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The polar psychrotrophic fungus Geomyces sp. WNF-15A can produce high-quality natural red pigment for the potential use as edible pigment. However, it shows low-temperature-dependent synthesis of red pigment, which limits its large-scale industrial applications due to the difficult and high-cost bioprocess control. This study aims to develop transposon-mediated mutagenesis methods to generate mutants that are able to synthesize red pigment at normal temperature. Four transposable systems, including single and dual transposable systems, were established in this fungus based on the Minos from Drosophila hydei and the Restless from Tolypocladium inflatum. A total of 23 production-dominant mutants and 12 growth-dominant mutants were thus obtained by constructed transposable systems. At 14 °C and 20 °C, the MPS1 mutant strain achieved the highest level of red pigment (OD520 of 43.3 and 29.7, respectively), which was increased by 78.4% and 128.7% compared to the wild-type, respectively. Of note, 4 mutants (MPS1, MPS3, MPS4 and MPD1) successfully synthesized red pigment (OD520 of 5.0, 5.3, 4.7 and 4.9, respectively) at 25 °C, which broke the limit of the wild-type production under normal temperature. Generally, the dual transposable systems of Minos and Restless were more efficient than their single transposable systems for mutagenesis in this fungus. However, the positive mutation ratios were similar between the dual and single transposable systems for either Minos or Restless. This study provides alternative tools for genetic mutagenesis breeding of fungi from extreme environments.

Plant height is a key agronomic trait that affects yield and is controlled by both phytohormone gibberellin (GA) and ultraviolet-B (UV-B) irradiation. However, whether and how plant height is modulated by UV-B-mediated changes in GA metabolism are not well understood. It has not been reported that the E3 ubiquitin ligase Anaphase Promoting Complex/Cyclosome (APC/C) is involved in the regulation of plant growth in response to environmental factors. We perform a forward genetic screen in soybean and find that a mutation in Glycine max Increased Leaf Petiole Angle1 ( GmILPA1 ), encoding a subunit of the APC/C, lead to dwarfism under UV-B irradiation. UV-B promotes the accumulation of GmILPA1, which ubiquitinate the GA catabolic enzyme GA2 OXIDASE-like (GmGA2ox-like), resulting in its degradation in a UV-B-dependent manner. Another E3 ligase, GmUBL1, also ubiquitinate GmGA2ox-like and enhance the GmILPA1-mediated degradation of GmGA2ox-like, which suggest that GmILPA1-GmGA2ox-like module counteract the UV-B-mediated reduction of bioactive GAs. We also determine that GmILPA1 is a target of selection during soybean domestication and breeding. The deletion (Indel-665) in the promoter might facilitate the adaptation of soybean to high UV-B irradiation. This study indicates that an evolutionary GmILPA1 variant has the capability to develop ideal plant architecture with soybean cultivars. Gibberellins (GA) negatively regulate UVB-mediated suppression of plant height in plants. Here, the authors show that GmILPA1-mediated degradation of GmGA2ox-like protein counteract the UV-B-mediated reduction of bioactive GAs contributing to the linkage between the affection of UV-B and GA on plant height of soybean.

Class I KNOTTED-like homeobox ( KNOXI ) genes are parts of the regulatory network that control the evolutionary diversification of leaf morphology. Their specific spatiotemporal expression patterns in developing leaves correlate with the degrees of leaf complexity between simple-leafed and compound-leafed species. However, KNOXI genes are not involved in compound leaf formation in several legume species. Here, we identify a pathway for dual repression of MtKNOXI function in Medicago truncatula . PINNATE-LIKE PENTAFOLIATA1 ( PINNA1 ) represses the expression of MtKNOXI , while PINNA1 interacts with MtKNOXI and sequesters it to the cytoplasm. Further investigations reveal that UNUSUAL FLORAL ORGANS ( MtUFO ) is the direct target of MtKNOXI, and mediates the transition from trifoliate to pinnate-like pentafoliate leaves. These data suggest a new layer of regulation for morphological diversity in compound-leafed species, in which the conserved regulators of floral development, MtUFO , and leaf development, MtKNOXI , are involved in variation of pinnate-like compound leaves in M. truncatula . This study reveals a pathway in which the transformation of trifoliate leaves into pinnate-like pentafoliate leaves is regulated by the conserved regulators of floral development ( MtUFO ) and leaf development ( MtKNOXI ) in M. truncatula .

