Diabetic wounds are characterized by chronic inflammation, partly due to the persistent accumulation of pro-inflammatory M1 macrophages. Asiaticoside (AS), a triterpenoid extracted from Centella asiatica, has known anti-inflammatory effects in several diseases, but the underlying mechanisms in diabetic wounds are still unclear. This study reveals that AS alleviates inflammation in diabetic wounds by activating ferroptosis of M1 macrophages. In vitro, AS reduces the number of M1 macrophages in a high glucose microenvironment and their secretion of proinflammatory cytokines with concurrent induction of ferroptosis. Further investigation shows that AS-activated ferroptosis is attributed to the downregulation of ferroportin 1 (FPN1) and ferritinophagy-induced degradation of ferritin heavy chain 1 (FTH1), which together increase the amount of intracellular free ferrous ions (Fe²⁺). In vivo, AS-encapsulated gelatin-methacryloyl hydrogels accelerates diabetic wound healing and shortens the inflammatory period by activating ferroptosis of M1 macrophages with the reduced expression of FPN1 and FTH1. These results suggest a promising AS-based strategy for treating inflammatory diseases associated with excessive activation of M1 macrophages.

The accumulation of senescent cells and their secretion of senescence-associated secretory phenotype (SASP) play important roles in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Small molecules, known as senolytics or senomorphics, have been effective in targeting senescent cells. Although senolytic drugs have been well-studied in pulmonary fibrosis, senomorphics with defined protein targets and potential applications are rarely investigated. In this study, we identified a widely sourced natural product, caffeic acid (CA), to act as a potent senomorphic that effectively inhibits the secretion of SASP in senescent lung cells. We demonstrated that the covalent binding of CA to Annexin A5 protein triggered its degradation, PKCθ deactivation, and the inhibition of the NF-κB inflammatory pathway in senescent cells. Notably, CA exhibited a promising effect in limiting inflammation in the lung and circulatory system, alleviating pulmonary pathology, and improving physical function in a bleomycin-induced pulmonary fibrosis mouse model. Our investigation suggests that Annexin A5 could be used as the target for the precise intervention of aging-related diseases such as IPF.

Messenger RNA (mRNA) therapeutics and vaccines have recently gained particular prominence following the COVID-19 epidemic. However, clinical translation of mRNAs is critically dependent on efficient and safe delivery in vivo. Currently, a plethora of mRNA delivery technology platforms (such as lipid nanoparticles) have been developed and have achieved stunning success. Nevertheless, many challenges remain to be overcome, including immunogenicity and toxicities, excessive liver accumulation, limited endosomal escape ability, low tissue bioavailability, poor mucosal immunity, and the need for cold chain storage. In recent years, extracellular vesicles (EVs) have emerged as an attractive mRNA delivery platform due to their favorable properties, such as low immunogenicity, natural capability to deliver RNAs, intrinsic targeting capacity, and the ability to negotiate with physiological barriers. In this review, we discuss the latest efforts to harness EVs for mRNA delivery and elaborate the behind mechanisms, aiming to offering insights into the rational design of effective and safe EV-based mRNA therapeutics and vaccines for biomedical applications. Additionally, we provide an overview of EV biogenesis, composition, cellular internalization, and their superiorities and challenges for mRNA delivery, with special emphasis on the state-of-the-art methodologies for packaging EVs with mRNAs.

Magnetothermal neuromodulation is a minimally invasive, deep-brain accessible, and tether-free technique. The precisely timed activation of thermosensitive ion channels, such as TRPV1, with local heat generated using magnetic nanoparticles is crucial for efficient neuromodulation. Nevertheless, this technique is greatly hindered by its long stimulus-response time and high safety risks due to the poor heat-generating performance of the nanomediators. Herein, we report the establishment of a ferrimagnetic vortex iron oxide nanoring (FVIO)-mediated magnetothermal neurostimulation technique that is efficient and safe. Compared with widely used superparamagnetic iron oxide nanomediators (SPIOs), the FVIOs triggered Ca²⁺ influx into HEK293T cells and cortical neurons at an Fe concentration of 51 µg mL⁻¹, which is 20.27-fold lower than that needed for SPIOs. In vivo magnetothermal stimulation in the central nucleus of the amygdala of mice further demonstrated that FVIOs with the optimal dose of 0.05 µg evoked fear behaviors with an average latency of 2.51 s, which was 2.3-fold faster than that in the SPIO (0.80 µg)-treated group. More importantly, FVIOs-mediated stimulation not only exhibited negligible histopathological alterations and proinflammatory cytokine expression but also successfully elicited fear behaviors in transgene-free mice. The FVIO-mediated efficient and safe neuromodulation has the potential for future neuroscience exploitation and neurological disease treatment.

