Latest ArticlesUlcerative colitis (UC) is a pressing clinical issue currently lacking effective therapeutic approaches. Here we conducted a screening on the natural compounds from traditional Chinese medicine to identify a potent lead, shikonin (SHK), applying a necroptosis cell model. The potency for treating UC was confirmed in a dextran sulfate sodium (DSS)-induced UC mouse model. Leveraging a photo-affinity labeling approach, heat shock protein family A member 8 (HSPA8), a key negative regulator of necroptosis, was identified as the direct target of SHK. The in vivo protection of SHK were validated through targeting HSPA8 based on necroptosis pathway. As a result, targeting HSPA8 by SHK or activate HSPA8 significantly impairs necroptosis signaling and mitigates UC. Our findings not only define HSPA8 as a novel therapeutic target for UC but also highlight SHK as a promising lead for treatment of this symptom.
Flexible wearable sensors require conductive elastomers that combine sustainability, durability, and reliable low-temperature performance. However, conventional hydrogels suffer from dehydration and freezing, while ionogels face challenges of leakage, high cost, and poor recyclability. Here, we introduce a novel polymerizable deep eutectic solvent (PDES) system based on natural lipoic acid and imidazolium derivatives, which serves as the foundation for constructing recyclable polymeric dynamic eutectic gels (PDDEGs). The PDES not only provides high ionic mobility and antifreeze capacity but also enables covalent crosslinking to form a robust yet dynamic polymeric network. Through synergistic hydrogen bonding, ionic conduction, and reversible zirconium coordination, PDDEGs achieve high stretchability, toughness, and strong adhesion. More importantly, they exhibit remarkable recyclability, efficient self-healing, and thermal remoldability, allowing solvent-free reprocessing, structural repair, and adaptive reshaping without performance loss. The gels remain flexible and conductive at −20 ℃ and function as reliable strain sensors with high sensitivity, fast response, and long-term durability in monitoring complex human motions. By combining a new class of polymerizable eutectic solvents with dynamic crosslinking, this work establishes a sustainable platform for next-generation wearable electronics capable of operating in extreme environments.
Spinal cord injury (SCI) is a severe neurological disorder often leading to long-term motor dysfunction and permanent disability. Bone marrow-derived mesenchymal stem cell (BMSC) transplantation has been explored to promote SCI recovery; however, the survival and efficacy of transplanted BMSCs are severely compromised by the excessive reactive oxygen species (ROS) present at the injury site. In this study, we developed a peptide hydrogel (MnO2-Gel) with excellent ROS-scavenging capacity and good biocompatibility. In vitro experiments demonstrated that MnO2-Gel significantly enhanced BMSC survival under oxidative stress conditions. In a rat model of SCI, co-injection of MnO2-Gel and BMSCs into the lesion site markedly improved locomotor recovery, indicating the potential of this combination strategy for treating SCI.
Hydrogel-encapsulated islet cell transplantation is an effective strategy to overcome immune rejection in type 1 diabetes (T1D). However, current research primarily focuses on the immune isolation function of hydrogels about islet cell, while the influence of their mechanical properties on islet cells is often overlooked. To address this oversight, a series of alginate-gelatin (Alg-Gel) hydrogels with different mechanical strengths were prepared by adjusting the molecular weight of sodium alginate and combining it with gelatin, designated as low- (LHG, 1.98 kPa), medium- (MHG, 4.21 kPa), and high-stiffness (HHG, 22.98 kPa) hydrogels. Among them, the medium-stiffness hydrogel (MHG) exhibited stress-relaxing properties, which can mimic the mechanical properties of native islets. Furthermore, it activated the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)/Wnt signaling pathway, providing a favorable three-dimensional (3D) microenvironment for insulin-producing INS-1 cells. When further loaded with platelet-rich plasma (PRP), the resulting MHG@PRP construct then leverages calcium-dependent activation of the growth factor-PI3K/Akt/mammalian target of rapamycin (mTOR) axis to enhance cellular physiological performance. It was demonstrated in vitro that MHG@PRP significantly improves islet cell viability and glucose-stimulated insulin secretion (GSIS). Furthermore, in vivo experiments using a streptozotocin (STZ)-induced diabetic mouse model confirmed that the MHG@PRP/cells construct effectively restores glycemic regulation. This hydrogel design, which synergistically combines biomechanical and biochemical cues, is expected to provide a novel and transformative paradigm for advanced islet cell therapy.
