Search Results (3,266)

Foodborne diseases represent a major public health concern, particularly those associated with dairy products contaminated with Staphylococcus aureus, a pathogen capable of producing heat-stable enterotoxins. This study evaluated the potential of native lactic acid bacteria (LAB) isolated from artisanal kefir grains as natural biocontrol agents in fermented dairy foods. Kefir grains obtained from three artisanal producers were microbiologically characterized, revealing LAB as the dominant group and the absence of Enterobacteriaceae. Strains belonging mainly to the genera Lactobacillus sensu lato, Leuconostoc, and Pediococcus were isolated and exhibited differentiated metabolic profiles. Safety assessment showed no hemolytic activity and an overall susceptibility to clinically relevant antibiotics, although genus-dependent intrinsic resistance patterns were observed. Several strains displayed enzymatic activities related to carbohydrate digestion and high tolerance to simulated gastrointestinal conditions, with survival rates exceeding 90% during both gastric and intestinal phases. Neutralized cell-free supernatant (CFS) demonstrated differential inhibitory activity, with significant antagonism of S. aureus and E. coli, comparable to those of commercial reference strains. In a yogurt model system stored at 4 °C, selected Lactobacillus and Pediococcus strains induced a progressive and significant reduction in S. aureus populations, achieving complete elimination to undetectable levels in shorter times than commercial probiotic strains. Overall, these results demonstrate that native LAB from artisanal kefir grains exhibit an adequate safety and functional profile, together with strong antagonistic activity, supporting their potential application as natural protective cultures to improve the food hygiene of fermented dairy products. Full article

Granary systems formed a core institutional foundation of state governance, famine relief, and social stabilization in premodern China. Using the complete corpus of the Twenty-Six Dynastic Histories, this study employs digital humanities methods—including text preprocessing, word-frequency analysis, collocation analysis, time-series comparison, and geographic co-occurrence analysis—to examine the long-term evolution and institutional structure of three major granary types: ever-normal granaries (ChangpingCang), charitable granaries (Yicang), and community granaries (Shecang). The results reveal significant temporal and spatial variation closely associated with dynastic stability, fiscal capacity, and disaster conditions. Ever-normal granaries evolved from early formation in the Western Han to institutional consolidation in the Tang, peak expansion in the Song, and functional diversification thereafter, operating as a centralized mechanism integrating price regulation, fiscal management, and famine relief. Charitable and community granaries, by contrast, display increasingly differentiated roles, reflecting a shift toward localized and socially embedded relief in later periods. Spatial analysis further demonstrates a hierarchical deployment pattern centered on political and agrarian cores and extended through transport corridors and frontier zones. Overall, the study highlights a multilayered relief system combining state authority and social participation, offering a data-driven reinterpretation of Chinese charity and governance. Full article

The coordinated development of achenes and receptacles in strawberry is critical for seed dispersal and fruit quality, yet the underlying molecular mechanisms remain poorly characterized. Utilizing RNA-seq analysis during the ripening transition stage, we identified pronounced transcriptomic divergence between achenes and receptacles, with receptacles exhibiting more dynamic gene expression shifts. Intriguingly, a substantial subset of differentially expressed genes (DEGs) displayed antagonistic expression patterns between these tissues, including the cytokinin degradation gene cytokinin oxidase/dehydrogenase 1 (FvCKX1), which was highly expressed in both tissues but with opposing temporal trends. Functional interrogation via transient silencing and overexpression revealed a tissue-specific regulatory role for FvCKX1. RNA interference (RNAi) suppression of FvCKX1 significantly enhanced receptacle expansion but delayed achene maturation, whereas overexpression inhibited receptacle growth while accelerating achene ripening. Abscisic acid (ABA), which positively regulates fruit enlargement, was elevated in FvCKX1 RNAi receptacles and notably reduced in overexpression fruits, indicating that FvCKX1 might negatively modulate ABA synthesis during strawberry fruit development. Our results demonstrate that FvCKX1 may function as a key regulator mediating the coordinated development between achenes and receptacles in strawberry. Full article

