bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic Effects of Hinokitiol through Regulating the SIRT1/NOX4 against Ligature-Induced Experimental Periodontitis
Authors: Kim Tae-Yeon , Kim Eun-Nam , Jeong Gil-Saeng
Published: May 2024

Hinokitiol (HKT) is one of the essential oil components found in the heartwood of Cupressaceae plants, and has been reported to have various bioactive effects, including anti-inflammatory effects. However, the improving effect of HKT on periodontitis, which is characterized by periodontal tissue inflammation and alveolar bone loss, has not been clearly revealed. Therefore, we investigated the periodontitis-alleviating effect of HKT and the related molecular mechanisms in human periodontal ligament cells. According to the study results, HKT downregulated SIRT1 and NOX4, which were increased by Porphyromonas gingivalis Lipopolysaccharide (PG-LPS) stimulation and were found to regulate pro-inflammatory mediators and oxidative stress through SIRT1/NOX4 signals. Additionally, by increasing the expression of osteogenic makers such as alkaline phosphatase, osteogenic induction of human periodontal ligament (HPDL) cells, which had been reduced by PG-LPS, was restored. Furthermore, we confirmed that NOX4 expression was regulated through regulation of SIRT1 expression with HKT. The in vitro effect of HKT on improving periodontitis was proven using the periodontal inflammation model, which induces periodontal inflammation using ligature, a representative in vivo model. According to in vivo results, HKT alleviated periodontal inflammation and restored damaged alveolar bone in a concentration-dependent manner in the periodontal inflammation model. Through this experiment, the positive effects of HKT on relieving periodontal tissue inflammation and recovering damaged alveolar bone, which are important treatment strategies for periodontitis, were confirmed. Therefore, these results suggest that HKT has potential in the treatment of periodontitis.
Modeling Melanoma Heterogeneity In Vitro: Redox, Resistance and Pigmentation Profiles
Authors: Carvalho Larissa Anastacio da Costa , Noma Isabella Harumi Yonehara , Uehara Adriana Hiromi , Siena Ádamo Davi Diógenes , Osaki Luciana Harumi , Mori Mateus Prates , Pinto Nadja Cristhina de Souza , Freitas Vanessa Morais , Junior Wilson Araújo Silva , Smalley Keiran S. M. , Maria-Engler Silvya Stuchi
Published: May 2024

Microenvironment and transcriptional plasticity generate subpopulations within the tumor, and the use of BRAF inhibitors (BRAFis) contributes to the rise and selection of resistant clones. We stochastically isolated subpopulations (C1, C2, and C3) from naïve melanoma and found that the clones demonstrated distinct morphology, phenotypic, and functional profiles: C1 was less proliferative, more migratory and invasive, less sensitive to BRAFis, less dependent on OXPHOS, more sensitive to oxidative stress, and less pigmented; C2 was more proliferative, less migratory and invasive, more sensitive to BRAFis, less sensitive to oxidative stress, and more pigmented; and C3 was less proliferative, more migratory and invasive, less sensitive to BRAFis, more dependent on OXPHOS, more sensitive to oxidative stress, and more pigmented. Hydrogen peroxide plays a central role in oxidative stress and cell signaling, and PRDXs are one of its main consumers. The intrinsically resistant C1 and C3 clones had lower MITF, PGC-1α, and PRDX1 expression, while C1 had higher AXL and decreased pigmentation markers, linking PRDX1 to clonal heterogeneity and resistance. PRDX2 is depleted in acquired BRAFi-resistant cells and acts as a redox sensor. Our results illustrate that decreased pigmentation markers are related to therapy resistance and decreased antioxidant defense.
Integrating Tensometer Measurements, Elastic Half-Space Modeling, and Long-Term Pavement Performance Data into a Mechanistic–Empirical Pavement Performance Model
Authors: Kozel Matúš , Remek Ľuboš , Ilovská Katarína , Mazurek Grzegorz , Buczyński Przemysław
Published: May 2024

Pavement performance models (PPMs) are utilized to predict pavement network conditions which is an essential part of any sustainable pavement management system (PMS). The reliability of a PMS and its outputs is proportional to the reliability of the PPM used. This article describes a mechanistic–empirical pavement performance model based on pavement response parameters—strains calculated in the pavement layers measured by tensometers embedded in the pavement surface and verified by calculations in the elastic half-space model and supplemented by empirical data from long-term pavement performance monitoring and accelerated pavement testing. Hence, the herein described PPM combines pavement serviceability evaluation, pavement bearing capacity, and the physico-mechanistic properties of paving materials. The analytical methods which were used to ascertain the physico-mechanistic characteristics, the material fatigue degradation model, and the surface degradation, unevenness in particular, are described. A comparison of the empirical PPM created in the last century used by the national road administrator to this day and the newly created PPM is presented. The comparison shows the difference in the calculated socio-economic benefits and subsequent cost–benefit analysis results. The comparison shows that the use of the old PPM may have produced false economic evaluation results that have led to poor decision making, partially explaining the unsustainable trend of road network management in our country.
Training of a Neural Network System in the Task of Detecting Blue Stains in a Sawmill Wood Inspection System
Authors: Wolszczak Piotr , Kotnarowski Grzegorz , Małek Arkadiusz , Litak Grzegorz
Published: May 2024

