Physical exercise-induced circAnks1b upregulation promotes protective endoplasmic reticulum stress and suppresses apoptosis via miR-130b-5p/Pak2 signaling in an ischemic stroke model.

AIMS: Physical exercise (PE) can accelerate post-stroke recovery. This study investigated contributions of circRNAs to PE-induced improvements in post-stroke neurological function. METHODS: Rats subjected to transient middle cerebral artery occlusion were left sedentary or provided running-wheel access for 4 weeks during recovery. CircRNAs from peri-infarct cortex were identified by high-throughput sequencing, and interactions with miRNAs by immunoprecipitation, fluorescence in suit hybridization, and dual-luciferase reporter assays. In vivo circRNA knockdown was achieved using shRNA-AAVs and in vitro overexpression by plasmid transfection. Transmission electron microscopy, western blotting, and TUNEL assays were conducted to explore circRNA contributions to endoplasmic reticulum (ER) stress and neuronal apoptosis. CircRNA levels were measured in plasma from stroke patients by qRT-PCR and associations with neurological scores assessed by Pearson's correlation analysis. RESULTS: PE upregulated circAnks1b, reduced infarct volume, and mitigated neurological dysfunction, while circAnks1b knockdown exacerbated neurological dysfunction and increased infarct size despite PE. CircAnks1b sponged miR-130b-5p, thereby disinhibiting Pak2 expression. Conversely, Pak2 downregulation disrupted PE-mediated protective ER stress, leading to reduced IRE1/XBP1 and heightened apoptosis. Plasma circAnks1b was higher in stroke patients receiving PE than sedentary patients and correlated negatively with neurological scores. CONCLUSIONS: CircAnks1b upregulation may be an effective therapeutic strategy for post-stroke recovery.

Influenza Vaccination Mediates SARS-CoV-2 Spike Protein Peptide-Induced Inflammatory Response via Modification of Histone Acetylation.

The effectiveness of coronavirus disease 2019 (COVID-19) vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain rapidly wanes over time. Growing evidence from epidemiological studies suggests that influenza vaccination is associated with a reduction in the risk of SARS-CoV-2 infection and COVID-19 severity. However, the underlying mechanisms remain elusive. Here, we investigate the cross-reactive immune responses of influenza vaccination to SARS-CoV-2 spike protein peptides based on in vitro study. Our data indicate enhanced activation-induced-marker (AIM) expression on CD4+ T cells in influenza-vaccination (IV)-treated peripheral blood mononuclear cells (PBMCs) upon stimulation with spike-protein-peptide pools. The fractions of other immune cell subtypes, including CD8+ T cells, monocytes, NK cells, and antigen-presenting cells, were not changed between IV-treated and control PBMCs following ex vivo spike-protein-peptide stimulation. However, the classical antiviral (IFN-γ) and anti-inflammatory (IL-1RA) cytokine responses to spike-protein-peptide stimulation were still enhanced in PBMCs from both IV-immunized adult and aged mice. Decreased expression of proinflammatory IL-1ß, IL-12p40, and TNF-α is associated with inhibited levels of histone acetylation in PBMCs from IV-treated mice. Remarkably, prior immunity to SARS-CoV-2 does not result in modification of histone acetylation or hemagglutinin-protein-induced cytokine responses. This response is antibody-independent but can be mediated by manipulating the histone acetylation of PBMCs. These data experimentally support that influenza vaccination could induce modification of histone acetylation in immune cells and reveal the existence of potential cross-reactive immunity to SARS-CoV-2 antigens, which may provide insights for the adjuvant of influenza vaccine to limit COVID-19-related inflammatory responses.

Emerging Potential Therapeutic Targets of Ferroptosis in Skeletal Diseases.

Ferroptosis is a new programmed cell death characterized by the accumulation of lipid peroxidation mediated by iron and inflammation. Since the transcentury realization of ferroptosis as an iron-dependent modality of nonapoptotic cell death in 2012, there has been growing interest in the function of ferroptosis and its relationship to clinical diseases. Recent studies have shown that ferroptosis is associated with multiple diseases, including degenerative diseases, ischemia reperfusion injury, cardiovascular disease, and cancer. Cell death induced by ferroptosis has also been related to several skeletal diseases, such as inflammatory arthritis, osteoporosis, and osteoarthritis. Research on ferroptosis can clarify the pathogenesis of skeletal diseases and provide a novel therapeutic target for its treatment. In this review, we summarize current information about the molecular mechanism of ferroptosis and describe its emerging role and therapeutic potential in skeletal diseases.

Structural priming from simple arithmetic to Chinese ambiguous structures: evidence from eye movement.

This article explores the domain generality of hierarchical representation between linguistic and mathematical cognition by adopting the structural priming paradigm in an eye-tracking reading experiment. The experiment investigated whether simple arithmetic equations with high (e.g., (7 + 2) × 3 + 1)- or low (e.g., 7 + 2 × 3 + 1)- attachment influence language users' interpretation of Chinese ambiguous structures (NP1 + He + NP2 + De + NP3; Quantifier + NP1 + De + NP2; NP1 + Kan/WangZhe + NP2 + AP). On the one hand, behavioral results showed that high-attachment primes led to more high-attachment interpretation, while low-attachment primes led to more low-attachment interpretation. On the other hand, the eye movement data indicated that structural priming was of great help to reduce dwell time on the ambiguous structure. There were structural priming effects from simple arithmetic to three different structures in Chinese, which provided new evidence on the cross-domain priming from simple arithmetic to language. Besides attachment priming effect at global level, online sentence integration at local level was found to be structure-dependent by some differences in eye movement measures. Our results have provided some evidence for the Representational Account.

The effect of language proficiency on L2 English learners' processing of morphologically complex words: Evidence from masked transposed letter priming.

The relative sequence of morphological decomposition and whole-word recognition during morphologically complex word (MCW) processing has attracted much attention in recent years. However, most studies have only focused on inflected and derived words while disregarding compound words, and have mainly examined the differences between native speakers and L2 learners without addressing language proficiency levels. This paper investigates the language proficiency effect on L2 English learners' processing of all the three types of MCWs in a masked transposed letter priming paradigm. Results showed that the high proficiency learners adhered to the Post-lexical Model in general, while the low proficiency learners presented a blurred tendency due to their poor whole-word memory and overall processing efficiency. Different morphological types caused gradable priming effects with compounds on the top of the continuum. In sum, language proficiency as well as morphological types impacts L2 learners' MCW processing mechanisms.