In the advent of Industry 5.0, the harmonious integration of human ingenuity and robotic precision in complex work environments is pivotal for sustainable industrial growth. The six-axis industrial robot, as an essential part of carrying out cyclic pick-and-place tasks in Industry 5.0, usually works in an extremely complex working environment. This intricate working environment makes the six-axis industrial robot difficult to reach the task points effectively, resulting in a lot of energy consumption. This not only impacts productivity but also leads to excessive energy consumption, which stands at odds with the Industry 5.0 principles of resource conservation. To solve this problem, a novel method to optimize the layout scheme of the six-axis industrial robot with the goal of minimizing the energy loss is creatively proposed in this paper. First, the reachable workspace and feasible workspace under constraints are mathematically modeled and then obtained. Second, the operability and the minimum singular value are utilized to evaluate the energy loss of the feasible workspace. Third, the whale algorithm is designed and improved to obtain the optimal layout scheme of the six-axis industrial robot. Finally, a case of the recliner's production line with the six-axis industrial robot (IRB140; ABB) is provided to validate the effectiveness of the proposed method. The results show that after optimization, the optimal layout scheme has been successfully obtained, and the energy loss has reduced from 0.2917 to 0.2309, a decrease of 20.84%, proving that the proposed method can obtain the optimal layout scheme with lower energy consumption.

Ulcerative colitis (UC) is a chronic and persistent clinical condition that is challenging to cure. Lysine crotonylation (KCr), a recently discovered post-translational modification (PTM), alters protein structure, stability, localization and activity in a variety of processes including cell differentiation and organism development. This study was designed to elucidate the pathophysiological relevance of KCr in UC and uncover potential underlying mechanisms involved. PTM proteomics was employed to track dynamic alterations in KCr sites and protein level in the colon tissue of dextran sulfate sodium (DSS)-induced UC model mice. Following the validation of differentially crotonylated proteins via Western blot assay, functional and mechanistic analyses of specific KCr sites were conducted in vitro. Gain-of-function or loss-of-function mutations were implemented at selected protein KCr sites. The differentially crotonylated proteins including citrate synthetase (CS) between the colon tissue of DSS-induced mice and control mice were predominantly associated with the tricarboxylic acid (TCA) cycle, as evidenced by significant enrichment in the KEGG pathway analysis. These proteins were primarily localized in mitochondria, suggesting a potential link among UC pathogenesis, mitochondria and the TCA cycle. Collectively, increased KCr restricts inflammasome activation by inducing mitophagy, thereby maintaining mitochondrial homeostasis, reducing oxidative stress and inhibiting apoptosis in UC. KCr represents a potential promising therapeutic target for the treatment of UC.

The intrinsic properties of black phosphorus (BP) nanomaterials (NMs) enable them for targeted binding to polo-like kinase 1 (PLK1), thus inhibiting its kinase activity. However, the mechanism and targeted binding sites underlying this interaction remain unclear. To elucidate the critical properties of PLK1 that facilitate its interaction with BPNMs, the binding ability of BPNMs was compared across PLK family proteins. Although BPNMs exhibited a weak binding affinity for PLK3, PLK1 demonstrated the most favorable physicochemical properties for its binding. Factors as surface charge, hydrophobicity, secondary and three-dimensional structures significantly affected the interaction of PLK family proteins to BPNMs. The binding affinity was primarily determined by amino acid residues at the binding interface, where arginine and proline played critical roles in mediating the interaction of BPNMs-PLK1. BPNMs inhibited PLK1 activation by binding to key residues of the kinase domain, including S49, Y203, D204, E206, and R207. In conclusion, this study elucidates the molecular basis of the specific interaction between BPNMs and PLK1, highlighting the pivotal role of the amino acid residues in NM-protein binding. This work demonstrates that NM-protein interactions are a mutual selection and driven by the physicochemical properties of both proteins and NMs.

