Search Results (20,878)

Under alkaline conditions, most commonly used preservatives exhibit limited efficacy and fail to meet the preservation requirements of coated tofu. This study aims to investigate the effects of metal-phenolic networks (MPNs) on quality deterioration, protein oxidation, conformation, and gel microstructure of coated tofu during cold storage (4 °C and 10 °C). The results showed that, compared with the untreated control group, MPNs treatment effectively inhibited protein oxidation, alleviated quality deterioration, delayed the degradation of color and texture, and reduced protein degradation, as evidenced by soluble protein contents that were 63.55% (4 °C) and 66.65% (10 °C) lower than those of the control group after 20 days of storage. MPNs treatment also improved the orderliness and stability of the protein secondary structure. In addition, electrophoretic analysis showed that MPNs markedly retarded the decline in band optical density of the 11S protein A subunit by 96.19% and 97.28% at 4 °C and 10 °C, respectively, and suppressed the increase in the B subunit by 13.28% and 73.20%, respectively. Moreover, MPNs treatment helped maintain a more compact gel network. Based on physicochemical characterization and Pearson correlation analysis, the preservative effect of MPNs on coated tofu under alkaline conditions was elucidated, revealing the internal correlation between the inhibition of quality deterioration and the regulation of protein oxidation. Specifically, MPNs mitigate protein disulfide bond loss, increase the β-sheet content, preserve the natural protein conformation and the relative proportion of 11S subunits, stabilize the gel microstructure, and thereby achieve quality preservation. These findings provide theoretical support and strategic reference for the development of preservation technologies for alkaline high-protein gel foods. Full article

Chronic liver injury is characterized by sustained activation of transforming growth factor-β (TGF-β) signaling within the fibrotic microenvironment, yet the contribution of TGF-β-associated metabolic remodeling to hepatic stellate cell (HSC) activation remains incompletely understood. Here, we investigated whether TGF-β signaling is associated with lipid metabolic remodeling in HSCs and whether pirfenidone (PFD) interferes with this process. We found that TGF-β1 was spatially associated with lipid accumulation in fibrotic liver tissue and that TGF-β1/2 promoted HSC proliferation. In vitro, TGF-β1/2 coordinately upregulated sterol regulatory element-binding protein 1 (SREBP1) and fatty acid synthase (FASN), accompanied by increased intracellular lipid accumulation and enhanced oleic acid (OA)-associated lipid responses. Low-dose OA further activated AKT/ERK/p70 S6K signaling in HSCs, whereas PFD attenuated these signaling events. In parallel, PFD suppressed TGF-β-associated lipid accumulation in vitro, reduced SREBP1/FASN expression in activated HSC-rich regions in vivo, and alleviated CCl₄-induced liver fibrosis. Together, these findings support a model in which TGF-β-associated lipogenic remodeling contributes to HSC activation and suggest that interference with this metabolic state may represent one component of the antifibrotic action of pirfenidone. Full article

Accurate prediction of electricity demand during hot seasons is essential for maintaining power system reliability, particularly in humid subtropical regions such as Guangdong, China, where high temperatures strongly influence consumption. However, many models rely primarily on air temperature and may not fully capture combined atmospheric effects. This study evaluates the potential of biometeorological thermal indices for improving summer electricity load forecasting. Daily maximum load and meteorological data during May–September 2019–2021 were analyzed using Back-Propagation Neural Network (BP), Random Forest (RF), and a Stacking ensemble model. Three indices—Effective Temperature (ET), Physiological Equivalent Temperature (PET), and the Universal Thermal Climate Index (UTCI)—were introduced as predictors. The ensemble model achieved the best performance, with Ensemble–UTCI yielding the highest accuracy (R² = 0.559, RMSE = 60.96 × 10⁴ kW, MAE = 45.10 × 10⁴ kW). Compared with temperature-based models, biometeorological indices consistently improved predictions, with UTCI performing best (average RMSE = 62.81 × 10⁴ kW). Bayesian analysis shows strong evidence of improvement in RF and ensemble models, but not in BP or linear models, indicating model dependence. During the July 2021 heat event, RF showed greater robustness, with PET–RF achieving the lowest error (MAPE = 3.03%). These results demonstrate the value of biometeorological indices for load forecasting in humid subtropical regions. Full article

