Search Results (2,422)

Background: Nicotinamide adenine dinucleotide (NAD⁺), its precursors, and its derivatives (collectively NADome) play a crucial role in cellular processes and maintain redox homeostasis. Understanding the dynamics of these metabolic pools and redox reactions can provide valuable insights into metabolic functions, especially cellular regulation and stress response mechanisms. The accurate quantification of these metabolites is challenging due to the interconversion between the redox forms. Methods: Our laboratory previously developed a zwitterionic hydrophilic interaction liquid chromatography (zic-HILIC)–tandem mass spectrometry method for the quantification of five essential pyridine nucleotides, including NAD⁺ derivatives and it’s reduced forms, with ¹³C isotope dilution and matrix-matched calibration. In this study, we have improved the performance of the chromatographic method and expanded its scope to twelve analytes for a comprehensive view of NAD⁺ biosynthesis and utilization. The analytical method was validated and applied to investigate Escherichia coli BL21 under varying oxygen supplies including aerobic, microaerobic, and anaerobic conditions. Conclusions: The intracellular absolute metabolite concentrations ranged over four orders of magnitude with NAD⁺ as the highest abundant, while its precursors were much less abundant. The composition of the NADome at oxygen-limited conditions aligned more with that in the anaerobic conditions rather than in the aerobic phase. Overall, the NADome was quite homeostatic and E. coli rapidly, but in a minor way, adapted the metabolic activity to the challenging shift in the growth conditions and achieved redox balance. Our findings demonstrate that the zic-HILIC-MS/MS method is sensitive, accurate, robust, and high-throughput, providing valuable insights into NAD⁺ metabolism and the potential significance of these metabolites in various biological contexts. Full article

Treatment-resistant asthma remains an unresolved clinical problem and a challenge for current medical science. Consequently, there is a growing and urgent need to develop novel or alternative therapeutic options for the treatment of asthma. The research problem raised in this study was to assess and compare mycophenolate mofetil (MMF), an inhibitor of inosine monophosphate dehydrogenase, and tofacitinib (TFB), a Janus kinase inhibitor, for anti-asthmatic properties, and consequently to determine whether these agents may have potential as alternative options for treatment of allergic asthma. For this purpose, we assessed the effect of administration of MMF and TFB on the development of a mouse model of allergic airway inflammation (AAI) and accompanying CD4⁺ (cluster of differentiation 4) T-cell immune response in the lung-draining mediastinal lymph nodes (MLNs) and lungs, i.e., in the inductive and effector sites, respectively, of the immune response underlying the development of allergic asthma. The results from a histopathological scoring system demonstrated that the administration of MMF and TFB did not prevent or abolish ovalbumin-induced AAI, but strongly attenuated its severity. The pulmonary function tests revealed that the treatment with MMF and TFB significantly reduced methacholine-induced bronchoconstriction. These results indicate that the treatment with TFB and MMF attenuated the development of ovalbumin-induced AAI. The magnitude of the anti-asthmatic effect was comparable between both agents. The study revealed that the impairment of the clonal expansion of effector CD4⁺ T cells in the MLNs is a critical event in the mechanism underlying the anti-asthmatic effect of MMF and TFB. Apart from this, the findings of the study strongly suggest that the suppression of the interleukin-33/suppression of tumorigenicity-2 signaling pathway may constitute an additional mechanism responsible for producing this effect. In turn, the results indicate that the anti-asthmatic action induced by the studied agents is not mediated by the generation of forkhead box protein 3-expressing CD4⁺ regulatory T cells. Clinical implication of the results: the results suggest that MMF and TFB may exert anti-asthmatic action, and thus they may be considered therapeutic options for the treatment of allergic asthma cases resistant to conventional/existing treatment. Full article

Recent research has demonstrated that global warming significantly enhances peak vegetation growth on the Tibetan Plateau (TP), underscoring the influence of climatic factors on vegetation dynamics. Nevertheless, the effects of different drought types on peak vegetation growth remain underexplored. This study utilized satellite-derived gross primary productivity (GPP) and the normalized difference vegetation index (NDVI) to assess the impacts of soil moisture (SM) and vapor pressure deficit (VPD) on peak vegetation growth (GPP_max and NDVI_max) across the TP from 2001 to 2022. Our findings indicate that NDVI_max and GPP_max exhibited increasing trends in most regions, displaying similar spatial patterns, with 65.28% of pixels showing an increase in NDVI_max and 72.98% in GPP_max. In contrast, the trend for SM primarily showed a decrease (80.86%), while VPD showed an increasing trend (74.75%). Through partial correlation analysis and ridge regression, we found that peak vegetation growth was significantly affected by SM or VPD in nearly 20% of the study areas, although the magnitude of these effects varied considerably. Furthermore, we revealed that hydrothermal conditions modulated the responses of peak vegetation growth to SM and VPD. In regions with annual precipitation less than 650 mm and an annual mean temperature below 10 °C, decreased SM and increased VPD generally inhibited peak vegetation growth. Conversely, in warm and humid areas, lower SM and higher VPD promoted peak vegetation growth. These findings are crucial for deepening our understanding of vegetation phenology and its future responses to climate change. Full article

