Search Results (34,120)

Toxoplasma gondii, the causative agent of toxoplasmosis, a disease widely distributed, is an intracellular parasite that invades host cells of different tissues using specialized endocytic activity. Recent studies suggest that tunneling nanotubes (TNTs), thin cell-surface projections, may participate in the parasite–host cell interaction. Here we report results that suggest the involvement of host-cell TNTs in the adhesion of T. gondii tachyzoites to epithelial LLC-MK² cells. Microscopy analysis showed that incubating cells in a medium containing 0.45 M sucrose induces reversible assembly of TNTs without affecting cell viability. The presence of extended TNTs correlated with increased parasite adhesion and reduced parasite entry, thus suggesting a structural or signaling role in mediating adhesion. TNTs assembled following sucrose incubation contain both actin and tubulin components as determined by immunofluorescence microscopy. These results highlight a possible functional relevance of TNTs in T. gondii host cell interaction, especially in parasite adhesion, opening new perspectives for understanding T. gondii-host cell interaction. Full article

Background and Objective: This study aimed to evaluate the impact of early functional rehabilitation on clinical outcomes and tuberosity healing in older patients undergoing reverse shoulder arthroplasty for proximal humeral fractures. We hypothesized that early functional rehabilitation would not compromise tuberosity healing and would result in comparable or improved outcomes versus postoperative immobilization. Methods: This retrospective matched-pair analysis included patients aged 70 years or older who underwent reverse shoulder arthroplasty for proximal humeral fractures, with 12 to 24 months of follow-up. Group allocation was time-based: earlier patients received immobilization and later patients underwent early rehabilitation. Matching was based on sex, age, body mass index, fracture classification (Neer), and glenosphere size. Outcomes included patient-reported scores, range of motion, and radiographic assessment of tuberosity healing using standardized imaging. Results: Forty patients (20 per group) with a mean age of 80.7 years and a mean follow-up of 16.1 months were included. The early rehabilitation group demonstrated significantly higher Constant scores (p = 0.044), age- and sex-adjusted Constant scores (p = 0.033), and greater active external rotation (p = 0.002). Anatomical tuberosity healing was seen in 28 of 40 patients (70%). Greater tuberosity healing occurred in 75% and lesser tuberosity healing in 85% of patients with available axial imaging. One deep infection occurred in the early rehabilitation group and was successfully managed. Conclusions: Early functional rehabilitation after reverse shoulder arthroplasty in older adults with proximal humerus fractures improved functional outcomes without compromising tuberosity healing. Full article

The third-quadrant operation of silicon carbide (SiC) MOSFETs is investigated from the perspective of carrier transport, focusing on the interaction between two parallel conduction paths. Through experimental characterization and TCAD simulation, the conduction behavior of the PiN body diode and MOS channel under various gate-source bias conditions is examined. Results reveal that body-effect-induced threshold voltage (Vth) reduction enables channel conduction even under negative gate bias. Based on this mechanism, a transfer-characteristic-based method is developed to identify gate-voltage boundaries between conduction modes. The impact of negative gate bias on reverse recovery parameters, peak current (I_rr), charge (Q_rr), and time (t_rr), is quantitatively evaluated. At the unit-cell level, current sharing between the two paths is analyzed, clarifying the physical mechanism governing their redistribution. Full article

Malaria is one of the major global public health issues. An estimated 282 million malaria cases occurred worldwide in 2024, and the overall prevention and control progress has stagnated or even reversed in some regions. Mass drug administration (MDA), as a potential strategy to accelerate malaria elimination, has regained attention. This paper reviews the evidence base, controversial focuses, and application strategies of MDA in malaria prevention and control. It aims to promote its scientific application in the elimination phase. MDA plays an important role in malaria prevention and control. However, this strategy is accompanied by core limitations such as long-term drug resistance risks, insufficient implementation sustainability, and a high failure rate of regional adaptation. It also faces challenges from multiple common malaria species, as well as the newly discovered Plasmodium knowlesi. We therefore propose an “MDA+” collaborative strategy integrating vaccines, digital monitoring, and cross-border cooperation, so as to optimize resource allocation, achieve full coverage control over various malaria parasites, and advance the global malaria elimination process. Full article

