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Liposomes are the earliest and most widely used nanoparticles for targeted drug delivery. Exosomes are nanosized membrane-bound particles and important mediators of intercellular communication. Combining liposomes and exosomes using various membrane fusion methods gives rise to a novel potential drug delivery system called membrane fusion-based hybrid exosomes (MFHE). These novel MFHEs not only exhibit potential advantageous features, such as high drug loading rate and targeted cellular uptake via surface modification, but are also endowed with high biocompatibility and low immunogenicity. Here, we provide an overview of MFHEs’ various preparation methods, characterization strategies, and their applications for disease treatment and scientific research.

Carcinoma-associated fibroblasts (CAFs) are the main cellular components of the tumor microenvironment and promote cancer progression by modifying the extracellular matrix (ECM). The tumor-associated ECM is characterized by collagen crosslinking catalyzed by lysyl oxidase (LOX). Small extracellular vesicles (sEVs) mediate cell-cell communication. However, the interactions between sEVs and the ECM remain unclear. Here, we demonstrated that sEVs released from oral squamous cell carcinoma (OSCC)-derived CAFs induce collagen crosslinking, thereby promoting epithelial-mesenchymal transition (EMT). CAF sEVs preferably bound to the ECM rather than being taken up by fibroblasts and induced collagen crosslinking, and a LOX inhibitor or blocking antibody suppressed this effect. Active LOX (αLOX), but not the LOX precursor, was enriched in CAF sEVs and interacted with periostin, fibronectin, and bone morphogenetic protein-1 on the surface of sEVs. CAF sEV-associated integrin α2β1 mediated the binding of CAF sEVs to collagen I, and blocking integrin α2β1 inhibited collagen crosslinking by interfering with CAF sEV binding to collagen I. CAF sEV-induced collagen crosslinking promoted the EMT of OSCC through FAK/paxillin/YAP pathway. Taken together, these findings reveal a novel role of CAF sEVs in tumor ECM remodeling, suggesting a critical mechanism for CAF-induced EMT of cancer cells.

Carcinoma-associated fibroblasts (CAFs) exhibit significant heterogeneity and are closely associated with progression, resistance to anticancer therapies, and poor prognosis in head and neck squamous cell carcinoma (HNSCC). However, the specific functional role of CAFs in HNSCC has been inadequately explored. In this study, we utilized a single-cell RNA sequencing dataset from HNSCC (GSE103322) to recluster CAFs via the Seurat pipeline. On the basis of the reported markers, we identified two CAF subtypes, LOX-myCAFs and LOX + iCAFs, and generated signature markers for each. Through unsupervised consensus clustering, we identified and characterized two molecular subtypes of HNSCC-TCGA, each exhibiting distinct dysregulated cancer hallmarks, immunological tumor microenvironments, and stemness characteristics. The robustness of the LOX + iCAF-related signature clustering, particularly in terms of prognosis and prediction of immunotherapeutic response, was validated in an ANOVA cohort via a GEO dataset (GSE159067) consisting of 102 HNSCC patients. A positive correlation was validated between the expression of LOX and that of CD86, a marker of M1 macrophage polarization. Further experiments involving the coculture of conditioned medium derived from LOX-silenced CAFs with CAL-27 and UM-SCC-1 cell lines revealed that LOX silencing led to decreased proliferation and migration of these cancer cells, which was mediated by epithelial-mesenchymal transition (EMT) through IL-34- induced CSF1R/Akt signaling. In summary, our single-cell and bulk RNA sequencing analyses revealed a LOX + iCAF-related signature that can predict the prognosis and response to immunotherapy in HNSCC patients. Additionally, the LOX gene was identified as a promising therapeutic target for HNSCC treatment.

The feeding behaviour of cows is an essential sign of their health in dairy farming. For the impression of cow health status, precise and quick assessment of cow feeding behaviour is critical. This research presents a method for monitoring dairy cow feeding behaviour utilizing edge computing and deep learning algorithms based on the characteristics of dairy cow feeding behaviour. Images of cow feeding behaviour were captured and processed in real time using an edge computing device. A DenseResNet-You Only Look Once (DRN-YOLO) deep learning method was presented to address the difficulties of existing cow feeding behaviour detection algorithms’ low accuracy and sensitivity to the open farm environment. The deep learning and feature extraction enhancement of the model was improved by replacing the CSPDarknet backbone network with the self-designed DRNet backbone network based on the YOLOv4 algorithm using multiple feature scales and the Spatial Pyramid Pooling (SPP) structure to enrich the scale semantic feature interactions, finally achieving the recognition of cow feeding behaviour in the farm feeding environment. The experimental results showed that DRN-YOLO improved the accuracy, recall, and mAP by 1.70%, 1.82%, and 0.97%, respectively, compared to YOLOv4. The research results can effectively solve the problems of low recognition accuracy and insufficient feature extraction in the analysis of dairy cow feeding behaviour by traditional methods in complex breeding environments, and at the same time provide an important reference for the realization of intelligent animal husbandry and precision breeding.

Atopic dermatitis (AD) is a chronic skin condition with intense pruritus, eczema, and dry skin. The recurrent intense pruritus and numerous complications in patients with AD can profoundly affect their quality of life. Obesity is one of its comorbidities that has been confirmed to be the hazard factor of AD and also worsen its severity. Nevertheless, the specific mechanisms that explain the connection between obesity and AD remain incompletely recognized. Recent studies have built hopes on various adipokines to explain this connection. Adipokines, which are disturbed by an obese state, may lead to immune system imbalances in people with AD and promote the development of the disease. This review focuses on the abnormal expression patterns of adipokines in patients with AD and their potential regulatory molecular mechanisms associated with AD. The connection between AD and obesity is elucidated through the involvement of adipokines. This conduces to the in-depth exploration of AD pathogenesis and provides a new perspective to develop therapeutic targets.

