Search Results (33,944)

Background: To investigate the effect of angiotensin-(1-7) [Ang-(1-7)] on serum metabolomics in obese type 2 diabetic (T2DM) mice. Methods: Four-week-old male C57BL/6 mice were fed a high-fat diet and intraperitoneally injected with streptozotocin (35 mg/kg) to establish an obese T2DM model. Mice were randomized into control, T2DM and T2DM+Ang-(1-7) groups (n = 6). Body weight and blood glucose were recorded weekly. At 10 weeks, blood glucose, serum inflammatory factors, lipid profiles, and pancreatic β-cell insulin secretion were detected; serum metabolite alterations were analyzed via untargeted metabolomics. Results: 1. Ang-(1-7) intervention decreased blood glucose (p < 0.05) and CRP levels (p < 0.01), and alleviated dyslipidemia (p < 0.05 or p < 0.01), as well as β-cell morphology and insulin expression in obese T2DM mice. 2. Non-targeted metabolomics analysis suggested that Ang-(1-7) may alleviate abnormal amino acid metabolic pathways by regulating levels of metabolites such as L-valine, L-proline, L-histidine, and glutamic acid. This intervention also tended to reduce multiple lipid metabolites, including Omega-3 Arachidonic Acid Ethyl Ester, phosphatidylcholine, and glycerophosphocholine, thereby participating in the modulation of lipid metabolism balance. KEGG enrichment analysis further indicated that Ang-(1-7) was involved in the regulation of protein digestion and the absorption pathway, as well as the HIF-1 signaling pathway related to oxidative stress, bile acid metabolism pathway, and other signaling pathways, and improving the insulin secretion pathway, pyrimidine metabolism, and TCA cycle energy metabolism pathway. Conclusions: Ang-(1-7) may partially improve metabolic disturbances in obese T2DM mice, which is potentially associated with the modulation of multiple metabolic processes, including amino acid metabolism, lipid metabolism, insulin secretion, and TCA cycle energy metabolism. Full article

The construction of green mines is a core strategy for promoting ecological civilization in China’s mining sector, yet its long-term ecological effects require quantitative assessment. Using a cement-grade limestone mine operated by Linyi Zhonglian Cement Co., Ltd. in Shandong Province as an illustrative case, we employed Landsat 8 OLI/TIRS imagery acquired in 2015, 2020, and 2025 to develop a five-indicator framework for assessing ecological environment quality. The selected indicators comprised greenness (NDVI), wetness, dryness (NDBSI), land surface temperature (LST), and dust concentration (MECDI). These five indicators were subsequently integrated via principal component analysis to generate the Mine Ecological Quality Index (Mine-EQI). Using this index, we applied the Theil–Sen median slope estimator alongside zonal statistics to examine ecological change trajectories across the full study area and three functional zones—the industrial square, haul roads, and active mining area—over the 2015–2025 period. The ecological outcomes attributable to the green mine policy were then quantified. The results show that (1) the mean Mine-EQI of the study area decreased from 0.3713 in 2015 to 0.3460 in 2025, exhibiting a slight overall decline. However, the rate of decline decreased from −6.1% during 2015–2020 to −0.7% during 2020–2025, yielding a Temporal Change Intensity index (TCI) of +88.5%, indicating that the ecological degradation trend has been effectively curbed. (2) Significant spatial heterogeneity was observed. The industrial square showed substantial improvement (Theil–Sen slope = +0.0726), while the haul roads (slope = −0.0705) and mining area (slope = −0.0408) continued to exhibit degradation trends. The improved areas (9.7% of the study area) were spatially coincident with green mine engineering projects. (3) The dust indicator (MECDI) decreased by 24.7% during 2020–2025, and the vegetation index (NDVI) increased by 19.5% over the decade, representing the dominant contributors to ecological improvement. This study reveals that China’s green mine policy has yielded remarkable ecological improvements in relatively stable functional zones such as industrial squares. In contrast, ecological restoration within persistently disturbed areas, including haul roads and mining pits, demands long-term sustained investment and governance. By integrating remote sensing techniques with policy analysis, this research establishes a replicable framework for evaluating progress toward sustainable mining practices. The findings directly support the monitoring of SDG 12 (Responsible Consumption and Production) and SDG 15 (Life on Land), providing a quantitative pathway to balance mineral resource extraction with ecological protection—a core sustainability challenge for resource-dependent regions. Full article

