Smart medicine最新文献

Long non-coding RNAs (lncRNAs) constitute a critical class of regulatory molecules involved in cancer biology and play pivotal roles in tumor initiation and progression. Nevertheless, the biological functions of many newly identified lncRNAs in non-small cell lung cancer (NSCLC), as well as their potential therapeutic relevance, remain insufficiently characterized. In this study, high-throughput sequencing analysis of paired NSCLC tumor tissues and adjacent non-tumorous samples revealed that LINC00973 is significantly upregulated in tumor specimens. Moreover, elevated LINC00973 expression was found to be closely associated with poor clinical outcomes in patients with NSCLC. Functional assays showed that LINC00973 knockdown inhibits NSCLC cell proliferation, migration, and invasion while inducing apoptosis, whereas overexpression produces opposite effects. These observations were confirmed in vivo, where LINC00973 depletion markedly suppressed tumor growth and metastasis. Mechanistically, LINC00973 interacts with and stabilizes deltex E3 ubiquitin ligase 3L (DTX3L), preventing its ubiquitination-mediated degradation and activating the AKT signaling pathway. Therapeutically, RGD-modified exosome-mediated delivery of LINC00973 siRNA significantly inhibited NSCLC progression in mouse models. Moreover, a synthetic biology-based strategy enabling hepatic production of exosomes carrying LINC00973-targeting siRNA achieved robust anti-tumor effects. Together, these findings establish LINC00973 as an oncogenic lncRNA that promotes NSCLC progression via DTX3L stabilization and highlight LINC00973 as a promising therapeutic target.

Skeletal muscle is essential for voluntary movement and exhibits a remarkable capacity for regeneration following injury. NFIX, a member of the Nuclear Factor I (NFI) family of transcription factors, plays a critical role in both skeletal muscle development and regeneration. Despite its emerging importance, the molecular basis of NFIX-mediated DNA recognition and transcriptional regulation in skeletal muscle remains poorly defined. Here, we demonstrate that NFIX promotes key cellular processes in skeletal muscle cells, as siRNA-mediated knockdown of NFIX significantly reduces cell proliferation, increases apoptosis, and impairs differentiation. Transcriptomic analysis revealed that NFIX regulates a network of genes involved in muscle metabolism, stress responses, and immune inflammatory responses. Biophysical characterization showed that NFIX exists as a monomer in solution and binds palindromic DNA with a 1:1 stoichiometry. A high-resolution crystal structure of the NFIX_DBD bound to palindromic DNA reveals a monomeric binding mode driven by base-specific recognition of the TGGCA motif. Mutations that disrupt key DNA-contacting residues abolished both DNA binding and transcriptional activation in luciferase reporter assays. Together, these findings define the molecular mechanism of NFIX-dependent gene regulation in skeletal muscle and establish a structural framework for its function, providing new insights into the potential therapeutic targeting of NFIX in muscle diseases.

Peripheral nerve injury (PNI) presents a significant clinical challenge due to the intrinsic limitations of nerve regeneration and poor functional recovery. Although nerve guidance conduits (NGCs) offer a promising alternative to autografts, their therapeutic efficacy is often constrained by insufficient bioactivity and electrical conductivity. To address these dual deficiencies, we engineered an electroactive living nerve conduit by integrating silk sericin (SS)-modified carbon nanotubes (SCNTs) with adipose-derived stem cells (ADSCs). The SCNTs serve as a conductive scaffold, whereas the ADSCs provide a sustained release of neurotrophic factors. This design creates a synergistic microenvironment to promote neuronal maturation and axonal regeneration. In an experimental rat model featuring a 10-mm sciatic nerve gap, ADSC/SCNT/RAM NGCs demonstrated regenerative performance comparable to autografts, facilitating axon connection and recovery of motor functions. Histological assessment revealed that the implanted ADSC/SCNT/RAM NGCs promoted the most extensive nerve and axon regeneration among all groups, as evidenced by the significantly higher counts of S100 calcium-binding protein B (S100-β)-positive cells (10,152 ± 986.00) and Neurofilament Protein 200 (NF200)-positive cells (11,517 ± 795.70). Corroborating these histological findings, functional analysis demonstrated that the ADSC/SCNT/RAM group achieved the highest sciatic nerve function index (SFI) at 12 weeks post-surgery (-58.06 ± 1.46), a value comparable to the Autograft group (-57.73 ± 1.80). This strategy proposes a promising tissue-engineered alternative to autografts for nerve repair.

