The inhibition of ferroptosis, a widespread form of nonapoptotic cell death, is considered a promising therapeutic approach for osteoarthritis (OA). Human amniotic epithelial stem cells (hAESCs) maintain multipotent differentiation potential, no tumorigenicity, low immunogenicity, and anti-inflammatory properties, rendering them highly biocompatible stem cells. Exosomes (Exo) are vesicular carriers for intercellular communication that participate importantly in regulating disease progression through paracrine signaling. In our study, under inflammatory stress conditions, actin alpha 2, smooth muscle antisense RNA1 (ACTA2-AS1) transcription was up-regulated in hAESCs, further delivered to chondrocytes via hAESC-derived Exo. Subsequently, ACTA2-AS1 could suppress ferroptosis in chondrocytes by facilitating the degradation of acyl-CoA synthetase long-chain family member 4 (ACSL4), a key regulator of ferroptosis, thereby modulating the progression of OA. In conclusion, for the first time, this study demonstrates the modulatory role of hAESC ACSL4 expression by releasing ACTA2-AS1-enriched Exo, leading to inhibited ferroptosis in chondrocytes and ultimately ameliorating OA progression. Thus, targeting Exo-mediated communication may offer novel therapeutic approaches for addressing OA linked to iron metabolism irregularities.

Phenotypic abnormalities in vascular smooth muscle cells (VSMCs) are believed to play essential roles in the progression of vascular diseases. Here, we explored the impact of fibroblast growth factor 21 (FGF21) on the phenotypic transition of VSMCs. Our findings revealed that FGF21 expression was substantially down-regulated in both human and mouse neointimal regions. Additionally, plasma FGF21 levels were lower in patients with atherosclerotic coronary artery disease (ASCAD) compared to those without ASCAD. Similarly, patients with restenosis exhibited reduced FGF21 levels compared to those without restenosis. In vivo, FGF21 deficiency accelerated intimal hyperplasia and decreased the number of contractile VSMCs in mouse neointima. However, hepatocyte-specific FGF21 knockout had no effect on ligation-induced intimal hyperplasia. Conversely, administration of recombinant FGF21 protein reduced neointima formation. This effect was abolished in mice with β-klotho VSMC-specific knockout, suggesting a direct effect of FGF21 on VSMCs. In vitro, FGF21 could promote the contractile phenotype transition of human aortic smooth muscle cells under basal or platelet-derived growth factor-BB incubation conditions. Furthermore, FGF21 activation led to the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), which subsequently formed a complex with the serum response factor (SRF)–myocardin complex. This complex increased the phosphorylation of SRF at serine 224, thereby enhancing the transcription activation of the SRF–myocardin complex. Finally, we revealed that treatment with the FGF21 analog efruxifermin or activation of p38 MAPK using anisomycin effectively inhibited neointima formation. Taken together, these results indicate that modulating FGF21 or its subsequent signal pathways could serve as a therapeutic strategy for vascular diseases characterized by abnormal VSMC phenotypic transition.

Mitochondria are highly dynamic organelles that are responsible for essential cellular functions such as calcium regulation, reactive oxygen species (ROS) production, metabolism, and apoptosis initiation. Mitochondrial dysfunctions are associated with a variety of pathologies, and the onset and progression of disease are accompanied by alterations in extracellular biochemical and mechanical signals. Recent studies have demonstrated that physicochemical cues, especially mechanical cues, exert pivotal roles in the organization of mitochondrial network and their metabolic functions. Therefore, understanding the mechanisms that orchestrate mitochondrial morphology and function is essential for elucidating their role in both health and disease. This review discusses novel insights into the recent advances regarding mitochondrial dysfunction across a spectrum of diseases and describes the effect of various factors. It then highlights the recently discovered mechanisms, particularly those involving matrix mechanical cues and cellular mechanical cues, summarizing the multiple pathways of mechanotransduction, such as integrin, Piezo1/TRPV4, and YAP/TAZ signaling pathways. Last, the review explores the potential future directions, stressing that understanding mitochondrial dysfunction is crucial for developing effective therapies to improve mitochondrial function and address related diseases.