Ophicarbonates provide an important natural record of mineral carbonation during serpentinization of ultramafic rocks and therefore offer insight into the mechanisms and limits of CO₂ fixation in low-temperature geological environments. This paper presents a synthesis and process-oriented reinterpretation of stable-isotope published and previously unpublished data, petrographic, and mineralogical evidence for carbonate formation under fluid-limited serpentinization conditions. Using mineralogical constraints together with a compiled δ¹³C–δ¹⁸O dataset that includes legacy measurements from the 1980s–1990s, we evaluate how multi-stage carbonate precipitation reflects evolving water–rock ratio, redox state, transport limitation, and deformation-controlled permeability. Particular attention is given to systematic differences between vein-hosted carbonates and dispersed intergranular or scattered-grain ophicarbonates, as these textural–isotopic relationships help identify fluid flux, carbon source, and reaction progress in ultramafic systems. The analysis shows that carbonation does not proceed uniformly but is restricted to overlapping reactive windows controlled by fluid availability, nucleation kinetics, and permeability evolution. These constraints help explain why carbonation may either intensify or stall during progressive serpentinization. The Author further discuss why kinetic barriers and Mg–Ca partitioning may redirect carbonate mineralogy toward calcite or metastable Mg-rich phases even where dolomite or magnesite may be thermodynamically favored. The results highlight the importance of coupling isotopic signatures with petrographic context in reconstructing carbonation pathways and provide a broader framework for understanding natural mineral sequestration of carbon in heterogeneous serpentinite systems. Full article

The rapid expansion of e-commerce has transformed market access in developing economies, yet its impact on the spatial structure of market participation remains insufficiently understood. While existing studies primarily examine welfare outcomes such as income growth and consumption smoothing, few investigate how digital platforms reshape the balance of market entry between urban and rural areas. Drawing on New Economic Geography and platform economics theory, this study proposes that e-commerce development rebalances urban–rural market vitality through three associative pathways: alleviating rural capital constraints, improving rural innovation environments, and promoting agricultural-industry agglomeration. Using county-level panel data covering 2725 Chinese counties from 2011 to 2022, we employ a Double Machine Learning (DML) framework to examine the association between designation as an “E-commerce into Rural Comprehensive Demonstration County” and changes in the urban–rural market vitality balance (URMAR). The results indicate that demonstration county designation is associated with a statistically significant reduction in urban–rural market disparity, as measured by both the Theil index and the absolute difference in new enterprise registrations. The directional URMAR indicator further reveals that this convergence is driven primarily by accelerated rural enterprise formation. Subsample analysis confirms that the rebalancing interpretation holds across counties with different baseline market structures. Mechanism analysis provides suggestive evidence consistent with all three proposed associative pathways. Heterogeneity analysis further reveals that these effects are stronger in economically developed eastern regions, in counties linked to higher-tier cities, and in secondary and tertiary industries. These findings advance a market-structure perspective on digital development that complements existing welfare-based approaches and offer policy insights for fostering balanced regional development through targeted digital and complementary investments. Full article