Cardiac fibrosis is a central determinant of heart failure progression and arises from pathological remodeling characterized by fibroblast activation, myofibroblast differentiation, and excessive extracellular matrix deposition. In contrast, physiological remodeling permits adaptive cardiac growth without net fibrosis. Pregnancy represents an underexplored physiological model of reversible cardiac remodeling. In response to hemodynamic load, the maternal heart undergoes hypertrophic growth that resolves postpartum, constituting a natural paradigm of fibrosis-resistant cardiac adaptation. Pregnancy and lactation are accompanied by profound endocrine and immune reprogramming of maternal tissues. We propose that this hormonal milieu orchestrates coordinated crosstalk among endothelial cells, fibroblasts, and immune cell populations to suppress profibrotic pathways and preserve extracellular matrix homeostasis. Candidate regulators include estrogen, progesterone, prolactin family peptides, relaxin, oxytocin, and components of the renin–angiotensin–aldosterone system. During the postpartum and lactational period, prolactin and oxytocin may further promote reverse remodeling. These hormones likely act by modulating local cytokine and growth factor networks that otherwise drive fibroblast activation. By focusing on non-myocyte cardiac cells and extracellular matrix dynamics, this review positions pregnancy as a translational model to uncover endogenous anti-fibrotic mechanisms and identify novel therapeutic strategies for cardiac fibrosis. Full article

Endothelial dysfunction (ED) arises in multiple pathologies, and its severity correlates with disease progression. Common ED biomarkers could provide prognostic value for associated complications. This study aims to identify shared ED biomarkers and assess their prognostic significance. Endothelial cells in culture (human microvascular endothelial cells, HMEC-1) were exposed to sera from patients in five disease groups (n = 20 patients/group)—liver cirrhosis with portal hypertension, idiopathic pulmonary arterial hypertension, placental disorders such as intrauterine growth restriction, coronary artery disease with acute myocardial infarction, and chronic kidney disease—or matched controls, in the absence/presence of anti-inflammatory (apixaban) and antioxidant (EUK134) compounds. We explored changes in: VCAM-1, ICAM-1, eNOS, VWF, extracellular matrix thrombogenicity, and reactive oxygen species (ROS). In serum samples, proteomics and metabolomics analyses (including lipids, amino acids, and polar metabolites) were performed through an extraction protocol to identify common ED biomarkers. Expression of VCAM-1, ICAM-1, VWF, platelet adhesion, and ROS increased in most groups versus controls (p < 0.05). Both drugs decreased all biomarker levels except eNOS (n = 6 for in vitro experiments). For serum ED biomarkers, 18 metabolites and 24 proteins showed AUC-ROC and hit rates >77.5%, and six metabolites were associated with event-free survival. These diseases share ED driven by systemic inflammatory, oxidative, and metabolic stress, are partially reversible in vitro, and are linked to biomarkers associated with clinical outcomes. Overall, ED emerges as a modifiable pathological axis with potential prognostic value. Full article

Neuronal activity and cerebral blood flow are tightly coupled to support the high metabolic demands of the brain. Disruption of neurovascular coupling is a defining feature of many neurodegenerative disorders such as Alzheimer’s disease, stroke, small vessel disease, Parkinson’s disease, and aging. Progress in understanding the mechanisms underlying neurovascular coupling requires experimental approaches that can simultaneously measure neuronal activity and vascular dynamics with high spatial and temporal resolution, while also enabling targeted perturbations of the system. Here, we present a methodological framework that combines chronic electrophysiological recordings with two-photon imaging of cerebral blood flow and optogenetic manipulation of the vasculature in vivo. Using a chronically implanted flexible electrode array, we obtain measurements of the single- and multi-unit spiking activity, as well as local field potentials. Concurrently, two-photon microscopy enables high-resolution measurements of vessel diameter and blood flow within individual vascular segments. In addition, optogenetic control of vascular smooth muscle cells allows for rapid and reversible manipulation of the vessel diameter through the same cranial window while simultaneously recording the neural and vascular activity. We provide detailed protocols for surgical implantation, data acquisition, and analysis, and discuss experimental considerations and limitations. This combined platform offers a powerful tool for mechanistic studies of neurovascular coupling and its dysfunction in disease models. Full article

