Search Results (29,569)

Background：In the bovine mammary gland, de novo fatty acid synthesis is a critical process for milk fat production, in which acetyl-CoA synthetase 2 (ACSS2) serves as a key enzyme by converting acetate into acetyl-CoA. This metabolic pathway is intricately regulated by non-coding RNAs, particularly through the competitive endogenous RNA (ceRNA) mechanism.Purpose: To elucidate the regulatory role and molecular mechanism of the circRNA-02213/miR-328/ACSS2 axis in the lipid metabolism of bovine mammary epithelial cells (BMECs). Methods: Bioinformatic prediction and dual-luciferase reporter assays were employed to verify the targeting interactions among circRNA-02213, miR-328, and ACSS2. In BMECs, qRT-PCR, Western blot, triglyceride/cholesterol quantification, Oil Red O staining, and cell proliferation assays were used to evaluate the effects of this axis on key lipid-metabolic indices and cellular phenotypes. Results: circRNA-02213 functioned as a molecular “sponge” that sequestered miR-328, thereby upregulating ACSS2 expression. Functionally, circRNA-02213 overexpression markedly promoted triglyceride and cholesterol synthesis, lipid droplet accumulation, and BMEC proliferation; whereas miR-328 exerted significant inhibitory effects on these lipid-metabolic processes and cell proliferation. Conclusion: This study demonstrates that circRNA-02213 acts as a ceRNA to relieve miR-328-mediated repression of ACSS2, constituting a critical network that regulates milk fat synthesis and metabolism. The circRNA-02213/miR-328/ACSS2 axis represents a potential molecular target for improving milk lipid quality in ruminants. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) represents a growing public health burden in the European Union (EU), largely driven by modifiable lifestyle factors such as diet. This systematic review aimed to synthesize observational evidence on the associations between nutritional exposures and incident T2DM across the EU-28, with a focus on regional heterogeneity and implications for EU-level nutrition policy. Methods: The review followed PRISMA 2020 guidelines and was registered in PROSPERO (CRD42020219994). Searches were conducted in different databases (PubMed, Embase, Scopus, Web of Science) identifying 23,437 records, from which 104 observational studies were included. Eligible studies involved adults (≥18 years) without T2DM at baseline and assessed dietary exposures in relation to T2DM incidence. Data extraction and methodological quality assessment were performed in duplicate using the NHLBI tool in Covidence. Results: Most included studies were cohort studies (77.9%), primarily conducted in Western, Northern, and Southern Europe. Diets characterized by high consumption of whole and minimally processed foods, such as fruits, vegetables, legumes, whole grains, and fermented dairy, consistently showed associations with lower T2DM risk. In contrast, high intake of red and processed meats, sugar-sweetened beverages, and ultra-processed foods was linked to higher risk. Adherence to Mediterranean or plant-based dietary patterns was associated with lower risk, whereas high animal-protein dietary patterns were detrimental. Conclusions: Nutritional determinants play a decisive role in shaping T2DM risk in the EU. Evidence supports prioritizing dietary patterns rich in plant-based and minimally processed foods while reducing ultra-processed and meat-based products. Tailored region-specific policies are needed to address the T2DM epidemic and guide effective prevention strategies. Full article

Karst landforms are characterized by high permeability, shallow soils, and steep slopes. Currently, traditional village development in karst mountainous areas tends toward homogenization, always overlooking geological features in conservation efforts. This study, focusing on all 757 traditional villages in Guizhou province, employed Geographic Information System (GIS), Geodetector, and Analytic Hierarchy Process (AHP) to develop a spatially suitable evaluation model that integrates objective driver analysis with subjective weight validation. The aim is to reveal the mechanisms by which geographic and disaster factors influence village distribution. Key findings include the following: (1) Traditional villages exhibit a dual-core clustered pattern centered on “Qiandongnan–Anshun”, with Qiandongnan having the highest concentration. (2) The selected factors—altitude (A), slope (B), aspect (C), flood sensitivity (D), and landslide sensitivity (E)—show explanatory power ranked as A > D > E > C > B. Interaction between any two factors nonlinearly enhances explanatory power. (3) Spatial suitability evaluation identified four suitability categories. Highly suitable areas are mainly in Qiandongnan, while unsuitable zones—containing only 7.66% of villages—are concentrated on the western Guizhou plateau. These results can inform conservation planning and spatial remediation across different administrative levels, providing a foundation for future development. Full article

