cu-Zn solid solutions current collectors as a scalable solution for high-energy-density AFLMBs.
Acaualblides A–E (1–5), five architecturally unprecedented macrolides, were isolated from fungus Acaulium album 429 and comprehensively characterized. Their structures were elucidated by high-resolution electrospray ionization mass spectrometry (HRESIMS), extensive spectroscopic analyses, and single-crystal X-ray diffraction. Compounds 1–3 possess unusual fourteen-membered macrolide frameworks bearing pyridine or thiophene moieties. Compound 4 represents the first heterodimer featuring a macrolide unit covalently linked to an aflatoxin B1 moiety through a C–C bond, while compound 5 is a unique homodimeric macrolide in which two identical units are connected by both a C-9/C-9′ carbon-carbon bond and a C-8/C-8′ thioether bridge. Plausible biosynthetic pathways for compounds 1–5 are proposed. Notably, compound 1 displayed significant immunosuppressive activity by inhibiting B-cell proliferation and activation through modulation of the B-cell receptor (BCR) signaling pathway.
The nose-to-brain drug delivery system has emerged as a transformative strategy for central nervous system (CNS) diseases therapy by leveraging the olfactory pathway to circumvent the blood-brain barrier. However, its clinical translation remains impeded by suboptimal olfactory deposition efficiency. A critical but poorly understood challenge lies in rational formulation design, particularly regarding how key physicochemical properties like viscosity govern the nasal drug delivery processes. Using rizatriptan nasal sprays as a viscosity-regulated model system (2–250 mPa s), we dissected how formulation viscosity governs olfactory deposition through synchronized macro-micro spray characteristics. A module 3D-printed human nasal cast was utilized to assess the olfactory deposition efficiency. Additionally, the spray pattern, plume geometry and real-time droplet size distribution were examined using laser diffraction analysis. The results demonstrate a non-monotonic olfactory deposition dependence on viscosity, peaking at 40 mPa s with 31.64% efficiency (31-fold enhancement vs. 2 mPa s). Furthermore, the increase of viscosity led to a reduction in plume angle and spray area, while simultaneously decreasing the stabilization stage fraction of droplets. Mechanistic analysis revealed two competing viscosity-mediated effects: (1) Macroscale plume narrowing that minimized anterior nasal losses; (2) Microscale destabilization of droplets that impaired turbinate transportation. This study elucidates that the viscosity-regulated precision olfactory deposition results from the equilibrium between macroscopic spray geometry and microscopic droplet dynamic, challenging the conventional single-parameter optimization paradigm. Our findings advance nose-to-brain drug delivery by deciphering the viscosity-regulated deposition mechanism, thereby paving the way for rationally designed nasal sprays with enhanced targeting efficiency for CNS diseases.
Precise gene therapy for hepatocellular carcinoma (HCC) remains challenging due to the lack of tumor-selective activation and biosafety concerns of conventional DNAzyme systems. Herein, we report a logic-gated, triple-responsive nanoplatform that enables spatiotemporal control of DNAzyme activation exclusively within the tumor microenvironment. The DNAzyme is rendered catalytically inactive through boronate caging and is loaded into an N-acetylgalactosamine (GalNAc)-functionalized zinc metal-organic framework (Zn-MOF) for HCC-targeted delivery. The system integrates three tumor-associated stimuli, acidic pH, Zn2+ release, and reactive oxygen species (ROS) generation, as a cascaded logic gate to ensure sequential and tumor-specific activation. Acidic pH triggers Zn-MOF degradation, releasing both Zn2+ and the caged DNAzyme. Zn2+ catalyzes ROS generation, which decages the DNAzyme and enables its Zn2+-dependent cleavage of oncogenic early growth response protein 1 (EGR-1) mRNA. This logic-gated activation strategy ensures high specificity, minimal off-target effects, and synergistic antitumor efficacy by combining chemodynamic therapy and gene silencing. The proposed nanoplatform offers a robust blueprint for highly selective and safe DNAzyme-based cancer therapies.
Gonadotropin-releasing hormone (GnRH) analogues are widely used polypeptide therapeutics whose clinical utility is limited by pseudo-allergic reactions mediated through histamine release. This study systematically investigated the correlation between GnRH analogue-induced histamine release and the mast cell receptor Mas-related G protein-coupled receptor X2 (MRGPRX2)-a key mediator of drug-induced pseudo-allergic reactions-sing integrated, in vivo, and structural analyses. In vitro experiments demonstrated that GnRH analogues trigger MRGPRX2-dependent Ca2+ mobilization and mast cell degranulation, resulting in dose-dependent increases in β-hexosaminidase, histamine, and tumor necrosis factor α (TNF-α) release. Among the analogues tested, nafarelin exhibited the highest potency, whereas buserelin exhibited the lowest. In vivo, these analogues induced mast cell degranulation and capillary dilation in mouse paw skin, leading to localized pseudo-allergic symptoms (edema and extravasation) that were confirmed to be MRGPRX2-mediated. Molecular docking revealed that the cationic amino acid at position eight of the GnRH analogues bound complementarily to the negatively charged center within the MRGPRX2 ligand-binding pocket, suggesting a mechanistic basis for receptor activation. Functional validation via Arg8-to-Glu substitution in triptorelin significantly attenuated MRGPRX2 activation. Collectively, this work elucidates the MRGPRX2-dependent molecular mechanism underlying GnRH analogue-induced histamine release and provides a foundation for designing safer analogues with reduced adverse effects.