The mobile industry has experienced long-run changes in its knowledge structure, including identifiable transition points observable through embedding-based semantic analysis. Using abstracts from 86,674 mobile industry publications published between 2005 and 2024, we embed documents with SPECTER2, build year-specific embedding distributions, and derive knowledge regimes by combining change-point detection with inter-year distribution distances. We then extract regime-specific topics via clustering and reconstruct topic lineages by aligning topic similarities to classify inheritance, differentiation, convergence, and disappearance. The analysis delineates three regimes spanning 2005 to 2012, 2013 to 2019, and 2020 to 2024, with pronounced transitions around 2012 to 2013 and 2019 to 2020. Regime 1 centers on foundational technologies such as wireless communication, power, sensors, and reliability. Regime 2 expands toward platforms, apps, and data analytics alongside cross-domain convergence. Regime 3 is characterized by strengthened 5G operations and data-driven services, together with the independent rise in policy, governance, and regulation topics. Transitions reflect recombination built on inherited knowledge rather than abrupt replacement, and post-transition topics display distinct growth typologies by network position and growth pattern. By integrating embedding-based changepoint detection with topic lineage reconstruction, we provide a reproducible account of regime transitions and quantitative evidence to inform the timing of corporate R&D, standard and platform strategies, and policy and regulatory design. Full article

Human liver stem cells (HLSCs) are a mesenchymal stromal cell (MSC)-like population isolated from adult liver biopsies. HLSCs share key characteristics with MSCs, including phenotype and differentiation capabilities. Previous studies have demonstrated that HLSCs promote regeneration in different experimental models of acute and chronic tissue injury and that HLSC-derived extracellular vesicles (HLSC-EVs) recapitulate the therapeutic effects of the cells of origin. This study aimed to determine whether HLSC-EVs, obtained and characterized under good manufacturing practice (GMP) conditions, can influence the progression of liver fibrosis in vivo. The EV production process was carried out under GMP conditions to generate batches of HLSC-EVs by tangential flow filtration. To assess their therapeutic potential, an in vivo model of hepatic fibrosis was established through administration of thioacetamide (TAA). In TAA-treated mice, EV administrations attenuated fibrosis progression. Molecular analyses showed a significant reduction in the expression levels of key pro-fibrotic genes. At the functional level, EV administration resulted in a significant reduction in plasma alanine aminotransferase levels and an increase in albumin levels, indicating improved liver function. These data indicate that HLSC-EVs, produced under GMP conditions, display antifibrotic effects in a chronic liver disease model, leading to improved liver function and histology. Full article