Background: Acquired resistance to the third-generation EGFR tyrosine kinase inhibitor osimertinib, often mediated by EGFR triple mutations, poses a major clinical challenge in non-small cell lung cancer (NSCLC) treatment. Among these, some rare mutations, such as L858R/T790M/L792H and L858R/T790M/G796R, create steric hindrance that directly interferes with osimertinib binding, yet effective targeted therapeutic strategies for these specific mutations remain lacking. Cudratricusxanthone A (CTXA), a natural xanthone derivative isolated from Cudrania tricuspidata Bur., has demonstrated various pharmacological activities, but its effects against EGFR triple-mutant NSCLC have not been systematically investigated. Methods: Stable Ba/F3 and NIH/3T3 cell lines expressing EGFR L858R/T790M/L792H or L858R/T790M/G796R triple mutations were generated via electroporation. The antiproliferative effects of CTXA were evaluated by MTT/MTS assays, colony formation, and wound healing assays. Cell cycle distribution and apoptosis were analyzed by flow cytometry. Protein expression of EGFR signaling pathway components (p-EGFR, p-ERK, p-AKT, p-STAT3) and cell cycle regulators (Cyclin D1, CDK4) were examined by Western blotting. Molecular docking and 200 ns molecular dynamics simulations were performed to investigate the stability and binding modes of CTXA to the mutant EGFR kinase domains. Results: The successfully established triple-mutant cell lines exhibited high EGFR expression, IL-3-independent growth, and significant resistance to osimertinib. CTXA inhibited the proliferation of all triple-mutant cell lines in a time- and concentration-dependent manner, with 48 h IC₅₀ values ranging from 0.362 to 2.488 μM. Mechanistically, CTXA suppressed EGFR autophosphorylation and downregulated downstream p-ERK, p-AKT, and p-STAT3. CTXA induced G1 phase cell cycle arrest by downregulating Cyclin D1 and CDK4, significantly promoted apoptosis, and inhibited cell migration. Molecular docking revealed that while osimertinib binding was blocked by steric hindrance from His-792 or Arg-796, CTXA adapted to the mutated ATP-binding pockets through multiple hydrogen bonds and extensive hydrophobic interactions. Molecular dynamics simulations confirmed the stable binding of CTXA to both mutant EGFR proteins over the 200 ns simulations. Conclusions: This study demonstrates for the first time that the natural compound CTXA possesses antitumor efficacy against EGFR L858R/T790M/L792H and L858R/T790M/G796R mutants by regulating EGFR-ERK/AKT/STAT3 signaling. Our findings position CTXA as a promising lead compound for tackling this challenging form of acquired resistance and highlight the value of natural products in multi-target antitumor drug discovery. Full article

In the context of global warming, the South China Sea is showing an accelerating warming trend, which highlights the impact of climate change on the marine environment of the South China Sea. The interdecadal variation of chlorophyll a concentration (Chl_a) directly reflects the long-term evolution pattern of the upper marine ecological environment in the South China Sea and has significant indicative significance for marine ecological protection. This study investigated the relationships between Chl_a concentration, sea surface temperature (SST), shortwave radiation (SSRD), mixed layer depth (MLD), wind speed (Wind), and geostrophic current (ugo) in the South China Sea over the past 27 years. Statistical methods were used to analyze the differentiated impacts of marine environmental factors under different climate backgrounds on Chl_a concentration. From 1998 to 2007 (P1), there was a decreasing trend in the early stage, from 2007 to 2015 (P2), there was an upward trend in the middle period, and from 2015 to 2024 (P3), there was an upward trend in the recent period. During these three stages, SST and MLD were the core influencing factors. The threshold of SST gradually increased over time, reaching 27.05 °C, 27.24 °C, and 27.32 °C, respectively. The average normalized information flow (NIF) of Chl_a concentration changed from positive to negative. In the early stage of P1, the SST in most areas of the South China Sea was less than 27.05 °C, and in the P2 and P3 periods, the SST in most areas reached the threshold. The thresholds of MLD were 22.33 m, 21.64 m, and 33.68 m, respectively. The average NIF of Chl_a concentration was positive in all periods. The MLD in most areas of the South China Sea did not reach the threshold in all three periods. These findings emphasize the different roles of marine environmental factors in regulating Chl_a concentration in the South China Sea, providing a scientific basis for the ecological health monitoring of marine fishery areas, disaster warning, and adaptive management in response to climate warming. Full article

