The cysteine protease OsEP3A plays a positive role in rice seedling growth and seed development. Its expression isinduced by nitrogen starvation in suspension-cultured cells. Promoter activity assays using GUS reporter constructs identified a 43-bp nitrogen-starvation-responsive sequence, providing a novel cis-regulatory target for enhancingnitrogen use efficiency. Nitrogen (N) is a critical macronutrient that influences plant growth, development, and productivity. This study characterizes the rice cysteine protease gene OsEP3A and its promoter to elucidate its role in N-mediated developmental and transcriptional regulation. Transgenic rice lines overexpressing (OsEP3A-Ox) or silenced (OsEP3A-Ri) for OsEP3A were generated to assess its physiological functions. Overexpression of OsEP3A significantly enhanced shoot and root growth, whereas RNAi-silenced plants exhibited reduced height, shorter roots, and smaller seeds compared to wild type, indicating that OsEP3A positively regulates seedling and seed development. Expression analyses revealed that OsEP3A transcription was strongly induced under N-deficient conditions and repressed by both inorganic (NH₄NO₃) and organic (glutamine, asparagine) N sources. Under N-limited hydroponic culture, OsEP3A-RNAi seedlings showed severely impaired growth, underscoring the gene’s essential role in internal N remobilization during deficiency. Promoter-reporter analyses using OsEP3A::GUS lines demonstrated strong activation of the OsEP3A promoter under N starvation and repression upon N resupply, suggesting N-dependent transcriptional control. Deletion and insertion analyses of the OsEP3A promoter identified a 43-bp N-starvation-responsive sequence (NSRS; − 278 to − 236 bp) as necessary and sufficient for starvation-induced transcriptional activation. This NSRS represents a novel cis-regulatory element responsive to N deprivation. Overall, OsEP3A acts as an N-starvation-activated cysteine protease that facilitates N recycling and seedling vigor, providing new insight into N-responsive regulatory mechanisms in rice and offering a potential molecular target for improving N-use efficiency in cereal crops.
Rheumatoid arthritis (RA) is marked by synovial inflammation, cartilage loss, and bone erosion, with macrophages playing a central role. Pyruvate carboxylase (PC), a mitochondrial enzyme, has been linked to inflammation, but its role in RA is unclear. We investigated the effects of pharmacological PC inhibition with ZY-444 in a collagen antibody-induced arthritis (CAIA) mouse model and assessed disease severity, cytokine production, and histopathology. In vitro, PC expressions were analyzed in U937 cells, macrophages, and LPS-activated macrophages. Functional analysis of PC knockdown was evaluated using qRT-PCR, ELISA, Western blotting, and apoptosis assays. In CAIA mice, ZY-444 treatment significantly reduced clinical severity, joint inflammation, macrophage infiltration, and histological severity, with efficacy comparable to dexamethasone. ZY-444 suppressed TNF-α and IL-6 in joints and decreased serum IL-6. In vitro, PC expression increased during macrophage differentiation and activation, while PC knockdown markedly reduced cytokine expression and secretion. Mechanistically, PC deficiency attenuated mitogen-activated protein kinase (MAPK) phosphorylation, enhanced macrophage apoptosis, and upregulated HIF-1α expression. PC regulates macrophage-driven inflammation in RA. Its inhibition alleviates disease pathology, supporting PC as a therapeutic target and ZY-444 as a potential repurposed anti-inflammatory agent.
Although equity markets are widely recognized as interconnected, the drivers of these linkages remain less well understood. This paper examines how equity return shocks are transmitted across nine developed stock markets from 2017 to 2023 and whether spillovers vary with macroeconomic conditions. Using daily benchmark index returns and the spillover framework of Diebold and Yilmaz in a rolling-window generalized vector autoregression setting, the study examines spillovers during the coronavirus disease 2019 pandemic and the Russia–Ukraine war, links total spillovers to monetary policy and policy uncertainty, and evaluates whether net directional spillovers differ across interest-rate environments. North American and European markets are net transmitters of return shocks, whereas Asian markets are net receivers. Total spillovers surged during the coronavirus disease 2019 pandemic and rose again around the Russia–Ukraine war. Determinant regressions show that total spillovers increased under a tighter United States monetary policy stance, higher United States policy uncertainty, and during the coronavirus disease 2019 pandemic. Net directional spillovers also varied with pandemic severity and interest rate environments, consistent with cross-border portfolio rebalancing.
Reducing semantic dilution and guiding answer candidates are crucial parts in visual question answering. Existing visual question answering systems lack effective Chinese embeddings and methods for narrowing the answer candidates based on question classification. To address these issues, we propose an architecture that integrate speech act detection module and hierarchical syntactic embedding module. The speech act detection module classifies question types and filters potential answers based on these types, thereby reducing the candidate answer space. The hierarchical syntactic transformer incorporates character, word, and phrase-level syntactic structures as input embeddings to the transformer. This hierarchical syntactic approach provides the transformer with richer contextual information from the question, thereby enhancing the effectiveness of embeddings in Chinese visual question answering systems. The proposed method is implemented and evaluated on the VQAv2 dataset. Experimental results demonstrate that our approach gains a modest but consistent 0.72
