Search Results (1,253)

This study investigates the hot deformation behaviour and microstructural evolution of two AISI 430 ferritic stainless steel variants: 0A (basic) and 1C (modified). These variants primarily differ in chemical composition, with 0A containing higher austenite-stabilizing elements (C, N) compared to 1C, which features lower interstitial content and slightly higher Si and Cr. This research aimed to optimize hot rolling conditions for enhanced forming properties. Uniaxial hot compression tests were conducted using a Gleeble thermo-mechanical system between 850 and 990 ${}^{\circ }$C at a strain rate of 3.3 s${}^{-1}$, simulating industrial finishing mill conditions. Analysis of flow curves, coupled with detailed microstructural characterization using electron backscatter diffraction, revealed distinct dynamic restoration mechanisms influencing each material’s response. Thermodynamic simulations confirmed significant austenite formation in both materials within the tested temperature range, notably affecting their deformation behaviour despite their initial ferritic state. Material 0A consistently exhibited a strong tendency towards dynamic recrystallization (DRX) across a wider temperature range, particularly at 850 ${}^{\circ }$C. DRX led to a microstructure with a high concentration of low-angle grain boundaries and sharp deformation textures, actively reorienting grains towards energetically favourable configurations. However, under this condition, DRX did not fully complete the recrystallization process. In contrast, material 1C showed greater activity of both dynamic recovery and DRX, leading to a much more advanced state of grain refinement and recrystallization compared to 0A. This indicates that the composition of 1C helps mitigate the strong influence of the deformation temperature on the crystallographic texture, leading to a weaker texture overall than 0A. Full article

Carbon flow tracking and spatial pattern optimization at the scale of urban functional zones are key scientific challenges in achieving carbon neutrality. However, due to the complexity of carbon metabolism processes within urban functional zones, related studies remain limited. To address these scientific challenges, this study, based on the “source–sink–flow” ecosystem services framework, develops an integrated analytical approach at the scale of urban functional zones. The carbon balance is quantified using the CASA model in combination with multi-source data. A network model is employed to trace carbon flow pathways, identify critical nodes and interruption points, and optimize the urban spatial pattern through a low-carbon land use structure model. The research results indicate that the overall carbon balance in Hangzhou exhibits a spatial pattern of “deficit in the center and surplus in the periphery.” The main urban area shows a significant carbon deficit and relatively poor connectivity in the carbon flow network. Carbon sequestration services primarily flow from peripheral areas (such as Fuyang and Yuhang) with green spaces and agricultural functional zones toward high-emission residential–commercial and commercial–public functional zones in the central area. However, due to the interruption of multiple carbon flow paths, the overall carbon flow transmission capacity is significantly constrained. Through spatial optimization, some carbon deficit nodes were successfully converted into carbon surplus nodes, and disrupted carbon flow edges were repaired, particularly in the main urban area, where 369 carbon flow edges were restored, resulting in a significant improvement in the overall transmission efficiency of the carbon flow network. The carbon flow visualization and spatial optimization methods proposed in this paper provide a new perspective for urban carbon metabolism analysis and offer theoretical support for low-carbon city planning practices. Full article

Human cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis is a complex parasitic disease marked by dynamic host–parasite interactions and immunomodulation. Extracellular vesicles (EV) derived from immune cells have emerged as key mediators of intercellular communication and potential biomarkers in infectious diseases. In this study, we combined a modified lymphocyte proliferation assay with nano-flow cytometry to quantify and phenotype EV released by CD4⁺, CD8⁺, and CD14⁺ cells in PBMC cultures from CL patients at different clinical stages: before treatment (PBT), during treatment (PDT), and post-treatment (PET) with antimonial. Healthy individuals (HI) were included as physiological controls. Upon stimulation with L. (V.) braziliensis antigens, we observed a distinct modulation of EV subsets. In the PBT group, CD4⁺ and CD14⁺ EV were significantly reduced, while CD8⁺ EV remained elevated. During PDT and PET, EV concentrations were restored across all subsets. These findings suggest that L. (V.) braziliensis selectively modulates the release of immune cell–derived EV, possibly as an immune evasion mechanism. The restoration of EV release following antimonial therapy highlights their potential as sensitive biomarkers for disease activity and treatment monitoring. This study offers novel insights into the immunoregulatory roles of EV in CL and underscores their relevance in host–parasite interactions. Full article

