Search Results (253)

NLRP1 is an inflammasome sensor protein expressed in barrier tissues of humans. Its activation in response to microbes or cellular stress triggers a cascade of molecular events, leading up to IL1β-driven inflammation and pyroptosis. Rare germline mutations of NLRP1 cause its persistent activation, resulting in autoinflammatory syndromes. Multiple self-healing palmoplantar carcinoma (MSPC) is one such syndrome, characterized by the appearance of recurrent keratoacanthomas (KAs) on the palms and soles. Here, we aimed to compare the subcellular localization of mutant NLRP1 in lesions from an MSPC patient to wild-type NLRP1 in non-MSPC-KAs and in skin from healthy donors. Using mass spectrometry, immunohistochemistry and immunoelectron tomography, we found that NLRP1 localized to mast cell granules in all MSPC lesions but also in healthy skin, a novel finding which implicates these cells in NLRP1-associated responses in human skin. Moreover, we found that mast cells expressing the A66V pathogenic variant of NLRP1 overpopulated MSPC-KAs, infiltrated the epidermis and degranulated, a behavior not seen in other lesions from this study. The released granules had the highest NLRP1 protein content and also contained NLRP3 and IL1β, suggesting the coexistence of inflammasome pathways within mast cells. Taken together, our findings propose cutaneous mast cells as a previously unrecognized NLRP1 reservoir in health and disease. Full article

Against the backdrop of multi-source water transfers and increasingly frequent extreme rainfall, short-term deterioration of reservoir inflow water quality has become a key risk to intake safety, treatment operations, and urban water-supply security. Traditional assessments based on static thresholds and annual or seasonal averages often fail to identify high-risk periods at the event scale. Using continuous online monitoring data from 2021 to 2024 for the inflow of Yuqiao Reservoir, Tianjin, China, this study developed a month-specific dynamic-threshold framework and green/yellow/red risk windows and integrated a reach-wise river–reservoir routing scheme; a two-box decay model; and a three-class risk trigger into a unified analytical framework for long-term background characterization, event propagation analysis, source-contribution interpretation, and early-warning evaluation. Results show that the permanganate index (COD_Mn) exhibits an overall stable-to-declining background with pronounced wet-season pulses, whereas total nitrogen (TN) and total phosphorus (TP) remain at moderate-to-high levels, with yellow/red risk windows clustering markedly in the wet season. In typical red and yellow events, nitrogen contributions from upstream control sections progressively accumulate toward the reservoir inlet along the river–reservoir cascade system, whereas in some events the residual contribution from unmonitored near-inlet inflows becomes dominant. The COD_Mn-based three-class trigger achieves an overall accuracy of approximately 71.5% and shows comparatively strong identification of yellow-level risk, while remaining conservative for red-level alarms. These findings indicate that coupling month-specific dynamic thresholds with event-scale routing-decay analysis and trigger-based classification can support inflow monitoring, intake-risk early warning, and coordinated operation of key upstream reaches and near-reservoir control zones in water-transfer–reservoir integrated systems. Full article