Cyclic dinucleotides, which act as agonists for the stimulator of interferon genes (STING), are pivotal in stimulating both adaptive and innate immune reactions for advancing cancer immunotherapy. However, their therapeutic potential is hampered by inherent limitations, including susceptible degradation and inefficient delivery. Herein, we design genetically engineered bacteria (2'3'-cGAMP@E.coli) capable of producing 2'3'-cGAMP in the cytoplasm and then fabricate personalized nanovaccines (nECTs) by assembling 2'3'-cGAMP@E.coli with autologous tumor antigens instead of complicated chemical synthesis. Our in vitro analysis confirms that nECTs are capable of potently stimulating dendritic cell activity and amplifying the cross-presentation of antigens by leveraging the STING signaling route, underscoring their potential to bolster immune response priming. Translating these findings into in vivo models, vaccination with nECTs leads to a pronounced infiltration of effector T cells into tumor sites, concurrent with an IFN-β-mediated remodeling of the suppressive tumor microenvironment by innate immune cells. Notably, the therapeutic efficacy of nECTs is further augmented when coupled with a fasting-mimicking diet regimen, highlighting the synergistic potential of this combinatory strategy. Collectively, this dual modality represents a significant stride towards enhancing the precision and effectiveness of immunotherapeutic interventions in oncology.

Photocatalysis has been recognized as a promising approach in cancer theranostics over the past years. To enhance therapeutic outcomes and overcome current limitations, significant attention has been directed toward the development of multi-energy integrated photocatalytic systems, particularly piezo-photocatalysts and photothermal-photocatalysts. Piezo-photocatalysis combines the piezoelectric effect with photocatalysis, offering superior efficiency, targeted action, and improved safety compared to traditional photocatalytic methods. By harnessing both mechanical and optical stimuli, this approach enables more precise and effective cancer therapies. On the other hand, photothermal-photocatalysis integrates heat induced by light with photocatalytic reactions, accelerating reaction rates and promoting the generation of reactive oxygen species. The synergistic interaction of heat and photocatalysis enhances tumor cell apoptosis more effectively than either modality alone. This review provides a systemic overview of the emerging multi-energy integrated photocatalytic strategies for cancer treatment. It begins with an exploration of the principles of piezo-photocatalysis and its potential to improve cancer therapies such as piezoelectric-enhanced single-modal photodynamic therapy (PDT), dual-modal sono-photodynamic therapy, and triple-modal hydrodynamic therapy/gas therapy (GT)/chemotherapy. Next, we delve into photothermal-photocatalysis and examine how its integration with additional treatment modalities, such as dual-modal photothermal/photocatalytic therapy (PTT/PCT) and PTT/PDT, can enhance therapeutic efficacy. Furthermore, we discuss more complex multi-modal treatments, including triple-modal PTT/PCT/chemotherapy, PTT/PCT/chemodynamic therapy (CDT), PTT/PCT/GT, PTT/PCT/immunotherapy (IT) and tetra-modal PTT/PCT/CDT/chemotherapy, PTT/PCT/CDT/ferroptosis therapy (FT), PTT/PCT/FT/IT, and PTT/PCT/GT/IT. Finally, we address the challenges and future directions in advancing these novel therapeutic paradigms. This review aims to provide a comprehensive resource for future research dedicated to advancing innovative multi-energy integrated photocatalytic systems in the field of cancer nanotheranostics.