Background/Objectives: This study aimed to investigate the influence of shade and thickness on the polymerization of SDR^® flow+, a low-viscosity bulk-fill composite, by assessing its degree of conversion (DC). Methods: An in vitro study was conducted using SDR^® flow+ composite resin. Specimens were prepared at two thicknesses (2 mm and 4 mm) and four shades (Universal, A1, A2, A3). Polymerization was performed using a high-intensity LED curing unit. The DC was assessed using Fourier-transform infrared spectroscopy (ATR-FTIR). Results: Both shade and thickness significantly influenced DC. Thicker specimens (4 mm) exhibited reduced polymerization compared to thinner specimens (2 mm). Darker shades, particularly A3, demonstrated the lowest DC values due to their higher chroma, which limits light penetration. In contrast, the Universal shade achieved higher DC values, even at increased depths, likely due to its greater translucency. Conclusions: Shade and thickness play a critical role in the polymerization of bulk-fill composites. Ensuring adequate polymerization is essential for the longevity of pediatric restorations. Further in vivo research is needed to confirm these findings and assess their clinical implications. Full article

Karst groundwater systems are critical to water supply and ecological sustainability in northern China, yet their heterogeneity poses challenges for flow characterization. The Yuquan Mountain (YM) Spring, historically a major karst spring in western Beijing, has experienced persistent drying, raising concerns about its recharge and flow mechanisms. This study integrates published isotope data, spatial distributions of Na⁺ and Cl⁻ as hydrochemical tracers, groundwater age estimates, and geophysical survey results to assess the recharge sources and flow pathways within the YM Spring catchment area. The analysis identifies two major recharge zones: the Tanzhesi area, primarily recharged by direct infiltration of precipitation through exposed carbonate rocks, and the Junzhuang area, which receives mixed recharge from rainfall and Yongding River seepage. Three potential flow pathways are proposed, including shallow flow along faults and strata, and a deeper, speculative route through the Jiulongshan-Xiangyu syncline. The synthesis of multiple lines of evidence leads to a refined conceptual model that illustrates how geological structures govern recharge, flow, and discharge processes in this karst system. These findings not only enhance the understanding of subsurface hydrodynamics in complex geological settings but also provide a scientific basis for future spring restoration planning and groundwater management strategies in the regions. Full article

The depletion of water resources caused by climate change and human activities is a pressing global issue. Lake Ereen is one of the ten natural landmarks of the Gobi-Altai of western Mongolia is included in the list of “important areas for birds” recognized by the international organization Birdlife. However, the construction of the Taishir Hydroelectric Power Station, aimed at supplying electricity to the western provinces of Mongolia, had a detrimental effect on the flow of the Zavkhan River, resulting in a drying-up and pollution of Lake Ereen, which relies on the river as its water source. This study assesses the pollution levels in Ereen Lake and determines the feasibility of its rehabilitation by redirecting the flow of the Zavkhan River. Field studies included the analysis of water quality, sediment contamination, and the composition of flora. The results show that the concentrations of ammonium, chlorine, fluorine, and sulfate in the lake water exceed the permissible levels set by the Mongolian standard. Analyses of elements from sediments revealed elevated levels of arsenic, chromium, and copper, exceeding international sediment quality guidelines and posing risks to biological organisms. Furthermore, several species of diatoms indicative of polluted water were discovered. Lake Ereen is currently in a eutrophic state and, based on a water quality index (WQI) of 49.4, also in a “polluted” state. Mass balance calculations and box model analysis determined the period of pollutant replacement for two restoration options: drying-up and complete removal of contaminated sediments and plants vs. dilution-flushing without direct interventions in the lake. We recommend the latter being the most efficient, eco-friendly, and cost-effective approach to rehabilitate Lake Ereen. Full article

Background: Aicardi-Goutières Syndrome (AGS) is a rare neuroinflammatory condition characterized by early-onset symptoms that extend outside the nervous system. Due to the rarity of the disease, the pathogenesis is not well understood, and its diagnosis and treatment remain elusive. We recently demonstrated mitochondrial abnormalities and increased reactive oxygen species (ROS) levels in lymphoblastoid cell lines (LCLs) derived from RNASEH2B- and RNASEH2A-mutated AGS patients. On this background, we turned our attention to metformin, the first-choice drug for type 2 diabetes, as a possible treatment acting on oxidative stress in RNASEH2-mutant AGS cells. Methods and Results: By means of flow cytometry, we found that metformin treatment significantly decreases ROS production in RNASEH2B- and RNASEH2A-mutated AGS LCLs. Of note, metformin treatment reduces the green JC-1 monomeric signal and, concurrently, increases the red JC-1 signal in both mutated LCLs, accounting for restoration of the mitochondrial membrane potential. Immunofluorescence staining shows a decrease in 8-oxoG levels only in RNASEH2B- mutated AGS LCLs. Finally, the significant upregulation of Forkhead Box O3 (FOXO3), cytochrome C somatic (CYCS), and superoxide dismutase 2 (SOD2) mRNA levels in RNASEH2B-mutated AGS LCLs after metformin treatment points to FOXO3 signaling as a possible mechanism to reduce oxidative stress. Conclusions: In conclusion, even if these pilot results need to be confirmed on a larger cohort, we shed light on metformin treatment as a valid approach to ameliorate oxidative stress-related inflammation in AGS patients. Full article

