Search Results (9,092)

Renal oncocytoma (RO) is a benign renal neoplasm characterized by dense accumulation of dysfunctional mitochondria possibly resulting from increased mitochondrial biogenesis and decreased mitophagy; however, the mechanisms controlling these mitochondrial changes are unclear. ROs harbor recurrent inactivating mutations in mitochondrial genes encoding the Electron Transport Chain (ETC) Complex I, and we hypothesize that Complex I loss in ROs directly impairs mitophagy. Our analysis of ROs and normal kidney (NK) tissues shows that a significant portion (8 out of 17) of ROs have mtDNA Complex I loss-of-function mutations with high variant allele frequency (>50%). ROs indeed exhibit reduced Complex I expression and activity. Analysis of the various steps of mitophagy pathway demonstrates that AMPK activation in ROs leads to induction of mitochondrial biogenesis, autophagy, and formation of autophagosomes. However, the subsequent steps involving lysosome biogenesis and function are defective, resulting in an overall inhibition of mitophagy. Inhibiting Complex I in a normal kidney cell line recapitulated the observed lysosomal and mitophagy defects. Our data suggest Complex I loss in RO results in defective mitophagy due to lysosomal loss and dysfunction. Full article

Green hydrogen is a clean, versatile, and future-oriented fuel that can play a key role in the energy transition, decarbonization of the economy, and climate protection. It offers an alternative to fossil fuels and can be used in various applications, including power generation, industry, and transportation. However, due to its wide flammability range, small molecular size, and high diffusivity, special attention must be paid to ensuring safety during its use, particularly in leakage control. This paper provides a review and analysis of equipment leakage testing methods used for natural gas, with a view to applying these methods to the leakage testing of gas meters intended for hydrogen-containing gas mixtures and pure hydrogen. Tests of simulated leaks were carried out using two common methods: the bubble method and the pressure decay method, for three different gases: nitrogen (most commonly used for leak testing), helium, and hydrogen. The results obtained from the tests and analyses made it possible to verify and select optimum leak-testing methods for gas meters designed for measuring fuels containing hydrogen. Full article

The sphingolipidoses Fabry disease, Gaucher disease and Acid sphingomyelinase deficiency (ASMD) are the three most common lysosomal storage diseases for which treatment is currently available. Timely diagnosis with estimation of the disease severity and possibilities of follow-up of patients, whether or not under therapy, is crucial for providing good care and for the prevention of possible lethal complications. With this research we provide an efficient and sensitive detection method; its implementation in clinical practice could optimize the diagnosis and follow-up of patients with Gaucher, Fabry and ASMD. This detection method on dried blood spots (DBS) was validated according to the international Clinical and Laboratory Standards Institute (CLSI) guidelines, looking at reproducibility, linearity, carry-over and lower limit of quantification. Analogously, validation and subsequent comparison of the method validation results using another matrix, the Capitainer blood sampling cards (Capitainers), was fulfilled. The results showed that this detection method is fully applicable clinically when using DBS as well as Capitainers. In addition, even additional improvements of some validation parameters were found when using the Capitainers. Twenty-six patient samples and fifteen healthy samples were analyzed for case finding control. All patient cases were detected without ambiguity. We present a high-resolution mass spectrometry method that provides an accurate analysis for targeted screening, aiming for improved/accelerated diagnosis when added in the diagnostic pathway and monitoring of Fabry, Gaucher and ASMD in DBS as well as in Capitainers, with the main advantages of a small volume of blood samples, guaranteeing stability and easy transportation from the collection site to the laboratory. Full article