As the staple crop in plateau agriculture, Tibetan hulless barley ( Hordeum vulgare L. var. nudum ) experiences dual stresses from challenging environments (abiotic stress) and pathogenic attacks (biotic stress). TGACG-binding transcription factors (TGAs) serve as master regulators orchestrating plant growth, developmental processes, and defense responses against biotic and abiotic stresses, with particularly pivotal functions in regulating plant immunity. Here, 10 HvnTGAs were identified in the Qingke genome, which were phylogenetically classified into five distinct clades. HvnTGA proteins possessed conserved structural domains, characteristic motif compositions, and three-dimensional architectures typical of the TGA family. Subcellular localization assays confirmed that both HvnTGA2 and HvnTGA6 were localized to the nucleus. RNA-seq profiling revealed that eight out of ten HvnTGA genes were differentially expressed following powdery mildew infection. The expression of HvnTGA2 and HvnTGA6 was specifically upregulated by ethephon (ETH) and methyl jasmonate (MeJA) treatment. Yeast two-hybrid (Y2H) assays demonstrated that both HvnTGA2 and HvnTGA6 could form homodimers. Furthermore, heterodimeric interactions were detected between HvnTGA2 and HvnTGA4, HvnTGA2 and HvnTGA6, as well as HvnTGA4 and HvnTGA6. Interaction assays based on split luciferase complementation assay (SLCA) confirmed the interaction between HvnTGA2 and HvnTGA6, as well as the self-interaction of HvnTGA6. The silencing of HvnTGA2 resulted in reduced expression of HvnPR-4 , enhanced susceptibility of Qingke to Pyrenophora graminea , and accumulation of ROS. This study comprehensively elucidates the regulatory mechanisms of TGA transcription factors in Qingke, a highland-adapted crop, provides novel molecular insights into plant-pathogen interactions.

Background Early diagnosis is crucial for reducing disability and improving long-term prognosis in patients with systemic Juvenile Idiopathic Arthritis (sJIA), but it remains a significant challenge. This study aims to identify non-invasive biomarkers with superior diagnostic efficacy for sJIA. Methods To predict early potential biomarker candidates and pathogenic mechanisms for sJIA, we performed scRNA-seq and Bulk RNA-seq on PBMCs from the Chinese sJIA cohort. The findings were validated through in vitro experiments and cell sequencing. We also established the relationship between UBE2D1 and other systemic diseases to determine possible complications of sJIA. Results Using scRNA-seq and Bulk RNA-seq, we discovered that UBE2D1 expression is closely related to disease activity levels, specifically in classical monocytes from sJIA patients. Functional enrichment suggested that UBE2D1 could enhance disease progression by activating NLRs. Follow-up data indicated a significant reduction in UBE2D1 expression and monocyte numbers before and after treatment. Pseudotime analysis revealed that UBE2D1 expression is initially high during monocyte development. Western blot results showed increased levels of UBE2D1 and NLRs marker proteins, which decreased upon introducing UBE2N and NF-κB inhibitors. Co-IP suggested that UBE2D1 mediates the activation of the NLRs pathway by interacting with IKB-α. The UBE2D1 complication map indicates that UBE2D1 might contribute to the development of various diseases across 17 different systems, including autoimmune diseases, the digestive system, and ocular conditions. Conclusions Our findings provide insights into the biological mechanisms of sJIA, indicating that UBE2D1, which is highly expressed in monocytes, may represent a candidate biomarker for early diagnosis and a potential method for clinical treatment strategies, pending further validation.

This study proposes a data-driven evaluation framework to quantify the impact of artificial intelligence (AI) on industrial process performance and enterprise value creation. The framework integrates enterprise value assessment based on the Feltham–Ohlson model with a multi-level performance evaluation framework that incorporates a hybrid Analytic Hierarchy Process (AHP) and Entropy Weight Method (EWM) for indicator weighting, together with Fuzzy Comprehensive Evaluation (FCE) for multi-dimensional aggregation. This integrated approach enables systematic analysis of AI-driven effects from the perspectives of intelligent investment input, operational governance environment, and process output performance. Using panel data from 3515 Chinese A-share listed firms (20,076 firm-year observations) during 2014–2022, a Process Performance Index (PI) is constructed to measure AI-enabled operational capability across resource allocation efficiency, coordination effectiveness, and production performance dimensions. Empirical results indicate that PI is positively associated with abnormal earnings and firm profitability, demonstrating that AI-enabled process capability contributes to sustained enterprise value growth. The findings further show increased digital technology investment intensity, knowledge-based human capital accumulation, and improved data governance conditions, accompanied by enhanced production and service performance. By explicitly integrating AHP–EWM weighting and FCE aggregation within the Feltham–Ohlson valuation structure, the proposed framework provides an interpretable quantitative mechanism linking AI adoption, operational capability development, and enterprise value creation. The results offer practical insights for evaluating intelligent transformation strategies in the context of Industry 5.0 and data-driven industrial development.