Tumor cell heterogeneity and multicellular interactions critically influence drug resistance, recurrence, and prognosis. Here, CPcellsubpopulation, a computational framework integrating scRNA-seq, bulk RNA-seq, and clinical data was developed to identify cancer progression-associated cell subpopulations. Then, the integrated analyses of scRNA-seq and spatial transcriptomics were performed to predict potential interactions, identify critical transcription factors, and predict candidate anticancer drugs. Across nine cancers, we detected cancer progression-associated cell subpopulations significantly linked to prognosis, with consistent patterns across cancer types. In renal cell carcinoma (RCC), we identified conserved metabolic^high UBE2C+ cancer cells linked to poor outcomes, metabolic reprogramming and low differentiation, and PLK1+ NK cells, plasma cells, and CDC20+ macrophages associated with advanced stages and unfavorable prognosis. Spatial mapping revealed spatial association of RCC progression-associated cancer and immune cell subpopulations, suggesting the potential role of the VEGF, GDF, PTN and IL16 pathways in the remodeling of the tumor microenvironment. Gene regulatory network analysis highlighted RAD21 as a key regulator linking metabolism and therapy resistance. This study provides a systematic pipeline to delineate cancer progression-associated cell subpopulations, uncovers metabolic^high UBE2C+ cancer cells as progression-associated tumor cell population, and nominates critical regulators and compounds as therapeutic targets. Full article

The genus Bacillus is widely recognized for its metabolic versatility, enabling it to colonize extreme environments, including sites contaminated with metals. In this study, we report the genome of B. velezensis strain HM1, isolated from sulfur-rich mine tailings from silver mining activities in southwestern Mexico. Isolation was performed by heat treatment followed by selective cultivation in a medium enriched with mine tailings extract (metals and sulfates), resulting in a single dominant morphotype corresponding to strain HM1. Whole-genome sequencing was carried out using the Illumina NovaSeq platform (2 × 250 bp). The assembled genome of strain HM1 has a size of 4,044,128 bp, distributed across 20 contigs, with an N50 of 700,388 bp and an L50 of 3, and an average coverage of 66.8×. The GC content was 46.31%, with an estimated completeness of 99.81% and contamination of 0.01%. Genome analyses indicate that the assembly corresponds to a single chromosome, with no evidence of plasmid replicons. Genome annotation identified 3950 coding sequences (CDSs), 83 tRNAs, 11 rRNAs, 26 ncRNAs, and 4 sORFs. Phylogenomic analysis, together with genomic similarity metrics (ANI > 98.6%, AAI > 98.8%, dDDH > 87%), confirms its classification as Bacillus velezensis. Functionally, the genome encodes multiple genes involved in resistance to metals and metalloids (including ABC transporters, efflux pumps, and biotransformation enzymes), as well as a complete pathway for sulfate assimilation. Collectively, these genomic features reveal a broad repertoire of adaptive strategies employed by strain HM1 to thrive in metal-contaminated environments. Full article

For more than seventy years, mathematics—particularly the calculus sequence—has defined both the rigor and the exclusivity of engineering education in the United States. While this structure was historically instrumental in professionalizing engineering, it has also produced unintended consequences: restricted access, misalignment with contemporary engineering practice, and persistent inequities in participation and degree attainment. This commentary argues that mathematics must be reimagined not as a barrier or filter, but as a gateway that enables engineering learning, persistence, and innovation. Building on The Engineering Mindset Report and decades of research in engineering education, learning sciences, and curricular reform, we examine how mathematics became a gatekeeping mechanism, assess its current impacts, and propose a framework for redesigning engineering mathematics around context, modularity, technology, and equity. We advocate for accessible, flexible, and technology-enabled pathways that emphasize modeling, data analysis, and conceptual understanding over procedural endurance. Such an approach has the potential to broaden participation, improve student success, and better align engineering education with the realities of 21st-century professional practice. Full article