The intra-articular application of drugs has gained considerable interest with regard to formulations for advanced drug delivery systems. It has been identified as a potential route for local drug delivery. A drug agent is usually incorporated into the hydrogel to prolong and control the drug release. This study aimed to design and evaluate an intra-articular hydrogel based sodium hyaluronate, which was modified with an additional polymer to enable the sustained release of the incorporated anti-inflammatory agent, diclofenac sodium (NaDic). Viscosity studies, drug release tests and FTIR−ATR measurements, as well as DSC analysis, were carried out to evaluate the obtained formulations. The viscosity measurements were performed using a rotational viscometer. The drug release was carried out by employing the apparatus paddle over the disk. The concentration of the released drug was obtained spectrophotometrically. The results revealed that the addition of the second polymer to the matrix influenced the dynamic viscosity of the hydrogels. The highest viscosity of (25.33 ± 0.55) × 10³ cP was observed when polyacrylic acid (PA) was doped in the formulation. This was due to the hydrogen bond formation between both polymers. The FTIR−ATR investigations and DSC study revealed the hydrogen bond formation between the drug and both polymers. The drug was released the slowest from hydrogel doped with PA and 17.2 ± 3.7% of NaDic was transported to the acceptor fluid within 8 h. The hydrogel based on hyaluronan sodium doped with PA and containing NaDic is a promising formulation for the prolonged and controlled intra-articulate drug delivery of anti-inflammatory agents. Full article

While the Ankom RF system facilitates efficient high-throughput in vitro fermentation studies, its high cost and limited flexibility constrain its broader applicability. To address these limitations, we developed and validated a low-cost, modular gas monitoring system (FerME), assembled from commercially available components. To evaluate its performance and reproducibility relative to the Ankom RF system (Ankom Technology, Macedon, NY, USA), in vitro rumen fermentation experiments were conducted under strictly controlled and identical conditions. Whole rumen contents were collected approximately 2 h post-feeding from individual mid- or late-lactation dairy cows and immediately transported to the laboratory. Each fermenter received 50 mL of processed rumen fluid, 100 mL of anaerobically prepared artificial saliva buffer, and 1.2 g of the donor cow’s diet. Bottles were sealed with the respective system’s pressure sensors, flushed with CO₂, and incubated in a 50 L water bath maintained at 39 °C. FerME (New Taipei City, Taiwan) and Ankom RF fermenters were placed side-by-side to ensure uniform thermal conditions. To assess the effect of filter bag use, an additional trial employed Ankom F57 filter bags (Ankom Technology, Macedon, NY, USA; 25 μm pore size). Trial 1 revealed no significant differences in cumulative gas production, volatile fatty acids (VFAs), NH₃-N, or pH between systems (p > 0.05). However, the use of filter bags reduced gas output and increased propionate concentrations (p < 0.05). Trial 2, which employed filter bags in both systems, confirmed comparable results, with the FerME system demonstrating improved precision (CV: 4.8% vs. 13.2%). Gas composition (CH₄ + CO₂: 76–82%) and fermentation parameters remained consistent across systems (p > 0.05). Importantly, with 12 pressure sensors, the total cost of FerME was about half that of the Ankom RF system. Collectively, these findings demonstrate that FerME is a reliable, low-cost alternative for real-time rumen fermentation monitoring and could be suitable for studies in animal nutrition, methane mitigation, and related applications. Full article

Background: Disruptions in freight transportation—such as service delays, infrastructure failures, and labor strikes—pose significant challenges to the reliability and efficiency of intermodal networks. To address these challenges, this study introduces Adaptive Intermodal Transportation (AIT), a resilient and flexible planning framework that enhances Synchromodal Freight Transport (SFT) by integrating real-time disruption management. Methods: Building on recent advances, we propose two novel strategies: (1) Reassign with Delay Buffer, which enables dynamic rerouting of shipments within a user-defined delay tolerance, and (2) (De)Consolidation, which allows splitting or merging of shipments across services depending on available capacity. These strategies are incorporated into a re-planning module that complements a baseline optimization model and a continuous disruption-monitoring system. Numerical experiments conducted on a Great Lakes-based case study evaluate the performance of the proposed strategies against a benchmark approach. Results: Results show that under moderate and high-disruption conditions, the proposed strategies reduce delay and disruption-incurred costs while increasing the percentage of matched shipments. The Reassign with Delay Buffer strategy offers controlled flexibility, while (De)Consolidation improves resource utilization in constrained environments. Conclusions: Overall, the AIT framework demonstrates strong potential for improving operational resilience in intermodal freight systems by enabling adaptive, disruption-aware planning decisions. Full article