Photoelectrocatalysis reduction of CO₂ into products such as CO and CH₄ is an effective strategy for improving carbon utilization and advancing the development of renewable energy. Improving the catalytic efficiency by regulating the polarization behavior of the electrode has been proven to be an effective method. In this study, a method for preparing a Ti:Fe₂O₃/CuFeO₂-v photoanode with oxygen vacancies and heterojunctions for PEC CO₂ reduction is reported. Oxygen vacancies not only enhance the carrier transport ability of the electrode and improve the resistance polarization, but also regulate the material's magnetic properties. Based on this, we utilize the magnetic fluid dynamics (MHD) effect to reduce the thickness of the diffusion layer on the electrode surface, thereby improving mass transfer and solving the concentration polarization problem. This adjustment increased the current density to 1.49 mA cm⁻² and increased the CO yield to 154.27 mL h⁻¹. This method innovatively applies the MHD insights of the electrochemical oxygen evolution reaction (OER) to photoelectrochemical CO₂ reduction, aiming to optimize the electrode reaction kinetics for efficient CO₂ conversion, marking a significant progress in the field of photocatalytic CO₂ reduction.

Ammonia, as a carbon-free nitrogen-based hydrogen carrier, has attracted significant interest in addressing the approaching energy model innovation in light of its high hydrogen content, low cost, ease of storage, and transport. However, the additional energy consumption and environmental pollution caused by the traditional Haber–Bosch ammonia production and thermal ammonia catalytic cracking process enforce the exploration of clean and renewable ammonia cycling approaches. Electrochemical (EC) and photoelectrochemical (PEC) ammonia synthesis and oxidation for hydrogen generation have shown great potential for achieving an eco-friendly and sustainable green hydrogen economy. Exploring low-cost, highly active, and stable catalysts is pivotal for both EC and PEC systems to achieve efficient ammonia conversion properties. Transition metal-based catalysts (TMCs) have shown significant potential in EC and PEC catalytic systems because of their high catalytic activity, low cost, and excellent stability. We summarize the recent advanced progress of TMCs applied to EC and PEC ammonia synthesis and decomposition to hydrogen generation. Moreover, we discuss the challenges and perspectives on exploring transition metal-based materials in EC and PEC ammonia conversion. This review offers guidance for developing carbon-free nitrogen cycling as a hydrogen carrier.

Nonporous adaptive crystals (NACs) represent a unique class of supramolecular macrocycle-based crystalline organic materials that have garnered significant attention in supramolecular chemistry and beyond over the past decade. Unlike traditional porous materials, NACs are initially nonporous but can induce porosity through host–guest interactions in the solid-state, enabling exceptional performance in hydrocarbon separation. This review surveys the development of NACs based on novel macrocyclic arenes inspired by pillararene and calixarene structures, encompassing biphen[n]arene, tiara[n]arene, leaning pillararene, hybrid[n]arene, leggero pillararene, geminiarene, bowtiearene, rhombicarene, and other derivatives. Emphasizing their preparation, structural characteristics, and mechanisms of adsorptive selectivity, this comprehensive overview highlights their contributions to advancing supramolecular chemistry, functional materials, and beyond. Finally, the remaining challenges and perspectives are outlined. It is anticipated that this review will serve as a timely and valuable reference for researchers interested in NACs and related materials, stimulating further impactful studies in related fields.

Large bone defects present major problems in plastic, maxillofacial, and orthopedic reconstructive surgery. With respect to osseous tissues, currently, autologous and allogeneic bone grafts are commonly used clinical treatments, but there are limitations in terms of donor availability, morbidity, and risk of immunogenic reactions. Tissue-engineered bone constructs offer promising alternatives but struggle to replicate the complex biological functions of native bone, leading to suboptimal outcomes. The periosteum has been shown to be a key factor in bone regeneration and has a bilayered structure that is essential for bone integrity and repair. However, large bone defects cause damage to the periosteum and weaken its regenerative capacity. Therefore, periosteum organoids have been developed with the help of new organoid technology to achieve accelerated bone regeneration. This technology incorporates a variety of natural/synthetic materials and biologically derived factors that can be endowed with key biological functions for bone regeneration, such as, antimicrobial, immunomodulatory, neuromodulatory, angiogenic, and osteogenic capabilities. This review explores the structure and function of periosteum, the design and application of periosteum organoids and their potential integration with bone organoids. In addition, the recent advances and future directions for the use of such organoids in novel regenerative medicine and bone repair strategies are highlighted.

