Search Results (34,124)

Marine turtle and cetacean strandings along the Italian coastline represent critical ecological events that require systematic documentation, yet historical data have suffered from fragmentation and poor accessibility across heterogeneous archives. GeoCetus addresses this gap by providing a unified national framework for the centralized collection, management, and open visualization of these data. The platform’s architecture integrates a spatially enabled database with a modern RESTful API, utilizing automated workflows to push data to a public GitHub.com repository. This system unifies historical and contemporary datasets, comprising over 4700 georeferenced records dating back to 1999, while ensuring data quality through structured validation, qualified contributors and reverse geocoding. The results demonstrate a significant improvement in data interoperability and democratization, with the dataset expanding by an average of 150–300 new records annually under a CC-BY-SA license. By adhering to FAIR Data Principles, GeoCetus offers the necessary infrastructure to support real-time operational responses and reproducible ecological analyses. We conclude that this standardized, machine-readable approach is essential for evidence-based national conservation strategies and effective environmental monitoring. Full article

Kratom (Mitragyna speciosa) is a botanical candidate for pain management with potentially reduced opioid-related risks, partly through modulation of neuroimmune pathways involving Toll-Like Receptor 4 (TLR4). This study aimed to characterize the phytochemical profile of kratom ethanol extract and evaluate its effects on TLR4 signalling, neuroinflammatory cytokines, analgesic activity, withdrawal behaviours, and organ safety in morphine-dependent mice. Metabolite profiling was conducted using UHPLC–Q-Exactive Orbitrap HRMS, followed by molecular docking of major constituents to the TLR4 complex. In vivo assessments included flow cytometry and gene expression analyses of TLR4-mediated cytokines (NF-κB, IL-1β, IL-6), behavioural assays for antinociception, endurance, and withdrawal symptoms, and histopathological and biochemical evaluation of liver, kidney, and spleen tissues. More than 100 metabolites were identified, including mitragynine and flavonoids such as rutin and isoquercetin, which showed interactions with key TLR4 residues. Selected fractions suppressed pro-inflammatory cytokine expression, increased tail-pinch latency comparable to morphine, reduced withdrawal manifestations, and demonstrated nephroprotective and immunomodulatory effects, although mild reversible hepatic alterations were observed in specific fractions. Overall, kratom ethanol extract exhibited fraction-dependent analgesic and anti-neuroinflammatory activities associated with TLR4 modulation, supporting its potential as a botanical analgesic candidate while emphasizing the importance of safety optimization and standardized fraction development. Full article

Despite prolonged viral inhibition with combination antiretroviral therapy (ART), HIV-1 survives as genetically intact, replication-capable proviruses within durable CD4+ T-cell fractions, involving central memory, transitional memory, and stem cell-like memory populations, as well as within tissue-resident compartments including lymphoid follicles and gut-associated lymphoid tissue. Reservoir stability is preserved via clonal growth of infected cells and epigenetic processes that impose proviral transcriptional silencing. As a result, current therapeutic approaches seek to either directly alter proviral survival or to improve immune-driven elimination of infected cells. At the molecular level, investigational strategies such as CRISPR–Cas9 and CRISPR–Cas12 gene-editing systems are intended to remove or induce inactivating mutations inside embedded proviral DNA, as well as alter host entrance co-receptors such as CCR5 to provide cellular resistance to infection. In addition, pharmacologic latency regulation is being studied via histone deacetylase inhibitors, protein kinase C agonists, and bromodomain inhibitors to reverse latency, along with Tat inhibitors and other transcriptional repressors aimed to persistently silence proviral expression. Moreover, immunological techniques aim to counteract inefficient endogenous antiviral defenses. Broadly neutralizing antibodies with tailored Fc-driven effector functions are under examination for both neutralization and antibody-dependent cellular cytotoxicity. Therapeutic vaccine approaches seek to elevate polyfunctional HIV-specific CD8+ T-cell responses, while adoptive cellular approaches, involving CAR-T cells aiming HIV envelope epitopes, remain in early clinical research. Immune checkpoint blockade is also being investigated to reverse T-cell depletion inside reservoir-rich tissues. Nevertheless, the key obstacles continue to be the diverse reservoir composition, restricted tissue penetration, viral escape, and safety limitations. The molecular and translational obstacles that characterize attempts toward an HIV cure must be addressed through ongoing multidisciplinary research. Full article

Three crosslinked polyurethane copolymers were successfully synthesized as polymeric solid–solid phase change materials (SSPCMs) for thermal energy storage. These materials were fabricated utilizing trihydroxy compounds (glycerol, triethanolamine, and trimethylolethane) as chain extenders and polyethylene glycol (PEG) as the phase change functional segment. A comprehensive suite of characterization techniques was employed to investigate the chemical structures, thermal properties, and crystalline behaviors of the resulting SSPCMs. Fourier transform infrared (FTIR) spectroscopy confirmed the successful synthesis of the crosslinked polyurethane network. Polarizing optical microscopy (POM) and wide-angle X-ray diffraction (WAXD) analyses revealed that all three SSPCMs exhibit regular spherulitic morphologies with sharp diffraction peaks resembling those of pure PEG, although variations in spherulite size and diffraction intensity were observed among the samples. Differential scanning calorimetry (DSC) demonstrated the reversible latent heat storage and release capabilities of the synthesized SSPCMs, with a maximum endothermic enthalpy (ΔH_endo) of 115.7 J/g. Furthermore, thermal cycling tests and thermogravimetric (TG) analysis verified their exhibit excellent reusability, thermal reliability, and high thermal stability. Full article

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