Search Results (4,833)

Early life is a critical window for immune system development, during which the gut microbiome shapes innate immunity, antigen presentation, and adaptive immune maturation. Disruptions in microbial colonization—driven by factors such as cesarean delivery, antibiotic exposure, and formula feeding—deplete beneficial early-life taxa (e.g., Bifidobacterium, Bacteroides, and Enterococcus) and impair key microbial functions, including short-chain fatty acid (SCFA) production by these keystone species, alongside regulatory T cell induction. These dysbiosis patterns are associated with an increased risk of pediatric autoimmune diseases, notably type 1 diabetes, inflammatory bowel disease, celiac disease, and juvenile idiopathic arthritis. This review synthesizes current evidence on how the early-life microbiota influences immune maturation, with potential effects on the development of autoimmune diseases later in life. We specifically focus on human observational and intervention studies, where treatments with probiotics, synbiotics, vaginal microbial transfer, or maternal fecal microbiota transplantations have been shown to partially restore a disrupted microbiome. While restoration of the gut microbiome composition and function is the main reported outcome of these studies, to date, no reports have disclosed direct prevention of autoimmune disease development by targeting the early-life gut microbiome. In this regard, a better understanding of the early-life microbiome–immune axis is essential for developing targeted preventive strategies. Future research must prioritize longitudinal evaluation of autoimmune outcomes after microbiome modulation to reduce the burden of chronic immune-mediated diseases. Full article

The Wufeng–Longmaxi (WF–LMX) shale gas reservoirs at depths > 3500 m in the Lu203–Yang101 well block, southern Sichuan Basin, possess great exploration potential, but their reservoir characteristics and high-production mechanisms remain unclear. In this study, we employed multi-scale analyses—including core geochemistry, X-ray diffraction (XRD), scanning electron microscopy (SEM), low-pressure N₂ adsorption, and nuclear magnetic resonance (NMR)—to characterize the macro- and micro-scale characteristics of these deep shales. By comparing with shallower shales in adjacent areas, we investigated differences in pore structure between deep and shallow shales and the main controlling factors for high gas-well productivity. The results show that the Long 11 sub-member shales are rich in organic matter, with total organic carbon (TOC) content decreasing upward. The mineral composition is dominated by quartz (averaging ~51%), which slightly decreases upward, while clay content increases upward. Porosity ranges from 1% to 7%; the Long11-1-3 sublayers average 4–6%, locally >6%. Gas content correlates closely with TOC and porosity, highest in the Long11-1 sublayer (6–10 m³/t) and decreasing upward, and the central part of the study area has higher gas content than adjacent areas. The micro-pore structure exhibits pronounced stratigraphic differences: the WF Formation top and Long11-1 and Long11-3 sublayers are dominated by connected round or bubble-like organic pores (50–100 nm), whereas the Long11-2 and Long11-4 sublayers contain mainly smaller isolated organic pores (5–50 nm). Compared to shallow shales nearby, the deep shales have a slightly lower proportion of organic pores, smaller pore sizes with more isolated pores, inorganic pores of mainly intraparticle types, and more developed microfractures, confirming that greater burial depth leads to a more complex pore structure. Type I high-quality reservoirs are primarily distributed from the top of the WF Formation to the Long11-3 sublayer, with a thickness of 15.6–38.5 m and a continuous thickness of 13–23 m. The Lu206–Yang101 area has the thickest high-quality reservoir, with a cumulative thickness of Type I + II exceeding 60 m. Shale gas-well high productivity is jointly controlled by multiple factors: an oxygen-depleted, stagnant deep-shelf environment, with deposited organic-rich, biogenic siliceous shales providing the material basis for high yields; abnormally high pore-fluid pressure with preserved abundant large organic pores and increased free gas content; and effective multi-stage massive fracturing connecting a greater reservoir volume, which is the key to achieving high gas-well production. This study provides a scientific basis for evaluating deep marine shale gas reservoirs in southern Sichuan and understanding the enrichment patterns for high productivity. Full article