Against the global backdrop of carbon neutrality and the green transition of the construction sector, modern timber-framed buildings have emerged as a core enabler of sustainable construction. However, a systematic synthesis of research on indoor hygrothermal environments and thermal comfort in such buildings remains lacking, and the underlying coupling mechanisms—as well as pathways for performance optimization—are still insufficiently understood. To address these gaps, this study aims to systematically characterize and evaluate the performance features of indoor thermal and moisture environments in modern timber buildings, and to identify the key influencing factors and their underlying mechanisms. In accordance with the PRISMA 2020 guidelines for systematic reviews, this study identified and analyzed 203 high-quality peer-reviewed publications retrieved from three major academic databases, covering the period 2010–2025. Specifically, the literature search was conducted across the Web of Science, Scopus, and the China National Knowledge Infrastructure (CNKI), and visualization analysis was performed using VOSviewer 1.6.20 software. The results indicate that timber-framed buildings exhibit distinctive indoor hygrothermal characteristics: rapid temperature response, strong humidity buffering capacity, and superior thermal insulation performance compared with concrete structures, enabling indoor relative humidity to remain stably within the thermally comfortable range. Nevertheless, challenges persist, including summer overheating and elevated risks of mold growth under hot-humid conditions. Furthermore, the PMV model demonstrates significant predictive deviation for thermal comfort in timber-framed buildings; its application thus requires calibration incorporating both the hygrothermal properties of timber materials and occupants’ psychological adaptation. This study synthesizes the current state of research, identifies key influencing factors, and proposes climate-responsive optimization strategies to advance the development of robust thermal comfort models and support the low-energy, high-comfort design of timber-framed buildings. Full article

Ascosphaera apis, an obligate lethal fungal pathogen that infects bee larvae, and causes chalkbrood disease, poses a significant threat to the global beekeeping industry. Long non-coding RNAs (lncRNAs) are employed by pathogens to enhance infectivity and evade host immunity. Here, lncRNAs in A. apis spores (AaCK group) and the guts of 4-, 5-, and 6-day-old Apis cerana cerana worker larvae inoculated with A. apis spores (AaT1, AaT2, and AaT3 groups) were identified, characterized, and validated. Additionally, the expression pattern of fungal lncRNAs during infection was analyzed, followed by an investigation of the regulatory manners and roles of differentially expressed lncRNAs (DElncRNAs). A total of 1379 lncRNAs were identified in AaCK, AaT1, AaT2, and AaT3 groups using bioinformatics, involving various types such as sense lncRNAs, antisense lncRNAs, bidirectional lncRNAs, intergenic lncRNAs, and intronic lncRNAs. Additionally, 4, 9, and 75 up-regulated lncRNAs as well as 2, 1, and 15 down-regulated ones were identified in the 4-, 5-, and 6-day-old larval guts following A. apis inoculation. Fifteen DElncRNAs as potential antisense lncRNAs may interact with 15 sense-strand mRNAs in the AaCK vs. AaT3 comparison group. Cis-acting analysis identified 10, 16, and 136 upstream and downstream genes of DElncRNAs in the aforementioned comparison groups, involving a series of GO terms and KEGG pathways like metabolic process and biosynthesis of secondary metabolites. Following the trans-acting investigation, 752, 821, and 1327 co-transcribed genes with DElncRNAs were discovered, spanning an array of functional terms and pathways such as biological processes and glycerophospholipid metabolism. Analysis of a competing endogenous RNA (ceRNA) network indicated that 1 and 5 DElncRNAs in the AaCK vs. AaT1 and AaCK vs. AaT3 comparison groups potentially targeted 1 and 2 miRNAs, further targeting 208 and 286 mRNAs, respectively. Further analysis identified one ceRNA axis relevant to the MAPK signaling pathway and several ceRNA networks associated with the biosynthesis of secondary metabolites. Finally, RT-qPCR results confirmed that the expression trends of six randomly selected DElncRNAs were consistent with those in the transcriptome data. These findings not only offer a foundation for elucidating the mechanisms underlying DElncRNA-mediated A. apis infection but also enrich our understanding of honeybee host–fungal pathogen interactions. Full article