Farmland improvement has become an overwhelmingly favorable policy in developing countries, being expected to leverage a sustainable agricultural total factor productivity (ATFP) to increase their agricultural competitiveness. Worldwide farmland improvement projects are experiencing an evolution from single goals to comprehensive goals (e.g., comprehensively improve the farmland quality by decreasing farmland abandonment and fragmentation and meanwhile improving soil–water conditions and machinery affordability). However, performances of comprehensive farmland improvement projects have been questioned, especially considering its implementary complexity and regional heterogeneity. This study applies a continuous difference-in-difference (DID) method to China’s provincial panel data (2005–2020) to analyze the impact of the high-standard farmland construction policy (which started China’s national project on comprehensive farmland improvement) on ATFP. Results show the policy significantly increases ATFP by 0.101 units. Moreover, parallel trend and robustness test results indicate the policy effect has stability and continuity. Heterogeneity analysis results show the policy effect is greater in major grain-producing regions than non-major grain-producing regions, the central regions than western or eastern regions, and regions with high disease—pest control and soil—water conservation levels than areas with low levels. Mechanism analysis results show the policy effect is achieved through three paths—operation scale increase (mediating effect size is 16.13%), planting structure adjustment (mediating effect size 12.80%), and agricultural disaster reduction (mediating effect size 13.74%). Thus, this study advocates sustainable and specialized high-standard farmland construction: it suggests post-construction policies maintaining high-standard farmland quality and detailed policies considering different regions’ heterogeneity. Full article

Background: Colorectal cancer (CRC) mortality is predominantly driven by liver metastasis and poor responsiveness to chemotherapy. The histone methyltransferase SMYD3 has been implicated in oncogenic transcriptional programs; however, its downstream effectors and microenvironmental roles in CRC remain unclear. Methods: We investigated whether SMYD3 regulates the transcription and function of the membrane receptor CDCP1, which mediates Src/PKCδ signaling and promotes invasion and stromal remodeling. A combination of molecular assays, including ChIP-qPCR, Western blotting, and co-culture experiments, was employed to examine the SMYD3–CDCP1 axis and its impact on epithelial–mesenchymal transition (EMT), cancer-associated fibroblast (CAF) activation, and oxaliplatin (OXA) sensitivity. Results: SMYD3 directly bound to the CDCP1 promoter and catalyzed H3K4me3 enrichment, thereby enhancing CDCP1 transcription. Upregulated CDCP1 activated Src/PKCδ signaling, facilitating EMT and CAF activation within the tumor microenvironment. Genetic suppression of SMYD3 reduced metastatic potential and improved oxaliplatin response in vivo, while genetic or pharmacologic perturbation attenuated tumor–stroma crosstalk and enhanced oxaliplatin sensitivity in vitro. Conclusions: The SMYD3–CDCP1 axis drives CRC progression by epigenetically promoting CDCP1 transcription and remodeling the tumor microenvironment. Targeting this pathway may provide a promising therapeutic strategy to restrain metastasis and enhance chemotherapy efficacy in CRC. Full article