BackgroundType 2 diabetes mellitus complicated with chronic kidney disease (T2DM-CKD) is a common and severe complication of T2DM that predisposes patients to end-stage renal disease (ESRD), substantially increasing mortality risk and long-term medical economic burden. Currently, SGLT-2 inhibitors are used as the foundational treatment regimen in clinical practice. As validated by the global multicenter randomized controlled CONFIDENCE trial, simultaneous initiation of finerenone plus an SGLT-2 inhibitor can further enhance renal protection and delay kidney disease progression. Despite these advancements, long-term pharmacoeconomic data supporting this combination regimen in the Chinese population remain limited.ObjectiveFrom the perspective of China’s healthcare system, this study aimed to evaluate the cost-utility of the simultaneous initiation of finerenone and empagliflozin versus empagliflozin monotherapy in T2DM-CKD patients, based on the CONFIDENCE trial design.MethodsA Markov model was constructed to simulate the natural history of T2DM-CKD. The model cycle was 1 year, with a simulation time horizon of 30 years. The willingness-to-pay (WTP) threshold was set at three times China’s 2025 per capita GDP (¥299,100/QALY). Base-case analysis was performed, followed by one-way and probabilistic sensitivity analyses to assess the robustness of results.ResultsBase-case analysis revealed that the incremental cost-effectiveness ratio (ICER, a measure comparing the cost to the health benefit gained) of the finerenone plus empagliflozin regimen was ¥35,082.44/QALY (quality-adjusted life year), well below the WTP (willingness-to-pay) threshold. One-way sensitivity analysis indicated that the kidney disease progression coefficient (which measures the rate of worsening kidney disease) and the cost of finerenone were the most influential parameters; all parameter fluctuations within reasonable ranges retained the cost-effectiveness advantage. Probabilistic sensitivity analysis showed that the combination regimen was acceptable in 99.1% of 1,000 Monte Carlo simulations (computer-generated scenarios that model uncertainty), with all incremental QALYs positive, indicating highly robust results.ConclusionCompared with empagliflozin monotherapy, the combined initiation of finerenone plus empagliflozin offers significant cost-utility advantages in treating T2DM-CKD. These findings provide high-quality evidence for standardized clinical care, rational pharmacotherapy, the formulation of medical insurance policies, and optimal health resource allocation in Chinese patients with T2DM-CKD.

Background: Visceral fat plays a central role in cardiometabolic risk among people with type 2 diabetes mellitus (T2DM), yet its assessment in routine clinical practice remains largely dependent on imaging techniques or indirect anthropometric measures. Identifying accessible blood-based markers that reflect visceral adiposity may facilitate improved phenotyping in this population. This study aimed to investigate whether circulating coiled-coil domain–containing protein 3 (CCDC3) reflects visceral fat accumulation in adults with T2DM. Methods: Public RNA-sequencing datasets and human adipose tissue samples were analyzed to identify CCDC3 as a visceral fat–enriched secretory gene. In this cross-sectional study of 160 adults with T2DM undergoing dual-energy X-ray absorptiometry, plasma CCDC3 was measured by ELISA. Associations between plasma CCDC3 and visceral fat area (VFA) were examined using multivariable regression. Logistic regression models for abdominal obesity (VFA ≥ 100 cm2), with and without CCDC3, were evaluated using receiver operating characteristic (ROC) analysis, calibration curves, decision curve analysis (DCA), and Shapley additive explanations (SHAP). Results: Circulating CCDC3 levels were positively associated with VFA (β = 3.11, p < 0.001), independent of demographic and metabolic factors. Incorporating CCDC3 into the baseline model significantly improved discrimination of abdominal obesity (AUC 0.820 vs. 0.663; p = 0.009). Calibration curves and DCA supported better model fit and higher net clinical benefit with CCDC3. SHAP analysis showed that CCDC3 contributed the greatest incremental importance beyond waist circumference, sex, and age. Conclusions: Circulating CCDC3 may serve as a blood-based biomarker reflecting visceral adiposity in adults with T2DM and provides complementary information beyond traditional anthropometric measures.

Abiotic and biotic stress significantly limit crop yields. However, most stress‐tolerance genes identified to date provide resistance to either biotic or abiotic stress and inhibit normal plant growth, limiting their application in breeding. We identified the soybean (Glycine max) NAC transcription factor gene GmST2, which is induced by salt and Botrytis cinerea stresses. Through comprehensive analyses of transgenic GmST2‐overexpressing lines, CRISPR‐Cas9 mutants, and heterologous expression systems in Arabidopsis thaliana and Nicotiana tabacum, we demonstrate that GmST2 confers dual resistance to salinity stress and B. cinerea while simultaneously enhancing plant growth under non‐stressed conditions. RNA‐seq revealed the enrichment of genes in the jasmonic acid (JA) pathway in GmST2‐overexpressing soybean. GmST2 directly binds to the promoters of GmAOC3 and GmAOC4, encoding key enzymes involved in JA biosynthesis, to promote their transcription, thereby enhancing JA accumulation and salt tolerance. Furthermore, we identified GmPRL1b, a WD40‐repeat protein, as a nuclear interactor that promotes GmST2 protein accumulation and functions upstream of GmST2 in regulating JA pathway genes. The elucidated GmPRL1b‐GmST2‐GmAOC3/4 regulatory module coordinates JA‐mediated cross‐protection against concurrent abiotic and biotic stresses. Evolutionary analysis indicates that GmST2 has undergone selection during soybean domestication, with the identified elite haplotype exhibiting enhanced salt tolerance. Our findings provide a molecular framework for developing stress‐resilient soybean cultivars, effectively addressing the trade‐off between stress resistance and plant productivity.