Advanced Science最新文献

Terahertz resonances embedded in crystalline heterostructures could close a spectral gap between conventional electronics and photonics while opening new windows on phenomena in non-equilibrium lattice dynamics. We show that femtosecond optical screening of the depolarization field in epitaxial PbTiO₃/SrTiO₃ superlattices launches a collective polar mode that oscillates near 1 THz and coherently spans the entire mini-Brillouin zone. Wave-vector-resolved pump-probe X-ray diffraction resolves a nearly dispersion-less oscillation at 0.87 and 0.94 THz at the zone boundary and zone center, respectively, persisting for ∼2.5 ps, corresponding to a weakly damped resonance. Dynamical phase-field simulations reveal the origin of the mode to mesoscopic rotation of closure-domain textures during the photoexcited transition from an unscreened to a screened electrostatic state. Varying the PbTiO₃ and SrTiO₃ ratio tunes the mode frequency continuously from 0.9 to 1.4 THz, providing a quantitative design rule for frequency-selectable THz oscillators in ferroelectric heterostructures. By coupling nanoscale polarization reconfiguration to long-wavelength coherent dynamics, this work establishes depolarization-field engineering to topology-driven THz functionality and expanding the landscape of collective lattice dynamics.

Microglia-mediated neuroinflammation is closely associated with the pathogenesis of secondary brain injury following spontaneous intracerebral hemorrhage (ICH). However, the relationship between immune response regulation and metabolic patterns in microglia remains unclear. Histone Deacetylases 1 and 2, a class of lysine deacetylases, regulates gene transcription by modulating histone acetylation modifications and is widely involved in various cellular activities of microglia. In this study, we observed that knockout of HDAC1/2 in microglia alleviated neurological deficits caused by ICH, preserved white matter integrity, and accelerated hematoma clearance post-ICH. Mechanistically, we found that after ICH, microglia exhibited increased expression of hexokinase 2 (HK2) and enhanced glycolysis. HDAC1/2 knockout/pharmacological inhibition affected the acetylation level of HK2, inhibited its glycolytic activity, and promoted a metabolic shift in activated microglia from glycolysis to fatty acid oxidation. This shift was associated with reduced pro-inflammatory responses and enhanced phagocytic activity in microglia. Enhanced fatty acid oxidation may have a detrimental effect on mitochondrial function, and HDAC1/2 inhibition simultaneously promoted mitophagy in microglia. Additionally, HDAC1/2 inhibition triggered microglial apoptosis and suppressed proliferation, ultimately leading to a reduction in microglial cell numbers. Overall, this study reveals the potential mechanisms by which targeting HDAC1/2, through acetylation modifications and transcriptional regulation, modulates microglial function and metabolism after ICH, thereby exerting protective effects.

Retraction: J. Li, C. Tang, X. Zhang, R. Xing, and Q. Guo, "Histone Lactylation-Driven Upregulation of VRK1 Expression Promotes Stemness and Proliferation of Glioma Stem Cells," Advanced Science 12, no. 44 (2025): e03897, https://doi.org/10.1002/advs.202503897. The above article, published online on 24 September 2025, in Wiley Online Library (http://onlinelibrary.wiley.com/), has been retracted by agreement between the authors; the journal Editor-in-Chief, Kirsten Severing; and Wiley-VCH GmbH. Following publication, the authors notified the journal that they had discovered an unintentional statistical error introduced during the gene-screening process using multiple databases for lactate-regulated glioma stem cell stemness. Specifically, when re-analyzing the GSE145699 dataset to nominate candidate genes, the authors observed that VRK1 does not consistently reach statistical significance when different pairing strategies are applied in paired t-tests. This instability undermines the reliability of the gene selection step (noted in Results 2.2) and cannot be rectified by a correction. These results were critical to the main interpretation of the data presented in the article, and as such, the article must be retracted.

About 25% of long noncoding RNAs (lncRNAs) contain Alu elements, yet their functional significance remains largely unexplored. We previously found that lnc-APUE was upregulated in hepatocellular carcinoma (HCC) and correlated with high recurrence rates. However, the pathogenic roles of lnc-APUE upregulation in tumor metastasis and its underlying mechanism are still unknown. Here, we showed that an Alu element in lnc-APUE could base-pair with the Alu element in 3'-untranslated region of E-cadherin coding gene (CDH1), triggering CDH1 mRNA decay and E-cadherin loss, consequently enhancing hepatoma cell migration and invasion. These effects of lnc-APUE were abrogated by deleting or mutating its Alu element, or by silencing STAU1 or UPF1, two key components of the STAU1-mediated mRNA decay (SMD) pathway. Mouse xenograft models revealed that overexpression of wild-type lnc-APUE, but not Alu-deleted lnc-APUE, reduced E-cadherin levels and promoted tumor metastasis, whereas silencing lnc-APUE had opposite effects. Furthermore, TGFβ1 stimulation induced SMAD2 binding to the lnc-APUE promoter, activating its transcription. Silencing lnc-APUE blocked TGFβ1-driven migration and invasion, identifying lnc-APUE as a downstream target and critical mediator of TGFβ1 signaling. Collectively, we define a new TGFβ1/SMAD/lnc-APUE/E-cadherin axis: TGFβ1 activates lnc-APUE to promote cancer metastasis through Alu element-driven STAU1-mediated CDH1 mRNA decay and subsequent E-cadherin downregulation.