Earthquakes can severely disrupt power distribution networks, causing extensive outages and disconnection from the transmission grid. This paper proposes a two-stage restoration method tailored for post-earthquake distribution systems. First, earthquake-induced damage is modeled using ground motion prediction equations (GMPEs) and fragility curves, and degraded network topologies are generated by Monte Carlo simulation. Then, a time-domain generator start-up model is developed as a mixed-integer linear program (MILP), incorporating cranking power and radial topology constraints. Further, a prioritized load recovery model is formulated as a mixed-integer second-order cone program (MISOCP), integrating power flow, voltage, and current constraints. Finally, case studies demonstrate the effectiveness and general applicability of the proposed method, confirming its capability to support resilient and adaptive distribution network restoration under various earthquake scenarios. Full article

This study was developed to identify the optimal (most cost-effective) strategies to reduce sediment and phosphorus loadings in the Upper Soldier Creek, Kansas, USA, watershed using the Watershed Management Optimization Support Tool (WMOST) suite of programs. Under average precipitation, loading targets for upland total phosphorus (TP) could be met with use of grassed swales for treating urban area runoff and of contouring for agricultural runoff. For a wet year, the same target could be met, but with use of a sand filter with underdrain for the urban runoff. Both annual and daily TP loading targets from Total Maximum Daily Loads (TMDLs) were exceeded in simulations of best management practice (BMP) solutions for 14 alternative future climate scenarios. We expanded the set of BMPs to include stream bank stabilization (physical plus riparian restoration) and two-stage channel designs, but upland loading targets could not be met for either TP or total suspended solids (TSS) under any precipitation conditions. An optimization scenario that simulated the routing of flows in excess of those treated by the upland BMPs to an off-channel treatment wetland allowed TMDLs to be met for an average precipitation year. WMOST can optimize cost-effectiveness of BMPs across multiple scales and climate scenarios. Full article

Background/Objectives: Restored CD4 absolute counts (CD4AC) and CD4/CD8 ratio in the setting of continuous antiretroviral treatment (ART) do not exclude a low-level immune activation associated with HIV reservoirs, microbial translocation, or the side effects of ART itself, which accelerates the aging of people living with HIV (PLHIV). To delineate biomarkers of incomplete immune restoration in PLHIV on successful ART, we evaluated T-lymphocyte mitochondrial parameters in relation to phenotypic markers of immune exhaustion and senescence. Methods: PLHIV with sustained viral suppression, CD4AC > 500 and CD4/CD8 ratio >0.9 on ART (n = 39) were compared to age-matched ART-naïve donors (n = 27) and HIV(–) healthy controls (HC, n = 35). CD4 and CD8 differentiation and effector subsets (CCR7/CD45RA and CD27/CD28), activation, exhaustion, and senescence markers (CD38, CD39 Treg, CD57, TIGIT, and PD-1) were determined by flow cytometry. Mitochondrial mass (MM) and membrane potential (MMP) of CD8 and CD4 T cells were evaluated with MitoTracker Green and Red flow cytometry dyes. Results: ART+PLHIV differed from HC by increased CD4 TEMRA (5.3 (2.1–8.8) vs. 3.2 (1.6–4.4), p < 0.05), persistent TIGIT+CD57–CD27+CD28– CD8+ subset (53.9 (45.5–68.9) vs. 40.1 (26.7–58.5), p < 0.05), and expanding preapoptotic TIGIT–CD57+CD8+ effectors (9.2 (4.3–21.8) vs. 3.0 (1.5–7.3), p < 0.01) in correlation with increased CD8+ MMP (2527 (1675–4080) vs.1477 (1280–1691), p < 0.01). These aberrations were independent of age, time to ART, or ART duration, and were combined with increasing CD4 T cell MMP and MM. Conclusions: In spite of recovered CD4AC and CD4/CD8 ratio, the increased CD8+ MMP, combined with elevated markers of exhaustion and senescence in ART+PLHIV, signals a malfunction of the CD8 effector pool that may compromise viral reservoir latency. Full article