Joint action involves more than coordinated activity; it is cooperation grounded in shared intentionality, whereby partners represent an activity as something “we” are doing together. This “we-mode” stance should shape attention and memory, making partner-relevant information psychologically significant because it supports a collective goal. Using a joint-search paradigm, we tested whether people automatically attend to and remember partner goals. Pairs of participants searched for targets from different item categories, and trials were successful only when both responded correctly. A surprise recognition test followed the joint-search task assessing memory for the items. Across Experiments 1 (animate stimuli) and 2 (inanimate stimuli), participants showed better recognition of partner-goal items compared to distractors. Participants also showed enhanced attention to partner-goal items in Experiment 2. In Experiment 3, participants completed the same task, and returned three days later for a recognition test first followed by a second joint-search task with switched targets. Participants continued to show superior recognition for partner-goal items, and search efficiency improved after targets switched, indicating that partner-goal was retained over time and supported later cooperation. Together, these findings demonstrate that human cognition supports joint actions over time by organizing attention and memory around what “we” are doing together. Full article

Mycosporine-like amino acids (MAAs), a class of secondary metabolites characterized by a cyclohexenone or cyclohexenimine ring structure bound to amino acid residues, are widely distributed in algae. These compounds exhibit strong ultraviolet-absorbing and antioxidant activities, making them attractive candidates for natural sunscreen formulations. However, the low productivity of MAAs in microalgae severely hampers commercial viability. Asterarcys sp., a fast-growing, heat- and light-tolerant microalga, has recently been demonstrated to produce high levels of MAAs under UV irradiation. In this study, phosphorus limitation was found to stimulate rapid MAAs accumulation in Asterarcys sp. SCSIO-46548. After eight days of cultivation, microalgal cells grown in phosphorus-free medium (0 mg L⁻¹) showed a sixfold higher MAAs content (1.08% DW) compared to the group supplied with 5.60 mg L⁻¹ phosphorus (0.18% DW). However, the accumulation of MAAs began to plateau under phosphorus deprivation. Based on integrated homology alignment with cyanobacteria and functional domain validation, a putative biosynthetic pathway for mycosporine-serine in Asterarcys sp. SCSIO-46548 was proposed. Importantly, the gene expression of desmethyl-4-deoxygadusol synthase (DDGS) exhibited a 2.75-fold upregulation under phosphorus limitation. Complementary bioinformatic analyses further characterized the subcellular localization and major physicochemical properties of the candidate enzymes involved. In conclusion, phosphorus limitation is an effective strategy to enhance MAAs production in Asterarcys sp. SCSIO-46548 by upregulating the expression of key biosynthetic genes, such as DDGS. This finding provides an effective solution to the low MAAs productivity in microalgae cultivation. Full article

Uridine diphosphate glucuronosyltransferases (UGTs) are critical phase II detoxification enzymes; however, their mutational landscape and protective roles against chemical carcinogenesis in hepatocellular carcinoma (HCC) remain poorly defined. Here, targeted sequencing of ten liver-enriched UGT genes in 38 paired tissues from a Chinese HCC cohort revealed striking mutation frequencies in UGT2B15 (44.74%), UGT2B10 (36.84%), and UGT2B17 (26.32%). This genomic instability was accompanied by a profound downregulation of UGT2B15 mRNA (9.02-fold decrease, p < 0.001) and protein levels (Z-score = 2.32, p = 0.0093) in tumors, with higher UGT2B15 expression correlating with improved overall survival in TCGA cohorts (HR = 1.724, p = 0.012). Mechanistically, we identified the androgen receptor (AR) as a direct transcriptional regulator of UGT2B15 and UGT2B17, with dihydrotestosterone (DHT) inducing dose-dependent increases in their expression, thereby linking endocrine signaling to hepatic detoxification. Transcriptomic profiling following UGT2B15 knockdown in HCC cells revealed a significant enrichment in chemical carcinogenesis-related pathways. Crucially, UGT2B15 deficiency severely exacerbated carbon tetrachloride (CCl₄)- and ethanol-induced hepatotoxicity both in vitro and in vivo. Our study uncovers a profound impairment of UGT-mediated detoxification in HCC and establishes the AR–UGT2B15 axis as a critical barrier against chemical-induced liver injury, highlighting its potential as a chemopreventive target in carcinogen-exposed populations. Full article