Background: A major technical challenge in single-cell transcriptomics is the absence of an integrative analytic pipeline that can simultaneously leverage gene regulatory network (GRN) architecture, AI-assisted gene panel discovery, and functional relevance analyses to generate coherent biological insights. Existing approaches often treat these components independently, focusing on clusters, marker genes, or predictive features without integrating them into a mechanistically grounded framework. Consequently, comprehensive screening that links regulatory association, gene signature screening, and functional interpretation within single-cell datasets remains limited, underscoring the need for an integrated strategy. Methods: We developed an integrative bioinformatics pipeline based on Gene regulatory network–AI–Functional Analysis (GAFA), combining latent-space integration, unsupervised clustering, diffusion pseudotime analysis, lineage-resolved generalized additive modeling, GRN inference, and machine learning-based gene panel discovery. This framework enables systematic mapping of cell-state structure, reconstruction of differentiation and effector trajectories, and identification of transcriptional and regulatory features strongly associated with clinical outcomes. As a case study, we applied the pipeline to NK cell transcriptomes from six CML patients (two early relapse, two late relapse, two durable treatment-free remission—TFR; 15 samples) collected at TKI discontinuation and 6–12 months after therapy cessation. Results: We reanalyzed publicly available scRNA-seq data from a previously published CML cohort to evaluate NK-cell transcriptional programs associated with treatment-free remission and relapse. We resolved six transcriptionally distinct NK cell states spanning CD56^bright-like cytokine-responsive, early activated, terminally mature, cytotoxic, lymphoid trafficking, and HLA-DR⁺ immunoregulatory populations, each exhibiting outcome-specific compositional differences. Pseudotime analysis revealed two major NK cell lineages—a maturation trajectory and a cytotoxic effector trajectory. TFR samples displayed balanced occupancy of both lineages, whereas early relapse samples showed marked depletion of the maturation branch and preferential accumulation in cytotoxic end states. AI-guided feature selection and random forest modeling identified an 18-gene panel that distinguished NK cells from TFR and relapse samples in an exploratory manner. Among them, CST7, FCER1G, GNLY, GZMA, and HLA-C were conventional NK-associated genes, whereas ACTB, CYBA, IFITM2, IFITM3, LYZ, MALAT1, MT2A, MYOM2, NFKBIA, PIM1, S100A8, S100B, and TSC22D3 were novel. The GRN inference further uncovered outcome-specific regulatory modules, with RUNX3, EOMES, ELK4, and REL regulons enriched in TFR, whereas FOSL2 and MAF regulons were enriched in relapse, and their downstream targets linked to IFN-γ signaling, metabolic reprogramming, and immunoregulatory feedback circuits. Conclusions: This AI-enabled single-cell analysis demonstrates how NK cell state composition, differentiation trajectories, and regulatory network rewiring collectively shape TFR versus relapse following TKI discontinuation in CML. The integrative pipeline provides a modular framework that could be extended to additional datasets for data-driven biomarker discovery and mechanistic stratification, and highlights candidate transcriptional regulators and NK cell programs that may be leveraged to improve remission durability, pending validation in larger patient cohorts. Full article

This study investigated the structural and anti-inflammatory properties of Zophobas morio lipids (ZMLs). The fatty acid (FAs) composition showed a higher proportion of unsaturated FAs, mainly consisting of oleic (30.30%) and linoleic acids (20.05%), than saturated FAs, including palmitic (24.80%) and stearic acids (12.96%). In addition, FT-IR and ¹H-NMR analyses confirmed that ZML possessed a typical triglyceride structure, with long-chain alkyl groups. Thermogravimetric analysis (TGA) indicated that ZML exhibited high thermal stability, with a degradation peak at 369 °C. Differential scanning calorimetry (DSC) displayed a thermal transition at −8 °C, corresponding to the crystallization of unsaturated FAs in ZML. ZML significantly inhibits lipopolysaccharide (LPS)-induced pro-inflammatory M1 macrophage polarization by suppressing nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, thereby attenuating the expression of inflammatory mediators. Additionally, ZML alleviated inflammatory oxidative stress by activating the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant pathway. Notably, ZML not only induced M2 macrophage polarization in quiescent macrophages but also reprogrammed M1 macrophages toward the anti-inflammatory M2 phenotype. These findings suggest that ZML is a natural nutritional lipid source and a potential therapeutic agent for modulating inflammatory response. Full article

Excessive nitrogen (N) fertilization is widely used to increase rice yield, but it often leads to lodging by weakening culm strength. This study aimed to elucidate the structural and molecular mechanisms underlying nitrogen-induced changes in culm lodging resistance in rice. Field and pot experiments with two nitrogen levels were conducted using a randomized design with three biological replicates to evaluate the effects of high nitrogen application on culm mechanical properties, secondary cell wall development, and associated metabolic pathways. Mechanical measurements and microscopic analysis revealed that high nitrogen significantly reduced culm rigidity and impaired sclerenchyma development. To investigate the underlying mechanisms, integrated transcriptomic and proteomic analyses were performed on developing internodes. Differentially expressed genes and proteins were predominantly enriched in carbohydrate metabolism and phenylpropanoid biosynthesis pathways. Notably, key enzymes involved in lignin biosynthesis were consistently downregulated at the protein level under high-nitrogen conditions. In contrast, genes and proteins related to cellulose and hemicellulose biosynthesis exhibited transient inhibition at early stages followed by recovery or upregulation at later stages. Consistent with these findings, histochemical staining and quantitative assays demonstrated a significant reduction (14–16%) in lignin content in the fourth internode, whereas cellulose content showed no substantial change. Furthermore, lignin biosynthetic genes (OsCAD2, Os4CL3, and OsCOMT) were persistently suppressed during critical stages of secondary wall formation, while cellulose synthase genes (OsCESA4, OsCESA7, and OsCESA9) displayed more variable and less sustained expression patterns. Collectively, these results demonstrate that excessive nitrogen application weakens rice culms primarily by inhibiting lignin accumulation rather than cellulose deposition. The preferential suppression of the phenylpropanoid pathway and disruption of secondary cell wall formation provide a mechanistic basis for nitrogen-induced lodging susceptibility in rice. Full article