This study investigates the impact of oil prices and exchange rates on the manufacturing output of small and medium-sized enterprises (SMEs) in Kazakhstan using data from the period 2000 to 2023, within the framework of the ARDL model. In the Kazakhstani economy, approximately 60% of SMEs operate in the wholesale and retail trade sectors, a factor that has been taken into consideration in interpreting the effects of macroeconomic variables on SME output. The results of the long-run analysis reveal that the exchange rate has a significant and strong positive effect on SME manufacturing output. Although oil prices do not directly exert a statistically significant influence on production output, the study identifies an indirect effect of oil revenues on SME output via the exchange rate channel. In the short-run findings, both exchange rates and oil prices are found to have significant effects on production output; in particular, oil prices exhibit a positive impact in the short term, which partially reverses in subsequent periods. The error correction term indicates a rapid adjustment back to equilibrium in the long run. These results highlight the high sensitivity of SME production performance in Kazakhstan to exchange rate fluctuations and underscore the indirect influence of oil prices through exchange rate movements. The study recommends enhancing the financial resilience of SMEs, minimizing exchange rate risks, and closely monitoring changes in energy prices. Furthermore, it suggests the development of policies aimed at promoting SMEs’ involvement in foreign currency-generating activities, as well as protecting enterprises in the wholesale and retail sectors against price volatility. In this context, the study makes a valuable contribution by providing a comprehensive evaluation of the effects of macroeconomic variables on SME manufacturing output. Full article

This study aimed to investigate the molecular mechanisms underlying dopaminergic injury induced by gestational and lactational atrazine (ATR) exposure in rat offspring, with a particular focus on non-coding RNA-mediated regulation. Pregnant rats were exposed to ATR during gestation and lactation. Offspring underwent behavioral testing at postnatal day 21 (PND21) and were sacrificed for midbrain tissue collection at PND28. Behavioral alterations, histopathological changes in the substantia nigra, and dopaminergic marker expression were assessed to evaluate ATR-induced neurotoxicity. Whole-transcriptome sequencing was then performed to identify differentially expressed mRNAs, miRNAs, and lncRNAs, followed by co-expression, protein–protein interaction, and competing endogenous RNA (ceRNA) network analyses. Key targets were validated by qRT-PCR. Candidate molecules identified from transcriptomic and ceRNA analyses were further examined in an ATR-induced neurotoxicity model established in RA-differentiated SK-N-SH cells. Dual-luciferase reporter, Ago2-RNA immunoprecipitation, and biotin-labeled RNA pull-down assays were used to examine putative binding relationships and molecular interactions. In addition, lentivirus-mediated Elavl4 overexpression was performed to further evaluate the role of this candidate regulator in ATR-induced Nurr1 downregulation. Gestational and lactational ATR exposure induced significant behavioral abnormalities in rat offspring. These changes were accompanied by histopathological alterations in the substantia nigra, including reduced TH immunoreactivity, as well as abnormal expression of dopaminergic markers, characterized by decreased TH and Nurr1 levels and increased α-syn expression. Together, these findings indicate the presence of dopaminergic injury. Whole-transcriptome analysis further revealed widespread dysregulation of mRNAs, miRNAs, and lncRNAs in ATR-exposed offspring. Subsequent integrative analysis suggested a potential ceRNA regulatory relationship among Elavl4, miR-301a-5p, and Nurr1, which was further supported by qRT-PCR. Dual-luciferase reporter, RIP, and RNA pull-down assays supported direct interactions between miR-301a-5p and both Elavl4 and Nurr1, as well as their association with the Ago2-containing silencing complex. Moreover, Elavl4 overexpression partially reversed ATR-induced Nurr1 downregulation in vitro. Gestational and lactational ATR exposure induced behavioral abnormalities and dopaminergic injury in rat offspring. Whole-transcriptome analysis combined with experimental validation suggests a potential association between the Elavl4/miR-301a-5p/Nurr1 ceRNA axis and ATR-induced dopaminergic injury, providing insight into the post-transcriptional mechanisms underlying developmental neurotoxicity. Full article