Immune checkpoint inhibitors (ICI) have demonstrated prolonged efficacy in certain melanoma patients, yet a significant portion of patients do not experience clinical improvement, with the mechanisms underlying this resistance still not fully understood. Using established cell markers, we partitioned the single-cell transcriptome into clusters, finding a notable link between NK cells and patient response to immunotherapy. We further identified four distinct subpopulations of NK cells, profiling marker gene sets and unique biological functions associated with each subpopulation. This analysis provides insights into the trajectory of NK cell development and differentiation, along with identifying the transcription factors driving these processes. The study pinpointed NK cluster 01 as pivotal in influencing patient sensitivity and prognosis during immunotherapy. Single-cell transcriptome and spatial transcriptomics (ST) analysis revealed the proximity of NK cluster 01 cells to melanoma cells, hinting at a potential regulation of cell-cell interaction via the IFN-II signaling pathway network. ST analysis revealed the spatial arrangement and interaction of NK cluster 01 cells with melanoma cells. This study explores the feasibility of targeting NK cluster 01 cells with small molecule drugs via molecular docking, offering a promising approach to bolster the clinical utility of NK cell therapy. We comprehensively analyze the heterogeneity of NK cells within melanoma, elucidate the potential regulatory interactions between NK cells and other microenvironmental components, and establish a basis for the future clinical utilization of distinct NK cell subsets as therapeutic targets.

Human osteoarthritis (OA) displays sex-specific patterns in its clinical presentation. Key features of the disease-such as prevalence, age of onset, progression, and response to treatment-vary between males and females. These differences have been associated with sex hormones, as well as anatomical, biomechanical, and behavioral distinctions between the sexes. However, the underlying mechanisms driving these sex-specific disparities in OA pathogenesis remain largely unknown. In this study, we analyzed transcriptomic data from human knee articular cartilage to investigate sex-specific gene expression in articular chondrocytes. We identified genes that are uniquely or predominantly expressed in either males or females in healthy cartilage. Notably, many of these sex-biased genes were significantly dysregulated in osteoarthritic cartilage, particularly those with higher expression in females. Furthermore, female-specific OA genes may exert protective effects on cartilage degeneration, whereas male-specific OA genes could impair cartilage homeostasis. Our findings provide insights into the genetic regulation of OA and highlight the influence of sex on its molecular pathology.

Due to the ability to precisely control and manipulate fluids at the microscale, microfluidics provides unmatched advantages such as reduced sample size, rapid analysis, and enhanced sensitivity. Microfluidic technology has emerged as a revolutionary approach in pediatric healthcare, offering innovative solutions for diagnostics, monitoring, and treatment. This review presents a comprehensive overview of the recent advancements and future directions of microfluidic technology in the field of pediatrics. We begin with a brief introduction of several types of microfluidic devices that are more common in the pediatric field. Then, the substantial advances in biomedical applications of microfluidics in pediatric healthcare are explored, encompassing diagnosis, research, and treatment. Finally, challenges and limitations such as material selection, device standardization, stability, and regulatory considerations are also discussed that must be addressed to increase the utilization of microfluidics in the pediatric clinical field. Overall, this review underscores the transformative potential of microfluidics to improve the quality of healthcare and outcomes for pediatric patients, while also highlighting the opportunities for future research and development in this burgeoning field.