Global warming is attributed to an increased frequency of high ambient temperatures and humidity, elevating the prevalence of high-temperature-related illness and death. Evidence over recent decades highlights that tailored nutritional strategies are essential to improve performance and optimise health during acute and chronic exertional-heat exposure. Therefore, the purpose of this review is to discuss the efficacy of various nutritional strategies and ergogenic aids on responses during and following acute and chronic exertional-heat exposure. An outline is provided surrounding the application of various nutritional practices (e.g., carbohydrate loading, fluid replacement strategies) and ergogenic aids (e.g., caffeine, creatine, nitrate, tyrosine) to improve physiological, cognitive, and recovery responses to acute exertional-heat exposure. Additionally, this review will evaluate if the magnitude and time course of chronic heat adaptations can be modified with tailored supplementation practices. This review highlights that there is robust evidence for the use of certain ergogenic aids and nutritional strategies to improve performance and health outcomes during exertional-heat exposure. However, equivocal findings across studies appear dependent on factors such as exercise testing modality, duration, and intensity; outcome measures in relation to the ergogenic aid’s proposed mechanism of action; and sex-specific responses. Collectively, this review provides evidence-based recommendations and highlights areas for future research that have the potential to assist with prescribing specific nutritional strategies and ergogenic aids in populations frequently exercising in the heat. Future research is required to establish dose-, sex-, and exercise-modality-specific responses to various nutritional practices and ergogenic aid use for acute and chronic exertional-heat exposure. Full article

Fish and shellfish pathogens of the Harveyi clade of the Vibrio genus cause significant losses to aquaculture yields and profits, with some of them also causing infections in humans. The present study aimed to evaluate the presence of Harveyi clade fish and shellfish pathogens and their possible diversification in response to environmental drivers in southeastern USA waters. The presence and abundance of potential pathogens were evaluated via the detection and quantitation of six Harveyi-clade-specific virulence genes (toxR, luxR, srp, vhh_a, vhh, and vhp; VGs) in environmental DNA with clade-specific primers. The environmental DNA was obtained from water and sediments collected from three Georgia (USA) cultured clam and wild oyster grounds. In sediments, the VG concentrations were, on average, three orders of magnitude higher than those in water. The most and least frequently detected VGs were vhp and toxR, respectively. In water, the VGs split into two groups based on their seasonal trends. The first group, composed of luxR, vhp, vhha, and vhh, peaked in August and remained at lower concentrations throughout the duration of the study. The second group, composed of toxR and srp, peaked in June and disappeared between July and December. The first group revealed a high adaptation of their carriers to an increase in temperature, tolerance to a wide range of pH, and a positive correlation with salinity up to 25 ppt. The second group of VGs demonstrated a lower adaptation of their carriers to temperature and negative correlations with pH, salinity, potential water density, conductivity, and dissolved solids but a positive correlation with turbidity. No such trends were observed in sediments. These data reveal the role of VGs in the adaptability of the Harveyi clade pathogens to environmental parameters, causing their diversification and possibly their stratification into different ecological niches due to changes in water temperature, acidity, salinity, and turbidity. This diversification and stratification may lead to further speciation and the emergence of new pathogens of this clade. Our data urge further monitoring of the presence and diversification of Harveyi clade pathogens in a global warming scenario. Full article