Solid waste remains a global crisis in which massive amount of solid waste is disposed of in landfills and the environment yearly, leading to detrimental environmental pollution and loss of resources. However, the current downcycling technologies, such as pyrolysis and gasification, usually require extensive energy input and harsh operating conditions, posing a high possibility of causing secondary pollution. In pursuit of a sustainable future, artificial photosynthesis arises as one of the promising but arduous approaches to reform solid waste into fuels and commodity chemicals under benign conditions. Under this backdrop, this review aims to present a thorough overview of the recent advancement in solid waste transformation through photocatalysis. To begin with, the principles of solar-driven conversion pathways for solid waste are discussed under different reaction conditions. Then this review also highlights the merits of artificial photosynthesis and diverse state-of-the-art photocatalysts for solid waste valorization. Special emphasis is placed on elucidating the application of external-field-assisted photocatalysis (e.g. photothermocatalysis, photoelectrocatalysis, photobiocatalysis, and piezo-photocatalysis) for solid waste upcycling to explore the synergistic effects on performance improvement. Finally, insights on the challenges and prospects in photocatalytic solid waste conversion are presented to bridge a new exemplification towards a sustainable circular economy in the future.

Lithium–sulfur batteries (LSBs) have garnered significant concern as materials with high energy density for energy storage. Nevertheless, their severe shuttle effect and delayed redox kinetics limit their practical application. Herein, a strategy based on the regulation of oxygen vacancy concentration in CoWO₄ has been proposed to accelerate polysulfide kinetics. Experiments and density functional theory calculations reveal that catalytic materials with the appropriate number of oxygen vacancies (CWO-M) have moderate adsorption energy and optimal catalytic capacity for polysulfides due to strong p–d orbital hybridization. More importantly, CWO-M not only accelerates the reduction of sulfur during discharge but also significantly accelerates the oxidation of Li₂S during charging, showing a favorable bidirectional catalytic effect. Benefiting from these unique advantages, the CWO-M/S-based battery exhibits an excellent rate performance of 768 mAh g⁻¹ at 2 C and a capacity retention of 91.1% after 100 cycles at 0.2 C. Stable cycling performance with a high capacity of nearly 4 mAh cm⁻² was achieved even after 100 cycles at a high sulfur loading of 8.02 mg cm⁻² and a low electrolyte/sulfur (E/S) ratio of 8 µL mg S⁻¹. This work provides significant insights into bidirectional catalysts by modulating the oxygen vacancy concentration for application in LSBs.

Rapid advances in synthetic biology are driving the development of microbes as therapeutic agents. While the immunosuppressive tumor microenvironment creates a favorable niche for the systematic delivery of bacteria and therapeutic payloads, these can be harmful if released into healthy tissues. To address this limitation, we designed a spatiotemporal targeting system for engineered Escherichia coli Nissle 1917, controlled by azide-modified hyaluronic acid hydrogel and near-infrared radiation induction. Using a temperature-driven genetic status switch, the system produced durable therapeutic output and promoted the therapeutic activity in solid tumors. The combination of azide-modified hyaluronic acid hydrogel and temperature-sensitive, engineered Escherichia coli Nissle 1917 provided spatiotemporal targeting of solid tumors, not only showing significant therapeutic effects on primary solid tumors, but also inhibiting the metastasis and recurrence of cancer cells by enhancing tumor-infiltrating lymphocytes. This system has potential for clinical application.

Gas therapy has been limited in its application as a robust standalone antitumor strategy due to the restricted gas production and cytotoxicity. To address this challenge, we employed electrotoxic PtRu composite metal nano-berries (PR) loaded with various therapeutic gas donors to construct a groundbreaking electric field-induced cascade gas therapy (EGT) platform, which generated a great electro-stress storm at tumor sites, exerting electrotoxicity and immunity functions against solid tumors, including those of large volume, through three pathways. Initially, electric field stimulation effectively boosted the release rate and yield of therapeutic gases from the EGT platform. Further, gas molecules reacted with reactive oxygen species (ROS) to either form oxidation coordination (CO and ROS) or generate more potent therapeutic components (RNS produced from ROS and NO), contributing to an electro-stress storm that augmented the cytotoxic potential of the gas components. Subsequently, this electro-stress storm further activated the tumor immune response, identifying and capturing escaped tumor cells, which held significant implications for treating tumors, including non-solid tumors with indistinct boundaries. In summary, the EGT platform leveraged an electro-stress storm to achieve ablation of large volume solid tumors and suppressed metastatic tumors, paving new pathways for gas-based therapeutic strategies.

