Research最新文献

Background: Ibrutinib, a potent Bruton's tyrosine kinase inhibitor with marked efficacy against hematological malignancies, is associated with the heightened risk of atrial fibrillation (AF). Although ibrutinib-induced AF is linked to enhanced oxidative stress, the underlying mechanisms remain unclear. Objective: This research aimed to explore the molecular mechanism and regulatory target in ibrutinib-induced AF. Methods: We performed in vivo electrophysiology studies using ibrutinib-treated mice, and then employed proteomic and single-cell transcriptomic analyses to identify the underlying targets and mechanisms. The effects of A-kinase anchoring protein 1 (AKAP1) depletion on mitochondrial quality surveillance (MQS) were evaluated using both in vivo and ex vivo AKAP1 overexpression models. Results: Atrial AKAP1 expression was significantly reduced in ibrutinib-treated mice, leading to inducible AF, atrial fibrosis, and mitochondrial fragmentation. These pathological changes were effectively mitigated in an overexpression model of ibrutinib-treated mice injected with an adeno-associated virus carrying Akap1. In ibrutinib-treated atrial myocytes, AKAP1 down-regulation promoted dynamin-related protein 1 (DRP1) translocation into mitochondria by facilitating DRP1 dephosphorylation at Ser637, thereby mediating excessive mitochondrial fission. Impaired MQS was also suggested by defective mitochondrial respiration, mitochondrial metabolic reprogramming, and suppressed mitochondrial biogenesis, accompanied by excessive oxidative stress and inflammatory activation. The ibrutinib-mediated MQS disturbance can be markedly improved with the inducible expression of the AKAP1 lentiviral system. Conclusions: Our findings emphasize the key role of AKAP1-mediated MQS disruption in ibrutinib-induced AF, which explains the previously observed reactive oxygen species overproduction. Hence, AKAP1 activation can be employed to prevent and treat ibrutinib-induced AF.

Recently, the high incidence of oral mucosal defects and the subsequent functional impairments have attracted widespread attention. Controlling scaffold geometry pattern has been proposed as a strategy to promote cell behavior and facilitate soft tissue repair. In this study, we innovatively construct an integrated dual-layer heterogeneous polycaprolactone (PCL) scaffold using melt electrowriting (MEW) technology. The outer layer was disordered, while the inner layer featured oriented fiber patterns: parallel (P-par), rhombic (P-rhomb), and square (P-sq). Our findings revealed that the P-rhomb and P-sq scaffolds exhibited superior surface wettability, roughness, and tensile strength compared to the pure disordered PCL scaffolds (P) and P-par. Compared to the commercial collagen membranes, the outer layer of PCL can effectively inhibit bacterial adhesion and biofilm formation. Furthermore, the P-rhomb and P-sq groups demonstrated higher gene and protein expression levels related to cell adhesion and cell migration rates than did the P and P-par groups. Among them, P-sq plays an important role in inducing the differentiation of gingival fibroblasts into myofibroblasts rich in α-smooth muscle actin (α-SMA). Additionally, P-sq could reduce inflammation, promote epithelial regeneration, and accelerate wound healing when used in full-thickness oral mucosal defects in rabbits. Overall, the integrated dual-layer heterogeneous PCL scaffold fabricated by MEW technology effectively inhibited bacterial adhesion and guided tissue regeneration, offering advantages for clinical translation and large-scale production. This promising material holds important potential for treating full-thickness mucosal defects in a bacteria-rich oral environments.

Various lipid metabolism-related factors are essential for Zika virus (ZIKV) replication. In this study, we revealed a crucial role of diacylglycerol O-acyltransferase 2 (DGAT2) in ZIKV replication using a short hairpin RNA-based gene knockdown technique. The replication of ZIKV was significantly inhibited by DGAT2 depletion in multiple cell lines and restored by trans-complementation with DGAT2. Mechanistically, DGAT2 is recruited in the viral replication complex by interacting with non-structural (NS) proteins. Among them, both human and murine DGAT2s can be cleaved by NS2B3 at the ¹²²R-R-S¹²⁴ site. Interestingly, the cleavage product of DGAT2 becomes more stable and is sufficient to promote the lipid droplet (LD) formation independent of its enzymatic activity. This work identifies DGAT2 as a novel target of the viral protease NS2B3 and elucidates that DGAT2 is recruited by viral proteins into the replication complex, thereby playing a proviral role by promoting LD formation, which advances our understanding of host-flavivirus interaction.

Layered Ni-rich oxide cathodes in lithium-ion batteries (LIBs) often struggle with poor thermal safety and capacity fade. Xin and colleagues' studies in Nature and Nature Energy demonstrate a novel high-entropy (compositionally complex) doping strategy, introducing "cocktail effects" from multiple constituents. This approach substantially improves cycling performance and stability, reduces material cost, and may pave the way toward the development of advanced electrodes for next-generation LIBs.

