Latest ArticlesFairly assessing energy barrier that shifts coordinated lithium (Li) to naked Li on the interface, as well as deeply exploring interfacial descriptors that can interpret rapid interfacial redox kinetics with anion-dominated electrolyte species, has been long-standing fundamentals to design well-performing electrolytes for low-temperature Li metal batteries. The Li de-solvation concept is merely a picture that can describe the transformation of coordinated Li to naked Li. This work highlights the importance of Li de-coordination instead of Li de-solvation to illustrate such Li transformation behavior, since it considers entire Li de-sheath events (both solvent and anion). Theoretical calculations inform that anions entering into the first Li solvation sheath (mimic to the weak solvation electrolyte) unavoidably elevate the Li de-coordination energy due to the intrinsically greater ion–ion than ion–dipole interactions in the bulk electrolyte. The subsequent interfacial model suggests that interfacial charge exchange is a more effective descriptor to mediate interfacial redox kinetics and interpret experimental results that anion-rich Li species exhibit better battery performances. This work underscores anion effects on the Li de-coordination in the bulk electrolyte and charge exchange in the interface, hoping to unveil the fundamental causes why anion-prevailed Li species work well in low-temperature Li metal batteries.
Recent researches have revealed the potential utility of extrachromosomal circular DNAs (eccDNAs) as biomarkers in various diseases. However, the association between plasma eccDNAs and myocardial infarction (MI) remains unclear. In this study, we extracted plasma eccDNA from blood samples of individuals with acute MI and conducted Circle-Seq. We identified an MI-related eccDNA (MIRECD) with high expression levels in the plasma of patients with MI. Sanger sequencing validated its loop construction and sequence. Mechanistically, MIRECD could aggravate necroptosis via regulating the expression of mixed-lineage-kinase-domain-like pseudokinase (MLKL). Kaplan–Meier analysis demonstrated that the incidences of major adverse cardiac events (MACEs) and cardiovascular mortality were higher in individuals with elevated MIRECD levels. Univariate and multivariate Cox regression analyses indicated that MIRECD independently predicted the occurrence of MACEs in patients with MI. The addition of MIRECD enhanced the discrimination and reclassification ability compared with conventional risk factors. In conclusion, our study identified a novel eccDNA, MIRECD, which might regulate myocardial necroptosis through MLKL. MIRECD has the potential to serve as a reliable indicator for predicting the prognosis and stratifying the risk of MI.
The Metaverse is a decentralized, immersive 3-dimensional virtual environment that merges the physical and virtual worlds, fundamentally transforming digital interaction and garnering widespread attention. However, its primary platforms face challenges such as low-quality content and underdeveloped virtual environments, leading to a subpar user experience. Artificial intelligence-generated content (AIGC) has emerged as a key driver in Metaverse development, enabling the efficient and cost-effective creation of digital content. AIGC also promotes personalized content, further enhancing the appeal of the Metaverse. Although AIGC holds great promise, comprehensive investigations into its underlying models and applications remain limited. This study begins with the core neural network architectures of generative AI and examines the relationship between the Metaverse and AIGC. It delves into the deep learning technologies that support AIGC, providing both qualitative and quantitative analyses of their advantages, limitations, and hardware constraints. We also review existing practical applications of the Metaverse, highlighting the challenges and future opportunities in key domains such as healthcare and education. The research concludes that while AIGC can markedly accelerate the development of the Metaverse, its technology must be more closely aligned with development needs to deliver a truly immersive experience. The integration of AIGC and the Metaverse represents the convergence of artificial intelligence, computer graphics, and human–computer interaction. This interdisciplinary synergy has the potential to redefine the way we create, interact with, and experience digital environments, pushing the boundaries of creativity and immersion.