Although the coupling coordination relationship (CCR) between ecological environment and economic development has received extensive scholarly attention, investigations into the underlying mechanisms of this coupling coordination remain insufficient. Taking the Chishui River Basin (CRB) in Southwest China as the study area, this study integrates remote sensing data and county-level statistical datasets. Firstly, the quality of the ecological environment and economic development level of the CRB are systematically evaluated. Secondly, an improved coupling coordination degree model (ICCDM) is adopted to quantify the CCR between the ecological environment and economic development, as well as its spatiotemporal evolution characteristics. Finally, an obstacle degree model and panel Tobit model are employed to explore the influencing factors of the CCR from both intrinsic and extrinsic perspectives. The results show that during the study period, both the ecological environment index (EEI) and the economic development index (EDI) in the CRB exhibited upward trends, with pronounced inter-county disparities. The CCR between ecological environment and economic development was continuously optimized, and the coupling coordination degree (CCD) displayed a distinct spatial gradient pattern of downstream regions > midstream regions > upstream regions. Obstacle degree analysis identifies significant heterogeneity in the obstacle factors for CCR improvement across the basin: Renhuai and Zunyi are dominated by ecological environment constraints, while 11 counties including Chishui and Xishui are mainly restricted by economic development constraints. Industrial structure, ecological endowment, industrialization level and government capacity are vital positive driving factors for the CCR in the CRB, whereas Terrain conditions act as a key negative restraining factor. This study indicates that the overall coupling coordination level between ecological environment and economic development in the CRB is still relatively low and requires further enhancement. Therefore, region-specific differentiated regulation strategies are urgently needed to achieve high-level coordinated development between the ecological environment and economy in the CRB. Full article

This study analyzes the evolution of rural welfare vulnerability among agricultural households in Peru under the influence of extreme climate events, particularly those associated with the El Niño–Southern Oscillation. The research employs a Socio-Climatic Vulnerability Index (SCVI) constructed from microdata of the National Household Survey (ENAHO) covering the period 2000–2018. Using a longitudinal and territorial perspective, the study evaluates how climate shocks affect household welfare dynamics across Peru’s major geographic regions. The results show that extreme weather events systematically increase rural vulnerability in the years they occur, followed by partial recovery in subsequent periods, indicating temporary but recurrent welfare disruptions. Significant regional heterogeneity is observed. Coastal departments exhibit increasing vulnerability linked to hydro-meteorological exposure and rapid territorial expansion. The Andean region shows the highest and most volatile vulnerability levels due to geographic isolation, infrastructure constraints, and persistent socioeconomic inequalities. Amazonian regions present relatively lower initial vulnerability but display gradual increases associated with climate variability and limited connectivity. Decomposition of the SCVI reveals that improvements in demographic and educational conditions contribute positively to resilience, whereas the productive-economic dimension remains highly sensitive to climatic shocks. Although agricultural households demonstrate adaptive responses and coping strategies, structural gaps hinder full welfare recovery. These findings highlight the need for territorially differentiated climate adaptation policies that strengthen human capital, diversify rural livelihoods, and improve institutional support to enhance long-term resilience in vulnerable rural communities. Full article