This article presents the operation of an automatic pine sawn timber inspection system, which was developed at the Woodinspector company and is offered commercially. The vision inspection system is used to detect various wood defects, including knots, blue stain, and mechanical damage caused by worms. A blue stain is a defect that is difficult to detect based on the color of the wood, because it can be easily confused with wood defects or dirt that do not impair its strength properties. In particular, the issues of detecting blue stain in wood, the use of artificial neural networks, and improving the operation of the system in production conditions are discussed in this article. While training the network, 400 boards, 4 m long, and their cross-sections of 100 × 25 [mm] were used and photographed using special scanners with laser illuminators from four sides. The test stages were carried out during an 8-hour workday at a sawmill (8224 m of material was scanned) on material with an average of 10% blue stain (every 10th board has more than 30% of its length stained blue). The final learning error was assessed based on defective boards detected by humans after the automatic selection stage. The system error for 5387 boards, 550 m long, which had blue staining that was not detected by the scanner (clean) was 0.4% (25 pieces from 5387), and 0.1 % in the case of 3412 boards, 610 mm long, on which there were no blue stains, but were wrongly classified (blue stain). For 6491 finger-joint boards (180–400 mm), 48 pieces were classified as class 1 (clean), but had a blue stain (48/6491 = 0.7%), and 28 pieces did not have a blue stain, but were classified as class 2 (28/3561 = 0.7%).
Effect of Rubber Cup Rotational Speeds during Tooth Polishing on Sound, Early Caries, and Cracked Tooth Surfaces
Authors: Chun A-Young , Kim Hee-Eun
Published: May 2024

High-speed rubber cup polishing can exacerbate tooth surface damage, especially when preexisting conditions such as early caries or cracks exist. This study aimed to quantify the extent of damage to sound teeth based on rotating rubber cup speed and assess the damage in relation to the tooth surface condition. Using a rubber cup, 36 sound teeth were polished at 100, 3000, and 10,000 rpm, and 24 teeth with early carious lesions and 24 cracked teeth were polished at 3000 and 10,000 rpm. Polishing was performed using a rubber cup and prophylaxis paste, applying an on–off method (3.0 N force for 3 s). Damage depth was quantified using a surface profilometer and examined using scanning electron microscopy. Polishing at 10,000 rpm caused significantly more damage to sound teeth than polishing at lower speeds (depth increase: 71.45 ± 15.12 µm at 100 rpm; 61.91 ± 17.82 µm at 3000 rpm; p < 0.001). Teeth with early carious lesions or cracks demonstrated more damage after polishing than sound teeth (p < 0.05). Therefore, the rotational speed of the rubber cup has a critical impact on the extent of enamel damage. Higher speeds can increase the damage depth in both sound and damaged tooth surfaces.
Global Precipitation for the Year 2023 and How It Relates to Longer Term Variations and Trends
Authors: Adler Robert F. , Gu Guojun
Published: May 2024

In this paper, the global distribution of precipitation for 2023, in terms of global totals and regional anomaly patterns, is analyzed using information from the new Global Precipitation Climatology Project (GPCP) V3.2 Monthly product, including how the precipitation amounts and patterns from 2023 fit into the longer record from 1983–2023. The tropical pattern of anomalies for 2023 is dominated by the effect of the El Nino which began during the Northern Hemisphere spring, after three plus years of La Nina conditions. The transition from La Nina conditions through 2022 shows the rapid change in many regional features from positive to negative anomalies or the reverse. Comparison of the observed regional trend maps with climate model results indicates similarity between the observations and the model results forced by observed SSTs, while the “free-running” model ensemble shows only a broad general agreement over large regions. Global total precipitation shows about a 3% range over the span of data, with El Nino and La Nina years prominent as positive and negative features, with 2023 showing a small positive global anomaly. The ITCZ (Inter-Tropical Convergence Zone) latitude band, 0–10° N, sets a record high mean rain rate in 2023 after a steady upward trend over the decades, probably a response related to global warming.
Evaluation and Wind Field Detection of Airborne Doppler Wind Lidar with Automatic Intelligent Processing in North China
Authors: Zhang Xu , Lin Zhifeng , Gao Chunqing , Han Chao , Fan Lin , Zhao Xinxi
Published: May 2024

Airborne wind measurement is of great significance for understanding atmospheric motion and meteorological monitoring. In this paper, we present the development and verification of an airborne Doppler wind lidar (ADWL), featuring an approach proposed to integrate a real-time wind retrieval method with an intelligent processing method for automatic adaptive wind detection. Several verification experiments were conducted to evaluate the measurement effectiveness, including comparisons with a calibrated ground-based Doppler wind lidar (GDWL) and a sounding balloon. Compared with the sounding balloon, the ADWL demonstrated mean errors of 0.53 m/s for horizontal wind velocity and 4.60° for wind direction. The correlation coefficients consistently exceeded 0.98 in all linear analyses. Employed in multiple airborne wind detection events in North China at altitudes up to 6600 m, the ADWL provided effective wind field results with a vertical resolution of 50 m and a data rate of 2 Hz. The wind field results obtained during the detection events validate the ADWL’s capabilities in diverse environments and underscore its potential for the comprehensive detection of meteorological information.
Exploring Spatio-Temporal Precipitation Variations in Istanbul: Trends and Patterns from Five Stations across Two Continents
Authors: Kara Yiğitalp , Yavuz Veli , Temiz Caner , Lupo Anthony R.
Published: May 2024