Recovery of the stratospheric ozone layer following the ban on ozone-depleting substances represents one of the most successful examples of international environmental policy. However, the long-term fate of ozone under continuing climate change remains uncertain. We present the first multi-century projections of ozone evolution to 2200 using emission-driven CMIP7 scenarios in the SOCOL-MPIOM chemistry-climate model. Our results show that despite the elimination of halogenated compounds, total column ozone exhibits non-monotonic evolution, with an initial increase of 8–12% by 2080–2100, followed by a decline to 2200, remaining 4.5–7% above the 2020 baseline. Stratospheric ozone at 50 hPa shows a monotonic decline of 2–11% by 2200 across all scenarios, with no recovery despite ongoing Montreal Protocol implementation. Critically, even in the high-overshoot scenario where CO₂ concentrations decline from 830 to 350 ppm between 2100 and 2200, stratospheric ozone continues to decrease. Intensification of the Brewer-Dobson circulation in warmer climates reduces ozone residence time in the tropical stratosphere, decreasing photochemical production efficiency. This dynamic effect outweighs the reduction in ozone-depleting substances, leading to persistent stratospheric ozone depletion despite total column ozone enhancements in polar regions. Spatial analysis reveals pronounced regional differentiation: Antarctic regions show sustained total column enhancement of +18–26% by 2190–2200, while tropical regions decline to levels below baseline (−4 to −5%). Our results reveal fundamental asymmetry between climate forcing and ozone response, with characteristic adjustment timescales of 100–200 years, and have critical implications for long-term atmospheric protection policy. Full article

Background: Recombinant human arginase (rhArg) has been proven to exhibit an anticancer effect via arginine starvation. To further improve the efficacy of rhArg, we examined the feasibility of a combination strategy with Bcl-2 inhibitors (ABT263 and ABT199) or an antidiabetic drug (metformin) and investigated the mechanistic basis for these strategies. Methods: The combination effects were evaluated in a panel of human cancer cell lines modeling pancreatic ductal carcinoma (PDAC), triple-negative breast cancer (TNBC), colorectal cancer (CRC) and glioblastoma (GBM). Western blot analysis was used to evaluate the expression of apoptotic and cell cycle markers. MTT assay was used to evaluate the combination efficacy. Flow cytometric assays were used to investigate the apoptotic and cell cycle effects. Results: The combination of rhArg with sublethal doses of ABT263 significantly induced dose-dependent apoptosis, with elevated expression of apoptotic markers and a CI of 0.47 in U251. The combination inhibited CDK2 and cyclin A expression, indicating that the observed synergy also resulted from cell cycle arrest. We also found that rhArg + metformin was synergistic in a time-dependent manner. Compared to other amino acid depletion agents, rhArg + ABT263 was the most favorable combination pair. Conclusions: The combination of rhArg and ABT263 enhanced apoptosis and cell cycle arrest, demonstrating a potential broad-spectrum antitumor strategy. Full article

Fermented forest litter (FFL) is a biofertilizer obtained by anaerobic fermentation of forest litter combined with agricultural by-products. Its production involves an initial one-month solid-state fermentation of oak litter mixed with whey, molasses and wheat bran, followed by a one-week submerged fermentation-called the “activation” phase-during which the solid FFL is fermented with sugarcane molasses diluted in water. This study aimed to evaluate the effects storage duration (6, 18 and 30 months), and temperature (ambient and 29 °C) on the activation phase. For this purpose, pH, sugar consumption and metabolite production dynamics were monitored. Under all experimental conditions, the pH dropped to values close to 3.5, sucrose was rapidly hydrolyzed, and glucose was preferentially consumed over fructose. Fructose was metabolized only after glucose was depleted, suggesting the involvement of fructophilic microorganisms. The time-course evolution of lactic acid (LA) concentration was adequately fitted by the Gompertz model (R² > 0.970). The highest LA_max concentration (6.30 g/L) and production rate (2.16 g/L·d) were obtained with FFL stored for 6 months. Acetic acid (AA) and ethanol were also detected reaching maxima values of 1.19 g/L and 0.96 g/L, respectively. Their profiles varied depending on the experimental conditions. Notably, the AA/LA ratio increased with the age of the FFL. Overall, sugar consumption and metabolite production were significantly slower at ambient temperature, than at 29 °C. These results contribute to a better understanding of the metabolic dynamics during FFL activation and highlight key parameters that should be considered to optimize future biofertilizer production processes. Full article