Cascade reservoirs on the Drina River (Bosnia and Herzegovina) are heavily modified water bodies that require reliable biological tools for assessing trophic status and ecological potential. Under the Water Framework Directive (WFD), assessments of surface water ecological status and potential rely on biological quality elements, since aquatic communities integrate and respond to prevailing environmental conditions and thus serve as reliable indicators of water quality. This study aims to (i) describe phytoplankton diversity, biomass, and functional-group composition along the Drina reservoir cascade, (ii) examine monthly changes across the studied reservoirs, (iii) determine trophic status and ecological potential, and (iv) provide a preliminary estimate of total phosphorus thresholds that may support future setting of ecological potential boundaries. Phytoplankton composition and functional groups were analysed in three longitudinally connected reservoirs of the Drina River during four monthly surveys in 2024. A total of 80 phytoplankton taxa were recorded, with diatoms dominating most of the study period. The highest biomasses were recorded for Fragilaria crotonensis, Dinobryon divergens, Acanthoceras zachariasii and Sphaerocystis sp., while the dominant functional groups were P, E, A, and F. Phytoplankton assemblage structure showed moderate spatial differentiation among the reservoirs. Mean chlorophyll a and Carlson’s Trophic State Index indicated eutrophic conditions in the Višegrad Reservoir and mesotrophic conditions in the Perućac and Zvornik reservoirs, while biomass showed a pronounced summer maximum, particularly in Perućac. Ecological potential was generally classified as good or better, except for a moderate classification in the Zvornik Reservoir in late summer. The good/moderate TP boundary was estimated at 39 µg L⁻¹, linking EQR-based ecological assessment with the onset of eutrophic conditions. Overall, this study represents the first application of the phytoplankton functional group approach in cascade reservoirs in Bosnia and Herzegovina and may provide a valuable basis for the development of a phytoplankton-based monitoring framework in lakes and reservoirs, which is currently lacking. Full article

Defining the near-surface signal reflecting the deep sub-surface leakage is a critical challenge in the risk assessment of geologic carbon storage (GCS) projects, often exacerbated by decoupled deep-to-shallow modeling. This study quantifies the mass distribution and phase evolution of leaked CO₂ through deep reservoir-caprocks, intermediate aquifer, and near-surface soil, thereby showing the sub-surface retention characteristics and the detectability of near-surface signals. A geological model from the deep reservoir to the soil layer was constructed to simulate CO₂ leakage through the caprock and migration into overlying strata in 1000 years. Using the simulator of GPSFLOW, this study evaluates the evolution of fluid phases and the mass distribution during the injection for 100 years and the post-injection periods. The results indicate that (1) at the moment the injection ceases, 87.43–99.06% of the CO₂ remaining within the system is retained within the reservoirs, with less than 8.42% reaching the intermediate aquifer. Remarkably, although the CO₂ ultimately reaching the near-surface soil is less than 0.00073% of the total mass retained within the system, this mass accumulation translates to a concentration anomaly with a signal-to-noise ratio of 368 relative to the background baseline. (2) Sensitivity analysis reveals that the injection rate affects the timing of fluid transport—a tenfold increase in injection rate (from 3.17 to 31.7 kg/s) accelerates the upward movement of CO₂, advancing its arrival at the near-surface by 15 years without changing the overall mass partitioning. The permeability anisotropy ratio affects CO₂ migration and phase distribution—decreasing the vertical to horizontal permeability ratio (1, 0.5, 0.25, 0.125) reduces connectivity, which delays the upward transfer and increases the amount of the aqueous CO₂. However, specifically in the soil layer, the aqueous CO₂ accumulation reveals a non-monotonic trend that peaks at an intermediate ratio of 0.25. (3) CO₂ shows a cascading distribution across formations where reservoirs provide the primary storage, and the intermediate aquifer reduces the mass available for near-surface accumulation. This attenuation effect significantly reduces the CO₂ mass that reaches the soil layer, thereby controlling the strength and duration of near-surface environmental signals. This work offers a theoretical reference for formulating near-surface monitoring strategies for CO₂ leakage in GCS. Full article

Mercury (Hg) bioaccumulation in freshwater fish represents a major pathway of human exposure, particularly in cascade reservoir systems where hydrological retention and legacy contamination can enhance methylmercury (MeHg) formation and trophic transfer. This study quantified total mercury (THg) concentrations in seven tissues of seven fish species from the Arda River cascade (Bulgaria). Multi-tissue measurements were integrated with morphometric predictors, multivariate statistical analyses, and combined deterministic and probabilistic human-health risk assessments. Muscle and liver contained the highest THg concentrations, whereas gills and gonads exhibited the lowest levels. Predatory species and larger individuals accumulated significantly more Hg, reflecting trophic magnification and size-dependent exposure. A longitudinal gradient across the cascade reservoirs suggests hydrological retention effects influencing mercury distribution. Species- and tissue-specific size–Hg relationships further indicate heterogeneous bioaccumulation dynamics among taxa. Risk assessment indicated acceptable exposure for adults and pregnant women at average consumption (140 g·week⁻¹), but elevated exposure for children consuming high-Hg predators. Monte Carlo simulations (N = 30,000) revealed upper-tail risks, while Safe Weekly Intake thresholds provided species-specific consumption limits. These findings highlight the value of integrating multi-tissue monitoring with probabilistic risk modelling to support evidence-based fish-consumption advisories in contaminated freshwater systems. Full article

