Atherosclerosis (AS) is a chronic inflammatory condition influenced by glucose and lipid disorders, oxidative stress, and thrombosis, reflecting the complexity of its pathological process. The development of accurate experimental models that simulate human AS is essential for understanding its initiation and progression. This review summarizes the current AS research models and analyzes their specific application scenarios. We discuss tissue-engineered blood vessels (TEBVs) and vessels-on-a-chip (VoCs), which leverage tissue engineering and precise microenvironmental control to construct in vitro models that closely resemble the structure and function of human AS. Isolated vessel segments from live animals provide a valuable tool for investigating human AS due to their physiological similarity, controllability, and reproducibility. The review further outlines the construction of AS animal models through high-fat diets and gene-editing techniques, highlighting how immune-inflammatory responses, mechanical arterial injury, and hemodynamic changes accelerate model development. This comprehensive analysis highlights the potential of AS models to revolutionize theranostic applications in clinical translational research, paving the way for more personalized and effective treatments for AS in the near future.

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.

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.

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.

Macrophages are ubiquitous within the human body and serve pivotal roles in immune surveillance, inflammation, and tissue homeostasis. Phenotypic plasticity is a hallmark of macrophages, allowing their polarization into distinct phenotypes M1 (pro-inflammatory, anti-tumor) and M2 (anti-inflammatory, pro-tumor) in response to local microenvironmental cues. In tumor tissues, the polarization of tumor-associated macrophages profoundly shapes the tumor microenvironment, influencing tumor progression, immune evasion, and metastasis. Therefore, the ability to image and monitor macrophage polarization is essential for comprehending tumor biology and optimizing therapeutic strategies. With the rapid advancement of nanomedicine, a diverse array of nanoprobes has been engineered to specifically target tumor-associated macrophages, offering new avenues for noninvasive in vivo imaging and real-time monitoring of macrophage dynamics within the tumor microenvironment. This perspective highlights recent advancements in macrophage-targeting nanoprobes for imaging macrophage polarization both in vitro and in vivo. It also addresses the current challenges in the field, such as enhancing probe sensitivity, specificity, and biocompatibility, while outlining the future directions for the development of next-generation nanoprobes aimed at precision oncology.

Nano-/microrobots have been demonstrated as an efficient solution for environmental remediation. Their strength lies in their propulsion abilities that allow active “on-the-fly” operation, such as pollutant detection, capture, transport, degradation, and disruption. Another advantage is their versatility, which allows the engineering of highly functional solutions for a specific application. However, the latter advantage can bring complexity to applications; versatility in dimensionality, morphology, materials, surface decorations, and other modifications has a crucial effect on the resulting propulsion abilities, compatibility with the environment, and overall functionality. Synergy between morphology, materials, and surface decorations and its projection to the overall functionality is the object of nanoarchitectonics. Here, we scrutinize the engineering of nano-/microrobots with the eyes of nanoarchitectonics: we list general concepts that help to assess the synergy and limitations of individual procedures in the fabrication processes and their projection to the operation at the macroscale. The nanoarchitectonics of nano-/microrobots is approached from microscopic level, focusing on the dimensionality and morphology, through the nanoscopic level, evaluating the influence of the decoration with nanoparticles and quantum dots, and moving to the decorations on molecular and single-atomic level to allow very fine tuning of the resulting functionality. The presented review aims to lay general concepts and provide an overview of the engineering of functional advanced nano-/microrobot for environmental remediation procedures and beyond.

Circular RNAs (circRNAs) are differentially expressed in cardiac hypertrophy; however, the exact function and mechanisms during hypertrophy development are still unknown. Here, we explored the role of a newly discovered circRNA in the pathogenesis of myocardial hypertrophy. It was found that circ-0001283 promoted the progression of cardiac hypertrophy by interacting with myosin light chain 3 (MYL3) to inhibit the protein ubiquitination and enhance its protein expression, not by the competitive endogenous RNA mechanism. Further investigation demonstrated that the reduced hypertrophy induced by circ-0001283 knockdown was counteracted by overexpression of MYL3. Mechanistically, MYL3 facilitated myocardial hypertrophy by inducing autophagy in cells via PI3K/Akt/mTOR and ERK signaling pathways. In summary, circ-0001283 can bind directly to MYL3 and up-regulate its expression, thereby promoting autophagy to accelerate cardiac hypertrophy. Circ-0001283 may serve as a potential therapeutic target for cardiac hypertrophy.