This study aims to reveal the long-term station-based characteristics of precipitation in Istanbul, a mega city located on the continents of Europe and Asia, with complex topography and coastline along the Marmara and Black Seas. Using data from five different stations, three located in the European continent and two in the Asian continent, with measurement periods ranging from 72 to 93 years, wet and dry days have been identified, statistics on precipitation conditions during the warm and cold seasons have been generated, categorization based on precipitation intensities has been performed, and analyses have been conducted using extreme precipitation indices. At stations located in the northern part of the city, higher annual total precipitation has been observed compared to those in the south. A similar situation applies to the number of wet days. While during the cold season, the wet and dry day counts are nearly the same across all stations, this condition exhibits significant differences in favor of dry days during the warm season. Apart from dry conditions, “moderate” precipitation is the most frequently observed type across all stations. However, “extreme” events occur significantly more often (6%) during the warm season compared to the cold season (2%). Long-term anomalies in terms of annual precipitation totals have shown similarity between stations in the north and south, which has also been observed in longitudinally close stations. Despite the longer duration of the cold season and stronger temperature gradients, extreme rainfall events are more frequent during the warm season, primarily due to thunderstorm activity. While trend analyses revealed limited significant trends in precipitation intensity categories and extreme indices, the study highlights the importance of comprehensive examination of extreme rainfall events on both station-based and regional levels, shedding light on potential implications for regional climate change. Lastly, during the cold season, the inter-station correlation in terms of annual total precipitation amounts has been considerably higher compared to the warm season.
Finite Reynolds Number Effect on Small-Scale Statistics in Decaying Grid Turbulence
Authors: Tang Shunlin , Danaila Luminita , Antonia Robert Anthony
Published: May 2024

Since about 1997, the realisation that the finite Reynolds number (FRN) effect needs to be carefully taken into account when assessing the behaviour of small-scale statistics came to the fore. The FRN effect can be analysed either in the real domain or in the spectral domain via the scale-by-scale energy budget equation or the transport equation for the energy spectrum. This analysis indicates that the inertial range (IR) is established only when the Taylor microscale Reynolds number Reλ is infinitely large, thus raising doubts about published power-law exponents at finite values of Reλ, for either the second-order velocity structure function (δu)2¯ or the energy spectrum. Here, we focus on the transport equation of (δu)2¯ in decaying grid turbulence, which represents a close approximation to homogeneous isotropic turbulence. The effect on the small-scales of the large-scale forcing term associated with the streamwise advection decreases as Reλ increases and finally disappears when Reλ is sufficiently large. An approach based on the dual scaling of (δu)2¯, i.e., a scaling based on the Kolmogorov scales (when the separation r is small) and another based on the integral scales (when r is large), yields (δu)2¯∼r2/3 when Reλ is infinitely large. This approach also yields (δu)n¯∼rn/3 when Reλ is infinitely large. These results seem to be supported by the trend, as Reλ increases, of available experimental data. Overall, the results for decaying grid turbulence strongly suggest that a tendency towards the predictions of K41 cannot be dismissed at least at Reynolds numbers which are currently beyond the reach of experiments and direct numerical simulations.
Boundary Layer Height and Trends over the Tarim Basin
Authors: Salam Akida , He Qing , Abbas Alim , Wu Tongwen , Zhang Jie , Jie Weihua , Liu Junjie
Published: May 2024

This study aimed to examine the spatio-temporal variations in the atmospheric boundary layer height (ABLH) over the Tarim Basin (TB). Monthly ABLH data from the ERA-Interim dataset from January 1979 to December 2018 were used. Periodicity analysis and the Mann–Kendall Abrupt Changes test were employed to identify the change cycle and abrupt change year of the boundary layer height. The Empirical Orthogonal Function (EOF) method was utilized to determine the spatial distribution of the boundary layer height, and the RF method was used to establish the relationship between the ABLH and influencing factors. The results demonstrated that the highest values of ABLH (over 1900 m) were observed in the middle parts of the study area in June, and the ABLH exhibited a significant increase over the TB throughout the study period. Abrupt changes in the ABLH were also identified in 2004, as well as in 2-, 5-, 9-, and 15-year changing cycles. The first EOF ABLH mode indicated that the middle and northeast regions are relatively high ABLH areas within the study area. Additionally, the monthly variations in ABLH show a moderately positive correlation with air temperature, while exhibiting a negative correlation with air pressure and relative humidity.
Pollution Characteristics and Sources of Ambient Air Dustfall in Urban Area of Beijing
Authors: Zhou Yin , Li Beibei , Huang Yuhu , Zhao Yu , Yang Hongling , Qin Jianping
Published: May 2024