Matrix extracellular phosphoglycoprotein (Mepe), present in bone and dentin, plays important multifunctional roles in cell signaling, bone mineralization, and phosphate homeostasis. Mepe expression in bone cells changes in response to pulsating fluid shear stress (PFSS), which is transmitted into cells through integrin-based adhesion sites, i.e., α and β subunits. Whether and to what extent PFSS influences Mepe expression through the modulation of integrin α and/or β subunit expression in pre-osteoblasts is uncertain. Therefore, we aimed to test whether low and/or high PFSS affects Mepe expression via modulation of integrin α and/or β subunit expression. MC3T3-E1 pre-osteoblasts were treated with ± 1 h PFSS (magnitude: 0.3 Pa (low PFSS) or 0.7 Pa (high PFSS); frequency: 1 Hz). Single integrin fluorescence intensity in pre-osteoblasts was increased, but single integrin area was decreased by low and high PFSS. Expression of two integrin α subunit-related genes (Itga1 and Itga5 2) was increased by low PFSS, and one (Itga5 2) by high PFSS. Expression of five integrin β subunit genes (Itgb1, Itgb3, Itgb5, Itgb5 13, and Itgb5 123) was increased by low PFSS, and three (Itgb5, Itgb5 13, and Itgb5 123) by high PFSS. Interestingly, Mepe expression in pre-osteoblasts was only modulated by low, but not high, PFSS. In conclusion, both low and high PFSS affected integrin α and β subunit expression in pre-osteoblasts, while integrin β subunit expression was more altered by low PFSS. Importantly, Mepe gene expression was only affected by low PFSS. These results might explain the different ways that Mepe-induced changes in pre-osteoblast mechanosensitivity may drive signaling pathways of bone cell function at low or high impact loading. These findings might have physiological and biomedical implications and require future research specifically addressing the precise role of integrin α or β subunits and Mepe during dynamic loading in bone health and disease. Full article

Oil spills pose significant threats to marine and coastal ecosystems, necessitating advanced methodologies for environmental sensitivity and vulnerability assessments. This study enhances existing frameworks to better manage oil spill risks in the Caspian Sea, a region characterized by its ecological sensitivity and economic dependence on oil extraction. Utilizing the Environmental Sensitivity Index (ESI), we adapted global standards to the unique conditions of the Caspian Sea and built a sensitivity map of the coastline, which later became one of the components of the integral sensitivity map for the entire Caspian Sea, which includes several biotic and abiotic components. We also developed a comprehensive geodatabase incorporating topographic, infrastructural, and hydrodynamic data. Through the sophisticated modeling of oil spill scenarios using the Oil Spill model of the MIKE 21 software (Release 2016) suite, we simulated spills of varying magnitudes to analyze their potential impacts on the marine and coastal environment. The results enabled the creation of vulnerability maps, pinpointing areas at highest risk and facilitating strategic response planning. Our study demonstrates the critical importance of integrating advanced geospatial analyses and dynamic modeling techniques to improve oil spill preparedness and response strategies. The findings of this study suggest that enhanced monitoring and adaptive management strategies are essential for protecting the Caspian Sea from environmental risks posed by its oil industry. Full article

One of the manifests of air-sea interactions is the change in sea level due to meteorological forcing through wind stress and atmospheric pressure. When meteorological conditions conducive to water level increase coincide with high tides during spring tides, the sea level may rise higher than expected and pose a flood risk to coastal low-lying areas. In Hong Kong, specifically when the northeast monsoon coincides with the higher spring tides in late autumn and winter, and sometimes even compounded by the storm surge brought by late-season tropical cyclones (TCs), the result may be coastal flooding or sea inundation. Aiming at forecasting such sea level anomalies on the scale of hours and days with local tide gauges using a flexible and computationally efficient method, this study adapts a data-driven method based on empirical orthogonal functions (EOF) regression of non-uniformly lagged regional wind field from ECMWF Reanalysis v5 (ERA5) to capture the effects from synoptic weather evolution patterns, excluding the effect of TCs. Local atmospheric pressure and winds are also included in the predictors of the regression model. Verification results show good performance in general. Hindcast using ECMWF forecasts as input reveals that the reduction of mean absolute error (MAE) by adding the anomaly forecast to the existing predicted astronomical tide was as high as 30% in February on average over the whole range of water levels, as well as that compared against the Delft3D forecast in a strong northeast monsoon case. The EOF method generally outperformed the persistence method in forecasting water level anomaly for a lead time of more than 6 h. The performance was even better particularly for high water levels, making it suitable to serve as a forecast reference tool for providing high water level alerts to relevant emergency response agencies to tackle the risk of coastal inundation in non-TC situations and an estimate of the anomaly contribution from the northeast monsoon under its combined effect with TC. The model is capable of improving water level forecasts up to a week ahead, despite the general decreasing model performance with increasing lead time due to less accurate input from model forecasts at a longer range. Some cases show that the model successfully predicted both positive and negative anomalies with a magnitude similar to observations up to 5 to 7 days in advance. Full article