Sustainable production in dental and orthodontic 3D printing has gained increasing attention due to environmental concerns and the need for cost-effective and resource-saving solutions. This study presents a proof of concept for using recycled polymers and fused granular fabrication (FGF) in a closed-loop 3D printing approach, omitting intermediate filament manufacturing. A desktop 3D printer served as the kinematic platform and was modified with a pellet-based extruder to directly process recycled polyethylene terephthalate glycol (PETG) flakes, obtained by shredding previously printed PETG parts, into dental models. Dimensional accuracy was evaluated using optical 3D scanning analysis. The results indicate that models produced from recycled PETG are, in principle, suitable for dental and orthodontic applications within the investigated scope. This technical note provides initial evidence supporting the integration of recycled thermoplastics into dental and orthodontic model fabrication as part of sustainable additive manufacturing workflows. Potential pathways for workflow integration in clinical and laboratory environments, as well as directions for future research, are outlined, including the optimization of printing parameters and process stability. The main technical challenges were unreliable feedstock flow, causing bridging and jamming, while thermal creep from insufficient inlet cooling promoted premature softening of the flakes, causing torque spikes and unstable feeding. Full article

The multidirectional bioactivity of betulin (BN), its widespread occurrence in plants, relatively low toxicity, and acceptable safety profile make it an attractive scaffold for scientific research and potential therapeutic applications. Due to the presence of reactive functional groups (C-3-OH and C-28-OH), BN is an interesting source of new semisynthetic bioactive compounds obtained via structural modifications of the parent backbone. In our study, we designed new BN–amino acid (BNAA) molecular hybrids, aiming to exploit synergistically the properties of both components. We prepared and evaluated a total of 18 new compounds for antitumor activity against the two human cancer cell lines (HCT 116 and MCF-7) and one non-cancerous cell line (NHDF) using a standard Cell Counting Kit-8 (CCK-8) assay. The potential signaling pathways of the obtained BN derivatives were identified based on the measurement of p21 and Bax mRNA expression levels using the RT-qPCR method. We successfully synthesized a series of new BN hybrids by conjugation of the C-3 and C-28 hydroxyl groups via a succinyl (-CO-CH₂-CH₂-CO-, Suc) linker with selected amino acid methyl esters. The structures of all obtained BNAA molecular hybrids were confirmed by spectroscopic analysis (¹H and ¹³C NMR) and high-resolution mass spectrometry (HR-MS). Analysis of the biological activity of the obtained BN derivatives indicated that both the attached amino acids and the substituents at C3 carbon alter BN activity. The obtained BN–amino acid hybrids represent a useful platform for further optimization, especially derivatives (3a, 3e, 3f, and 7d), which showed the most relevant biological profiles in this study. Full article

China’s steel decarbonization is a key sustainability challenge because cleaner production routes must be evaluated not only by their mitigation potential, but also by their implications for industrial continuity, cost affordability, resource security, and transition manageability. This study develops a national-scale soft-linked sustainability assessment framework that translates policy-conditioned macro signals into a multi-period, multi-objective optimization model of steelmaking-route transition from 2025 to 2050. Three policy environments are examined: carbon-control pressure, electricity-cost support for electrified routes, and their combined application. The model evaluates route portfolios by cumulative system cost, emissions, and transition adjustment intensity, linking mitigation with affordability and implementation feasibility. Results show that policy environments do not shift pathways uniformly; instead, they reshape the feasible trade-off frontier and alter which route combinations emerge as plausible compromise solutions. Across scenarios, scrap-based electric arc furnace steelmaking (Scrap-EAF) becomes the central medium-term route, while blast furnace–basic oxygen furnace steelmaking (BF-BOF) contracts but remains residual. Hydrogen-based direct reduced iron–electric arc furnace steelmaking (H₂-DRI-EAF) expands under favorable conditions, but does not become dominant by 2050 under the baseline national-scale parameterization. Overall, this study contributes to sustainability-oriented industrial transition analysis by showing how policy-conditioned environments reshape route feasibility, transition sequencing, affordability–mitigation trade-offs, and the practical manageability of China’s steel-sector decarbonization. Full article