Fishery resources of tuna serve as a vital source of global protein. This study investigates the key environmental drivers influencing the spatial distribution of yellowfin tuna (Thunnus albacares) in the western tropical Pacific Ocean. A comprehensive dataset was constructed by linking the catch per unit effort (CPUE) from 43 Chinese longline fishing vessels (2008–2019) with 24 multi-source environmental variables. To accurately model this complex relationship, a total of 16 machine learning regression models, including advanced ensemble methods like Light Gradient Boosting Machine (LightGBM), Random Forest, and Categorical Boosting Regressor (CatBoost), were evaluated and compared using multiple performance metrics (e.g., Coefficient of Determination [R²], Root Mean Squared Error [RMSE]). The results indicated that the Light Gradient Boosting Machine (LightGBM) model achieved superior performance, demonstrating excellent nonlinear fitting capabilities and generalization ability. For robust feature interpretation, the study employed both the model’s internal feature importance metrics and the SHapley Additive exPlanations (SHAP) method. Both approaches yielded highly consistent results, identifying temporal (month), spatial (longitude, latitude), and key seawater temperature indicators at intermediate depths (T450, T300, T150) as the most critical predictors. This highlights significant spatiotemporal heterogeneity in the distribution of Thunnus albacares. The analysis suggests that mid-layer ocean temperatures directly influence catch rates by governing the species’ vertical and horizontal movements. In contrast, large-scale climate indices such as the Oceanic Niño Index (ONI) exert indirect effects by modulating ocean thermal structures. This research confirms the dominance of spatiotemporal and thermal variables in predicting yellowfin tuna distribution and provides a reliable, data-driven framework for supporting sustainable fishery management, resource assessment, and operational forecasting. Full article

Spatial pattern analysis is essential for understanding forest structure and successional dynamics. Focusing on natural secondary forests in the subalpine region of western Sichuan, China, we established two 1-hectare permanent plots to investigate the spatial distribution of dominant tree species and assess the soil’s water-holding properties, aiming to clarify the relationship between species spatial patterns and edaphic conditions. The pioneer species Betula albosinensis exhibited a unimodal diameter distribution with scarce seedling presence, indicating limited regeneration. In contrast, Abies fargesii var. faxoniana showed a typical inverse J-shaped diameter distribution, suggesting stable population recruitment. At fine spatial scales, dominant species generally exhibited aggregated distributions, with A. fargesii var. faxoniana seedlings showing the strongest clumping; however, as the spatial scale increased, distributions tended toward randomness, likely due to self-thinning and density-dependent interactions. Bivariate spatial association analysis revealed that B. albosinensis was positively associated with A. fargesii var. faxoniana and Picea asperata at small scales, suggesting a potential facilitative effect of B. albosinensis on Pinaceae species. Moreover, capillary water-holding capacity was significantly higher in areas with greater conifer dominance, underscoring the strong environmental filtering effect of microhabitat moisture on community spatial structure. Collectively, our results suggest an ongoing mid- to late-successional shift from pioneer broadleaved to shade-tolerant conifer dominance, with concurrent changes in species composition and soil conditions. This study provides empirical insight into spatial successional processes and highlights their ecological implications for hydrological regulation in subalpine secondary forests. Full article

The Apuseni-Banat-Timok-Srednogorie Metallogenic Belt is one of the most important polymetallic metallogenic belts in the western segment of the Tethys, where numerous porphyry-type, skarn-type, and epithermal deposits are developed. However, scholars have noted a lack of systematic chronological and geochemical studies of andesites within this belt. Furthermore, the metallodynamic mechanisms controlling mineralization—such as oceanic plate exhumation and plate tearing—remain controversial. To complement the available research, this study focuses on andesites from the Čukaru Peki area in Serbia and integrates zircon U-Pb dating, molybdenite Re-Os isotopic analysis, and whole-rock geochemical analysis. The results reveal that plagioclase andesitic breccia and fine-grained plagioclase amphibole andesite were emplaced during the Late Cretaceous. Consistently, the molybdenite isochron age (81.46 ± 0.60 Ma, MSWD = 1.30) constrains the mineralization event to the same period. Both rock types exhibit geochemical signatures typical of island arc volcanic rocks, characterized by high SiO₂ contents and low Al₂O₃, MgO, and TiO₂ contents, as well as pronounced fractionation between light and heavy rare earth elements (LREEs and HREEs). The magma source is the mantle wedge metasomatized by fluid-rich melts derived from the dehydration of the subducted oceanic crust. Additionally, the primary magma produced by partial melting of this metasomatized mantle wedge assimilated and was contaminated by continental crustal material predating the Vardar Ocean’s closure during its ascent. Our findings suggest that the regional andesites are products of the exhumation of the Vardar Ocean. This study aims to provide a theoretical foundation for mineral exploration in the Timok ore cluster and, simultaneously, support the identification of ore prospecting targets in andesite alteration zones. Full article