Given its global distribution and high transmissibility in the environment, Candida auris poses a serious threat to global public health. However, the underlying mechanisms of its adaptive strategies remain poorly understood. Here we delineate the pan-genome structures of 1,306 representative C. auris isolates collected from 28 countries. In addition to the clade-related genetic diversity and highly variable pan-genomes, we identify the key regulatory modules and genes specific to C. auris in response to 32 different host microenvironment-mimicking stresses. Through comparative analysis with evolutionarily close fungal relatives, we uncover both shared and species-specific transcriptional responses in C. auris. Intriguingly, our results reveal a distinct pathogenic role for the conserved iron regulon in this species. Unexpectedly, we also identify an evolutionarily divergent functional role for RIM101 in regulating both pathogenicity and commensalism of C. auris. Mechanistically, the high-affinity glucose transporters were found to enhance the tolerance to alkaline stress through alleviation of RIM101-dependent glucose repression in the host microenvironment. These findings provide mechanistic insights into the evolutionarily divergent adaptive strategies in both commensalism and virulence of the emerging critical priority fungal pathogen, C. auris.

Polymeric conductive patches have conventionally been employed to facilitate the repair of infarcted myocardium by enhancing myocardial electrical conduction and providing mechanical support. However, it remains a challenge to restore the electrical conduction and diastolic–systolic functions with stable and anisotropic mechanical and electrical cues in the dynamic physiological environment. Herein, inspired by the hierarchical myocardial fiber microscopic striated structure, we established a weaving-based processing method to compound a striated polypyrrole conductive coating on the surface of highly oriented elastic fiber bundles. This unique design endows the patch with exceptional stretchability (elongation at break > 400%), stable conductance (ΔR/R₀ = 0.04 within 20% strain), and excellent fatigue resistance (ΔR/R₀ = 0.01 after 1,000,000 cycles). In addition, the precision process grounded on woven molding accomplished the tunable mechanical and electrical properties of the patch, which facilitates the achievement of long-term, stable, and anisotropic mechanical–electrical coupling with the infarcted myocardium. The rat MI model experiments demonstrated that this anisotropic conductive patch can not only improve cardiac function and electrical activity over an extended period, but also effectively inhibit myocardial inflammation and fibrosis and promote angiogenesis. This study proposes a promising MI-treatment patch and highlights the potential of woven technology in processing biomaterials composed of both rigid and elastic materials.

Hepatocellular carcinoma (HCC) is characterized by high morbidity and mortality, with limited effective treatment options. N-acetyltransferase 10 (NAT10) is the only known acetyltransferase for mRNA ac4C modification and is recognized as a biomarker for HCC, promoting its progression. However, the critical role of NAT10 in hepatocarcinogenesis remains to be fully elucidated, and the identification of suitable small-molecule inhibitors targeting NAT10 is of great interest. Here, we report that NAT10 promotes HCC progression by stabilizing SMAD family member 3 (SMAD3) mRNA through ac4C modification. Clinically, NAT10 is highly expressed in HCC tissues and is significantly associated with poor prognosis. Functionally, NAT10 downregulation inhibits HCC cell proliferation, invasion, and epithelial-mesenchymal transition, while promoting anoikis in vitro. Additionally, NAT10 depletion significantly impairs tumor growth, metastasis, and hepatocarcinogenesis in vivo. Mechanistically, NAT10 enhances oncogene SMAD3 mRNA stability via ac4C modification, thereby activating TGF-β signaling pathway. We also identify a novel small-molecule inhibitor, NAT10-2023, which effectively blocks NAT10 activity. Notably, NAT10-2023 treatment significantly reduces intracellular RNA ac4C modification levels and disrupts NAT10-RNA interactions, leading to suppressed tumor progression. Overall, NAT10 drives HCC progression via SMAD3 mRNA stability regulation, and NAT10-2023 could be a promising therapeutic candidate for targeting NAT10 in cancer treatment.