Large-scale hydropower development provides substantial socio-economic and energy benefits but simultaneously introduces complex ecological and environmental challenges that require comprehensive scientific assessment. This study systematically evaluates the effects of the leading reservoir (Longpan hydropower station, referring to the uppermost and principal flow-regulating dam in the cascade) in the middle reaches of the Jinsha River’s operation on the water environment of the mainstream Yangtze River, China, with the aim of clarifying its water quality responses and supporting evidence-based basin management. Based on an analysis of the current water quality conditions of the Yangtze River and a comparative review of the operational experience of the Three Gorges Reservoir, this research explores the mechanisms through which large reservoirs alter hydrological and ecological processes. These mechanisms include reduced flow velocity, prolonged water residence time, weakened pollutant dispersion, and increased risk of algal blooms in tributaries. To quantitatively assess these impacts, an improved river dilution–mixing model was developed and applied to simulate the water quality response during the dry season (February–April) under different discharge scenarios. Key downstream monitoring sections were examined. The modeling results indicate that the operation of the Leading reservoir can moderately reduce dry-season concentrations of key pollutants (e.g., total phosphorus, permanganate index) at downstream sections by approximately 2–5% on average, with spatially heterogeneous effects. Although the overall improvement magnitude remains limited, the combined effects of sediment deposition and in situ degradation may yield more pronounced real-world benefits. The findings underscore the importance of optimizing the regulatory function of the Longpan Reservoir through coordinated operation within the cascade reservoir system. It is recommended to integrate water resource allocation, water quality management, and aquatic ecosystem protection, alongside enhanced pollution control and ecological restoration in key zones. The methodology and findings provide a referenced framework for assessing the water-environmental implications of large-scale reservoir regulation in other major river systems. Full article

The sustainable use of freshwater resources includes balancing between human demand for water and the long-term health of river systems. Although dams and reservoirs are essential for water supply, flood control and energy generation, they can induce significant hydrological alterations, affecting water quality, sediment transport, downstream water availability, and aquatic and riparian ecosystems. In this study, we employed multifractal analysis to investigate hydrological changes in the São Francisco River basin, Brazil, resulting from the construction of a cascade of dams and reservoirs. We applied multifractal detrended fluctuation analysis (MFDFA) to daily streamflow time-series spanning the period from 1929 to 2016, at locations both upstream and downstream of cascade dams, and for periods before and after dam construction. We calculated multifractal spectra f(α) and analyzed key complexity parameters: the position of the spectrum maximum α_0, representing the overall Hurst exponent H; the spectrum width W indicating the degree of multifractality; and the asymmetry parameter r, which reflects the dominance of small (r > 1) and large (r < 1) fluctuations. We found that after the construction of Sobradinho dam, located in the Sub-Middle São Francisco region, streamflow dynamics shifted towards a regime characterized by uncorrelated increments (H~0.5) and stronger multifractality (larger W), with the dominance of small fluctuations (r > 1). In contrast, the cumulative effect of all cascade dams downstream, in the Lower São Francisco region, led to streamflow regime with similarly uncorrelated increments (H~0.5), but with weaker multifractality (smaller W) and a dominance of large fluctuations (r < 1). The novelty of this work is the use of a sliding-window MFDFA approach to explore the temporal evolution of streamflow multifractality. This method uncovered otherwise hidden aspects of hydrological alterations, such as increasing tendency in spectrum width, indicating stronger multifractality and higher complexity of streamflow dynamics after the dam construction. These results demonstrate that multifractal analysis is a powerful tool for assessing the complexity of hydrological changes induced by human activities. Full article