Herein, we report a highly efficient synthesis of aliphatic nitro compounds bearing multi-contiguous stereocenters in good yields (up to 72%) with excellent diastereo- and enantio-selectivities (up to 12:1 dr, and >99% ee) by combining copper-catalyzed asymmetric conjugate addition of dialkylzinc reagents to nitroalkenes with iridium-catalyzed asymmetric allylic substitution reaction. Stereodivergent construction of nonadjacent stereocenters (1,3-positions) has been achieved by combining two chiral catalysts with different enantiomers. By first introducing a chiral center at the β-position of the nitro group, highly diastereoselective control has been achieved in iridium-catalyzed allylic substitution reaction of prochiral nitro compounds.

This review systematically examines the association between vasculitis and malignancies by summarizing the risk of tumor-associated vasculitis, their clinical characteristics, and proposed pathogenic mechanisms across different vasculitic subtypes. Relevant case reports and mechanistic studies are integrated to provide a comprehensive overview of this entity. The findings offer practical value for rheumatologists in distinguishing primary vasculitis from malignancy-associated forms and optimizing patient surveillance, and for oncologists in improving recognition of tumor-associated vasculitis to reduce the risk of misdiagnosis, supporting more accurate clinical decision-making and risk management.

Variations in both transcription and translation of genes play a pivotal role in shaping complex traits and disease phenotypes. However, systematic analyses of genetic variants regulating transcription and translation, as well as their contribution to the genetic architecture of complex traits, remain scarce. Here, by generating a multi-omics dataset consisting of 132 datasets (48 transcriptomic, 48 translational, 30 proteomic, and 6 WGS) across 16 tissues from two breeds, with 3 pigs per breed, we demonstrated widespread translational buffering/amplification across tissues and breeds, with translation efficiency (TE) contributing significantly to phenotypic variation. Through integrative analysis of transcriptional and translational profiles, population genetics, and dual-luciferase reporter assays, we developed a novel framework for prioritizing gene regulatory networks (GRNs) underlying complex traits. Using this framework, we identified 33 functional 5'UTR variants linked to pork production traits, modulating 14 target genes through changes in TE. RNA interference assays confirmed the involvement of AQP4 and MYO18B in myogenic differentiation. In particular, the AQP4 variant (chr6_111421187) likely alters TE by modifying RNA secondary structure, while MYO18B variants (chr14_43476491) affect TE via RNA-binding protein interactions. More broadly, our framework can serve as a paradigm for uncovering the genetic basis of complex traits, extending beyond traditional transcriptional regulation.

Activation of retina-specific CD4⁺ T cells capable of breaking through the blood-retinal barrier (BRB) was significantly associated with the onset and progression of autoimmune uveitis (AU). Antigen-presenting cells (APCs) orchestrate this process by presenting retinal antigens to naïve CD4⁺ T cells and driving their differentiation into autoreactive CD4⁺ T cells. Here, we report an intestinal APCs-targeted strategy for treating AU based on orally administered nanoCEL (diameter: 37.06 ± 0.12 nm), a pH-responsive nanomedicine exhibiting a great gastric acid stability and a pH-responsive drug release behavior. After oral administration, nanoCEL effectively penetrates the intestinal mucus barrier and targets APCs in the intestine. Using an experimental autoimmune uveitis rat model, oral administration of nanoCEL (2 mg/kg) exhibits a superior therapeutic efficacy than free CEL treatment by suppressing the antigen-presenting ability of APCs and impairing pathogenic T cell differentiation. Additionally, nanoCEL medication protects the BRB from the damage of pathogenic T cells by the reduction of the infiltration of peripheral immune cells and the activation of retinal glial cells. Compared to free CEL, oral administration of nanoCEL remarkably enhances drug bioavailability and improves biosafety without apparent systemic toxicity. Thus, the proposed APC-targeted nanodrug delivery system might be a promising strategy to treat AU.

In vivo generation of chimeric antigen receptor-T (CAR-T) cells offers an innovative approach to CAR-T therapy; however, current in vivo CAR-T technologies rely on synthetic carriers or viral particles, which raise immunogenicity and safety concerns in clinical applications. Extracellular vesicles (EVs) are cell-derived natural nano-platforms with improved biocompatibility and the potential to deliver the transgene for in vivo CAR-T generation. In this study, we pioneered a CD3ε nanobody (Nb)-CD63 chimeric construct and stably expressed it on HEK-293T cell-derived EVs to produce CD3ε-targeting EVs, which were further loaded with Nb-CAR.BiTE (Nb-CAR with secretable bispecific T-cell engager) transgene through electroporation. The CD3ε-Nb EVs selectively delivered Nb-CAR.BiTE transgene into CD3⁺ cells in vivo and exerted robust antitumor activity against various solid tumors. The CD3-targeting property of CD3ε-Nb EVs combined with the characteristics of Nb-CAR.BiTE construct may enhance memory CAR-T proportion, prolong anti-tumor immunity, and strengthen resilience against tumor antigen rechallenge. Notably, the CD3ε-Nb EVs exhibited minimal immunogenicity risks compared to lipid-based and lentiviral carriers, despite their comparable anti-tumor activity. Taken together, the CD3-targeting EVs could drive the in vivo generation of bispecific CAR-T cells to effectively eliminate cancers and improve memory response with minimal immunogenicity.