The river buffalo is an economically important livestock species supplying milk and meat. However, a multi-tissue transcriptomic atlas for the key dairy river buffalo breeds, Murrah and Nili-Ravi, has not yet been established, and the lack of stable reference genes has hindered in-depth studies of their biological functions and the molecular mechanisms underlying key economic traits such as lactation. We established a multi-tissue gene expression atlas across 20 tissues and identified 717 housekeeping genes (HKGs), and RPL37A and EEF2 were further shown to be stable candidate reference genes under the conditions tested. We found 8368 tissue-specific genes (TSGs), predominantly enriched in the reproductive system. Exploratory analysis of mammary tissue (dry-period vs. public lactating samples, confounded by batch effects) revealed mammary-enriched hub genes including LALBA; these findings are preliminary and require validation. Dynamic analysis across lactation stages (early, peak, mid-, late) identified candidate genes including SEC14L2 and ACSM3. Phenotypic data showed strong negative correlations between milk yield and protein/fat content, and a positive correlation with lactose content. However, causal or regulatory roles were not inferred due to lack of paired individual-level data. Cross-dataset comparisons are descriptive only, and are not key conclusions. In summary, this study lays the foundation for advancing research in lactation trait genetics and functional genomics in river buffalo, with novel reference genes and lactation stage-specific transcriptional dynamics as its main contributions. Full article

The differentiation of dental papilla cells (DPCs) into functional odontoblasts is critical for dentinogenesis, yet the role of mitochondrial dynamics remains unclear. Here, we investigated the functional role of mitochondrial fission and mitochondria-associated endoplasmic reticulum membranes (MAMs) in the odontogenic differentiation of DPCs. Using in vitro differentiation models combined with confocal microscopy, transmission electron microscopy, and gain- and loss-of-function approaches, we found that odontogenic induction triggered early mitochondrial fragmentation and increased MAM formation. Dynamin-related protein 1 (DRP1) mediated mitochondrial fission, which in turn regulated MAM architecture and promoted differentiation. Malic enzyme 2 (ME2) acted as an upstream regulator, facilitating DRP1 recruitment and organizing MAM integrity. Notably, disruption of the ME2-DRP1-MAM axis impaired dentin formation both in vitro and in vivo, either by ME2 knockdown or pharmacological inhibition of DRP1 (Mdivi-1). These findings establish the ME2-DRP1-MAM axis as a critical metabolic–organellar switch driving odontoblast differentiation, providing new mechanistic insights into dentinogenesis and identifying potential therapeutic targets for dentin–pulp complex regeneration. Full article

In the context of global digital transformation, scientifically examining the spatio-temporal evolution patterns and transition mechanisms of the digital economy at the municipal level is crucial for promoting coordinated regional development. This study takes 281 prefecture-level cities in China from 2011 to 2023 as its research units. Exploratory Spatio-Temporal Data Analysis (ESTDA) is employed to analyze its spatio-temporal dynamics, while a panel quantile regression model nested with spatio-temporal transition types is used to reveal the driving mechanisms. The findings indicate that (1) the overall development level of China’s municipal digital economy has steadily increased, yet significant regional heterogeneity persists, characterized by a pattern of “eastern leading, central fastest-growing, and western lagging,” with considerable room for overall improvement. (2) The digital economy exhibits a significant positive spatial correlation. High–high agglomeration areas remain stable in the southeastern coast, whereas low–low agglomeration areas are concentrated in the central-western and northeastern regions. The spatial pattern demonstrates strong stability and path dependence. (3) LISA time paths reveal drastic changes in local spatial structures in provinces such as Heilongjiang, Inner Mongolia, Hubei, Guangdong, and Guangxi, while East and Central China remain relatively stable. Tortuosity analysis indicates that spatial linkages in the western region are becoming active yet unstable. (4) The quantile regression nested with transition types identifies four mechanisms: “Economic development-Technological innovation” serves as the fundamental driving mechanism across all regions. Low-quantile areas face a complex situation with dual suppression from “opening-up and urbanization” coexisting with drivers from “human capital, government intervention, and industrial structure.” High-quantile areas are synergistically driven by “urbanization, human capital, government intervention, and advanced industrial structure.” This study provides a decision-making reference for overcoming the dilemma of “low-level club convergence” in digital economy development and formulating differentiated regional policies. Full article

The low-carbon transition of the power sector is fundamental to achieving “Dual Carbon” goals, where demand-side management plays an increasingly vital role in transforming flexible loads into renewable energy accommodation and active emission-reduction resources. However, existing low-carbon demand response mechanisms based on dynamic carbon emission factors only reflect average system states and fail to quantify the incremental carbon impact of marginal load changes. To address this limitation, this paper proposes a novel marginal carbon emission factor-driven low carbon demand response mechanism. Unlike traditional methods, the proposed mechanism utilizes marginal carbon emission factors as a high-sensitivity guiding signal to inform users of the real-time emission and renewable energy consumption variations caused by their consumption adjustments. Furthermore, considering the forecasting errors of high-penetration renewable energy, the uncertainty of marginal carbon emission factors is explicitly considered. Case studies are conducted to compare the proposed method with the conventional method through comparative analyses based on the modified PJM-5 system. Results demonstrate that the MCEF-driven approach provides more precise carbon-reduction and renewable energy utilization signals to achieve superior system-wide decarbonization performance and sustainable development. Full article