Urban Water Systems (UWS) are complex infrastructures that interact with energy, food, ecosystems and socio-political systems, and are under growing pressure from climate change and resource depletion. Planning circular interventions in this context requires system-level analysis to avoid fragmented, siloed decisions. This paper develops the Hydrosocial Resource Urban Nexus (HRUN) framework that integrates hydrosocial thinking with the Water–Energy–Food–Ecosystems (WEFE) nexus to guide UWS design. We conduct a structured literature review and analyse different configurations of circular interventions, mapping their synergies and trade-offs across socioeconomic and environmental functions of hydrosocial systems. The framework is operationalised through a typology of circular interventions based on their circularity purpose (water reuse, resource recovery and reuse, or water-cycle restoration) and management scale (from on-site to centralised), while greening degree (from grey to green infrastructure) and digitalisation (integration of sensors and control systems) are treated as transversal strategies that shape their operational profile. Building on this typology, we construct cause–effect matrices for each intervention type, linking recurring operational patterns to hydrosocial functionalities and revealing associated synergies and trade-offs. Overall, the study advances understanding of how circular interventions with different configurations can strengthen or weaken system resilience and sustainability outcomes. The framework provides a basis for integrated planning and for quantitative and participatory tools that can assess trade-offs and governance effects of different circular design choices, thereby supporting the transition to more resilient and just water systems. Full article

With the rapid depletion of natural graphite, the synthesis of artificial graphite from high-carbon precursors has garnered growing interest. However, conventional artificial graphitization typically requires extremely high temperatures. This study demonstrates that natural halloysite mineral can serve as an effective catalyst to lower the graphitization temperature threshold of anthracite. The results show that halloysite exerts a pronounced catalytic effect within the temperature range of 1400–2300 °C. The enhancement in graphitization is primarily attributed to the formation and subsequent decomposition of intermediate phases between halloysite and the carbon matrix. From 1400 to 1700 °C, the interlayer spacing decreases significantly with halloysite as a catalyst due to the nucleation of highly ordered “multilayer graphene” structures surrounding intermediates. However, these graphene layers exhibit a confined and curved morphology that spatially restricts crystallite growth, resulting in relatively small in-plane (L_a) and stacking (L_c) crystallite dimensions. Moreover, multilayer graphene originating from intermediate crystal corners tends to generate numerous dislocation defects. From 1700 to 2300 °C, significant increases in both L_a and L_c are observed, accompanied by a marked improvement in structural order. This evolution is driven by the progressive inward decomposition of intermediate phases, which causes the “circular-shaped” graphene domains to collapse at the dislocation defects and subsequent straightening of the curved graphene layers. These findings provide new microstructural insights into mineral-catalyzed graphitization mechanisms in anthracite and present a promising pathway toward energy-efficient production of synthetic graphite. Full article

With the continuous increase in well depth and the gradual depletion of formation energy, the pump-setting depths in rod-pumped wells have increased significantly, leading to higher suspension loads at the pumping unit. The application of glass fiber-reinforced plastic (FRP) sucker rods can effectively reduce suspension loads due to their low density and high tensile strength. However, the mechanical performance of FRP rods is highly sensitive to temperature, which poses challenges for their application in deep and high-temperature wells. In FRP–steel hybrid sucker-rod string design, the influence of temperature—particularly on FRP rods—must therefore be carefully considered to prevent failures such as rod parting or coupling separation. This study systematically investigates the effects of temperature on the mechanical properties of FRP sucker rods, including elastic modulus, flexural shear strength, and tensile strength. Based on the operating characteristics of sucker-rod pumping systems and established design criteria, a temperature-aware design methodology for FRP–steel hybrid rod strings is developed and implemented in dedicated design software. The proposed approach enables rational determination of the FRP–steel partition depth under thermal constraints while satisfying mechanical safety requirements. A field case study is conducted to validate the design results, demonstrating that the software provides reliable and practical guidance for hybrid rod-string design in deep wells. Full article