Introduction: Drugs and biocompatible nanoparticles have raised significant potential in advancing the bone regeneration. Electrospinning technology enables the full realization of the value of drugs and nanoparticles. Methods: In this study, we have successfully fabricated core–sheath nanofibers solely composed of polycaprolactone (PCL) polymer. Simvastatin (SIM) was confined to the core of the nanofibers while nanohydroxyapatite (nHA) was loaded on the nanofiber surface. Results: All the prepared nanofibers exhibited a cylindrical micromorphology, and the core–sheath structure was exploited using a Transmission Electron Microscope. X-ray pattern results indicated that SIM was in an amorphous state within nanofibers, while Fourier Transform InfraRed spectroscopy showed excellent chemical compatibility among SIM, nHA, and PCL. The actual loading of nHA within the nanofiber was determined by a thermogravimetric test due to the high melting point of nHA. Core–sheath nanofibers could release SIM for 672 h, which was attributed to the core–sheath structure. Furthermore, nanofibers loaded with SIM or nHA had a positive impact on cell proliferation, with the core–sheath nanofibers displaying the most favorable cell proliferation behavior. Discussion: Such a synergistic facilitation strategy based on materials and nanostructure may encourage researchers to exploit new biomedical materials in future.

This paper focuses on how regulatory bodies respond to artificial intelligence (AI)-enabled medical devices. To achieve this, we present a comparative overview of the United States (USA), European Union (EU), and China. Our search in the governmental database identified 59 AI medical devices approved in China as of July 2023. In comparison to the rules-based regulatory approach in China, the approaches in the USA and EU are more standards-oriented.

Dental pulp regeneration is a promising strategy for addressing tooth disorders. Incorporating this strategy involves the fundamental challenge of establishing functional vascular networks using dental pulp stem cells (DPSCs) to support tissue regeneration. Current therapeutic approaches lack efficient and stable methods for activating DPSCs. In the study, we used a chemically modified microRNA (miRNA)-loaded tetrahedral-framework nucleic acid nanostructure to promote DPSC-mediated angiogenesis and dental pulp regeneration. Incorporating chemically modified miR-126-3p into tetrahedral DNA nanostructures (miR@TDNs) represents a notable advancement in the stability and efficacy of miRNA delivery into DPSCs. These nanostructures enhanced DPSC proliferation, migration, and upregulated angiogenesis-related genes, enhancing their paracrine signaling effects on endothelial cells. This enhanced effect was substantiated by improvements in endothelial cell tube formation, migration, and gene expression. Moreover, in vivo investigations employing matrigel plug assays and ectopic dental pulp transplantation confirmed the potential of miR@TDNs in promoting angiogenesis and facilitating dental pulp regeneration. Our findings demonstrated the potential of chemically modified miRNA-loaded nucleic acid nanostructures in enhancing DPSC-mediated angiogenesis and supporting dental pulp regeneration. These results highlighted the promising role of chemically modified nucleic acid-based delivery systems as therapeutic agents in regenerative dentistry and tissue engineering. Graphical abstract

Precision medicine leverages stem cell-derived models to dissect complex interactions underlying disease-driven neuromuscular damage. However, such reductionist models form stochastic structures without external guidance, while available engineering solutions remain intricate. Here, simplified surface modification engineering is used to render spatially patterned human motor assembloids-on-a-chip by geometric confinement. The anisotropic architecture of skeletal muscle organoids (hSkM) can be conferred solely by localized mechanobiological cues within this predefined device without aligned scaffolds or adjuncts. The hSkM-orchestrated coupling of motor neuron spheroids (hMNS) promotes synergistic neuromuscular development. Furthermore, integration of optogenetic and microelectrode array mapping enables visualization of functional patterning in assembloids. Applied to oxygen deprivation model, hSkM exhibits structural anomalies, fatigable muscle remodeling and dysfunction, recapitulating muscle pathologies in intermittent hypoxia (IH)-associated respiratory disorders. Electrical activity mapping reveals the heterogeneity in neuromuscular responses to IH, indicating the neuroregulatory etiology of muscle dysfunction. Finally, we identify mitochondrial bioenergetic imbalance as a key IH target, proposing evaluation of NAD + salvage pathway-targeting agents. Our findings provide an accessible platform with translational potential for neuromuscular physiopathology research. Challenges in simplicity and accessibility limit the current widespread applicability of neuromuscular models. Here, the authors present a readily fabricated, organised human motor assembloids-on-a-chip approach for neuromuscular research and hypoxia disease modelling.

Obstructive sleep apnea (OSA) is a common syndrome that features a complex etiology and set of mechanisms. Here we summarized the molecular pathogenesis of OSA, especially the prospective mechanism of upper? airway dilator fatigue and the current breakthroughs. Additionally, we also introduced the molecular mechanism of OSA in terms of related studies on the main signaling pathways and epigenetics alterations, such as microRNA, long non-coding RNA, and DNA methylation. We also reviewed small molecular compounds, which are potential targets for gene regulations in the future, that are involved in the regulation of OSA. This review will be beneficial to point the way for OSA research within the next decade.