Exploration (Beijing, China)最新文献

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.

Zhang and colleagues show that drinking-water supplementation of D-mannose serves as an effective and potential therapeutic of type 2 diabetes, with improvement of both liver health and bone mass. The effect is exerted through suppressing macrophage release of extracellular vesicles based on metabolic control of CD36 expression. These findings shed light on translational pharmaceutical strategies of type 2 diabetes.

This paper illustrates a hierarchical nano-/micro-structured superhydrophilic surface that delays the Leidenfrost effect to 273 °C, enabling sustained boiling at extreme superheats. Counterintuitively, lower droplet impact velocity further postpones the Leidenfrost point by manipulating liquid-solid impact dynamics, offering new strategies for high-temperature thermal management in aerospace and automotive applications.

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.

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.

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.

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.

Protecting neuronal mitochondria by eliminating the mitochondrial ROS (mtROS) storm is crucial to abrogate the neuronal damage cascade of ischemic stroke ischemia reperfusion (ISIR), which is a long-standing challenge in the field of ischemic stroke (IS). Existing blood-brain barrier (BBB) penetration methods are usually unable to distinguish between healthy brain tissue and cerebral infarction tissue, and BBB targeting is not compatible with mitochondrial targeting, resulting in a huge barrier to the specific elimination of mtROS in neuronal mitochondria in ISIR. This study introduces an elegantly designed tannic acid, polydopamine, and Mo-based heteropolyacid ternary composite nanomedicine (TPM), which not only has a superb ability to eliminate multiple ROS thanks to the introduction of polydopamine, but also can actively recognize the injured BBB site, specifically enter the neurons in the cerebral infarction area, and then highly specifically target the mitochondria of neurons to efficiently eliminate mtROS. TPM could significantly inhibit neuronal apoptosis by protecting mitochondria and eliminate inflammation by inhibiting activation of the STING pathway, thereby significantly reducing the size of cerebral infarction. This sequential targeting of TPM from the injured BBB to neuronal mitochondria provides a promising strategy to treat ISIR in the clinical setting.

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.

Reactive oxygen species (ROS) have gained increasing attention in electrochemiluminescence (ECL) as endogenous co-reactants, yet their application in the most widely used tris(bipyridine)-ruthenium(II) system remains limited due to the scarcity of suitable co-reactant accelerators (CRAs) with selective oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) catalytic activity. Here, this work reports a series of facet-tunable homogeneous NiNPs catalysts, which can stimulate ECL at distinguishable cathodic/anodic potentials in tris(bipyridine)-ruthenium(II) system. Experimental studies and theoretical calculation results reveal that the Ni(1 1 0) surface, with its lower charge density, impedes the fourth step of 4e⁻ ORR, thus favoring 2e⁻ pathway and consequently promoting substantial ROS generation and ECL at the cathode. Conversely, the Ni(1 1 1) and (2 0 0) surface prompt robust and stable anodic ECL via hydroxyl radical by controlling the OER. These excellent CRAs link cathodic/anodic ECL with ORR/OER, offering a novel strategy for precisely designing predictable non-precious metal CRAs. Furthermore, sensitive immunosensors were developed using these CRAs, demonstrating successful application in potential-resolved ECL analysis for practical purposes.