In response to global sustainability challenges, this study investigates how Digital New-Quality Productive Forces (DNQPF), which integrate digitalization with green innovation, contribute to Sustainable Industrial Structural Upgrading (SISU) in China. Using panel data from 30 provinces spanning 2011–2023, a multidimensional DNQPF index was constructed, and a comprehensive econometric framework was applied, including two-way fixed effects, mediation and moderation analyses, Hansen threshold models, and Spatial Durbin models. The results indicate that DNQPF significantly enhances SISU (β = 0.291, p < 0.01), with household consumption upgrading serving as the key mediating channel. Regional heterogeneity is evident: Eastern provinces show strong effects (β = 0.295, p < 0.01) and central provinces exhibit catch-up potential (β = 0.467, p < 0.10), while the Western and Northeastern regions display insignificant effects due to digital infrastructure disparities. The threshold effects reveal diminishing returns beyond a DNQPF level of 0.239 (coefficient decline from 0.518 to 0.323, p < 0.01), a marketization level of 6.181, and an innovation level of 9.520. Spatial analysis further confirms positive spillovers (direct effects = 0.282–0.320; indirect effects = 0.260–1.317; p < 0.05). These findings enrich endogenous growth theory by integrating digital and green development into emerging economies and underscore DNQPF’s role in advancing SDG 9 (Industry, Innovation, and Infrastructure) and SDG 12 (Responsible Consumption and Production). Coordinated digital–green strategies, institutional reforms, and inclusive infrastructure are therefore critical for achieving sustainable industrial transformation in China and beyond. Full article

The fatty acid composition of some seed oils from plants of emerging interest was studied. The benefits towards human health were evaluated by taking into account current recommendations regarding dietary intake of essential, polyunsaturated, and monounsaturated fatty acids and by discussing the pathologies for which such fatty acids exert protective action. Species studied were Hemp (Cannabis sativa), Flax (Linum usitatissimum), Milk Thistle (Silybum marianum), Perilla (Perilla frutescens), Borage (Borago officinalis), and Black Cumin (Nigella sativa). Seeds were subjected to cold milling in order to maintain their original nutritional characteristics. Chemical analyses were performed via the dual-detector gas chromatography technique by means of Flame Ionization Detection (FID) and mass spectrometry (MS) and by applying a modified version of the AOAC Official Method 991.39, thanks to which it was possible to obtain the fatty acid composition expressed as mg per gram of oil: such information is not always available in the literature for the species studied here. Comparison with the fatty acid international guidelines about the recommended intakes in g/day was made. This allowed us to evaluate whether such oils are suitable to be used as fatty acid food supplements to rebalance the Western diet, which is shown to be inadequate by numerous studies. Results show that seed oils from Cannabis sativa, Linum usitatissimum, and Perilla frutescens are suitable to be used as food supplements while seed oils from Silybum marianum, Borago officinalis, and Nigella sativa are not. It is important to note that any possible benefits from other parts of the plant (leaves, stems, flowers, and roots) are not studied or questioned by the present research, which focuses solely on fatty acids in the oil extracted from the seeds. Full article