Reservoir operation under climate change poses significant challenges for hydropower-dependent countries, particularly in cascade reservoir systems. This study aims to derive optimal future operating rule curves for the Nam Khan 2 and Nam Khan 3 cascade reservoirs in Lao PDR to maximize hydropower generation under climate change. Genetic Algorithm (GA), Invasive Weed Optimization (IWO), and Harmony Search (HS) were integrated with a reservoir simulation model to optimize monthly upper and lower rule curves. Future reservoir inflows were generated using climate projections from the INM-CM5-0 climate model’s SSP245 scenario for 2025–2050. The aim was to maximize average annual electricity generation for the entire cascade system while ensuring practicable reservoir operation. The optimized rule curves obtained from all three algorithms exhibited similar seasonal patterns, reflecting regional hydrological characteristics. The proposed rule curves significantly improved hydropower performance compared to the existing operating policies. For Nam Khan 2, average annual electricity generation increased from 324.089 GWh under current operations to 788.246, 787.100, and 786.561 GWh using GA, IWO, and HS. Similarly, Nam Khan 3 achieved substantial improvements, with average annual generation increasing from 156.029 GWh to 270.049, 266.840, and 266.547 GWh. The optimized rule curves also contributed to better storage regulation and reduced variability in energy production. The findings demonstrate that integrating metaheuristic optimization techniques with reservoir simulation models provides an effective framework for adaptive hydropower-oriented reservoir operation under future climate uncertainty. Full article

Southwest China’s karst region has developed a dam- and reservoir-dense pattern in which cascaded hydropower on mainstem rivers coexists with small hydropower on tributaries, forming a foundation for the region’s low-carbon energy supply. Under China’s “dual-carbon” targets and a strengthening ecological civilization agenda, it is urgent to clarify the mechanisms driving habitat quality (HQ) change under compound disturbances from cascaded hydropower, urbanization, and related pressures—especially the nonlinear pathway through which engineering disturbance propagates to ecological responses via land-use restructuring. To address this need, we develop a Cascade disturbance–Land restructuring–Habitat response chain framework and integrate an InVEST–IntPLUS–OPGD modeling approach to capture HQ dynamics in the Wujiang River Basin (1980–2020), attribute the interactive effects of coupled natural–social drivers, and project ecological responses under alternative 2035 scenarios. Results show that: (1) The basin maintained a stable ecological matrix, with forest land and cropland consistently >82.5% and forest cover near 50%, while construction land increased by 972.15 km² and water bodies by 354.23 km² (2) Mean HQ stayed high and declined by only 1.42%, with high and medium–high HQ dominating (>65%). HQ degradation is concentrated in urban expansion areas and reservoir shorelines, whereas most mountainous/forested regions remain stable; and (3) HQ spatial differentiation is mainly shaped by the synergy between forest structure and NDVI, while nonlinear urbanization edge effects impose stronger stress than hydropower development itself. Scenario simulations further indicate that a water protection pathway can enhance HQ by building integrated “water–forest” corridors that promote blue–green synergy. Overall, this study supports improved trade-off design between energy supply and ecological protection in vulnerable karst regions. Full article

