Cell therapy is a promising strategy for acute liver failure (ALF), while its therapeutic efficacy is often limited by cell loss and poor arrangement. Here, inspired by liver microunits, we propose a novel spatially ordered multicellular lobules for the ALF treatment by using a microfluidic continuous spinning technology. The microfluidics with multiple microchannels was constructed by assembling parallel capillaries. Sodium alginate (Alg) solution encapsulating human umbilical vein endothelial cells (HUVECs), hepatocytes, and mesenchymal stem cells (MSCs) are introduced into the middle channel and the 6 parallel outer channels of the microfluidics, respectively. Simultaneously, Ca²⁺-loaded solutions are pumped through the innermost and outermost channels, forming a hollow microfiber with hepatocytes and MSCs alternately surrounding the HUVECs. These microfibers could highly resemble the cord-like structure of liver lobules, bringing about outstanding liver-like functions. We have demonstrated that in ALF rats, our biomimetic lobules can effectively suppress excessive inflammatory responses, decrease cell necrosis, and promote regenerative pathways, leading to satisfied therapeutic efficacy. These findings underscore the potential of spatially ordered multicellular microfibers in treating related diseases and improving traditional clinical methods.

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.

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.

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.

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.

Thrombus is a blood clot that forms in a blood vessel at the point of flaking. Thrombosis is closely associated with cardiovascular diseases caused by different sources and factors. However, the current clinical methods of thrombus diagnosis and treatment still have problems with targeting, permeability, stability, and biosafety. Therefore, in recent years, based on the development of micro/nano technology, researchers have tried to develop some new strategies for the diagnosis and treatment of thrombosis. Due to the unique structural characteristics, the micro-nano materials in physiological environments show excellent transport and delivery properties such as better in vivo circulation, longer life span, better targeting ability, and controllable cellular internalization. Especially, elasticity and stiffness are inherent mechanical properties of some well-designed micro-nano materials, which can make them better adapted to the needs of thrombosis diagnosis and treatment. Herein, this review first introduces the thrombotic microenvironment to characterize the thrombus development process. Then, to fine-tune the pathological occurrence and development of thrombosis, the role of elastic micro-nano materials for thrombus diagnosis and treatment is summarized. The properties, preparation methods, and biological fate of these materials have been discussed in detail. Following, the applications of elastic micro-nano materials in biomedical imaging, drug delivery, and therapy of thrombosis are highlighted. Last, the shortcomings and future design strategies of elastic micro-nano materials in diagnosis and treatment of clinical thrombosis are discussed. This review will provide new ideas for the use of nanotechnology in clinical diagnosis and treatment of thrombus in the future.

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.

Developing advanced tissue-engineered membranes with biocompatibility, suitable mechanical qualities, and anti-fibrotic and anti-inflammatory actions is important for tympanic membrane (TM) repair. Here, we present a novel acoustically transmitted decellularized fish swim bladder (DFB) loaded with mesenchymal stem cells (DFB@MSCs) for TM perforation (TMP) repair. The DFB scaffolds are obtained by removing the cellular components from the original FB, which retains the collagen composition that favors cell proliferation. Benefitting from their spatially porous structures and excellent mechanical properties, the DFB scaffolds can provide a suitable microenvironment and mechanical support for cell growth and tissue regeneration. In addition, by loading mesenchymal stem cells on the DFB scaffolds, the resultant DFB@MSCs system exhibits remarkable anti-fibrotic and anti-inflammatory effects, together with the ability to promote cell migration and angiogenesis. In vivo experiments confirm that the prepared DFB@MSCs scaffolds can not only alleviate inflammatory response caused by TMP but also promote new vessel formation, TM repair, and hearing improvement. These features indicate that our proposed DFB@MSCs stent is a prospective tool for the clinical repair of TM.

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 rapid evolution of deep learning has markedly enhanced protein–biomolecule binding site prediction, offering insights essential for drug discovery, mutation analysis, and molecular biology. Advancements in both sequence-based and structure-based methods demonstrate their distinct strengths and limitations. Sequence-based approaches offer efficiency and adaptability, while structure-based techniques provide spatial precision but require high-quality structural data. Emerging trends in hybrid models that combine multimodal data, such as integrating sequence and structural information, along with innovations in geometric deep learning, present promising directions for improving prediction accuracy. This perspective summarizes challenges such as computational demands and dynamic modeling and proposes strategies for future research. The ultimate goal is the development of computationally efficient and flexible models capable of capturing the complexity of real-world biomolecular interactions, thereby broadening the scope and applicability of binding site predictions across a wide range of biomedical contexts.