Plastic pollution is a major global challenge, especially nanoplastics (NPs) emerging as harmful pollutants due to their small size, reactivity, and persistence in ecosystems. Among them, cigarette butts composed of cellulose acetate (CA) are one of the most widespread and hazardous sources of terrestrial NPs. In this study, the immunotoxic, biochemical, and histopathological effects of cellulose acetate nanoplastics (CA-NPs) derived from smoked cigarette butts (SCB-NPs), unsmoked cigarette butts (USCB-NPs), and commercial cellulose acetate (CCA-NPs) were evaluated on the earthworm Allolobophora caliginosa. Adult worms were exposed for 30 days to 100 mg/kg CA-NPs in artificial soil under controlled laboratory conditions. Results revealed that SCB-NPs induced the most pronounced alterations, including increased lysozyme and metallothionein levels, reduced phagocytic and peroxidase activities, and depletion of protein and carbohydrate reserves. Histological examination showed vacuoles in epithelial layer vacuolization, space between muscle fiber disruption, and degeneration in gut and body wall, especially under SCB-NP exposure. USCB-NPs and CCA-NPs caused milder but still significant effects. Taken together, these findings highlight that the high toxicity of SCB-NPs is due to the presence of combustion-derived toxicants (nicotine, polycyclic aromatic hydrocarbons, and heavy metals), which exacerbate oxidative stress, immune suppression, and tissue damage in soil invertebrates. This study underscores the ecological risk of cigarette butt-derived NPs and calls for urgent policy measures to mitigate their terrestrial impacts. Full article

This review synthesizes the literature on the degradation and decomposition of holopelagic Sargassum, with a focus on process dynamics, including microbial contribution, process descriptions, and ecological impacts. Our objective is to consolidate a robust knowledge framework to inform and optimize management strategies in affected areas. Overall, we observed that the current literature relies primarily on isolated field ecological descriptions rather than a coherent, unified research line; mechanistic studies, including bacterial pathways and factors controlling degradation, remain scarce. At the fine scale, microbial community shifts during decomposition are strongly linked to the sequential utilization of distinct organic substrates, thereby favoring the proliferation of microorganisms capable of degrading complex organic molecules and of bacterial groups involved in sulfur respiration, methanogenesis, and nutrient recycling. In the case of sulfur respiration, groups such as Desulfobacterales and Desulfovibrionales may be responsible for the reported H₂S emissions, which pose significant public health concerns. At a broad scale, degradation occurs both on beaches during emersion and in the water column during immersion, particularly during massive accumulations. The initial stages are characterized by the release of organic exudates and leachates. Experimental and observational studies confirm a strong early-stage release of H₂S until the substrate is largely depleted. Depending on environmental conditions, a significant amount of biomass can be lost; however, this loss is highly variable, with notable consequences for contamination studies. Leachates may also contain low but ecologically significant amounts of arsenic, posing a potential contamination risk. Decomposition contributes to water-quality deterioration and oxygen depletion, with impacts at the individual, population, and ecosystem levels, yet many remain imprecisely attributed. Although evidence of nutrient enrichment in the water column is limited, studies indicate biological nutrient uptake. Achieving a comprehensive understanding of degradation and decomposition, including temporal and spatial dynamics, microbiome interactions, by means of directed research, is critical for effective coastal management, improved mitigation strategies, industrial valorization, and accurate modeling of biogeochemical cycles. Full article

As shallow coal resources become increasingly depleted, coal mining is extending to greater depths, making mine thermal hazards an increasingly prominent issue. This paper proposes a novel system for synergistic geothermal energy extraction from deep coal mine aquifers and coal seam cooling, aimed at achieving integrated geothermal exploitation and mine thermal hazard control. Based on a high-temperature mine in the Yuanyanghu Mining Area of Ningxia, a dual-stage, single-branch three-dimensional numerical model was established to simulate the effects of water injection pressure, water injection temperature, and level spacing on the system’s cooling performance and geothermal energy extraction efficiency. The results indicate that increasing injection pressure enhances early-stage geothermal energy extraction capacity and coal seam cooling rate, but the heat extraction power declines over long-term operation as the produced water temperature approaches the injection temperature. Lowering injection temperature significantly improves water–rock heat exchange efficiency, accelerates coal seam cooling, and increases geothermal energy extraction. Increasing level spacing helps improve geothermal energy extraction power but weakens the direct cooling effect on the coal seam. Considering the influence patterns of each parameter, the optimal combination was determined as water injection pressure of 10 MPa, water injection temperature of 10 °C, and level spacing of 80 m, which delivers the best overall performance by enabling rapid coal seam cooling and sustained geothermal energy extraction, with a cumulative geothermal output reaching 129.45 MW after 10 years of operation. This study provides a theoretical basis and technical reference for the integrated management of thermal hazards and geothermal resource development in deep coal mines. Full article