Extracorporeal cardiopulmonary resuscitation (ECPR) is an established intervention for select patients experiencing refractory cardiac arrest. Among modifiable predictors of survival and neurologic recovery during ECPR implementation, timely restoration of circulation remains critical in the setting of refractory cardiac arrest (CA). The in-hospital cardiac arrest (IHCA) setting is particularly amenable to reducing the low-flow interval through structured system-based design and implementation. Despite increasing utilization of ECPR, the literature remains limited regarding operational standards, quality improvement metrics, and performance evaluation. Establishing operational standards and performance metrics is a critical first step toward systematically reducing low-flow interval duration. In support of this aim, we conducted a comprehensive literature review structured around the Extracorporeal Life Support Organization (ELSO) framework for ECPR implementation. At each step, we synthesized evidence-based best practices and identified operational factors that directly influence time-to-circulation. Our goal is to provide a stepwise evaluation of ECPR initiation to consolidate existing best practices and highlight process components with potential for further study and standardization. We further evaluated the literature surrounding key technical components of ECPR, including cannula selection, placement technique, and positioning. Ongoing research is needed to refine and standardize each stage of the ECPR workflow. Developing optimized, protocol-driven approaches to ensure rapid, high-quality deployment will be essential for improving outcomes with this lifesaving but resource-intensive therapy. Full article

The ongoing genetic erosion of natural Prunus armeniaca populations in their native habitats underscores the urgent need for targeted conservation and restoration strategies. This study provides the first comprehensive characterization of P. armeniaca populations in the Almaty region of Kazakhstan, integrating morphological descriptors (46 parameters), molecular markers, geobotanical, and remote sensing analyses. Geobotanical and remote sensing analyses enhanced understanding of accession distribution, geological features, and ecosystem health across sites, while also revealing their vulnerability to various biotic and abiotic threats. Of 111 morphologically classified accessions, 54 were analyzed with 13 simple sequence repeat (SSR) markers and four DNA barcoding regions. Our findings demonstrate the necessity of integrated morphological and molecular analyses to differentiate closely related accessions. Genetic analysis identified 11 distinct populations with high heterozygosity and substantial genetic variability. Eight populations exhibited 100% polymorphism, indicating their potential as sources of adaptive genetic diversity. Cluster analysis grouped populations into three geographic clusters, suggesting limited gene flow across Gorges (features of a mountainous landscape) and greater connectivity within them. These findings underscore the need for site-specific conservation strategies, especially for genetically distinct, isolated populations with unique allelic profiles. This study provides a valuable foundation for prioritizing conservation targets, confirming genetic redundancies, and preserving genetic uniqueness to enhance the efficiency and effectiveness of the future conservation and use of P. armeniaca genetic resources in the region. Full article

This study examines the use of a mass-abatement scalable system with managed aquifer recharge (MAR-MASS) as a sustainable solution for restoring salinized aquifers and improving water quality by removing dissolved salts. It offers a practical remediation approach for aquifers affected by salinization in coastal regions, agricultural areas, and contaminated sites, where variable-density flow poses a challenge. Numerical simulations assessed hydrogeological properties such as hydraulic conductivity, anisotropy, specific yield, mechanical dispersion, and molecular diffusion. A conceptual model integrated hydraulic conditions with spatial and temporal discretization using the FLOPY API for MODFLOW 6 and the IFM API for FEFLOW 10. Python algorithms were run within the high-performance computing (HPC) server, executing simulations in parallel to efficiently process a large number of scenarios, including both preprocessing input data and post-processing results. The study simulated 6950 scenarios, each modeling flow and transport processes over 3000 days of method implementation and focusing on mass extraction efficiency under different initial salinity conditions (3.5 to 35 kg/m³). The results show that the MAR-MASS effectively removed salts from aquifers, with higher hydraulic conductivity prolonging mass removal efficiency. Of the scenarios, 88% achieved potability (0.5 kg/m³) in under five years; among these, 79% achieved potability within two years, and 92% of cases with initial concentrations of 3.5–17.5 kg/m³ reached potability within 480 days. This study advances scientific knowledge by providing a robust model for optimizing managed aquifer recharge, with practical applications in rehabilitating salinized aquifers and improving water quality. Future research may explore MAR-MASS adaptation for diverse hydrogeological contexts and its long-term performance. Full article