This study focuses on the assessment of the ecological vulnerability of lands in the western regions of Kazakhstan (WKR) using the MEDALUS (Mediterranean Desertification and Land Use) model in combination with satellite remote sensing data. Particular attention is given to the influence of climatic factors, soil properties, vegetation condition, and anthropogenic pressure. As part of the analysis, key indicators were calculated, including the Soil Quality Index (SQI), Vegetation Quality Index (VQI), Climate Quality Index (CQI), and Management Quality Index (MQI). Based on these parameters, an Environmental Sensitivity Area (ESA) index was developed, allowing the classification of the territory into five vulnerability classes ranging from low to critical sensitivity. The results indicate that 52.7% of the territory of the WKR falls within the high-risk zone for land degradation. The most pronounced changes were observed in the southern oblasts of the region, particularly in Mangystau oblast (MAN), where 98.7% of the land is classified as degraded and 74.3% of the territory falls under the category of extremely high ecological vulnerability. In addition, a steady decline in precipitation levels has been identified, contributing to the intensification of aridization processes across the region. Correlation analysis showed that the strongest relationships with the final ESA index were observed for the Vegetation Quality Index (VQI) and Climate Quality Index (CQI), both with correlation coefficients of r = 0.93 and an average coefficient of determination R² = 0.87. The Soil Quality Index (SQI) also demonstrated a strong correlation (r = 0.86). In contrast, the Management Quality Index (MQI) exhibited a generally weak correlation, except in the MAN oblast, where within the Very Low Quality (VLQ) class areas, it showed a moderate correlation (r = 0.68, p < 0.0001). The results highlight the critical role of natural factors—particularly vegetation condition, climate, and soil quality—in shaping the ecological vulnerability of the region. Findings emphasize the need for a comprehensive, multi-criteria approach in developing strategies for sustainable land management under conditions of ongoing climate change. Full article

Serotonin is a key neurotransmitter involved in visual processing. Selective serotonin reuptake inhibitors (SSRIs), such as Escitalopram, enhance serotonergic transmission and exert neuroprotective effects. Although these actions are well established in the central nervous system, their influence on retinal neurons remains unclear. This study investigated whether Escitalopram provides neuroprotection to retinal neurons following ischemic injury. Rats received Escitalopram or vehicle for 12 weeks. Retinal ischemia was induced by unilateral episcleral vein cauterization. A subset of animals received a retrobulbar injection of meclofenamic acid (MFA). Retinal function was assessed using electroretinography, intraocular pressure (IOP) was monitored, and retinas were collected for immunofluorescence and Western blot. Cauterization increased IOP in both groups, inducing retinal blood flow disturbances. Immunofluorescence showed a reduced number of retinal ganglion cells after cauterization, which was alleviated by SSRI treatment. Escitalopram also elevated expression of the brain-derived neurotrophic factor. Electroretinography revealed improved photopic negative response (PhNR) amplitudes in Escitalopram-treated rats, indicating improved retinal ganglion cell function. Following MFA, PhNR remained stable in SSRI-treated animals, whereas a significant impairment was observed in the vehicle-treated group. These findings demonstrate that Escitalopram provides neuroprotection by reducing both functional and structural damage in the retina and may represent a promising therapeutic strategy for retinal neurodegeneration. Full article

The curative management of localized esophageal and esophagogastric junction (EGJ) cancers has undergone major changes over the past decade, shaped by multimodal strategies integrating chemotherapy, chemoradiotherapy, surgery, and more recently, immunotherapy. For esophageal squamous cell carcinoma (SCC), neoadjuvant or definitive chemoradiotherapy remains the standard of care in Western countries. In contrast, for adenocarcinoma (AC) of the esophagus and EGJ, perioperative chemotherapy has emerged as the preferred strategy. Despite these advances, long-term outcomes remain suboptimal, and recurrence continues to pose a major challenge, highlighting the need to optimize patient selection and treatment sequencing. The integration of immunotherapy in the perioperative or adjuvant setting has recently led to improvements in surrogate endpoints yet overall survival benefit remains under investigation. For patients with tumors harboring microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR), checkpoint inhibitors show exceptional activity, and non-operative management may be feasible in select cases. Conversely, human epidermal growth receptor 2 (HER2)-targeted strategies, although effective in metastatic disease, have not yet translated into practice-changing benefit in the curative setting. The role of circulating tumor deoxyribo nucleic acid (DNA) and functional imaging as real-time tools to assess response and guide treatment adaptation is also being actively explored. This review provides a comprehensive overview of current standards, ongoing developments, and future directions for the treatment of localized esophageal and EGJ cancers, with a focus on emerging personalization strategies and biomarker-driven approaches aimed at improving cure rates and minimizing treatment-related morbidity. Full article