Graphite remains the predominant negative electrode material in commercial lithium-ion batteries (LIBs); however, its practical performance is increasingly limited by interface-driven degradation rather than bulk intercalation. This review examines the interconnected electrochemical, mechanical, and safety challenges associated with uncoated and coated graphite, with particular focus on how solid electrolyte interphase (SEI) formation and evolution deplete cyclable lithium, increase interfacial resistance, and induce polarization that leads to lithium plating and dendritic growth during rapid charging and low-temperature operation. Electrolyte and solvation engineering are highlighted as coating-free strategies to mitigate these issues by reducing Li⁺ desolvation barriers and directing interphase chemistry toward thinner, more ion-conductive, fluorinated SEI films that inhibit plating while maintaining high-rate capability. Coated graphite approaches are compared, including carbon, inorganic, and polymer coatings that function as artificial SEI layers to minimize direct electrolyte contact, stabilize interphase composition, and enhance mechanical durability. Key trade-offs are discussed, including decreased first-cycle coulombic efficiency (FCCE) due to increased surface area, transport limitations arising from excessively thick coatings, nonuniform coverage leading to local current hotspots, and side reactions induced by the coatings. The discussion is further extended to sodium and potassium systems, explaining how larger ion sizes, unfavorable thermodynamics, and significant lattice expansion hinder their insertion into graphite, and summarizing strategies such as interlayer expansion and alternative carbon architectures that improve reversibility for larger ions. This review concludes that achieving durable, safe, and fast-charging graphite electrodes requires an integrated interfacial design that combines optimized graphite morphology, electrode architecture, and electrolyte chemistry. Full article

Chemotherapy-induced mucositis (CIM) is a dose-limiting toxicity of cancer therapy that is mainly associated with mitochondrial dysfunction in epithelial cells. We investigated whether GV1001, a mitochondrial protective peptide from human telomerase reverse transcriptase (hTERT), attenuates 5-fluorouracil (5-FU)-induced mucositis in a murine model. 5-FU induced notable mortality, leukopenia, and mucositis in the gastrointestinal (GI) tract, including tongue, esophagus and small intestine. It promoted epithelial–mesenchymal transition (EMT), nuclear factor kappa-B (NF-κB) activation, systemic and mucosal inflammation, DNA damage, impaired cell proliferation, and apoptosis throughout the GI tract. GV1001 blocked 5-FU–associated mortality, significantly attenuated leukopenia, and notably prevented mucositis. GV1001 also suppressed 5-FU-induced DNA damage, EMT, loss of proliferative capacity, apoptosis, and NF-κB activation in mucosal epithelium. In normal human keratinocytes, 5-FU inhibited the cell proliferation, disrupted mitochondrial function, as evidenced by reduced mitochondrial membrane potential, increased reactive oxygen species (ROS) production, impaired electron transport chain (ETC) complex integrity, decreased ATP synthesis, and cytochrome c release into the cytosol. GV1001 markedly mitigated these 5-FU-induced mitochondrial defects. Taken together, GV1001 mitigates CIM by most likely preserving mitochondrial integrity and function, supporting its potential as a strategy to prevent cancer chemotherapy-associated mucosal injury in patients. Full article

Background/Objectives: Malaria remains a major global health burden, particularly in sub-Saharan Africa, where the recent invasion and urban expansion of Anopheles stephensi are increasing transmission risk in densely populated areas. Conventional vector control strategies, including widespread insecticide application, are progressively losing efficacy due to the rapid spread of resistance. These limitations have accelerated the development of genetic control approaches aimed at either suppressing vector populations or replacing them with genetically modified mosquitoes incapable of transmitting pathogens, with the shared objective of reducing disease transmission. For population suppression strategies, an essential component is a conditional regulatory system that enables precise control of toxic or otherwise deleterious effector proteins. The most widely used platform, the tetracycline-dependent (Tet) system, modulates gene expression in response to tetracycline. However, this system can exhibit leaky expression and variable regulation, which may compromise its reliability and limit its application in certain contexts. The dihydrofolate reductase (DHFR) destabilization domain (DD) system, developed in Drosophila, offers an alternative strategy for post-translational control of protein stability. In this system, proteins fused to a destabilization domain are rapidly degraded unless stabilized by the small molecule trimethoprim (TMP), enabling tight and reversible control. In Drosophila and prior reports, this system has been associated with relatively low fitness costs, although such effects have not been systematically evaluated in mosquitoes. Before adapting this system for mosquito genetic control, it is therefore essential to assess the impact of TMP exposure on key life-history traits. Methods: Here, we assessed the effects of varying TMP concentrations on mosquito development, survival, and reproductive output. Results: Our results demonstrate that low concentrations of TMP exposure had no detectable effects on immature development, adult survival, or reproductive output under the conditions tested, supporting the implementation of the DHFR-DD system in mosquitoes. Importantly, these effects were dose-dependent, with moderate to high TMP concentrations producing measurable impacts on mosquito fitness. Conclusions: These findings provide a foundational step toward the development of more precise and reliable conditional expression systems for genetic vector control, advancing innovative strategies to mitigate malaria transmission in high-risk regions. Full article