Sodium–glucose co-transporter-2 inhibitors (SGLT2is) and GLP-1 receptor agonists (GLP-1 RAs) are now established as cornerstone therapies for patients with type 2 diabetes mellitus (T2DM), given their cardiovascular and renal protective properties. However, their use in patients with peripheral artery disease (PAD) remains controversial due to concerns raised in early trials about potential increases in lower limb complications, particularly amputations. This narrative review examines current evidence on the association between SGLT2is and GLP-1 RAs in PAD-related outcomes, including limb events, amputation risk, and cardiovascular and renal endpoints. Drawing from randomized controlled trials, real-world cohort studies, and systematic reviews, we provide an integrated perspective on the safety and utility of SGLT2is and GLP-1 RAs in individuals with PAD, highlight patient selection considerations, and identify areas for future investigation. Full article

Cystic fibrosis (CF), the most common hereditary lung disease in Caucasians, is caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR). We evaluated CFTR function using a newly developed Ussing chamber system, the Multi Trans Epithelial Current Clamp (MTECC), in an in vitro model of human airway epithelia. Air–liquid interface (ALI) cultures were established from nasal brushings of healthy controls (HC) and CF patients with biallelic CFTR variants. ALI layer thickness was similar between groups (HC: 62 ± 13 µm; CF: 55 ± 9 µm). Immunofluorescence showed apical CFTR expression in HC, but reduced or absent signal in CF cultures. MTECC enabled continuous measurement of transepithelial resistance (Rt), potential difference (PD), and conductance (G_t). G_t was significantly reduced in CF cultures compared to HC (0.825 ± 0.024 vs. −0.054 ± 0.016 mS/cm²), indicating impaired cAMP-inducible ion transport by CFTR. Treatment of CF cultures with elexacaftor, tezacaftor, and ivacaftor (Trikafta^®) increased G_t, reflecting partial restoration of CFTR function. These findings demonstrate the utility of MTECC in detecting functional differences in CFTR activity and support its use as a platform for evaluating CFTR-modulating therapies. Our model may contribute to the development of personalized treatment strategies for CF patients. Full article

In the summer of 2022, central and eastern China experienced prolonged extreme high temperatures and severe drought, leading to significant economic losses. To gain a more profound understanding of this drought event and furnish a reference for forecasting similar events in the future, this study examines the circulation anomalies associated with the drought. Employing a diagnostic method focused on temperature and moisture anomalies, this study introduces a novel approach to quantify and compare the relative significance of moisture transport and warm air dynamics in contributing to the drought. This study examines the atmospheric circulation anomalies linked to the drought event and compares the relative contributions of water vapor transport and warm air activity in causing the drought, using two parameters defined in the paper. The results show the following: (1) The West Pacific Subtropical High (WPSH) was more intense than usual and extended westward, consistently controlling the Yangtze River Basin. Simultaneously, the polar vortex area was smaller and weaker, the South Asian High area was larger and stronger, and it shifted eastward. These factors collectively led to weakened water vapor transport conditions and prevailing subsiding air motions in the Yangtze River Basin, causing frequent high temperatures. (2) By defining I_q and I_t to represent the contributions of moisture and temperature to precipitation, we found that the drought event in the Yangtze River Basin was driven by both reduced moisture supplies in the lower troposphere and higher-than-normal temperatures, with temperature playing a dominant role. Full article

Famatinite (Cu₃SbS₄) is an earth-abundant, nontoxic material with potential for thermoelectric energy generation applications. Herein, rapid, energy-efficient, and facile one-pot modified polyol synthesis was utilized to produce gram-scale quantities of phase-pure famatinite (Cu_2.7M_0.3SbS₄, M = Cu, Zn, Mn) nanoparticles (diameter 20–30 nm) with controllable and stoichiometric incorporation of transition metal dopants on the Cu-site. To produce pellets for thermoelectric characterization, the densification process by spark plasma sintering was optimized for individual samples based on thermal stability determined using differential scanning calorimetry and thermogravimetric analysis. Electronic transport properties of undoped and doped famatinite nanoparticles were studied from 225–575 K, and the thermoelectric power factor was calculated. This is the first time electronic transport properties of famatinite doped with Zn or Mn have been studied. All famatinite samples had similar resistivities (>0.8 mΩ·m) in the measured temperature range. However, the Mn-doped famatinite nanomaterials exhibited a thermoelectric power factor of 10.3 mW·m⁻¹·K⁻¹ at 575 K, which represented a significant increase relative to the undoped nanomaterials and Zn-doped nanomaterials engendered by an elevated Seebeck coefficient of ~220 µV·K⁻¹ at 575 K. Future investigations into optimizing the thermoelectric properties of Mn-doped famatinite nanomaterials are promising avenues of research for producing low-cost, environmentally friendly, high-performing thermoelectric materials. Full article