The hydrogen evolution reaction (HER) is a cornerstone of green hydrogen production, yet its efficiency is constrained by the sluggish kinetics of water splitting. High-entropy catalysts (HECs), single-phase materials incorporating multiple principal elements, have emerged as a transformative solution. Their unique attributes including vast compositional flexibility, tunable electronic structures, and synergistic multi-element interactions, enable them to overcome the activity, stability, and cost limitations of conventional catalysts. Despite rapid performance advancements, the rational design of HECs is fundamentally hampered by critical knowledge gaps, particularly in identifying true active sites under operando conditions and predicting long-term stability. This work critically assesses these challenges, systematically summarizing the latest progress in HECs design, synthesis, and structure–activity relationships. By bridging fundamental principles with practical applications, we provide a forward-looking perspective on key research directions. Distinct from recent progress-focused reviews, this work establishes a strategic roadmap by systematically diagnosing seven grand challenges across the science-to-technology pipeline and proposing corresponding countermeasures. This framework aims to guide future research efforts toward the rational design and practical deployments of HECs for practical and cost-effective green hydrogen production. Full article

In future active distribution networks with high penetrations of renewable energy, flexible loads are expected to play an increasingly important role as reserve resources to support the sustainable and reliable operation of power grids. Accurate evaluation of flexible load reserve capacity is therefore essential for reliable reserve scheduling. Existing research mainly focuses on the operational characteristics and physical constraints of flexible loads, while insufficiently accounting for user response willingness and the uncertainty of user decision-making behavior, which may lead to biased reserve capacity assessments and impair the sustainability of reserve supply in actual grid operation. To address this issue, this paper proposes a results-oriented reserve capacity evaluation method for flexible loads that explicitly incorporates user response willingness. Specifically, a fuzzy logic system is developed to quantitatively characterize the response willingness of electric vehicle (EV) and air-conditioning (AC) users under multiple influencing factors. Then, a probabilistic modeling approach for user decision-making behavior is established using the theory of planned behavior, enabling explicit representation of behavioral uncertainty. Furthermore, a comprehensive reserve capacity evaluation framework for flexible loads is constructed by integrating user willingness states, sustainable response duration, and operational power constraints. Finally, the case studies demonstrate that the proposed method can effectively improve the objectivity of flexible load reserve capacity assessments while maintaining high user participation willingness, thus supporting the long-term sustainable application of flexible loads as grid reserve resources. Full article

To investigate the response mechanism of cold-resistant Enshi black pig breeds under cold stress, nine Enshi black pigs were randomly divided into three groups with three pigs in each: a control group (18 ± 2 °C for 58 d), a cold-stress-acclimated group (3 to 8 °C to −17 to −21 °C for 58 d), and an acute cold stress group (−17 to −21 °C for 3 d). RNA-seq technology was used to analyze mRNA and lncRNA expression patterns in subcutaneous adipose tissue under cold stress. The results showed that, under acute cold stress, many metabolic pathways were activated, including those involved in rapid energy supply (e.g., the citric acid cycle/TCA cycle, fatty acid degradation and metabolism, and glycolysis/gluconeogenesis), signal transduction pathways (e.g., PI3K Akt, MAPK, PPAR, HIF-1, mTOR, and FoxO), and immune and cellular homeostasis pathways (chemokine signaling pathway, T cell receptor signaling, Toll-like receptor signaling, and apoptosis and autophagy regulation). Under cold stress acclimation, metabolic regulatory pathways (e.g., AMPK, mTOR, FoxO, HIF-1, glycolysis/gluconeogenesis, and fatty acid degradation), immune and inflammatory regulatory pathways (Toll-like receptors, NOD like receptors, and T/B cell receptor signaling pathways), and signal transduction and cell homeostasis pathways (MAPK, PI3K Akt, NF-κB, Notch signaling pathways, apoptosis, and autophagy regulation) were continuously activated to ensure the stability of adipose tissue structure and function. Acute cold stress activated more pathways than cold stress acclimation, but both led to significant changes in energy metabolism. The results identified the molecular regulatory mechanisms of adipose tissue under cold stress, providing a basis for the subsequent breeding of new cold-resistant pig breeds. Full article