Marine biofouling causes severe economical and environmental challenges to marine industries and maritime activities. Biofouling prevention has emerged as one of the most pressing issues in water-related industries. Recently, the slippery liquid-infused porous surfaces (SLIPSs) have shown great potential for biofouling prevention across a broad spectrum of fouling organisms. However, our understanding of the mechanisms by which SLIPSs prevent biofouling remains limited. In this study, we discovered that oil-infused polydimethylsiloxane elastomer (i-PDMS), a silicone-based SLIPS variant, significantly inhibited the sensory responses of the fouling mussel Mytilopsis sallei, particularly at its sensory organ, the foot. Using bioinformatics and molecular biology analyses, we demonstrated that i-PDMS disrupts larval settlement of M. sallei by interfering with the mechanosensitive transient receptor potential melastatin-subfamily member 7 (TRPM7) channel, which is highly expressed in the foot during the settlement process. Furthermore, adhesion assays and molecular dynamics simulations revealed that the secreted foot proteins of the mussel are unable to effectively interact with the i-PDMS surface due to nanoscale fluctuations at the material interface. These findings enhance our understanding of how fouling organisms sense and adhere to surfaces and provide deeper insights into the antifouling mechanisms of SLIPS.

Familial hypercholesterolemia (FH) is a lipoprotein disorder characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) and an increased risk of premature atherosclerotic cardiovascular disease. Recent evidences have shown that several glycerophospholipid species were markedly altered in experimental FH animals and exhibited diverse bioactivities. Nevertheless, the glycerophospholipid profiles and their associated biological implications in human FH remain largely unknown. In this study, we sought to comprehensively delineate the glycerophospholipid phenotypes in human FH and to investigate the functional roles of key FH-altered glycerophospholipid molecules on cholesterol metabolism. Targeted analysis of 328 glycerophospholipid metabolites was used to profile the differentiated alterations in patients with homozygous FH (HoFH; n = 181), heterozygous FH (HeFH; n = 452), and non-FH hypercholesterolemia (n = 382). Our findings revealed that the glycerophospholipid phenotypes of FH and non-FH hypercholesterolemia were dominated by a spectrum of metabolites involved in the lysophosphatidic acid (LPA) metabolism. Among the LPA features, palmitoyl-LPA (16:0) showed significant association with the clinical levels of LDL-C and total cholesterol in HoFH and HeFH populations. Using functional metabolomic strategy and murine FH model, we demonstrated that supplementation with LPA 16:0 elevated the plasma levels of LDL and free/esterified cholesterol and exacerbated the atherosclerotic lesions. Conversely, inhibition of autotaxin-mediated LPA 16:0 production significantly ameliorated dyslipidemia. Mechanistically, we uncovered that LPA 16:0 could disrupt hepatic cholesterol homeostasis by impairing cholesterol excretion and inhibiting primary bile acid synthesis. In summary, our study offers novel insights into lipid metabolism in human FH and posits that targeting LPA metabolism may represent a promising therapeutic strategy for reducing cholesterol levels in the FH population.

Biomimetic dry adhesive structures, inspired by geckos’ climbing abilities, have attracted research attention in recent years. However, achieving superior adhesion on a rough surface remains an important challenge, which limits practical applications. Conventional bionic adhesion methods perform well on smooth surfaces, but adhesion strength drastically decreases on rough surfaces due to the reduced contact area. Generally, various adhesive structures have been proposed to increase the contact area without assessing adhesion states, against obtaining good performance on rough surfaces. If an intelligent adhesive approach could be introduced on rough surfaces, it would be beneficial for promoting the development of gecko-inspired adhesives. However, existing adhesive structures with the sensing function usually utilize the adhesive function to support the sensing function, i.e., a sensor with an adhesive function; for other few structures, the sensing function supports adhesion, but they do not focus on improving adhesion performance on rough surfaces. Inspired by the synergistic effect of a kinematic system during the crawling process of geckos, this study proposes an intelligent adhesive structure for rough surfaces. The proposed structure combines a hierarchical bionic dry adhesive structure based on gecko paw microhairs with a flexible capacitive sensor unit. Experimental observations and analytical modeling demonstrate that incorporating mushroom-shaped bionic dry adhesive structures with inclined support micropillars can reduce interface contact stiffness, notably enhancing adhesion on rough surfaces while allowing real-time monitoring of contact states. Moreover, this innovative smart adhesive structure facilitates morphology sensing of contact interfaces, presenting potential advancements in bionic adhesion for morphology sensing applications.