Since 2016, the Ministry of Ecology and Environment and the Beijing Municipal Government have adjusted the minimum concentration limit for ambient air dustfall several times, indicating that they attach great importance to dustfall. To grasp the pollution characteristics and sources of dustfall, in this work, the filtration method was used to determine the insoluble dustfall and water-soluble dustfall in the urban area of Beijing. From our analysis, the influence of the meteorological parameters on dustfall was found, and the chemical components of dustfall were determined. The positive matrix factorization (PMF) model was also utilized to analyze the sources of dustfall. The results indicated that the average amount of dustfall in 2021–2022 was 4.4 t·(km2·30 d)−1, and the proportion of insoluble dustfall deposition was 82.4%. Dustfall was positively correlated with the average wind speed and temperature and negatively correlated with the relative humidity and rain precipitation. The impact of the meteorological parameters on insoluble dustfall and water-soluble dustfall was the opposite. The average proportions of crustal material, ions, organic matter, element carbon, trace elements, and unknown components were 48%, 16%, 14%, 1.4%, 0.20%, and 20%, respectively. The proportions of the crustal material and ions were the highest in spring (57%) and summer (37%). The contribution rates of fugitive dust source, secondary inorganic source, mobile source, coal combustion source, snow melting agent source, and other sources were 42.4%, 19.3%, 8.3%, 3.0%, 2.7%, and 24.3%, respectively. This study supported dustfall pollution control by analysing the pollutant characteristics and sources of dustfall from the standpoint of total chemical components. In order to better control dustfall pollution, control measures and evaluation standards for fugitive dust pollution should be formulated.
Wind Shear and Aircraft Aborted Landings: A Deep Learning Perspective for Prediction and Analysis
Authors: Khattak Afaq , Zhang Jianping , Chan Pak-Wai , Chen Feng , Hussain Arshad , Almujibah Hamad
Published: May 2024

In civil aviation, severe weather conditions such as strong wind shear, crosswinds, and thunderstorms near airport runways often compel pilots to abort landings to ensure flight safety. While aborted landings due to wind shear are not common, they occur under specific environmental and situational circumstances. This research aims to accurately predict aircraft aborted landings using three advanced deep learning techniques: the conventional deep neural network (DNN), the deep and cross network (DCN), and the wide and deep network (WDN). These models are supplemented by various data augmentation methods, including the Synthetic Minority Over-Sampling Technique (SMOTE), KMeans-SMOTE, and Borderline-SMOTE, to correct the imbalance in pilot report data. Bayesian optimization was utilized to fine-tune the models for optimal predictive accuracy. The effectiveness of these models was assessed through metrics including sensitivity, precision, F1-score, and the Matthew Correlation Coefficient. The Shapley Additive Explanations (SHAP) algorithm was then applied to the most effective models to interpret their results and identify key factors, revealing that the intensity of wind shear, specific runways like 07R, and the vertical distance of wind shear from the runway (within 700 feet above runway level) were significant factors. The results of this research provide valuable insights to civil aviation experts, potentially revolutionizing safety protocols for managing aborted landings under adverse weather conditions, thereby improving overall airport efficiency and safety.
Indoor Air Quality (IAQ) Management in Hong Kong: The Way Forward
Authors: Tsang Tsz-Wun , Mui Kwok-Wai , Wong Ling-Tim
Published: May 2024

There has been an increasing awareness of indoor air quality (IAQ) management in green building designs, driven by the need to mitigate potential health risks and create sustainable and healthy indoor environments. The COVID-19 pandemic has further highlighted the critical role of ventilation and IAQ in reducing the risk of indoor airborne transmission. Governments and organisations worldwide have responded to this growing concern by implementing ventilation requirements and updating IAQ standards and guidelines. In the case of Hong Kong, a developed and densely populated city characterised by high-rise buildings, this study aims to provide a strategic framework for non-governmental agencies to address IAQ issues effectively. A comprehensive review of policies, regulations, and guidelines by international bodies and individual governments, along with an examination of the current IAQ management scheme in Hong Kong, has been conducted. Drawing inspiration from successful IAQ management strategies, the study aims to identify insights and potential pathways for the city’s future development of IAQ management strategies. Overall, this research highlights the importance of proactive IAQ management for buildings and offers a roadmap for Hong Kong’s pursuit of healthier indoor environments.
Unsteady and Inhomogeneous Turbulent Fluctuations around Isotropic Equilibrium
Authors: Bos Wouter J. T.
Published: May 2024

Extracting statistics for turbulent flows directly from the Navier–Stokes equations poses a formidable challenge, particularly when dealing with unsteady or inhomogeneous flows. However, embracing Kolmogorov’s inertial range spectrum for isotropic turbulence as a dynamic equilibrium provides a conceptual starting point for perturbation theory. We review theoretical results, combining perturbation approaches, and phenomenological turbulence closures, which allow us to gain valuable insights into the statistics of unsteady and inhomogeneous turbulence. Additionally, we extend the ideas to the case of the mixing of a passive scalar.
The Heterogeneous Effects of Microscale-Built Environments on Land Surface Temperature Based on Machine Learning and Street View Images
Authors: Zhang Tianlin , Lin Zhao , Wang Lei , Zhang Wenzheng , Zhang Yazhuo , Hu Yike
Published: May 2024