Energy efficiency presents significant potential, especially for Western Balkan (WB) countries, if effectively addressed through energy efficiency measures. The building sector, which includes residential, commercial, and public buildings, is the most energy-intensive sector globally. Public buildings in the Western Balkan countries are characterized by poor energy efficiency performance. The average energy consumption in public buildings is anticipated to exceed double the European Union (EU) requirement, given that more than 60-70% of these structures were built over 60 years ago with no regard for energy efficiency. This study assesses the Public Building–Energy Efficiency Readiness Index (PB-EERI) to evaluate how legislative specificity, institutional capacity, financing mechanisms, renovation guidelines, energy market conditions, and societal awareness collectively influence the readiness of Western Balkan economies to enhance energy efficiency in public buildings. The index serves as an operational diagnostic to identify the presence of enabling conditions, determine the most significant gaps, and prioritize policy efforts accordingly. This study presents a novel approach by integrating, within a single transparent index, (i) the existence of energy laws, (ii) market feasibility, (iii) renovation needs of public buildings, and (iv) societal awareness. The awareness pillar is both central and novel. By utilizing harmonized Regional Cooperation Council (RCC) data, this article quantifies societal awareness, thereby ensuring that the index accurately reflects the importance of stakeholder comprehension in the success of renovating initiatives for public buildings. The theoretical framework derives from the application of composite indicators in numerous studies and reports to illustrate the status of energy or energy efficiency. The methodology for developing this indicator is derived from the Organization for Economic Co-operation and Development (OECD) Handbook on Constructing Composite Indicators. For the aggregation method, the summation of weighted and normalized sub-indicators was used. The PB-EERI reveals considerable regional variations, with total scores ranging from around 39 to 72% and concentrating around the mid-0.5s. The findings reveal systematic differences in most indicators’ performance. The legal framework indicator significantly influences variation between countries, together with market conditions and societal awareness. Energy efficiency in public buildings, praised as the “first fuel”, should be prioritized beyond mere compliance with EU regulations. The PB-EERI emphasizes that success relies more on the capacity to transform formal strategies into concrete renovation programs, quantifiable objectives, and higher awareness of society to ensure uptake of the renovation measures. Full article

Centella asiatica, a widely used medicinal herb in Oriental and increasingly Western medicine, is applied for wound healing, dermatological disorders, and gastrointestinal illness. We investigated the effects of fermented C. asiatica extract (FCAE), prepared with Lactobacillus, on airway inflammation in a murine model of chronic obstructive pulmonary disease (COPD) induced by cigarette smoke extract (CSE) and lipopolysaccharide (LPS). CSE/LPS stimulation caused marked immune cell infiltration in airways. FCAE (100 and 200 mg/kg) reduced neutrophils in the bronchoalveolar lavage fluid (BALF) by 26.03% and 70.11%, respectively, and decreased activated T cells and B cells in the lung, mediastinal lymph nodes, and Peyer’s patches, while inhibiting collagen fibrosis. FCAE significantly reduced IL-1α (32.51%), CXCL1 (47.63%), CXCL2 (45.37%), and TNF-α (39.51%) levels in the BALF compared with the control group. It also downregulated the expression of muc5ac (58.39%), CXCL1 (67.32%), CXCL2 (57.60%), and TNF-α (54.61%) and suppressed p-STAT3 activation by 50.22%. Furthermore, FCAE enhanced tracheal phenol red secretion by 229.62%, indicating expectorant activity. UPLC analysis identified nine components, which, together with FCAE, inhibited RANTES, TNF-α, and IL-6 in inflammation-induced BEAS-2B cells. Overall, FCAE attenuates immune activation and airway inflammation, supporting its potential as a candidate therapy or functional food for respiratory diseases. Full article