Serine serves as a metabolic nexus in tumors, coordinating one-carbon metabolism, nucleotide synthesis, and redox regulation. While serine transporters (SerTs) are known to be dysregulated in cancer, their functional nanoscale organization remains unresolved due to the limitation of resolution imaging and available probes. Here, we developed a substrate-based fluorescent probe (Ser-probe) enabling direct stochastic optical reconstruction microscopy of SerTs, revealing malignancy-associated clustering assembly of SerTs that correlates with transport capacity. Compared to MDA-MB-231 cells, MCF7 cells with higher endogenous serine biosynthetic capacity exhibited more pronounced SerT/glucose transporter (GluT) co-clustering, suggesting that their spatial assemblies closely correlate with serine transport and biosynthetic functions in maintaining serine homeostasis. Their cluster morphology and co-assembly were revealed to depend critically on lipid rafts and glycan cross-linking, identifying the key determinants of spatial distribution to enable mechanistic understanding and potential regulation. Glucose deprivation weakened SerT/GluT clustering and their colocalization, which may be caused by their attenuated functional cooperativity in serine homeostasis maintenance under glucose-dependent suppression of serine synthesis. Pharmacological inhibition of phosphoglycerate dehydrogenase (PHGDH) initially enhanced SerT/GluT aggregation and colocalization, but this effect gradually attenuated as doses increased. The strategic combination of a PHGDH inhibitor with glucose restriction or free sialic acid synergistically disrupted SerT/GluT nanoscale organization, amplifying the anti-tumor efficacy of the PHGDH inhibitor and establishing the metabolic plasticity of transporter assemblies as a targetable vulnerability. This work establishes a fundamental link between transporter spatial assembly and tumor serine metabolic reprogramming, providing a new perspective to better understand SerT dysfunction in tumor metabolic reprogramming, offering novel therapeutic avenues for targeting serine metabolism in cancer.
With the increasing demand for high sensitivity, low interference, and micro-size of deep ultraviolet spectral information in the field of photoelectric detection, low-dimensional diamond-based ultraviolet photoelectric detection has attracted great interest. However, although the diamond-based material has a high mobility, its lack of free electrons seriously hinders its conductivity and detection ability. Therefore, improving the free electron level of diamond-based materials has become the primary goal for achieving high-performance applications. Here, we demonstrate a diamondene photodetector formed by van der Waals heterostructure bonding, which has a high level of free electrons and is more advantageous for ultraviolet light. The diamondene photodetector realized by this method has a high responsivity of 2.04 A/W and D* higher than 1012 Jones, and the external quantum efficiency is as high as . In the detection of imaging applications, ultraviolet imaging with very low photon number is realized, and clear imaging can be achieved only under the light intensity with a photon number of 28. It is of great substantial for the development and theoretical research of ultra-high sensitivity ultraviolet photodetectors in the future.
pH and temperature in the gastrointestinal (GI) tract are correlated with many diseases, but patients suffer from the pain of traditional testing methods. Functionalized capsule robots for GI tract sensing offer a potential approach for early GI disease diagnosis. However, most capsule robots struggle with control and sensing integration. In addition, the friction encountered by capsule robots during navigation poses a challenge for their application. Here, a capsule robot with a low coefficient of friction is proposed to continuously detect pH and temperature. The hydrogel skin reduces the surface friction coefficient by more than 4 times and achieves an average propulsion speed of 12.79 mm s−1 in a living porcine small intestine. The capsule system enables continuous detection over a pH range of 2 to 8 and a temperature of 36 to 40 °C. We demonstrate capsule robots’ capability of multimodal locomotion through complex stomach and small intestine environment. It solves the problem that capsule robots used for sensing functions cannot be precisely controlled and achieves drive–control–sensing integration.
Activation of hepatic stellate cells (HSCs) represents a central pathological event in liver fibrogenesis, and targeted clearance of activated HSCs is considered to be a promising therapeutic strategy. However, our understanding of the underlying molecular mechanisms is limited. Here, we report that Oroxylin A (OA) inhibited the activation of HSCs by inhibiting the dual roles of Sirtuin 7 (SIRT7). Single-cell transcriptome sequencing analysis and bioinformatics analysis were employed to identify critical pathways, followed by validation through molecular assays including Western blotting, immunofluorescence, and co-immunoprecipitation. In human samples, animal models, and primary cultures, the translational relevance of molecular discoveries was heightened. OA binds to the Gln299 and Asp305 residues of SIRT7, triggering a dual regulatory program in hepatic fibrosis. OA suppresses SIRT7, triggering succinylation-dependent proteasomal degradation of protein arginine methyltransferase 5 (PRMT5). This cascade attenuated symmetric dimethylation of cyclic GMP-AMP synthase (cGAS), thereby activating the cGAS-stimulator of interferon genes (STING) signaling and promoting HSC senescence. Concurrently, OA-elicited SIRT7 inhibition promotes externalized calreticulin (ecto-CRT) expression, thereby enhancing natural killer (NK) cell recognition and targeted elimination of activated HSCs. However, enzymatically dead mutant SIRT7 (H187Y) also suppressed ecto-CRT expression promoted by OA, showing that it is independent of its desuccinylase activity. Our findings reveal a dual regulatory mechanism whereby SIRT7 inhibition by OA coordinates PRMT5 degradation-mediated cellular senescence and ecto-CRT-dependent NK cell immune clearance of HSCs. This work establishes SIRT7 as a pivotal therapeutic target and provides mechanistic insights for developing antifibrotic strategies.