This study examines the hydroclimatic controls on reservoir storage dynamics in the Sinni River basin (southern Italy), with a specific focus on the Monte Cotugno dam—the largest earth-fill reservoir in Europe. Using monthly precipitation data (2000–2024) from eight gauges and standardized indicators (SPI at multiple timescales and SRI for storage), we apply robust trend, correlation, autocorrelation, and causality analyses, supported by advanced preprocessing (TFPW), to disentangle climatic influences from anthropogenic pressures. Results show a statistically significant and persistent decline in the SRI series, indicating progressive storage depletion, despite stationary or slightly positive trends in precipitation at annual and hydrologically relevant timescales. These findings highlight the dominant role of cumulative operational losses and systemic inefficiencies—rather than sustained climatic drying—as primary drivers of reservoir decline. Granger causality and lagged-correlation analyses reveal that multi-month to annual precipitation anomalies (SPI-3, SPI-6, SPI-12) exert the strongest influence on storage variations, yet the basin’s ability to convert rainfall into effective reservoir supply is severely constrained by infrastructural and management limitations. The study underscores the urgent need to integrate climate-based monitoring with infrastructural modernization and governance reforms to address the combined climatic and anthropogenic pressures increasingly affecting Mediterranean water systems. Full article

Platelet-rich fibrin (PRF) is widely used in regenerative dentistry and oral surgery for its ability to promote tissue healing and modulate cellular responses. However, PRF contains not only platelets but also leukocytes and plasma components, complicating efforts to define the specific contribution of platelets to its biological activity. To address this, we used washed, leukocyte-depleted platelets activated with thrombin to generate platelet-released supernatant (PRS), which was applied to gingival fibroblasts. RNA sequencing identified 147 upregulated and 39 downregulated genes (|log₂ fold change| ≥ 2, FDR < 0.001), including cytokines IL11 and CXCL8 previously associated with PRF, as well as mitosis-related genes such as centromere-associated proteins, cell division cycle proteins, kinesin-like proteins, and shugoshins, consistent with gene ontology analyses. Validation by RT-PCR and immunoassays confirmed robust upregulation of IL11 and CXCL8. Functionally, PRS activated TGF-β signaling, indicated by Smad2/3 nuclear translocation, but did not induce NF-κB signaling. These findings demonstrate that platelets are major contributors to PRF’s biological effects, independent of leukocytes and plasma, and elicit a pronounced mitogenic and TGF-β-dominant response in gingival fibroblasts. They also provide insight into the cellular mechanisms underlying PRF-mediated tissue regeneration. Full article

This study develops a green, high-performance, cement-based grout by replacing manufactured sand with iron tailings sand (ITS) at ratios of 0–50% to address resource depletion. Fluidity, mechanical strength, and expansion rates were experimentally evaluated to determine engineering feasibility. The results indicate that while ITS inclusion reduces fluidity due to particle morphology, it significantly enhances compressive strength through a physical filling effect. Specifically, the 30% replacement group achieved a peak 28-day compressive strength of 100.4 MPa. Comprehensive analysis identifies 40% as the optimal replacement rate, where the grout strictly satisfies relevant industry specifications regarding fluidity, early strength, and volume stability. This research demonstrates the practical significance of utilizing industrial solid waste to produce high-performance sleeve grout for prefabricated construction. Full article

Selective inhibition of CYP17A1 17,20-lyase is critical for treating hyperandrogenic disorders without the cortisol-depleting side effects of non-selective drugs like abiraterone. We evaluated tanshinones from Salvia miltiorrhiza as potential selective inhibitors using biochemical assays and computational modeling. Dihydrotanshinone (DT) emerged as the superior candidate; at 10 µM, it inhibited 17,20-lyase activity by 56.6% while preserving >93% of 17α-hydroxylase activity. This yields a selectivity index of 8.67, drastically outperforming abiraterone (0.73). Furthermore, DT displayed minimal off-target inhibition of CYP21A2 (14.9%) compared to abiraterone (29.8%). Molecular modeling suggests DT’s efficacy arises from a unique, functionally disruptive binding pose rather than superior thermodynamic affinity. Consequently, DT is validated as a potent natural product lead. Its dual selectivity over 17α-hydroxylase and CYP21A2 establishes the tanshinone scaffold as a promising candidate for developing safer therapies that suppress androgens while sparing cortisol biosynthesis. Full article