This study aims to develop advanced phototheranostic agent to address the critical challenge of multi-modal therapy and immune microenvironment remodeling in immuno-phototherapy (IPT). Here we utilized a near infrared (NIR) o-IDTBR, and then assembled with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)] (DSPE-PEG-NH2) to prepare o-IDTBR nanoparticles (NPs). Theoretical calculations suggest that in the aggregated state, the energy gap between the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO), and the energy gap between the excited singlet and triplet states are reduced, as compared to the monomolecular state, leading to red-shifting absorption/emission wavelengths and enhancing the photothermal conversion and reactive oxygen species (ROS) generation, and thus improve the efficacy of photodynamic and photothermal therapies. These NIR laser-activated NPs effectively induced pyroptosis/apoptosis/necroptosis (PANoptosis) and promoted immunogenic cell death through mechanisms such as calreticulin (CRT) exposure, ATP secretion, and high mobility group box 1 (HMGB1) release. Notably, immune profiling revealed a reprogrammed tumor microenvironment in NPs and laser irradiation treated group. This phenotypic shift activated systemic antitumor immunity. Our work constructs an advanced phototheranostic agent with aggregation-induced red-shifting absorption and fluorescence wavelengths, and enhancing photothermal conversion and ROS generation capabilities, and establishes a synergistic paradigm of "imaging guidance, inducing local multi-modal cell death, systemic immune activation".
Chronic diabetic wounds are characterized by persistent inflammation and impaired angiogenesis, presenting a major therapeutic challenge. Here, we report a three-dimensional (3D)-printed polycaprolactone (PCL) scaffold integrating shikonin (SK), a bioactive compound derived from Lithospermum erythrorhizon, to achieve controlled drug release and multifunctional wound repair. The PCL/SK scaffold exhibited a porous, breathable architecture with high mechanical integrity and biocompatibility, enabling sustained SK release over 72 h. In a diabetic mouse wound model, the PCL/SK scaffold significantly accelerated wound closure, enhanced collagen deposition, and increased the density of anti-inflammatory CD206+ macrophages compared to free SK or PCL controls. Transcriptomic and immunohistochemical analyses revealed that PCL/SK treatment upregulated angiogenesis-related genes, including vascular endothelial growth factor (Vegf), platelet endothelial cell adhesion molecule 1 (Pecam1) and TEK receptor tyrosine kinase (Tek), meanwhile elevated CD31+ and VEGF+ endothelial markers, concomitant with improved blood perfusion. Mechanistically, this effect was attributed to synergistic anti-inflammatory and pro-angiogenic modulation by sustained SK delivery and the supportive PCL microenvironment. These findings establish a bioactive drug-biomaterial hybrid platform that leverages controlled release to coordinate immune resolution and vascular regeneration, offering a promising strategy for chronic diabetic wound management and broader regenerative applications.
Immune-mediated inflammatory diseases (IMIDs) are a class of chronic, relapsing disorders characterized by dysregulated immune activation and persistent inflammation. These conditions affect multiple organs, severely compromising patients' quality of life and increasing the global healthcare burden. Conventional treatments, such as glucocorticoids, immunosuppressants, and biologics, face limitations including low delivery efficiency, off-target effects, and poor patient adherence, whether administered topically or systemically. With the growing recognition of IMID pathogenesis as a multitargeted process, precision-based strategies and localized, patient-friendly drug delivery systems are increasingly needed. Microneedle (MN) technology has emerged as a promising transdermal and transmucosal platform for minimally invasive, site-specific therapeutic delivery in IMID treatment. By precisely targeting immune cells in the skin, oral mucosa, and eyes, MNs offer a novel approach to precision immunotherapy. This review explores recent advances in MN-based therapies for IMIDs, emphasizing their potential to transform the management of allergic conditions, autoimmune diseases, inflammatory skin disorders, infection-related chronic inflammation, oral disorders, and ocular disorders. Furthermore, the challenges hindering the clinical translation of MNs are discussed, along with perspectives on their future development. We anticipate that this review will provide innovative insights into precision immunotherapy for IMIDs.