To precisely and reasonably describe the contribution of interatomic and intermolecular interactions to the physicochemical properties of complex systems, a chemical message passing strategy as driven by graph neural network is proposed. Thus, by distinguishing inherent and environmental features of atoms, as well as proper delivering of these messages upon growth of systems from atoms to bulk level, the evolution of system features affords eventually the target properties like the adsorption wavelength, emission wavelength, solubility, photoluminescence quantum yield, ionization energy, and lipophilicity. Considering that such a model combines chemical principles and natural behavior of atom aggregation crossing multiple scales, most likely, it will be proven to be rational and efficient for more general aims in dealing with complex systems.

Exercise is one of the preferred management strategies for diabetic patients, but the exercise mode including type, intensity, and duration time is quite different for each patient because of individual differences. Inadequate exercise has no effect on the blood glucose control, while overexercise may cause serious side effects, such as hypoglycemia and loss of blood glucose control. In this work, we report a closed-loop feedback mode for exercise management in diabetes. A minimally invasive, biocompatible microneedle electrode patch was fabricated and used for continuously monitoring the glucose in the interstitial fluid. Further, in conjunction with using a wireless electrochemical device, the glucose signals can be analyzed to output the potency of exercise and give advice on exercise management. A custom exercise given by this closed-loop feedback mode can reduce the used dose of insulin and avoid side effect during and after exercise. We believe that this work can provide a novel comprehensive guidance for diabetic patients.

Introduction: Brain age prediction using neuroimaging data and machine learning algorithms holds significant promise for gaining insights into the development of neurodegenerative diseases. The estimation of brain age may be influenced not only by the imaging modality but also by multidomain clinical factors. However, the degree to which various clinical factors in individuals are associated with brain structure, as well as the comprehensive relationship between these factors and brain aging, is not yet clear. Methods: In this study, multimodal brain magnetic resonance imaging data and longitudinal clinical information were collected from 964 participants in a population-based cohort with 16 years of follow-up in northern China. We developed a machine learning-based algorithm to predict multimodal brain age and compared the estimated brain age gap (BAG) differences among the 5 groups characterized by varying exposures to these high-risk clinical factors. We then estimated modality-specific brain age in the hypertension group based on hypertension-related regional imaging metrics. Results: The results revealed a significantly larger BAG estimated from multimodal neuroimaging in subjects with 4 or 5 risk factors compared to other groups, suggesting an acceleration of brain aging under cumulative exposure to multiple risk factors. The estimated T1-based BAG exhibited a significantly higher level in the hypertensive subjects compared to the normotensive individuals. Conclusion: Our study provides valuable insights into a range of health factors across lifestyle, metabolism, and social context that are reflective of brain aging and also contributes to the advancement of interventions and public health initiatives targeted at the general population aimed at promoting brain health.

Transmissive metasurfaces are essentially conducive to stealth, absorbers, and communications. However, most of the current schemes only allow microwave to transmit and generally adopt multilayer structures or thick dielectric substrates to improve the electromagnetic performance, restricting optical transmission and conformal application. In addition, most metasurfaces still require metal wires and external power suppliers for programmability. Here, we propose and design an intelligent transmissive microwave metasurface with optical sensing and transparency, which provides both microwave and optical channels without redundant optical devices and power suppliers, and the 2 transmission channels are associated with each other. The metasurface is realized by validly integrating photosensitive materials into microwave meta-structures. As a demonstration, we fabricate an ultrathin optically transparent transmissive metasurface based on polyethylene terephthalate substrate and photoresistors, whose thickness is only 0.125 mm. We further construct cross-wavelength transmission links based on the metasurface sample and experimentally validate that the microwave transmissions vary with light intensities under full-polarization and large-angle incidences, and this metasurface possesses high optical transparency. The intelligent transmissive microwave metasurface with optical sensing and transparency has potential applications in optical-microwave hybrid transmission devices and stealth technology.

This commentary underscores the importance and implications of the study "Biomolecular condensates with complex architectures via controlled nucleation," led by Jan C. M. van Hest and Tuomas P. J. Knowles, published in Nature Chemical Engineering. The research team developed a novel system to investigate the structure of biological condensates using quaternized amylose, carboxymethylated amylose, and single-stranded DNA. They successfully created multiphase droplets with distinct dense phases and demonstrated that droplet architecture can be controlled through temperature and salt concentration adjustments. This study offers valuable insights into the formation and function of membraneless organelles in cells and suggests promising applications for designing biomimetic materials and therapeutic strategies.

In recent years, one-dimensional (1D) implantable sensors have received considerable attention and rapid development in the biomedical field due to their unique structural characteristics and high integration capability. These sensors can be implanted into the human body with minimal invasiveness, facilitating real-time and accurate monitoring of various physiological and pathological parameters. This review examines the latest advancements in 1D implantable sensors, focusing on the material design of sensors, device integration, implantation methods, and the construction of the stable sensor-tissue interface. Furthermore, a comprehensive overview is provided regarding the applications and future research directions for 1D implantable sensors with an ultimate aim to promote their utilization in personalized healthcare and precision medicine.