Current tools for predicting the thrombolysis risk in patients after stroke exhibit limited event prediction in early post-thrombolysis hemorrhagic events. This highlights an unmet medical need to improve the tools for stroke management. We developed an explainable 2-stage machine learning model for stroke risk stratification to predict the risk of bleeding, composite complications, and all-cause death in patients before and after thrombolysis therapy. The model integrated LightGBM, XGBoost, random forest model (RF), decision tree model (DT), and logistic regression model (LR), and was trained on data from 5,333 patients from Tongji Hospital, achieving improved predictive accuracy in the post-thrombolysis stage compared to the pre-thrombolysis stage. The model exhibited increased area under the curve (AUC) of 0.7581 [95% confidence interval (CI), 0.6955 to 0.8177] and 0.7234 (0.6527 to 0.7909) (bleeding), 0.7625 (0.7324 to 0.7936) and 0.7035 (0.6685 to 0.7392) (composite complications), and 0.9264 (0.8736 to 0.9660) and 0.845 (0.7454 to 0.9375) (death) in post-thrombolysis stage than in pre-thrombolysis stage. External validation using data of 526 patients across 2 different hospitals confirmed the robustness of the model. Key predictors such as temperature, vital signs, and demographic factors were identified. A prototype embedding the best-performing model was constructed. This model enhances thrombolysis risk prediction and supports personalized patient care management, demonstrating its potential for clinical decision support system integration into stroke management strategies.

Chronic stress exposure is a potent risk factor for anxiety, disrupting adaptive responses and increasing vulnerability. Astrocytes, as essential regulators of synaptic function and neuroimmune homeostasis, are implicated in mood regulation and neuropsychiatric pathogenesis. However, the precise molecular mechanisms of astrocytes involved in stress-induced anxiety remain poorly understood. In this study, we reveal a pivotal role of astrocytic brain-derived neurotrophic factor (BDNF) in modulating anxiety sensitivity through coordinated regulation with hippocampal CA1 neurons. Chronic restraint stress induces anxiety-like behaviors and disrupts presynaptic glutamatergic transmission in hippocampal CA1 neurons, with astrocytes potentially playing a central regulatory role in a Ca²⁺-dependent manner. Pharmacological manipulation confirms the involvement of BDNF/TrkB signaling, while knockdown of astrocytic BDNF further impairs synaptic function and exacerbates stress-induced anxiety. Transcriptomic analysis suggests interferon-related signaling pathways as potential downstream effectors, amplifying anxiety sensitivity through altered astrocytic activation and neuroimmune dynamics. Our study provides critical mechanistic insights into astrocytic regulation of anxiety sensitivity and highlights astrocytic BDNF as a promising therapeutic target for stress-related anxiety disorders.

Resolving the sources of HONO formation is an indispensable aspect in understanding the enhancement of atmospheric oxidation. However, the contributing sources of high HONO formation rate remain unclear during humid haze episodes. The photochemical conversion of surface nitrate (NO₃⁻), considered as the dominant contributor to the daytime HONO generation, exhibits severe constraint under high relative humidity (RH) conditions. Unexpectedly, ammonium (NH₄⁺) on the surface of photoactive mineral dust shows a gradual acceleration of HONO generation with increasing RH under simulated solar irradiation, especially at high RH. This reversed observation stems from a change in the photochemical pathway for the HONO formation from NO₃⁻ and NH₄⁺. The photochemical conversion of surface NO₃⁻ is determined by photogenerated electrons (NO₃⁻→NO₂→NO₂⁻→HONO), while the superoxide radical (∙O₂⁻) generated during photochemical reaction drives the surface NH₄⁺ to directly form HONO with the pathway (NH₄⁺∙+∙O₂⁻→NO₂⁻ + H₂O→HONO). Under high RH conditions, oxygen molecules (O₂) have greatly better access to photogenerated electrons than NO₂, resulting in an interruption of the procedure from NO₂ to NO₂⁻ during NO₃⁻ conversion. Therefore, the favorably generated ∙O₂⁻ fuels the photochemical conversion of surface NH₄⁺ while inhibiting the conversion of NO₃⁻ to diurnal HONO formation. This work highlights the overlooked contribution of HONO formation from NH₄⁺, especially under high RH conditions, and advances the understanding of a renewed role for O₂ in atmospheric chemical processes.