This paper proposes a method based on Computational Fluid Dynamics (CFD) and the detection of Wind Energy Extraction Latency for a given wind turbine (WT) designed for ultra-short-term (UST) wind energy forecasting over complex terrain. The core of the suggested modeling approach is the Wind Spatial Extrapolation model (WiSpEx). Measured vertical wind profile data are used as the inlet for stationary CFD simulations to reconstruct the wind flow over a wind farm (WF). This wind field reconstruction helps operators obtain the wind speed and available wind energy at the hub height of the installed WTs, enabling the estimation of their energy production. WT power output is calculated by accounting for the average time it takes for the turbine to adjust its power output in response to changes in wind speed. The proposed method is evaluated with data from two WTs (E40-500, NM 750/48). The wind speed dataset used for this study contains ramp events and wind speeds that range in magnitude from 3 m/s to 18 m/s. The results show that the proposed method can achieve a Symmetric Mean Absolute Percentage Error (SMAPE) of 8.44% for E40-500 and 9.26% for NM 750/48, even with significant simplifications, while the SMAPE of the persistence model is above 15.03% for E40-500 and 16.12% for NM 750/48. Each forecast requires less than two minutes of computational time on a low-cost commercial platform. This performance is comparable to state-of-the-art methods and significantly faster than time-dependent simulations. Such simulations necessitate excessive computational resources, making them impractical for online forecasting. Full article

The spiral case plays a role in providing stable and uniform water flow in the pump-turbine unit, and the overall structure with the surrounding concrete is an important foundation for the safe and stable operation of the unit and power plant. In order to clarify the comprehensive bearing capacity of preloading steel spiral case under pump operating conditions, this study is based on the theory of the fluid–structure coupling and contact model and uses ANSYS CFX 2021 R1 and mechanical to analyze the flow fluctuation characteristics and dynamic structural response of a preloading steel spiral case and surrounding concrete under different preloading pressures in the intermediate head pump condition. The results indicate that the main frequency of pressure fluctuations inside the main frequency (1 fn) of pressure fluctuations inside the spiral case is influenced by the unstable flow. The contact state between the preloading steel spiral case and concrete is closely related to the relative magnitude of preloading pressure and hydraulic pressure. Higher preloading pressure can lead to an increase in initial preloading clearance, resulting in a decrease in contact area. The vortex motion inside the spiral case is the main factor affecting the distribution of deformation. The rotor–stator interaction also has a certain impact on the vibration of the spiral case structure, even though the influence of rotor–stator interaction on pressure fluctuation inside the spiral case is already small. The monitoring points where the maximum values of static stress and dynamic stress are located are different. Increasing the preloading pressure value does not always guarantee the safety of concrete structures, as the sticking contact area in early contact transfers most of the stress of the spiral case, resulting in significant stress concentration. Under the working conditions of this study, the concrete in contact with the inner edge and nose vane is subjected to excessive loads. Therefore, it is necessary to reinforce the structure with steel bars or other methods to improve its tensile strength. A minimum preloading pressure value of 3.2 MPa is beneficial for reducing the risk of concrete cracking. The research results can provide a deeper understanding of the behavior of preloading steel spiral cases under pump conditions and guide optimization design. Full article

Fractional order filters are increasingly used due to their flexibility and continuous stepped stopband attenuation rate. The current work presents a deterministic design plan for an optimal fractional-order Legendre low-pass filter along with a stochastic investigation of its parametric uncertainty. First, the filter’s order was determined using the provided parameters, then the flower pollination algorithm was used to tune the transfer function parameters. This method uses the phase delay and magnitude response functions to quantify the desired output. Circuit diagrams, LT spice simulations, and a case study were used to validate the method. In addition, the effects of various components on stability and the performance metrics were further examined. Next, each of the described fractional system parameters (R1, R2, the ratio R4R3, Cα, and Cβ) was modeled as an uncertain term in a distinct cases, referred to as Cases I–V, respectively, and their combined effect was investigated as Case VI. These uncertain parameters were implemented using both random variables and stochastic processes. The system response was assessed using the Monte Carlo simulation method, and the mean, standard deviation, probability density function, and lower and upper bounds were plotted. Additionally, the key statistics of the cutoff frequency were tabulated in all cases. Many findings are addressed by the provided system solutions; briefly, the results revealed that the impact of uncertainty cases on system response, in descending order, was Case VI, Case III, Case V, Case II, Case I, and Case IV. Furthermore, the system demonstrated instability in Cases III and VI, which drew the designers’ attention to these two cases. Full article

Cooperative vehicle infrastructure technology has emerged as a cutting-edge and indispensable trend within the transportation sector. While addressing the supply-side requisites of the technology, it is equally important to investigate its demand-side response. To investigate the public acceptance of cooperative vehicle infrastructure technology and its influencing factors, this paper constructs an extended Technology Acceptance Model (TAM). Then, the paper employs the structural equation model (SEM) to validate the path hypotheses of the model, and pinpoints the variables that significantly influence the intention to use the technology. Moreover, the Bayesian network (BN) model is utilized to assess the magnitude of the effects of diverse influencing factors on the acceptance of the technology. The research findings can provide recommendations for the government to expedite the promotion and implementation of cooperative vehicle infrastructure technology. Full article