Global climate change has exacerbated alterations in urban thermal environments, significantly impacting the daily lives and health of city residents. Measuring and understanding urban land surface temperatures (LST) and their influencing factors is important in addressing global climate change and enhancing the well-being of residents. However, due to limitations in data precision and analytical methods, existing studies often overlook the microscale examination closely related to residents’ daily lives, and lack a deep exploration of the spatial heterogeneity of the influencing factors. This leads to these results being ineffective in guiding the planning and construction of cities. Taking Shenzhen as a case study, our study investigates the effects of various microscale build environment characteristics of LST using street view images and machine learning. A convolutional neural network model adopting the SegNet architecture is used to perform semantic segmentation on street view images, extracting features of the microscale urban-built environment. The LST is inverted through the Google Earth Engine (GEE) platform. By using Multiscale Geographically Weighted Regression (MGWR) models, our study reveals the comprehensive impact of the urban-built environment on LST and its significant spatial heterogeneity. The findings indicate that the proportions of sky, roads, and buildings are positively correlated with LST, while trees have a significant cooling effect. Although earth and water can reduce LST, their overall contribution is minimal due to limitations in their area and distribution patterns. This study not only reveals the key factors affecting urban LST at the microscale but also emphasizes the necessity of considering the spatial heterogeneity of these factors’ impacts. This suggests the need for targeted strategies for different areas to effectively improve the urban thermal environment and achieve sustainable urban development.
Estimating Concurrent Probabilities of Compound Extremes: An Analysis of Temperature and Rainfall Events in the Limpopo Lowveld Region of South Africa
Authors: Sigauke Caston , Ravele Thakhani
Published: May 2024

In recent years, there has been increasing interest in the joint modelling of compound extreme events such as high temperatures and low rainfall. The increase in the frequency of occurrence of these events in many regions has necessitated the development of models for estimating the concurrent probabilities of such compound extreme events. The current study discusses an application of copula models in predicting the concurrent probabilities of compound low rainfall and high-temperature events using data from the Lowveld region of the Limpopo province in South Africa. The second stage discussed two indicators for monitoring compound high temperature and low rainfall events. Empirical results from the study show that elevations ranging from 100–350 m, 350–700 m and 700–1200 m exhibit varying probabilities of experiencing drought, with mild droughts having approximately 64%, 66%, and 65% chances, moderate droughts around 36%, 39%, and 38%, and severe droughts at approximately 16%, 19%, and 18%, respectively. Furthermore, the logistic regression models incorporating the southern oscillation index as a covariate yielded comparable results of copula-based models. The methodology discussed in this paper is robust and can be applied to similar datasets in any regional setting globally. These findings could be useful to disaster management decision makers, helping them formulate effective mitigation strategies and emergency response plans.
The Wind Profile Characteristics of Super Typhoon Lekima Based on Field Measurement
Authors: Wang Yanru , Qi Qianqian , Zheng Shuqin , Fu Bin , Zhang Maoyu , Wang Xu , Zhang Chuanxiong , Zhou Lei
Published: May 2024

Many cities in coastal areas are prone to typhoon disasters due to their location on the Pacific storm path, and the direct effect of catastrophic winds can lead to the destruction of low-rise buildings and severe damage to high-rise structures. The purpose of this study was to enhance the understanding of boundary layer wind profiles of strong typhoons in coastal areas and reduce property losses and casualties caused by wind disasters. Based on the field measurements of wind profile acoustic radar in coastal areas, the variation characteristics of the boundary layer wind profile during the passage of super typhoon Lekima were first studied in depth, and the evolution law of the typhoon boundary layer profile was summarized. Then, the effects of typhoon horizontal structure, topography, wind speed, and time distance on the characteristics of the typhoon profile were discussed, respectively. Finally, the evolution characteristics of wind profile parameters were obtained by fitting three wind profile theoretical models. Due to the strong variability of typhoon profile morphology, the theoretical model of wind profile is only applicable to the wind profile from the bottom to the low-level jet height of typhoons, while wind parameters are closely related to the spatial location of the typhoon wind field.
Volcanic Glass as a Proxy for Paleotopography Suggests New Features in Late-Miocene Oregon
Authors: Cohen Julian , Bershaw John , Hugo Richard
Published: May 2024

Volcanic glass has been used extensively as a paleoaltimeter. Deuterium (2H) concentrations in glass have been found to be stable over geologic timescales, making δ2H (also known as δD) a reliable proxy for ancient water chemistry. However, continued work revolves around better understanding how different factors affect preserved water in volcanic ash. Here, we analyze δD in the Rattlesnake Tuff (RST), a widespread ca. 7 Ma ash-flow tuff, and create a paleoisoscape to assess variations in δD across Oregon during that time. To this end, 16 ash samples were collected across central and eastern Oregon from various flow units within the RST. Samples were analyzed for δD using a temperature conversion elemental analyzer (TC/EA) connected to a mass spectrometer and elemental composition using a scanning electron microscope (SEM). We compared the isotopic results to modern water and published ancient water proxy data to better constrain changes in climate and topography across Oregon throughout the Neogene. We also estimated wt. % H2O by calculating excess (non-stoichiometric) oxygen from SEM elemental data. We did not observe significant variations in δD among the flow units from single locations, nor was there a significant relationship between the prepared glass shard composition and wt. % H2O or δD, supporting the use of volcanic glass as a reliable paleoenvironmental indicator. Our results show significant spatial variation in δDwater values of RST, ranging from −107‰ to −154‰. δD values of ancient glass were similar to modern water near the Cascade Mountains but became relatively negative to the east near the inferred eruptive center of the RST, suggesting that a significant topographic feature existed in the vicinity of the RST eruptive center that has since subsided.
Impact of COVID-19 Lockdown on Inhaled Toxic Elements in PM2.5 in Beijing: Composition Characterization and Source-Specific Health Risks Assessment
Authors: Zhao Mingsheng , Ren Lihong , Yang Xiaoyang , Gao Yuanguan , Li Gang , Liu Yani
Published: May 2024