Bud sport mutations are valuable sources of citrus germplasm innovation and provide an ideal system to dissect genetic regulation of specific traits. The Ponkan mandarin (Citrus reticulata Blanco cv. Ponkan) bud sport mutant “Pumpkin mandarin” displays a Pumpkin-shaped, ribbed peel protrusion phenotype with elevated soluble sugars, but its molecular basis remains unclear. Here, wild-type Ponkan (PG) and Pumpkin mandarin (NG) were compared across six developmental stages (90–240 days after flowering, DAF) for fruit appearance and internal quality, peel firmness, and tissue morphology; RNA-seq was performed on mature peel at 240 DAF. Peel protrusion was detectable as early as flowering. NG showed significantly lower mature fruit weight and consistently higher soluble sugar content throughout development. Peel firmness exhibited a stage-dependent reversal: NG exceeded PG before 180 DAF, PG exceeded NG at 180–210 DAF, and NG again exceeded PG at 240 DAF. RNA-seq generated 41.38 Gb of high-quality data and identified 580 differentially expressed genes (DEGs; 411 upregulated, 169 downregulated). DEGs were enriched in cell wall organization/modification, phenylpropanoid biosynthesis, starch and sucrose metabolism, cutin/wax biosynthesis, and photosynthesis. Expansin (EXP) and GH18 genes were upregulated, while NAM genes encoding NAC transcription factors were downregulated, suggesting an imbalance between cell wall loosening and structural maintenance in protrusion formation. Peel DEGs also included upregulated sucrose synthase (SUS) and sugar transporter (SUT) genes, indicating carbohydrate-related reprogramming in mutant peel. We propose a preliminary network in which NAM may function upstream, cell wall remodeling represents a principal effector module, and the peel carbohydrate metabolism acts as an accompanying module. Full article

Peroxisome proliferator-activated receptor γ (PPARγ), encoded by the PPARG gene on chromosome 3p25.2 in humans, is a ligand-dependent transcription factor that belongs to the nuclear receptor family. In various tissues, PPARγ controls cell differentiation, proliferation, or fusion. Its essential role in the development and functions of the placenta is now well established. To date, the specific functions of its RNA isoforms, encoded by ten exons, in trophoblast biology, including cell fusion and invasion, remain unknown. As translation is mainly regulated by the 5′UTR sequences of mature mRNA, this region was analyzed, and four previously unreported exonic sequences were revealed. Their expressions were confirmed and quantified in villous cytotrophoblasts from term placenta and in chorionic villi from both first-trimester and term placenta. Distinct expression patterns were observed: one exon showed weak expression in placental and chorionic cells, another exhibited stable expression throughout pregnancy, while two exons specific to villous cytotrophoblasts displayed increased expression during the first trimester, suggesting a role in oxygen-responsive mechanisms. Among these, one may be involved in villous trophoblast differentiation. These findings demonstrate that the PPARG gene is composed of 14 exons and is highly regulated depending on cell type and the stage of cell differentiation. Full article

Amid the accelerating global green transition, urban Low-Carbon Sustainable Development (LCSD) has emerged as a critical governance challenge. Despite a growing body of research on low-carbon initiatives, the role of local governments in shaping urban LCSD outcomes remains inadequately explored. To address this gap, this study develops a resource–pressure analytical framework that systematically examines how local governments’ resource endowments and pressures jointly condition LCSD. Drawing on panel data from 262 Chinese cities spanning the period 2011–2021, we construct city-level composite indicators of LCSD performance and investigate the underlying driving mechanisms through a combination of statistical analyses and geographically and temporally weighted regression. Our findings yield three principal insights: (1) although overall LCSD has progressed steadily, inter-regional disparities have widened, characterized by persistent structural misalignments and a discernible shift in spatial clustering from the northeast toward southeastern coastal regions; (2) supervisory pressure and economic resources consistently emerge as the most robust and influential determinants of LCSD; and (3) both resource-based and pressure-based drivers display significant spatiotemporal heterogeneity: economic and technological resources exert particularly strong effects in the northwest and central-west regions, respectively, while policy pressures generate differentiated impacts across cities. This research contributes to the theoretical refinement of low-carbon governance frameworks and furnishes robust empirical evidence to inform context-sensitive and regionally differentiated policy design. Full article