Background: Influenza vaccine uptake among healthcare workers is crucial for preventing influenza infections, yet its effectiveness needs further investigation. Objectives: This prospective observational study aimed to assess the protective effect of influenza vaccination among healthcare workers in Shenzhen. Methods: We enrolled 100 participants, with 50 receiving the 2023–2024 quadrivalent influenza vaccine (QIV) and 50 serving as unvaccinated controls. Epidemiological data were collected when the participants presented influenza-like illness. Serum samples were collected at three time points (pre-vaccination and 28 and 180 days after vaccination). Hemagglutination inhibition (HI) assay was performed against the strains included in the 2023–2024 QIV (H1N1, H3N2, BV and BY strains) to assess antibody protection levels. Demographics comparisons revealed no significant differences between the vaccinated and control groups (p > 0.05), ensuring group comparability. Results: The incidence of influenza-like illness was significantly lower in the vaccinated (18%) compared to the control group (36%; p = 0.046; OR = 0.39; 95% CI: 0.15 to 0.98). The vaccinated group also exhibited a higher rate of consecutive two-year vaccinations (48% vs. 24% in the control group, p < 0.05). Additionally, the vaccinated healthcare workers were more inclined to recommend vaccination to their families (80% vs. 48%, p < 0.05). HI titers against H1N1 (p < 0.01), H3N2 (p < 0.01), BV (p < 0.001) and BY (p < 0.01) significantly increased in the vaccinated group at 28 days post-vaccination. Moreover, a marked and sustained increase in HI titers against the H3N2 strain (p < 0.001) was observed at 180 days post-vaccination, highlighting the vaccine’s enduring impact on the immune response. The fold change in the HI titers, indicative of the magnitude of the immune response, was significantly higher for H1N1 (p < 0.01), H3N2 (p < 0.001), BV (p < 0.01) and BY (p < 0.05) among the vaccinated individuals compared to the control group, underscoring the vaccine’s efficacy in eliciting a robust and sustained antibody response. Conclusion: Influenza vaccination significantly reduces the incidence of influenza-like illness among healthcare workers and promotes a sustained immune response. The study supports the importance of annual vaccination for this group to enhance personal and public health. Full article

Background: The COVID-19 pandemic has profoundly affected young adults’ lives globally, including those in Germany. This study investigated mental health and quality of life during the pandemic, with a particular focus on mood. Immune fitness, the body’s capacity to respond to health challenges (such as infections) by activating an appropriate immune response, was assessed as a physical health indicator. Methods: Data were collected from 317 participants, aged 18 to 35, via an online survey conducted between November 2021 and March 2022. Participants included 103 men (32.5%) and 214 women (67.5%), with a mean age of 25.5 years (SD = 4.1). Results: Compared to pre-pandemic levels, significant declines in mood, quality of life, immune fitness, and sleep quality were observed during the lockdown periods of the COVID-19 pandemic (p < 0.0125). The most pronounced effects were observed during the second lockdown, with declines extending into the second no-lockdown period for fatigue, depression, happiness, optimism, and immune fitness (p < 0.0125). Significant sex differences were found for the magnitude of mood effects (anxiety, depression, stress). No significant differences were found according to age or occupational status (student vs. work). Conclusions: The COVID-19 pandemic and associated lockdown periods had a significant negative effect on the mood, immune fitness, and well-being of young adults living in Germany. Full article

The mechanical response of granular materials is influenced significantly by both the magnitude and strain rate. While traditionally considered rate-independent in the quasi-static regime, granular media can exhibit rate effects in certain instances. This research uses two-dimensional discrete element modelling (DEM) to investigate the rate effects in one-dimensional compression tests by comparing non-crushable with crushable granular samples. This study indicates that micromechanical properties such as particle breakage and contact force distributions are predominant factors in dictating the macroscopic responses of the material. The DEM simulations highlight differences in macroscopic changes between crushable and non-crushable samples, demonstrating a clear correlation between mechanical properties and underlying microstructural features. Notably, the distribution of contact forces varies with strain rates, influencing the degree of particle breakage and, consequently, the overall rate-dependent behaviour. Further, this study explores the impact of post-breakage contact creation and progressive force redistribution, which contributes to observable differences in macroscopic stress under varying loading rates, which is quantified using coordination number, particle velocity, and fabric tensor profiles at two loading rates. Full article