In early 2020, China experienced a mass outbreak of a novel coronavirus disease (COVID-19). With an aim to evaluate the impact of emission variations on toxic element species in PM2.5 and the health risks associated with inhalation exposure during COVID-19, we collected PM2.5 filter samples in Beijing from January 1 to February 28, 2020. Positive matrix factorization (PMF) and a health risk (HR) assessment model were used to assess the health risks of the toxic elements and critical risk sources. The total concentration of eight toxic elements (Se, Cd, Pb, Zn, As, Cu, Ni, and Cr) in Beijing showed a trend of first increasing and then decreasing: full lockdown (322.9 ng m−3) > pre-lockdown (264.2 ng m−3) > partial lockdown (245.3 ng m−3). During the lockdown period, stringent control measures resulted in significant reductions (6−20%) in Zn, Pb, Cd, and Ni levels, while concentrations of Se, As, Cu, and Cr were unexpectedly elevated (14−348%). A total of five sources was identified: traffic emission, coal combustion, dust emission, industrial emission and mixed source of biomass burning and firework combustion. Total carcinogenic risk (TCR) of the selected toxic elements exceeded the US EPA limits for children and adults. As and Cr (IV) were the main contributors to non-carcinogenic and carcinogenic risks, respectively. For source-resolved risks, coal combustion was the main contributor to HI (43%), while industrial emissions were the main cause of TCR (45%). Additionally, increased contributions from coal combustion, biomass burning, and firework combustion during the full lockdown elevated the HI and TCR values.
Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation Analysis Reveal Insights into the Molecular Mechanism of Cordia myxa in the Treatment of Liver Cancer
Authors: Li Li , Mohammed Alaulddin Hazim , Auda Nazar Aziz , Alsallameh Sarah Mohammed Saeed , Albekairi Norah A. , Muhseen Ziyad Tariq , Butch Christopher J.
Published: May 2024

Traditional treatments of cancer have faced various challenges, including toxicity, medication resistance, and financial burdens. On the other hand, bioactive phytochemicals employed in complementary alternative medicine have recently gained interest due to their ability to control a wide range of molecular pathways while being less harmful. As a result, we used a network pharmacology approach to study the possible regulatory mechanisms of active constituents of Cordia myxa for the treatment of liver cancer (LC). Active constituents were retrieved from the IMPPAT database and the literature review, and their targets were retrieved from the STITCH and Swiss Target Prediction databases. LC-related targets were retrieved from expression datasets (GSE39791, GSE76427, GSE22058, GSE87630, and GSE112790) through gene expression omnibus (GEO). The DAVID Gene Ontology (GO) database was used to annotate target proteins, while the Kyoto Encyclopedia and Genome Database (KEGG) was used to analyze signaling pathway enrichment. STRING and Cytoscape were used to create protein–protein interaction networks (PPI), while the degree scoring algorithm of CytoHubba was used to identify hub genes. The GEPIA2 server was used for survival analysis, and PyRx was used for molecular docking analysis. Survival and network analysis revealed that five genes named heat shot protein 90 AA1 (HSP90AA1), estrogen receptor 1 (ESR1), cytochrome P450 3A4 (CYP3A4), cyclin-dependent kinase 1 (CDK1), and matrix metalloproteinase-9 (MMP9) are linked with the survival of LC patients. Finally, we conclude that four extremely active ingredients, namely cosmosiin, rosmarinic acid, quercetin, and rubinin influence the expression of HSP90AA1, which may serve as a potential therapeutic target for LC. These results were further validated by molecular dynamics simulation analysis, which predicted the complexes with highly stable dynamics. The residues of the targeted protein showed a highly stable nature except for the N-terminal domain without affecting the drug binding. An integrated network pharmacology and docking study demonstrated that C. myxa had a promising preventative effect on LC by working on cancer-related signaling pathways.
Unraveling the Etiology of Dilated Cardiomyopathy through Differential miRNA–mRNA Interactome
Authors: Bonet Fernando , Hernandez-Torres Francisco , Ramos-Sánchez Mónica , Quezada-Feijoo Maribel , Bermúdez-García Aníbal , Daroca Tomás , Alonso-Villa Elena , García-Padilla Carlos , Mangas Alipio , Toro Rocio
Published: May 2024