Disrupted matrix mechanics have been found to be highly associated with increased risks of many diseases, including neurodegenerative diseases and cancers. For centuries, the aged tissue matrix has been found to lose its mechanical integrity and exhibit altered biophysical properties. Whether the mechanical properties of matrix serve as a regulator for maintaining the health and function of cells remains unknown. Here, we propose that cells cultured within a tissue-mimicking mechanical microenvironment exhibit reprogrammed cellular behaviors. We first construct a tissue-mimicking hydrogel by combining both viscoelastic and nonlinear elastic components, on which fibroblasts crowd together to form mesenchymal aggregates instead of individually spreading out. The mesenchymal aggregates not only obtain the elevated expression of stemness genes but also exhibit enhanced bidirectional differentiation potentials. The formation of mesenchymal aggregates happens through the reorganization of the collagen network induced by the enhanced cell contraction. Compromising the cell contraction not only prevents the formation of mesenchymal aggregates but also eliminates cell reprogramming. Additionally, this mechanical reprogramming with tissue-mimicking hydrogels has been applied to non-small-lung cancer cells and promotes their adipogenic transdifferentiation, which eventually reverses their epithelial-to-mesenchymal transition genes and suppresses the expression of oncogenes/pro-oncogenes. Thus, our study paves the way for both regenerative medicine and cancer treatments with an approach termed mechanical reprogramming on tissue-mimicking hydrogels.
Mitotic chromosome formation depends on coordinated SMC complex activities, yet how condensin engages cohesin during this process remains unclear. Samejima et al. combined synchronized mitotic entry, auxin-inducible degrons, high-resolution Hi-C, live-cell imaging, quantitative proteomics, and polymer simulations to dissect condensin I, condensin II, and cohesin interplay in vertebrate cells. They showed that condensins actively displace extrusive cohesin to dismantle interphase chromatin and build nested mitotic loops. Condensin II generates large, helical loops, and condensin I forms finer loops, together yielding the canonical rodlike mitotic chromosome. Cohesin, while preserving sister-chromatid cohesion, relocates to loop tips without blocking condensin. The study also reports the first in vivo measurements of condensin loop-extrusion speed. This work establishes a mechanistic, quantitative framework for mitotic chromosome architecture and offers predictive models for future genome-organization- and SMC-related pathology studies.
Optical levitation provides a powerful platform for probing the physicochemical properties of nano- and microparticles. In optical levitation experiments involving nonreacting droplets, metastable states, or so-called “thermally locked” states, can emerge. However, there has been no report on thermal locking induced by chemical reactions or the impact of thermal locking on the reaction mechanisms or rates. Herein, we investigate the growth of optically levitated aqueous droplets in which sulfate forms through the SO2-NO2 and the SO2-Mn2+-O2 heterogeneous reactions—2 environmentally important sulfate formation pathways. We observe (semi-)discrete droplet growth occurring via consecutive thermally locked states, which result from the competition between water vapor condensation driven by sulfate formation and evaporation driven by droplet heating through resonant absorption of the trapping laser. By combining Mie theory-based analysis of the stimulated Raman scattering and droplet thermodynamics, we develop an approach to retrieve the key properties (e.g., temperature, pH, and molality) of thermally locked droplets and demonstrate that chemistry-driven thermal locking results in a signature particle growth pattern. Comparison of sulfate formation rates in locked versus unlocked droplets further reveals that thermal locking can accelerate chemical reactions or even change the dominant mechanism by promoting photoinduced reaction pathways. As light intensity enhancement within the droplet is localized near the droplet surface, the photoinduced reactions lead to droplet growth patterns similar to those driven by surface reactions. This work uncovers a novel phenomenon emerging from light–droplet interactions, offering a mechanistic framework for leveraging thermal locking to probe droplet properties and study chemical reactions under resonant conditions.