The development of large-scale cascade hydropower complexes has improved the navigation conditions of mountainous rivers but creates unique “continuous dam zones,” presenting complex challenges for port site selection due to hydrological variability and geological risks. To address the lack of specialized evaluation tools for this specific context, this paper constructs a comprehensive evaluation indicator system tailored for mountainous reservoir areas. The proposed system explicitly integrates critical engineering and physical constraints—specifically fluctuating backwater zones, geological hazards, and dam-bypass mileage—alongside ecological and social requirements. The Analytic Hierarchy Process (AHP) and Entropy Weight Method (EWM) are integrated using a Game Theory model to determine combined weights, and the Evaluation based on Distance from Average Solution (EDAS) model is applied to rank the alternatives. An empirical analysis of the Xiluodu Reservoir area on the Jinsha River demonstrates that operational efficiency, geological safety, and environmental feasibility constitute the critical decision-making factors. The results indicate that Option C (Majiaheba site) offers the optimal solution (ASi = 0.9695), effectively balancing engineering utility with environmental protection. Sensitivity analysis further validates the consistency and stability of this ranking under different decision-making scenarios. The findings provide quantitative decision support for project implementation and offer a replicable reference for infrastructure planning in similar complex mountainous river basins. Full article

Adipose tissue is far more than a passive reservoir for surplus energy: it is an active metabolic and endocrine organ that senses nutrient availability and orchestrates systemic energy balance. When caloric intake chronically exceeds expenditure, adipocytes become engorged with lipids and exposed to metabolic, mechanical, and hypoxic stress. To adapt, they initiate a fibro-inflammatory response that may be protective in the short term. As this response becomes chronic, adipocytes lose their metabolic flexibility, acquire a maladaptive fibro-inflammatory phenotype, and contribute to the cascade of inflammation, insulin resistance, and metabolic disease that characterizes obesity. In this review, we dissect the cellular and molecular cues that trigger fibro-inflammation, from nutrient excess and mitochondrial stress to hypoxia and immunometabolic rewiring, and highlight how these processes reshape adipocyte identity and tissue homeostasis. Full article

The operation of the Three Gorges Dam (TGD) has profoundly influenced sediment dynamics in the Three Gorges Reservoir (TGR), yet the long-term evolution of runoff–sediment interactions remains insufficiently quantified. Based on long-term hydrological data (1970–2023), this study analyzed the characteristics of runoff and sediment load and evaluated the impacts of the TGD on their relationship within the reservoir area. Results showed that TGD operation significantly altered sediment transport patterns and reshaped the runoff–sediment relationship, although these effects were constrained by temporal variations in upstream water and sediment supply. From 2003 to 2012, sediment transport regulation reached 11.7%, 50.9%, and 80.5% at Qingxichang, Wanxian, and Yichang stations, respectively, while regulation of the runoff–sediment relationship was 20.0% and 50.0% at Qingxichang and Wanxian. During 2013–2023, under the influence of cascade reservoirs in the upper Yangtze River, sediment regulation changed to 8.3%, 60.3%, and 75.2% at the three stations, with runoff–sediment regulation degrees of 21.7% and 54.2% at Qingxichang and Wanxian. The regulation effect displayed a clear spatial gradient, intensifying downstream along the reservoir. These findings demonstrate the dual role of TGD and upstream cascade reservoirs in shaping runoff–sediment dynamics, providing new insights into sediment management and ecological protection in large regulated rivers. Full article

This study investigates the Serial Discontinuity Concept (SDC) by analyzing the size of phytoplankton structures across 13 cascade dams in the fragmented East River, China. The results showed that dam flow-regulation minimized seasonal differences in total chlorophyll-a (Chl-a). Spatially, midstream Chl-a was higher during the dry period, whereas increased wet periods were linked to reservoir effects and nutrient conditions. Nano-phytoplankton dominated during both periods, while micro-phytoplankton declined during wet periods due to higher pH and transparency. Micro-Chl-a increased downstream in dry periods as a result of dissolved oxygen levels and silicate. Self-organizing maps revealed greater size–class variability during dry periods, with pH and conductivity identified as key regulators. Aulacoseira granulata (micro-phytoplankton) and Anabaena oscillarioides (also micro-phytoplankton) were co-dominant. This pattern suggests that the flow regulation and water impoundment by cascade dams during the wet period created localized lentic conditions with enhanced water stability, which favored the proliferation of these species, despite the increased seasonal discharge at the basin scale. These findings support the SDC in that (1) longitudinal Chl-a variations empirically validated SDC, especially during dry periods, and (2) a spatially periodic Chl-a pattern was identified, termed the Cascade Cycle of SDC (CC-SDC). Full article