Dilated cardiomyopathy (DCM) encompasses various acquired or genetic diseases sharing a common phenotype. The understanding of pathogenetic mechanisms and the determination of the functional effects of each etiology may allow for tailoring different therapeutic strategies. MicroRNAs (miRNAs) have emerged as key regulators in cardiovascular diseases, including DCM. However, their specific roles in different DCM etiologies remain elusive. Here, we applied mRNA-seq and miRNA-seq to identify the gene and miRNA signature from myocardial biopsies from four patients with DCM caused by volume overload (VCM) and four with ischemic DCM (ICM). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were used for differentially expressed genes (DEGs). The miRNA–mRNA interactions were identified by Pearson correlation analysis and miRNA target-prediction programs. mRNA-seq and miRNA-seq were validated by qRT-PCR and miRNA–mRNA interactions were validated by luciferase assays. We found 112 mRNAs and five miRNAs dysregulated in VCM vs. ICM. DEGs were positively enriched for pathways related to the extracellular matrix (ECM), mitochondrial respiration, cardiac muscle contraction, and fatty acid metabolism in VCM vs. ICM and negatively enriched for immune-response-related pathways, JAK-STAT, and NF-kappa B signaling. We identified four pairs of negatively correlated miRNA–mRNA: miR-218-5p-DDX6, miR-218-5p-TTC39C, miR-218-5p-SEMA4A, and miR-494-3p-SGMS2. Our study revealed novel miRNA–mRNA interaction networks and signaling pathways for VCM and ICM, providing novel insights into the development of these DCM etiologies.
Alpha-Melanocyte-Stimulating Hormone Maintains Retinal Homeostasis after Ischemia/Reperfusion
Authors: Ng Tat Fong , Cho Jenna Y. , Zhao John L. , Gardiner John R. , Wang Eric S. , Leung Elman , Xu Ziqian , Fineman Samantha L. , Lituchy Melinda , Lo Amy C. , Taylor Andrew W.
Published: May 2024

Augmenting the natural melanocortin pathway in mouse eyes with uveitis or diabetes protects the retinas from degeneration. The retinal cells are protected from oxidative and apoptotic signals of death. Therefore, we investigated the effects of a therapeutic application of the melanocortin alpha-melanocyte-stimulating hormone (α-MSH) on an ischemia and reperfusion (I/R) model of retinal degenerative disease. Eyes were subjected to an I/R procedure and were treated with α-MSH. Retinal sections were histopathologically scored. Also, the retinal sections were immunostained for viable ganglion cells, activated Muller cells, microglial cells, and apoptosis. The I/R caused retinal deformation and ganglion cell loss that was significantly reduced in I/R eyes treated with α-MSH. While α-MSH treatment marginally reduced the number of GFAP-positive Muller cells, it significantly suppressed the density of Iba1-positive microglial cells in the I/R retinas. Within one hour after I/R, there was apoptosis in the ganglion cell layer, and by 48 h, there was apoptosis in all layers of the neuroretina. The α-MSH treatment significantly reduced and delayed the onset of apoptosis in the retinas of I/R eyes. The results demonstrate that therapeutically augmenting the melanocortin pathways preserves retinal structure and cell survival in eyes with progressive neuroretinal degenerative disease.
NMR Spectroscopy in Diagnosis and Monitoring of Methylmalonic and Propionic Acidemias
Authors: Deleanu Calin , Nicolescu Alina
Published: May 2024

Although both localized nuclear magnetic resonance spectroscopy (MRS) and non-localized nuclear magnetic resonance spectroscopy (NMR) generate the same information, i.e., spectra generated by various groups from the structure of metabolites, they are rarely employed in the same study or by the same research group. As our review reveals, these techniques have never been applied in the same study of methylmalonic acidemia (MMA), propionic acidemia (PA) or vitamin B12 deficiency patients. On the other hand, MRS and NMR provide complementary information which is very valuable in the assessment of the severity of disease and efficiency of its treatment. Thus, MRS provides intracellular metabolic information from localized regions of the brain, while NMR provides extracellular metabolic information from biological fluids like urine, blood or cerebrospinal fluid. This paper presents an up-to-date review of the NMR and MRS studies reported to date for methylmalonic and propionic acidemias. Vitamin B12 deficiency, although in most of its cases not inherited, shares similarities in its metabolic effects with MMA and it is also covered in this review.
Unlocking Genetic Mysteries during the Epic Sperm Journey toward Fertilization: Further Expanding Cre Mouse Lines
Authors: Dai Pengyuan , Ma Chaoye , Chen Chen , Liang Min , Dong Shijue , Chen Hao , Zhang Xiaoning
Published: May 2024

The spatiotemporal expression patterns of genes are crucial for maintaining normal physiological functions in animals. Conditional gene knockout using the cyclization recombination enzyme (Cre)/locus of crossover of P1 (Cre/LoxP) strategy has been extensively employed for functional assays at specific tissue or developmental stages. This approach aids in uncovering the associations between phenotypes and gene regulation while minimizing interference among distinct tissues. Various Cre-engineered mouse models have been utilized in the male reproductive system, including Dppa3-MERCre for primordial germ cells, Ddx4-Cre and Stra8-Cre for spermatogonia, Prm1-Cre and Acrv1-iCre for haploid spermatids, Cyp17a1-iCre for the Leydig cell, Sox9-Cre for the Sertoli cell, and Lcn5/8/9-Cre for differentiated segments of the epididymis. Notably, the specificity and functioning stage of Cre recombinases vary, and the efficiency of recombination driven by Cre depends on endogenous promoters with different sequences as well as the constructed Cre vectors, even when controlled by an identical promoter. Cre mouse models generated via traditional recombination or CRISPR/Cas9 also exhibit distinct knockout properties. This review focuses on Cre-engineered mouse models applied to the male reproductive system, including Cre-targeting strategies, mouse model screening, and practical challenges encountered, particularly with novel mouse strains over the past decade. It aims to provide valuable references for studies conducted on the male reproductive system.
Kinetics of Human Serum Albumin Adsorption on Polycation Functionalized Silica
Authors: Nattich-Rak Małgorzata , Kosior Dominik , Morga Maria , Adamczyk Zbigniew
Published: May 2024

