Research最新文献

Emerging evidence highlights the central role of gut microbiota in maintaining physiological homeostasis within the host. Disruptions in gut microbiota can destabilize systemic metabolism and inflammation, driving the onset and progression of cardiometabolic diseases. In heart failure (HF), intestinal dysfunction may induce the release of endotoxins and metabolites, leading to dysbiosis and exacerbating HF through the gut-heart axis. Understanding the relationship between gut microbiota and HF offers critical insights into disease mechanisms and therapeutic opportunities. Current research highlights promising potential to improve patient outcomes by restoring microbiota balance. In this review, we summarize the current studies in understanding the gut microbiota-HF connection and discuss avenues for future investigation.

Excessive gonadotropin-releasing hormone (GnRH) is considered to be an initiating factor in the etiology of polycystic ovary syndrome (PCOS). GnRH neuronal axons terminate at the hypothalamic arcuate nucleus and median eminence, where tanycytes, specialized glial cells, have been proposed to modulate GnRH secretion through plasticity. However, the precise role of the "GnRH-tanycyte unit" during the pathological state of PCOS has not been thoroughly explored. In this study, we demonstrated the architecture and distribution of GnRH neurons and tanycytes. In PCOS-like mice, retracted tanycyte processes and dysregulated GnRH-tanycyte unit may create an environment conducive to the excessive secretion of GnRH and subsequent reproductive endocrine dysfunction. Mechanistically, excessive androgens impair hypothalamic neuroglial homeostasis by acting through the androgen receptor (AR) and its downstream target integrin β1 (Itgb1), thereby suppressing the FAK/TGF-βR1/Smad2 signaling pathway. Both selective deletion of AR and overexpression of Itgb1 in tanycytes counteracted the detrimental effects of androgens, alleviating endocrine dysfunction. Collectively, this study highlights the alterations in the GnRH-tanycyte unit mediated by androgen/AR/Itgb1 signaling and provides a novel perspective for developing therapies for hypothalamic hormone secretion disorders by maintaining solid neuroglial structures in the brain.

Background: Cardiovascular diseases (CVD) are a major global health issue strongly associated with altered lipid metabolism. However, lipid metabolism-related pharmacological targets remain limited, leaving the therapeutic challenge of residual lipid-associated cardiovascular risk. The purpose of this study is to identify potentially novel lipid metabolism-related genes by systematic genomic and phenomics analysis, with an aim to discovering potentially new therapeutic targets and diagnosis biomarkers for CVD. Methods: In this study, we conducted a comprehensive and multidimensional evaluation of 881 lipid metabolism-related genes. Using genome-wide association study (GWAS)-based mendelian randomization (MR) causal inference methods, we screened for genes causally linked to the occurrence and development of CVD. Further validation was performed through colocalization analysis in 2 independent cohorts. Then, we employed reverse screening using phenonome-wide association studies (PheWAS) and a drug target-drug association analysis. Finally, we integrated serum proteomic data to develop a machine learning model comprising 5 proteins for disease prediction. Results: Our initial screening yielded 54 genes causally linked to CVD. Colocalization analysis in validation cohorts prioritized this to 29 genes marked correlated with CVD. Comparison and interaction analysis identified 13 therapeutic targets with potential for treating CVD and its complications. A machine learning model incorporating 5 proteins for CVD prediction achieved a high accuracy of 96.1%, suggesting its potential as a diagnostic tool in clinical practice. Conclusion: This study comprehensively reveals the complex relationship between lipid metabolism regulatory targets and CVD. Our findings provide new insights into the pathogenesis of CVD and identify potential therapeutic targets and drugs for its treatment. Additionally, the machine learning model developed in this study offers a promising tool for the diagnosis and prediction of CVD, paving the way for future research and clinical applications.

Human breast milk serves as a vital source of nutrition for infants, and it also plays a critical role in shaping the infant gut microbiota and establishing intestinal homeostasis. This process substantially impacts immune function, neurodevelopment, and overall health. The noninvasive nature of breast milk collection makes it an ethical and accessible area for research, positioning it as a key focus for future studies. These future directions include the identification of novel bacteria combination, the establishment of comprehensive databases on infant microbiota, and the use of computational models to predict interactions between breast milk components and the gut microbiome. Additionally, the creation of diverse biological models and the establishment of infant stool banks will further enhance understanding of host-microbiome interactions and support disease prevention strategies.