Background/Objectives: Liuwei Dihuang (LWDH) is a classical plant-derived herbal formula widely used for cognitive decline. This study aimed to evaluate its efficacy and safety in cognitive disorders and to explore its potential pharmacological mechanisms using network pharmacology. Methods: We searched 11 databases through November 2024 for randomized controlled trials comparing LWDH plus conventional therapy with conventional therapy alone in cognitive disorders. Meta-analysis was performed for clinical outcomes, and herb–compound–target and disease-target datasets were integrated to identify core molecular modules. Results: Twelve randomized controlled trials involving 1137 participants were included. Adjunctive LWDH was associated with improvements in Mini-Mental State Examination scores (MD = 2.34, 95% CI 0.88–3.79), activities of daily living, and quality of life. However, substantial heterogeneity and methodological limitations, including unclear randomization and blinding, were observed across studies, indicating a potential risk of bias. Fewer adverse events were reported in the LWDH plus conventional treatment group, although reporting quality was limited. The overall risk of bias was judged as “some concerns”. Network pharmacology analysis identified a broad set of overlapping genes between LWDH-associated targets and cognitive disorder-related genes, which were further refined through filtering procedures. Subsequent analyses suggested associations with pathways related to neurodegeneration, apoptosis, and central nervous system function; however, these findings are exploratory and based on in silico predictions. Conclusions: LWDH may be associated with potential adjunctive benefits in cognitive disorders. However, given the methodological limitations and clinical heterogeneity of the included studies, the findings should be interpreted with caution. The proposed pharmacological mechanisms are exploratory and require further validation. Well-designed randomized controlled trials are needed to establish more robust evidence. Full article

Osteoporosis in women is strongly influenced by menopause, a major physiological transition that reshapes bone metabolism. Although low bone mineral density (BMD) in premenopausal women and osteoporosis in postmenopausal women share the clinical outcome of skeletal fragility, it remains unclear whether they reflect a shared molecular program or distinct regulatory mechanisms. Here, we compared genetic signals associated with premenopausal and postmenopausal low BMD in Korean women using two independent genotyping platforms with distinct variant coverage. After allele harmonization and heterogeneity testing, variants were classified as reversal signals, showing directionally discordant effects across menopausal status, or stable signals, showing concordant effects. Gene-level association analysis was performed using Multi-marker Analysis of GenoMic Annotation (MAGMA), followed by functional enrichment and network-based analyses. Reversal and stable signals showed distinct biological patterns. Reversal signals consistently converged on cyclic nucleotide-related pathways, including cyclic adenosine monophosphate/cyclic guanosine monophosphate (cAMP/cGMP) signaling and nitric oxide-mediated processes, whereas stable signals were more broadly distributed across pathways related to ion homeostasis, cell–substrate adhesion, and structural maintenance. These pathway-level patterns were reproducible across platforms despite limited SNP-level overlap. These findings suggest that low BMD across the menopausal transition is better resolved at the gene and pathway levels than at the level of individual SNPs. Full article

Ultraviolet radiation (UVR) exposure accelerates skin aging by disrupting cellular homeostasis and inducing epigenetic changes, such as promoter hypermethylation of key regulatory genes. However, the molecular mechanisms underlying UVR-driven epigenetic silencing remain poorly understood. By integrating high-throughput DNA methylation profiling with co-regulatory network analysis, we identified KIT as a hub gene in a photoaging-associated methylation module. Pathway enrichment further revealed coordinated hypermethylation of the canonical Wnt/β-catenin signaling pathway, establishing the Wnt/KIT axis as a critical epigenetic-signaling nexus in UVR-induced skin fibroblast aging. In immortalized human skin fibroblasts (HSFs), UVR suppressed Wnt signaling, leading to KIT promoter hypermethylation, transcriptional silencing, and premature photoaging. Gain-of-function studies revealed that reversing KIT hypermethylation either via Wnt pathway activation or KIT overexpression effectively mitigated photoaging-associated phenotypes. Crucially, we found that puerarin (PUE), a natural isoflavone, reversed UVR-induced epigenetic silencing by directly interacting with β-catenin, reactivating Wnt signaling, and restoring KIT expression. PUE treatment preserved cellular function in UVR-damaged fibroblasts. These findings establish the Wnt/β-catenin-KIT axis as a critical epigenetic driver of skin aging and highlight puerarin as a promising therapeutic candidate for targeted anti-aging intervention. Full article