As critical reservoirs of biodiversity and providers of ecosystem services, wetland ecosystems play a pivotal role in maintaining global ecological balance. They not only serve as habitats for diverse aquatic and terrestrial organisms but also play substantial roles in water purification, carbon sequestration, and climate regulation. However, intensified anthropogenic activities—including drainage, fertilization, invasion by alien species, grazing, and urbanization—pose unprecedented threats, leading to profound alterations in the functional traits of wetland plants. This review synthesizes findings from peer-reviewed studies published between 2005 and 2024 to elucidate the mechanisms by which human disturbances affect plant functional traits in wetlands. Drainage was found to markedly reduce plant biomass in swamp ecosystems, while mesophyte and tree biomass increased, likely reflecting altered water availability and species-specific adaptive capacities. Mowing and grazing enhanced aboveground biomass and specific leaf area in the short term but ultimately reduced plant height and leaf dry matter content, indicating potential long-term declines in ecological adaptability. Invasive alien species strongly suppressed the growth of native species, reducing biomass and height and thereby threatening ecosystem stability. Eutrophication initially promoted aboveground biomass, but excessive nutrient inputs led to subsequent declines, highlighting ecosystems’ vulnerability to shifts in trophic state. Similarly, fertilization played a dual role: moderate inputs stimulated plant growth, whereas excessive inputs impaired growth performance and exacerbated eutrophication of soils and water bodies. Urbanization further diminished key plant traits, reduced habitat extent, and compromised ecological functions. Overall, this review underscores the profound impacts of anthropogenic disturbances on wetland plant functional traits and their cascading effects on ecosystem structure and function. It provides a scientific foundation for conservation and management strategies aimed at enhancing ecosystem resilience. Future research should focus on disentangling disturbance-specific mechanisms across different wetland types and developing ecological engineering and management practices. Recommended measures include rational land-use planning, effective control of invasive species, and optimized fertilization regimes to safeguard wetland biodiversity, restore ecosystem functions, and promote sustainable development. Full article

Background: Pancreatitis, encompassing acute (AP), severe acute (SAP), and chronic (CP) forms, is a life-threatening inflammatory disorder with limited therapeutic options. Current management is largely supportive, highlighting the urgent need for novel interventions targeting underlying molecular pathways. Aim: This review summarizes recent advances in the pathogenesis of pancreatitis, focusing on calcium dysregulation, ferroptosis, and microRNA-mediated mechanisms while exploring the therapeutic potential of phytochemicals as disease-modifying agents. Summary: Aberrant calcium signaling, iron-dependent lipid peroxidation, and microRNA imbalance drive acinar cell injury, inflammatory cascades, and pancreatic fibrosis. Phytochemicals, including flavonoids, terpenoids, alkaloids, and phenolics, have shown protective effects in preclinical models through multi-targeted mechanisms. These include suppression of NF-κB-driven inflammation, activation of the Nrf2/HO-1 antioxidant pathway, modulation of ferroptosis via GPX4 and iron efflux, regulation of calcium signaling, and modulation of microRNA expression. Importantly, several phytochemicals attenuate acinar cell death, reduce cytokine release, and limit fibrosis, thereby improving outcomes in experimental pancreatitis. However, poor solubility, bioavailability, and pharmacokinetic limitations remain significant barriers. Emerging strategies such as nanotechnology-based formulations, prodrug design, and pharmacokinetic profiling, as well as bioavailability studies, may enhance their clinical applicability. Conclusions: Phytochemicals represent a promising reservoir of multitarget therapeutic agents for pancreatitis. Their ability to modulate oxidative stress, inflammatory and calcium signaling, ferroptosis, and microRNA networks highlights their translational potential. Future studies should focus on clinical validation, bioavailability optimization, and advanced delivery platforms to bridge the gap from bench to bedside. Full article