Sodium-ion batteries (SIBs) represent a compelling alternative to lithium-ion batteries for grid-scale energy storage, owing to the high natural abundance and low cost of sodium resources, as well as their strategic alignment with national energy security priorities. Nevertheless, the sluggish Na⁺ diffusion kinetics and limited specific capacity of anode materials continue to impede practical deployment. Herein, nitrogen-doped carbon-coated TiO₂ nanofibers (TiO₂/C-N) were rationally engineered through a facile electrospinning route integrated with synergistic defect and coating engineering. The in situ-formed N-doped carbon shell establishes a continuous, high-conductivity electron-transport network while simultaneously buffering volumetric strain during repeated (de)sodiation, thereby preserving long-term structural integrity. Electrochemical assessments demonstrate that the TiO₂/C-N electrode delivers a reversible specific capacity of 233.64 mAh g⁻¹ at 0.1 A g⁻¹ (initial Coulombic efficiency 54.13%). Quantitative kinetic analysis reveals a pronounced pseudocapacitive contribution of 41.4% at 1.2 mV s⁻¹, confirming a surface-controlled Na⁺ storage pathway that markedly enhances rate capability. Moreover, the electrode retains 245.5 mAh g⁻¹ after 150 cycles at 1 A g⁻¹, underscoring exceptional cycling stability. This work elucidates the synergistic regulation of N-doped carbon coating and pseudocapacitive kinetics in TiO₂-based anodes, offering a robust design strategy for high-rate, long-cycle-life SIB anodes. Full article

The rapid integration of distributed solar photovoltaic (PV) generation is reshaping low-voltage distribution grids (LVDGs), creating voltage rise, reverse power flow, and congestion challenges for distribution system operators (DSOs). Flexibility in generation and demand, broadly understood as the capability to adjust generation or consumption in response to variability and uncertainty in net load, is increasingly central to cost-effective grid operation under high PV penetration. This review examines flexibility and controllability options in LVDGs, focusing on voltage regulation methods, supply- and demand-side flexibility resources, and market-based coordination mechanisms. The Norwegian Regulation on Quality of Supply (FoL) provides the regulatory context: it enforces 1 min average voltage compliance, stricter than the 10 min averaging window of EN 50160, making short-duration voltage excursions operationally significant and directly influencing the trade-off between curtailment, grid reinforcement, and local flexibility measures. Inverter-based active–reactive power control emerges as the most cost-effective overvoltage mitigation option, complemented by local battery energy storage systems (BESS) and demand response for congestion relief and energy shifting. Key gaps include limited LV observability, insufficient application of quasi-static time series (QSTS) assessment in planning, and underdeveloped DSO-aggregator coordination frameworks. Combined inverter control, feeder-end storage, and demand-side flexibility can defer costly reinforcements, particularly in rural 230 V IT feeders where voltage constraints dominate. Full article

Topsoil sand content (TSC) is a critical indicator of soil degradation in black soil regions, yet its long-term dynamics remain poorly quantified. To address this, we developed an automated Landsat-based framework on Google Earth Engine (GEE) for mapping cropland TSC across the Northeast China Black Soil Region (NCBSR) from 1984 to 2023. The methodology integrates a hierarchical bare-soil extraction strategy using the Normalized Difference Bare Soil Index (NDBSI), Normalized Difference Vegetation Index (NDVI), and Normalized Difference Tillage Index (NDTI) with a Random Forest (RF) model optimized by three-band spectral indices and a “prediction-first” compositing workflow. Results demonstrate that the bare-soil extraction achieved an overall accuracy of 96%, while the TSC retrieval model maintained robust performance with a coefficient of determination (R²) of 0.80 and a root mean square error (RMSE) of 9.68%, together with satisfactory temporal transferability. Long-term mapping revealed a significant biphasic evolutionary trajectory: 23.4% of croplands experienced soil coarsening predominantly before 2000, followed by a partial reversal and stabilization in later decades. This framework provides a high-resolution, multi-decadal baseline for monitoring soil physical degradation and supports sustainable agricultural management in global black soil regions. Full article