Salt, drought and freezing stress were major abiotic factors limiting plant growth, development and yield. Halostachys caspica (Amaranthaceae), a halophyte native to saline-arid desert regions, tolerated multiple abiotic stresses, but its molecular mechanisms of stress tolerance remain unclear. By integrating the small RNA library and transcriptome data of H. caspica under high salinity, HcmiR172e was identified as a differentially expressed miRNA and selected for the study of multiple abiotic stress responses. Using its mature sequence (20 nt) to align with upregulated genes from the transcriptome, HcTOE3 (AP2 subfamily transcription factor belonging to the AP2/ERF family) was preliminarily predicted as its target gene through bioinformatic analysis. Our previous work demonstrated that HcTOE3 was strongly upregulated by multiple abiotic stresses, including salinity, drought, heat and low temperature. Furthermore, overexpression of HcTOE3 conferred freezing tolerance to Arabidopsis throughout the entire growth period. In this study, miRNA expression analyses showed that HcmiR172e was significantly downregulated in the assimilating branches of H. caspica under low temperature, heat, salt, drought, oxidative stress and abscisic acid (ABA) application. Tobacco transient expression assays and 5′RLM-RACE confirmed that HcmiR172e directly cleaved HcTOE3 transcripts in the region close to the 5′end of the ORF. HcmiR172e-overexpressing Arabidopsis displayed increased sensitivity to salt, drought, freezing stresses and ABA treatment, along with enhanced growth inhibition, elevated reactive oxygen species (ROS) accumulation, decreased osmolyte content and downregulation of stress-responsive genes. In contrast, HcTOE3-overexpressing Arabidopsis exhibited the opposite phenotypes, physiological responses and corresponding gene expression patterns under multiple stress treatments. These findings collectively elucidated the antagonistic regulatory roles of HcmiR172e and HcTOE3 in plant abiotic stress responses, providing novel molecular targets for engineering stress-tolerant crops for saline, arid, freezing environments. Full article

This study characterizes the volatile organic compound (VOC) profiles of young monovarietal red wines from five cultivars widely grown in Alentejo, Portugal—Aragonez, Castelão, Merlot, Syrah, and Trincadeira, across two consecutive vintages (2021 and 2022), in a total of 20 samples. Understanding how grape variety and harvest year shape VOC composition is essential for defining varietal typicity, supporting authenticity assessments, and guiding quality-driven enological practices. VOCs were extracted using headspace solid-phase microextraction (HS-SPME) and analyzed by gas chromatography coupled to time-of-flight mass spectrometry (GC–TOFMS), providing a semi-quantification of 142 volatile compounds across nine chemical families. Statistical analyses, including ANOVA and Principal Component Analysis (PCA), unveiled significant effects of variety, vintage, and their interactions on VOC composition, enabling clear discrimination of the wines. Notably, terpenes and C₁₃-norisoprenoids exhibited strong varietal differentiation patterns: Castelão and Trincadeira showed higher relative proportions of monoterpenes like linalool, β-citronellol, and geraniol, whereas Aragonez presented increased sesquiterpene levels including β-bisabolene and α-muurolene, and Syrah and Merlot displayed more diverse terpenoid patterns. Despite their lower abundance, C₁₃-norisoprenoids, particularly trans-β-ionone, consistently differentiated wines across vintages. A 100% ribbon chart of the main terpenoids and C₁₃-norisoprenoids highlighted genotype-driven and vintage-independent patterns, underscoring their potential as robust markers of Portuguese red wines. This study presents a high-resolution HS-SPME–GC–TOFMS chemometric workflow for the profiling and classification of young Alentejo red wines, highlighting consistent varietal patterns in terpene and C₁₃-norisoprenoid distributions under the studied conditions. Full article