In recent years, important progress has been made in the field of biosensing and wireless communications by using metamaterials and metasurfaces. These technologies enable efficient manipulation of electromagnetic waves through judiciously designed subwavelength structural units. This review begins by focusing on the design and optimization of terahertz metasurface sensors, emphasizing their unique advantages in biomedical diagnostics. It explores key technical challenges, such as material selection, device integration, and development of robust sensor for surface-specific modifications. Furthermore, the review discusses how metasurfaces, particularly as reconfigurable intelligent surfaces, dynamically modulate electromagnetic wave propagation in the microwave communications domain to enhance signal quality, improve communication efficiency, and showcase their potential in 5G and future 6G technologies. Finally, a comprehensive overview is provided regarding the challenges and future research directions for metamaterial and metasurface technologies in both biosensing and wireless communications, with the ultimate goal of promoting their applications in point-of-care devices and efficient communication systems.

Spinal cord injury (SCI) poses substantial challenges, often leading to permanent disability and requiring adequate neuronal regeneration for functional repair. Decellularized spinal cord (DSC) matrices hold promise due to their native 3-dimensional (3D) structure and extracellular matrix (ECM)-derived biochemical components. However, their limited mechanical properties and insufficient availability of growth factors hinder their effectiveness. To address these limitations, this study introduces a core–shell design that reinforces DSC with a hydrogel-based matrix capable of delivering essential growth factors while preserving its natural structure. By leveraging 3D printing and electrostatic adsorption, the engineered matrix retains the topological features of DSC while introducing new topographical and neurogenic cues. These instructive cues facilitated an 11-fold increase in the number of newly generated neuronal cells, demonstrating lineage-specific neuronal regeneration in vivo. Mechanistically, the synergistic effects of ECM-inspired structure and biochemical cues activated the ITGA2/ITGA11–ERK/AKT signaling axis and promoted M2 macrophage/microglia polarization, thereby reducing cavity and scar formation. This optimized microenvironment enhanced endogenous neurogenesis and supported functional recovery after SCI. Overall, this study developed a structure-inspired lineage-specific matrix that effectively stimulates endogenous neuronal regeneration, highlighting its potential for advancing spinal cord repair strategies.

Ischemic heart disease (IHD) remains a major global health challenge due to its persistently high incidence and mortality rates. Although early thrombolytic or interventional therapy reduces infarct size, myocardial ischemia–reperfusion injury (MIRI) often occurs when restoring blood flow to ischemic myocardium, paradoxically causing cardiomyocyte death. Unlike conventional cardioprotective agents, bioengineered nanomaterials enable targeted drug delivery to ischemic cardiomyocytes through tunable physicochemical properties. This improves therapeutic efficacy while reducing systemic exposure, providing innovative strategies for MIRI treatment. This review summarizes recent advances in nanomaterial-based MIRI therapies and critically evaluates their clinical translation potential, highlighting both opportunities and challenges.

Alcoholic cardiomyopathy (ACM) is a type of dilated cardiomyopathy unrelated to ischemia, which develops as a consequence of chronic alcohol consumption. While ethanol-induced irreversible cardiomyocyte death is implicated in ACM development and progression, the precise molecular mechanisms involved are still obscure. In the current study, we demonstrate that ethanol exposure promotes receptor-interacting serine/threonine-protein kinase 1 (RIPK1) autophosphorylation and enhances pRIPK1-associated apoptosis and necroptosis in ACM models both in vivo and in vitro. Through co-immunoprecipitation (Co-IP) combined with liquid chromatography–tandem mass spectrometry (LC-MS/MS) analysis, we identified ubiquitin-specific protease 53 (USP53) as a pivotal deubiquitinase involved in modulating RIPK1 activation following ethanol stimulation in cardiomyocytes. Mechanistically, we found that ethanol induced up-regulation of USP53 via transcriptional induction by early growth response 1 (EGR1). Subsequently, USP53 interacted with the intermediate domain of RIPK1 and removed K63-linked ubiquitination at lysine-377 (K377), facilitating RIPK1 phosphorylation and triggering downstream apoptotic and necroptotic pathways in cardiac cells. Further, alcohol-fed cardiomyocyte-specific USP53 knockout (USP53^CKO) mice exhibited improved survival rates and less cardiomyocyte death in hearts compared with the control group. Our study identifies USP53 as a novel regulator of RIPK1-dependent cell death and advances our understanding of the mechanistic pathways of ACM. These results highlight the USP53–RIPK1 signaling axis as a potential therapeutic target for mitigating ACM progression.