TRPV1 regulates neuronal and vascular function mediated by NO and CGRP. Systemic arterial hypertension (SAH) induces an imbalance in vascular mediators NO and CGRP by altering the transport of Ca²⁺ ions through TRPV1, generating cellular damage. We studied the effect of topical capsaicin (CS) treatment on cardiac mechanical work, oxidative stress (TAC, NO, BH4, and BH2), cellular damage (MDA, MTO, and 8HO2dG), and inflammation (IL-6 and TNFα), generated by SAH, which was induced by L-NAME, in male Wistar rats. CS was added to a moisturizing cream and applied to the abdomen of animals for two weeks. Experimental groups were as follows: (1) Control, (2) Control+Cream, (3) Hypertensive, and (4) Hypertensive+Cream. Hearts were exposed to ischemia-reperfusion (I-R) using the Langendorff technique to study the potential cardioprotection of CS. Expression of SOD1, SOD2, catalase, eNOS, pNOS, TRPV1, and CGRP in cardiac tissue was evaluated. In the Hypertensive group, TRPV1 activation by CS (Hypertensive+Cream) reduced oxidative stress (OS), decreasing cellular damage and inflammation and increasing TAC, modulating biochemical and tissue alterations induced by OS generated by SAH. In parallel, an increase in tissue levels and the expression of CGRP, TRPV1, and eNOS, induced by CS, was observed. These findings indicate that pretreatment with CS attenuates cardiac I-R and SAH injury in rats. The cardioprotective mechanism may be based on TRPV1-mediated CGRP overexpression. Full article

The widespread adoption of electric buses represents a major step forward in sustainable transportation, but also brings new operational challenges, particularly in terms of improving their efficiency and controlling costs. Therefore, battery energy consumption management is a key approach for addressing these issues. Accurate prediction of energy consumption and interpretation of the influencing factors are essential for improving operational efficiency, optimizing energy use, and reducing operating costs. Although existing studies have made progress in battery energy consumption prediction, challenges remain in achieving high-precision modeling and conducting a comprehensive analysis of the influencing features. To address these gaps, this study proposes a two-layer stacking framework for estimating the energy consumption of electric buses. The first layer integrates the strengths of three nonlinear regression models—RF (Random Forest), GBDT (Gradient Boosted Decision Trees), and CatBoost (Categorical Boosting)—to enhance the modeling capacity for complex feature relationships. The second layer employs a Linear Regression model as a meta-learner to aggregate the predictions from the base models and improve the overall predictive performance. The framework is trained on 2023 operational data from two electric bus routes (NO. 355 and NO. W188) in Changsha, China, incorporating battery system parameters, driving characteristics, and environmental variables as independent variables for model training and analysis. Comparative experiments with various ensemble models demonstrate that the proposed stacking framework exhibits superior performance in data fitting. Furthermore, XGBoost (Extreme Gradient Boosting, version 2.1.4) is introduced as a surrogate model to approximate the decision logic of the stacking framework, enabling SHAP (SHapley Additive exPlanations) analysis to quantify the contribution and marginal effects of influencing features. The proposed stacked and surrogate models achieved superior battery energy consumption prediction accuracy (lowest MSE, RMSE, and MAE), significantly outperforming benchmark models on real-world datasets. SHAP analysis quantified the overall contributions of feature categories (battery operation parameters: 56.5%; driving characteristics: 42.3%; environmental data: 1.2%), further revealing the specific contributions and nonlinear influence mechanisms of individual features. These quantitative findings offer specific guidance for optimizing battery system control and driving behavior. Full article