Although intracranial hypertension (ICH) has traditionally been framed as simply a numerical escalation of intracranial pressure (ICP) and usually dealt with in its clinical form and not in terms of its complex underlying pathophysiology, an emerging body of evidence indicates that ICH is not simply an elevated ICP process but a complex process of molecular dysregulation, glymphatic dysfunction, and neurovascular insufficiency. Our aim in this paper is to provide a complete synthesis of all the new thinking that is occurring in this space, primarily on the intersection of glymphatic dysfunction and cerebral vein physiology. The aspiration is to review how glymphatic dysfunction, largely secondary to aquaporin-4 (AQP4) dysfunction, can lead to delayed cerebrospinal fluid (CSF) clearance and thus the accumulation of extravascular fluid resulting in elevated ICP. A range of other factors such as oxidative stress, endothelin-1, and neuroinflammation seem to significantly impair cerebral autoregulation, making ICH challenging to manage. Combining recent studies, we intend to provide a revised conceptualization of ICH that recognizes the nuance and complexity of ICH that is understated by previous models. We wish to also address novel diagnostics aimed at better capturing the dynamic nature of ICH. Recent advances in non-invasive imaging (i.e., 4D flow MRI and dynamic contrast-enhanced MRI; DCE-MRI) allow for better visualization of dynamic changes to the glymphatic and cerebral blood flow (CBF) system. Finally, wearable ICP monitors and AI-assisted diagnostics will create opportunities for these continuous and real-time assessments, especially in limited resource settings. Our goal is to provide examples of opportunities that exist that might augment early recognition and improve personalized care while ensuring we realize practical challenges and limitations. We also consider what may be therapeutically possible now and in the future. Therapeutic opportunities discussed include CRISPR-based gene editing aimed at restoring AQP4 function, nano-robotics aimed at drug targeting, and bioelectronic devices purposed for ICP modulation. Certainly, these proposals are innovative in nature but will require ethically responsible confirmation of long-term safety and availability, particularly to low- and middle-income countries (LMICs), where the burdens of secondary ICH remain preeminent. Throughout the review, we will be restrained to a balanced pursuit of innovative ideas and ethical considerations to attain global health equity. It is not our intent to provide unequivocal answers, but instead to encourage informed discussions at the intersections of research, clinical practice, and the public health field. We hope this review may stimulate further discussion about ICH and highlight research opportunities to conduct translational research in modern neuroscience with real, approachable, and patient-centered care. Full article

Oxysterols such as 7-ketocholesterol (7KCh) contribute to the pathogenesis of autoimmune and chronic inflammatory diseases by inducing oxidative stress and promoting pro-inflammatory immune cell activation. Dendritic cells (DCs) play a central role in maintaining immune tolerance, and their dysregulation is a key driver of autoimmunity. Targeting DCs by using natural compounds offers a promising strategy to restore redox balance and suppress aberrant immune responses. This study investigated the immunomodulatory and antioxidant properties of Lupeol, a natural triterpenoid, in human monocyte-derived DCs exposed to 7KCh. Flow cytometry and cytokine profiling demonstrated that Lupeol preserved the immature, tolerogenic phenotype of DCs by promoting a dose-dependent increase in the anti-inflammatory cytokine IL-10. Lupeol also inhibited the 7KCh-induced upregulation of maturation markers (CD83, CD86) and suppressed the release of pro-inflammatory cytokines IL-1β and IL-12p70. Functionally, Lupeol-treated DCs directed T cell polarization toward an anti-inflammatory and regulatory profile while dampening the inflammatory responses triggered by 7KCh. This immunoregulatory effect was further supported by the decreased secretion of the pro-inflammatory cytokines IL-1β and IL-12p70 in DC culture supernatants. Mechanistic analyses using immunofluorescence showed that Lupeol alone significantly increased nuclear NRF2 levels and upregulated HO-1 expression. Western blot analysis further confirmed Lupeol’s ability to activate the KEAP1-NRF2 signaling pathway, as evidenced by increased expression of NRF2 and its downstream target, NQO1. The use of ML385, a selective NRF2 inhibitor, in ROS and cytokine assays supported the involvement of NRF2 in mediating the Lupeol antioxidant and anti-inflammatory effects in DCs. Notably, the oxidative burden induced by 7KCh limited the full activation of NRF2 signaling triggered by Lupeol. Furthermore, docking and MM/PBSA analyses revealed the specific interactions of Lupeol with the kelch domain of KEAP1. These findings suggest that Lupeol may serve as a promising orally available immunomodulatory agent capable of promoting tolerogenic DCs, offering potential applications in autoimmune and other chronic inflammatory diseases. Full article