Elucidating drug mechanisms of action and evaluating therapeutic efficacy require advanced techniques for real-time, dynamic monitoring of drug-target interactions in living systems. Recent advances in optical molecular probes have yielded powerful tools to visualize drug targets, quantify pharmacodynamic profiles, and track drug metabolism. In this review, we first summarize the major categories of optical imaging targets for chemotherapy assessment, followed by a systematic discussion of optical probe design strategies tailored to these targets. We then comprehensively review probe applications in drug screening, target validation, efficacy assessment, adverse effect evaluation, biodistribution analysis, and metabolic pathway tracking. Finally, we discuss the prospects and challenges of molecular optical imaging in precision medicine and clinical applications, while proposing potential breakthroughs and future directions. This review serves as a valuable reference for advancing optical probe design and application in drug development.
Realizing biologically authentic tactile–pain sensing in flexible electronic skins (e-skins) requires materials that combine linear touch encoding with strain-gated pain signaling, while also offering spatially resolved stimulus mapping and sustainable recyclability. Here, we present a recyclable neurothreshold-mimetic eutectogel (NeuroThres-Gel) based on a strain-induced percolation threshold modulation strategy. The prepared eutectogel demonstrated shear-thinning rheology, thermoplastic reprocessability, and environmental stability in wide temperature window. Under uniaxial strain, the conductive network remains intact and reversible up to a programmable critical strain (εt) of 80%. Beyond this threshold, geometric percolation collapse occurs, resulting in a sharp, nonvolatile resistive transition that mimics neuronal action potential firing and enables strain-gated pain-like signaling. Direct-ink-writing (DIW) of NeuroThres-Gel yielded microstructured sensor arrays with volumetrically distributed receptive fields, achieving spatially resolved, vectorial pain mapping. Critically, after five melt-recycle cycles, the NeuroThres-Gel sensors retained excellent spatial nociceptive perception and stable mechanical strength, highlighting the closed-loop recyclability enabled by the dynamic cross-linked network. Collectively, NeuroThres-Gel integrated programmable tactile-to-pain conversion, directional nociceptive sensing, and sustainable recyclability into a single platform, charting a pathway toward next-generation adaptive prosthetic feedback systems and human–machine interfaces.
Hydrogen sulfide (H2S) is a pivotal endogenous gaseous signalling molecule involved in various physiological processes. Although H2S exhibits significant anti-inflammatory effects at physiological concentrations, its clinical utility is hindered by the challenges associated with its high activity and difficulties in controlled release. We designed three photoactivatable H2S donors, HSDs (HSD1, HSD2, and HSD3), by integrating an H2S-releasing 1,4,2-dioxazole-5-thione scaffold with three fluorophores spanning the ultraviolet to red spectral range. Upon photo-irradiation, each donor induces a pronounced turn-on fluorescence (> 58-fold), accompanied by efficient H2S release (over 30%) without the formation of electrophilic by-products. Moreover, HSDs enable real-time quantitatively photo-triggered H2S-release in both live cells and murine models, and present anti-inflammatory and antioxidant effects in vivo. In a full-thickness cutaneous wound model, HSDs markedly accelerated wound healing, highlighting their potential as precision therapeutic agents for wound management. Collectively, we provide a translatable strategy to overcome the limitations of conventional H2S delivery systems and highlight the therapeutic promise of controlled H2S release in clinical application.
Tetrahedral framework nucleic acids (tFNAs) have emerged as a promising platform for a wide range of biomedical applications due to their unique structural stability, ease of synthesis, and excellent biocompatibility. This review provides a comprehensive overview of the various modification strategies for tFNAs, including vertex modification, edge functional loading, internal encapsulation, and surface coating. These modifications enable precise control over their biological activity, facilitating advancements in drug delivery, gene therapy, tissue engineering, and diagnostic imaging. Additionally, the structural engineering of tFNAs has enabled their integration into theranostic platforms, offering significant potential for personalized medicine. The review also discusses the challenges involved in the clinical translation of tFNAs, such as scalability, pharmacokinetic optimization, and regulatory approval, and presents a forward-looking perspective on the emerging trends that could further broaden the scope of tFNAs in clinical applications. Finally, we conclude by outlining the future prospects of tFNAs in next-generation therapeutic and diagnostic systems, highlighting their transformative potential in the biomedical field.
Nano-carriers are crucial for photosensitizer targeted delivery to overcome the poor selectivity of conventional photosensitizers. Recently, aptamer-guided DNA tetrahedron has become a potential carrier due to its great biocompatibility and target identification ability. However, the in vivo photodynamic therapy (PDT) of DNA tetrahedron-based photosensitizer delivery system remains a charming yet challenging mission. This work aims to construct a high-targeted photosensitizer delivery system for enhanced PDT treatment, relying on the combination of aptamer-guided DNA tetrahedron, graphene-oxide and photosensitizer. Three aptamers are linked to a DNA tetrahedron to build an aptamer-guided nano-carrier for targeting liver tumor cells. Aggregation-induced emission-active photosensitizer, TTVP, was loaded into the nano-carriers through intercalation and hydrophobic interaction, leading to the improvement of their PDT effect. Subsequently, TTVP-loaded nano-carriers were adsorbed on the graphene-oxide surface via hydrogen bonds and π-stacking interactions to elevate their target identification ability. Consequently, a photosensitizer delivery system was obtained. It selectively aggregated on the liver tumor tissues and presented potent therapeutic efficacy via reactive oxygen species (ROS) generation. This system provides a fresh pathway for in vivo high-targeted and enhanced PDT treatment based on DNA nano-carriers.
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