Atomic-scale polar topologies such as skyrmions offer important potential as technological paradigms for future electronic devices. Despite recent advances in the exploration of topological domains in complicated perovskite oxide superlattices, these exotic ferroic orders are unavoidably disrupted at the atomic scale due to intrinsic size effects. Here, based on first-principles calculations, we propose a new strategy to design robust ferroelectricity in atomically thin films by properly twisting 2 monolayers of centrosymmetric SrTiO₃. Surprisingly, the emerged polarization vectors curl in the plane, forming a polar skyrmion lattice with each skyrmion as small as 1 nm, representing the highest polar skyrmion density to date. The emergent ferroelectricity originates from strong interlayer coupling effects and the resulting unique strain fields with obvious ion displacements, contributing to electric polarization comparable to that of PbTiO₃. Moreover, we observe ultraflat bands (band width of less than 5 meV) at the valence band edge across a wide range of twist angles, which show widths that are smaller than those of common twisted bilayers of 2-dimensional materials. The present study not only overcomes the critical size limitation for ferroelectricity but also reveals a novel approach for achieving atomic-scale polar topologies, with important potential for applications in skyrmion-based ultrahigh-density memory technologies.

The prevention of air pollution-related cardiopulmonary disorders has been largely overlooked despite its important burden. Extracellular vesicles (EVs) have shown great potential as carriers for drug delivery. However, the efficiency and effect of EVs derived from different sources on ambient fine particulate matter (PM2.5)-induced cardiopulmonary injury remain unknown. Using PM2.5-exposed cellular and mouse models, we investigated the prevention of air pollution-related cardiopulmonary injury via an innovative strategy based on EV delivery. By using a "2-step" method that combines bibliometric and bioinformatic analysis, we identified superoxide dismutase 2 (Sod2) as a potential target for PM2.5-induced injury. Sod2-overexpressing plasmid was constructed and loaded into human plasma-, bovine milk-, and fresh grape-derived EVs, ultimately obtaining modified nanoparticles including PEV ^Sod2 , MEV ^Sod2 , and GEV ^Sod2 , respectively. GEV ^Sod2 , especially its lyophilized GEV ^Sod2 powder, exhibited superior protection against PM2.5-induced cardiopulmonary injury as compared to PEV ^Sod2 and MEV ^Sod2 . High-sensitivity structured illumination microscopy imaging and immunoblotting showed that GEV ^Sod2 powder treatment altered lysosome positioning by reducing Rab-7 expression. Our findings support the use of fruit-derived EVs as a preferred candidate for nucleic acid delivery and disease treatment, which may facilitate the translation of treatments for cardiopulmonary injuries.

Nanozymes are a class of nanomaterials that exhibit catalytic functions analogous to those of natural enzymes. They demonstrate considerable promise in the biomedical field, particularly in the treatment of bone infections, due to their distinctive physicochemical properties and adjustable catalytic activities. Bone infections (e.g., periprosthetic infections and osteomyelitis) are infections that are challenging to treat clinically. Traditional treatments often encounter issues related to drug resistance and suboptimal anti-infection outcomes. The advent of nanozymes has brought with it a new avenue of hope for the treatment of bone infections.

[This corrects the article DOI: 10.34133/2022/9850743.].

Smart contact lenses (SCLs), an innovative evolution of conventional contact lenses, have recently attracted increasing attention for their substantial potential for use in the healthcare field. With advancements in materials science and medical technology, SCLs have integrated electronic information technology with biomedical engineering to enable the incorporation of various medical functionalities. Recent developments have focused on applying SCLs to provide intelligent, efficient, and personalized healthcare solutions in the surveillance, diagnosis, and treatment of chronic ocular surface inflammation, glaucoma, and diabetes complications.

The brittleness of traditional ceramics severely limits their application progress in engineering. The multiscale structural design of organisms can solve this problem, but it still lacks sufficient research and attention. The underlined main feature is the multiscale hierarchical structures composed of basic nano-microstructure units arranged in order, which is currently impossible to achieve through artificial synthesis driven by high temperatures. This perspective aims to bridge the gap between biostructural materials and biomimetic ceramics, highlighting the relationship between bioinspired structures and interfacial interaction of structure densification in biomimetic ceramics. Therefore, we could accomplish densification and ceramic development at room temperature, consequently correlating the structure, properties, and functions of materials and accelerating the development of the next generation of advanced functional ceramics.