The adsorption kinetics of human serum albumin (HSA) on bare and poly-L-arginine (PARG)-modified silica substrates were investigated using reflectometry and atomic force microscopy (AFM). Measurements were carried out at various pHs, flow rates and albumin concentrations in the 10 and 150 mM NaCl solutions. The mass transfer rate constants and the maximum protein coverages were determined for the bare silica at pH 4.0 and theoretically interpreted in terms of the hybrid random sequential adsorption model. These results were used as reference data for the analysis of adsorption kinetics at larger pHs. It was shown that the adsorption on bare silica rapidly decreased with pH and became negligible at pH 7.4. The albumin adsorption on PARG-functionalized silica showed an opposite trend, i.e., it was negligible at pH 4 and attained maximum values at pH 7.4 and 150 mM NaCl, the conditions corresponding to the blood serum environment. These results were interpreted as the evidence of a significant role of electrostatic interactions in the albumin adsorption on the bare and PARG-modified silica. It was also argued that our results can serve as useful reference data enabling a proper interpretation of protein adsorption on substrates functionalized by polyelectrolytes.
Short-Term Panax Ginseng Extract Supplementation Reduces Fasting Blood Triacylglycerides and Oxygen Consumption during Sub-Maximal Aerobic Exercise in Male Recreational Athletes
Authors: Hernández-García Didier , Granado-Serrano Ana Belén , Martín-Gari Meritxell , Ensenyat Assumpta , Naudí Alba , Serrano Jose C. E.
Published: May 2024

Ginseng, a popular herbal supplement among athletes, is believed to enhance exercise capacity and performance. This study investigated the short-term effects of Panax ginseng extract (PG) on aerobic capacity, lipid profile, and cytokines. In a 14-day randomized, double-blind trial, male participants took 500 mg of PG daily. Two experiments were conducted: one in 10 km races (n = 31) and another in a laboratory-controlled aerobic capacity test (n = 20). Blood lipid and cytokine profile, ventilation, oxygen consumption, hemodynamic and fatigue parameters, and race time were evaluated. PG supplementation led to reduced total blood lipid levels, particularly in triacylglycerides (10 km races −7.5 mg/dL (95% CI −42 to 28); sub-maximal aerobic test −14.2 mg/dL (95% CI −52 to 23)), while post-exercise blood IL-10 levels were increased (10 km 34.0 pg/mL (95% CI −2.1 to 70.1); sub-maximal aerobic test 4.1 pg/mL (95% CI −2.8 to 11.0)), and oxygen consumption decreased during the sub-maximal aerobic test (VO2: −1.4 mL/min/kg (95% CI −5.8 to −0.6)). No significant differences were noted in race time, hemodynamic, or fatigue parameters. Overall, PG supplementation for 2 weeks showed benefits in blood lipid profile and energy consumption during exercise among recreational athletes. This suggests a potential role for PG in enhancing exercise performance and metabolic health in this population.
Development of a Novel In Silico Classification Model to Assess Reactive Metabolite Formation in the Cysteine Trapping Assay and Investigation of Important Substructures
Authors: Umemori Yuki , Handa Koichi , Yoshimura Saki , Kageyama Michiharu , Iijima Takeshi
Published: May 2024

Predicting whether a compound can cause drug-induced liver injury (DILI) is difficult due to the complexity of drug mechanism. The cysteine trapping assay is a method for detecting reactive metabolites that bind to microsomes covalently. However, it is cumbersome to use 35S isotope-labeled cysteine for this assay. Therefore, we constructed an in silico classification model for predicting a positive/negative outcome in the cysteine trapping assay. We collected 475 compounds (436 in-house compounds and 39 publicly available drugs) based on experimental data performed in this study, and the composition of the results showed 248 positives and 227 negatives. Using a Message Passing Neural Network (MPNN) and Random Forest (RF) with extended connectivity fingerprint (ECFP) 4, we built machine learning models to predict the covalent binding risk of compounds. In the time-split dataset, AUC-ROC of MPNN and RF were 0.625 and 0.559 in the hold-out test, restrictively. This result suggests that the MPNN model has a higher predictivity than RF in the time-split dataset. Hence, we conclude that the in silico MPNN classification model for the cysteine trapping assay has a better predictive power. Furthermore, most of the substructures that contributed positively to the cysteine trapping assay were consistent with previous results.
Brain-Derived Neurotrophic Factor, Nociception, and Pain
Authors: Merighi Adalberto
Published: May 2024

This article examines the involvement of the brain-derived neurotrophic factor (BDNF) in the control of nociception and pain. BDNF, a neurotrophin known for its essential role in neuronal survival and plasticity, has garnered significant attention for its potential implications as a modulator of synaptic transmission. This comprehensive review aims to provide insights into the multifaceted interactions between BDNF and pain pathways, encompassing both physiological and pathological pain conditions. I delve into the molecular mechanisms underlying BDNF’s involvement in pain processing and discuss potential therapeutic applications of BDNF and its mimetics in managing pain. Furthermore, I highlight recent advancements and challenges in translating BDNF-related research into clinical practice.