Lanthanide complexes attract significant attention for their narrow-band emission with nearly constant wavelengths; however, developing high-efficiency lanthanide-complex organic light-emitting diode (OLED) devices and methodologies remains a primary research focus. We selected neutral ligands [1,2,5]thiadiazolo[3,4-f][1,10]phenanthroline (TDZP) and its selenium (Se)-containing counterpart, [1,2,5]selenadiazolo[3,4-f][1,10]phenanthroline (SDZP), to form complexes with dibenzoylmethane (Hdbm). Detailed investigations combining theoretical calculations and experimental data reveal synergistic effects between excited-state lifetimes and charge carrier mobility in enhancing quantum efficiency. All the devices demonstrated characteristic lanthanide ion emission, with the Eu(dbm)3SDZP-based OLED achieving remarkable electroluminescent performance: a maximum quantum efficiency (EQEmax) of 6.7%, ranking among the highest reported values for Eu-based complex OLEDs. This integrated computational-experimental approach establishes a viable strategy for developing high-efficiency lanthanide-complex OLEDs.
Bioluminescence imaging has emerged as a vital tool for studying molecular dynamics in living organisms, owing to its high sensitivity, absence of background fluorescence, and independence from external excitation light sources, demonstrating significant potential for propelling self-illuminated theranostic applications. Among bioluminescent systems, NanoLuc luciferase (NLuc) demonstrates significant advantages over traditional luciferases due to its exceptional catalytic efficiency, small molecular size (19 kDa), stability, and ATP independence. However, its short emission wavelength (ca. 460 nm) is susceptible to tissue attenuation, which hinders deep-tissue applications, severely impeding its application in deep-tissue imaging and theranostics. Fortunately, bioluminescence resonance energy transfer (BRET) technology, combined with fluorescent protein fusions, protein tag techniques, and site-specific labeling with fluorescent dyes, effectively extends emission wavelengths, greatly enriching the toolkit for bioluminescence-based integrated theranostics. This review, for the first time, systematically summarizes groundbreaking strategies for engineered NLuc in “self-illuminating” theranostic applications. By elucidating its structure-function relationships, we focus on developments in NLuc engineering, substrate optimization, and the construction of BRET systems. The review critically assesses progress in deep-tissue imaging and spatiotemporally controlled phototherapy, providing a forward-looking roadmap for clinical translation in diagnostics and precision medicine.
Liver disease remains one of the most prevalent health concerns, attracting significant attention for its treatment options. As an emerging technology, messenger RNA (mRNA) technology has shown remarkable potential in the biomedical field, with RNA drugs offering distinct advantages such as rapid onset, safety, multiple target options, and ease of clinical translation. However, the inherent instability and susceptibility to degradation of mRNA molecules pose significant challenges for efficient and targeted delivery. Nanotechnology offers innovative solutions to these challenges, not only overcoming physiological barriers but also significantly enhancing the efficacy of mRNA drugs. As an ideal strategy for treating liver diseases, lipid nanoparticle (LNP)-encapsulated mRNA can activate regenerative pathways in hepatocytes within a short time frame, facilitating the treatment of liver injuries from various causes. This review highlights recent advancements in LNP-based mRNA delivery systems for treating different liver diseases. It begins with an introduction to mRNA drugs and their delivery systems, followed by a discussion on the targeting capabilities of LNP. It also emphasizes the application of LNP-based mRNA delivery systems in treating liver diseases. Finally, It outlines the current challenges faced by LNP-based mRNA delivery systems in liver disease treatment and anticipates future applications in addressing liver-related disorders. It is hoped that these insights presented here will help to further improve the application of mRNA-LNP technology in disease treatment. This review aims to provide a reference for researchers and clinicians in related fields and promotes the further development of this technology.
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