Eurasian aspen (Populus tremula L.) is a tree species with recognised ecological and economic importance for both natural and plantation forests. For the fast cloning of selected aspen genotypes, the method of plant propagation through in vitro culture (micropropagation) is often recommended. The efficiency of this method is related to the use of shoot-inducing chemical growth regulators, among which cytokinins, a type of plant hormone, dominate. Although cytokinins can inhibit rooting, this effect is avoided by using cytokinin-free media. This study sought to identify concentrations and combinations of growth regulators that would stimulate one type of P. tremula organogenesis (either shoot or root formation) without inhibiting the other. The investigated growth regulators included cytokinin 6-benzylaminopurine (BAP), auxin transport inhibitor 2,3,5-triiodobenzoic acid (TIBA), auxins indole-3-acetic acid (IAA) and indole-3-butyric acid (IBA), gibberellin biosynthesis inhibitor paclobutrazol (PBZ), and a gibberellin mixture (GA₄/₇). Both BAP and TIBA increased shoot number per P. tremula explant and decreased the number of adventitious roots, but TIBA, in contrast to BAP, did not inhibit lateral root formation. However, for the maintenance of both adventitious shoot and root formation above the control level, the combination of PBZ and GA_4/7 was shown to be especially promising. Full article

The Shahejie Formation in Nanpu Sag is a crucial region for deep-layer hydrocarbon exploration in the Bohai Bay Basin. To address the impact of faults on sublacustrine fan formation and spatial distribution within the study area, this study integrated well logging, laboratory analysis, and 3D seismic data to systematically analyze sedimentary characteristics of sandbodies from the first member of the Shahejie Formation (Es₁) sublacustrine fans, clarifying their planar and cross-sectional distributions. Further research indicates that Gaoliu Fault activity during Es₁ deposition played a significant role in fan development through two mechanisms: (1) vertical displacement between hanging wall and footwall reshaped local paleogeomorphology; (2) tectonic stresses generated by fault movement affected slope stability, triggering gravitational mass transport processes that remobilized fan delta sediments into the central depression zone as sublacustrine fans through slumping and collapse mechanisms. Core observations reveal soft-sediment deformation features, including slump structures, flame structures, and shale rip-up clasts. Seismic profiles show lens-shaped geometries with thick centers thinning laterally, exhibiting lateral pinch-out terminations. Inverse fault-step architectures formed by underlying faults control sandbody distribution patterns, restricting primary deposition locations for sublacustrine fan development. The study demonstrates that sublacustrine fans in the study area are formed by gravity flow processes. A new model was established, illustrating the combined control of the Gaoliu Fault and reverse stepover faults on fan development. These findings provide valuable insights for gravity flow exploration and reservoir prediction in the Nanpu Sag, offering important implications for hydrocarbon exploration in similar lacustrine rift basins. Full article

The coastal sandy land in northeast Hainan Province is typical for this land type, also exhibiting strong sand activity. This study is based on wind speed, wind direction, and sediment transport data obtained at a field meteorological station using an omnidirectional sand accumulation instrument from 2020 to 2024, studying the coastal aeolian environment and sediment transport distribution characteristics in the region. Its findings provide a theoretical basis for comprehensively analyzing the evolution of coastal aeolian landforms and the evaluation and control of coastal aeolian hazards. The research results show the following: (1) The annual average threshold wind velocity for sand movement in the study area is 6.84 m/s, and the wind speed frequency (frequency of occurrence) is 51.54%, dominated by easterly (NE, ENE) and southerly (S, SSE) winds. (2) The drift potential (DP) refers to the potential amount of sediment transported within a certain time and spatial range, and the annual drift potential (DP) and resultant drift potential (RDP) of Mulan Bay from 2020 to 2024 were 550.82 VU and 326.88 VU, respectively, indicating a high-energy wind environment. The yearly directional wind variability index (RDP/DP) was 0.59, classified as a medium ratio and indicating blunt bimodal wind conditions. The yearly resultant drift direction (RDD) was 249.45°, corresponding to a WSW direction, indicating that the sand in Mulan Bay is generally transported in the southwest direction. (3) When the measured data extracted from the sand accumulation instrument in the study area from 2020 to 2024 were used for statistical analysis, the results showed that the total sediment transport rate (the annual sediment transport of the observation section) in the study area was 110.87 kg/m·a, with the maximum sediment transport rate in the NE direction being 29.26 kg/m·a. These results suggest that when sand fixation systems are constructed for relevant infrastructure in the region, the construction direction of protective forests and other engineering measures should be perpendicular to the net direction of sand transport. Full article