Wounds represent a global and challenging healthcare issue, resulting in a cascade of consequences. Despite the widespread application of existing wound dressings, their performance and efficacy are significantly limited in terms of biocompatible matrices and functionalization for promoting vascularization and antimicrobial activity. In this study, we propose a drug-loaded microneedle based on a copolymer hydrogel composed of methacrylated chitosan and polyethylene glycol diacrylate incorporating antimicrobial peptide and vascular endothelial growth factor. These microneedles were applied to wounds where their degradation facilitated the release of the loaded drugs to exert antibacterial and angiogenic effects. In vitro experiments demonstrated that our microneedles exhibit uniform morphology, good structural integrity, controlled drug release, and other excellent properties. Upon interaction with cells and bacteria, they displayed biocompatibility and superior dual antibacterial capabilities. In an in vivo infectious wound model, the microneedles significantly promoted wound healing through their antibacterial and angiogenic effects, showing clear advantages over the control group. Thus, these drug-loaded microneedles serve as a multifunctional dressing, offering a promising novel strategy for wound repair.

Hydrogel patches have been serving as powerful tools for wound healing. Scientific attention in this field is focused on imparting the patches with novel structures, functions, and actives for promoting wound healing. In this paper, we have developed an innovative hydrogel patch with hierarchical structure and spatiotemporal actives release for efficient wound healing. This hydrogel patch was achieved by integrating asiatic acid (AA)-loaded pollens with chlorogenic acid (CA)-containing gelatin methacryloyl (GelMA) hydrogel. The high specific surface area and nanoporous structure of the pollens-integrated GelMA promote efficient loading and release of CA and AA, respectively. In wound treatment, the outer layer of GelMA first releases CA to fight infection. With the gradual degradation of GelMA, the pollens are exposed to the wounds and released AA, intensifying anti-inflammatory effects and promoting wound healing. These features indicate that this pollen-integrated hydrogel patch significantly accelerates the wound healing process in a spatiotemporal responsive manner, demonstrating great potential for clinical applications.

Tissue engineering is a great alternative to repair and regenerate damaged tissues and organs. Hydrogels are promising materials for tissue repair, but optimizing their various functions-such as adhesion, mechanical properties, and vascularization-to suit the complexity of different organs and tissues remains a significant challenge. In this study, we explore a tough and adhesive polydopamine (PDA)-silk-polyacrylamide (PAM) hydrogel inspired by the mussel-inspired adhesion of PDA and the vascularization potential of silk. Through a Schiff base reaction, self-polymerization occurs between the free dopamine and the conjugated dopamine on the silk chains, resulting in the formation of a PDA/silk prepolymer. The presence of PDA in the prepolymer endows the resulting PDA-silk-PAM hydrogel with excellent adhesiveness, strong mechanical properties, and good water absorption. By adjusting the degree of crosslinking, the hydrogel also demonstrates impressive deformability, making it suitable for engineering thicker and more complex tissues and organs. Moreover, benefiting from the vascularization capabilities of silk and the adhesive properties of PDA, the PDA-silk-PAM hydrogel effectively promotes vascularization and accelerates wound healing in full-thickness skin wounds on the backs of Sprague-Dawley rats. Overall, our study provides a straightforward approach to create versatile medical hydrogel with strong potential for clinical applications.

Chronic suppurative otitis media (CSOM) is a leading cause of hearing loss and otorrhea, and when associated with cholesteatoma, it can pose a serious threat to patients' lives. This study aims to identify differences in tissue metabolites between patients with CSOM, both with and without cholesteatoma. Metabolomic profiles were measured in tissue samples from 42 surgically treated CSOM patients (35 with cholesteatoma, 7 without cholesteatoma). Significantly altered metabolites associated with CSOM were identified using a non-targeted metabolomics approach and a targeted metabolomics approach. The 42 patients were divided into screening and validation sets. The non-targeted analysis revealed 484 distinct differential metabolites and 32 metabolic pathways that differed between CSOM with and without cholesteatoma in the screening set. Targeted metabolomics confirmed that levels of azobenzene and marimastat in the validation set exhibited trends similar to those observed in the non-targeted analysis. Azobenzene and marimastat were found to be associated with the differences between CSOM with and without cholesteatoma, as well as with bone erosion in the middle ear. This study identified novel potential metabolic pathways and metabolites, providing insights into their possible roles in the inflammatory processes and bone erosion associated with CSOM and cholesteatoma.