Search

Vitamin A is an essential nutrient in animals, playing important roles in animal health. In the pig industry, proper supplementation of vitamin A in the feed can improve pork production performance, while deficiency or excessive intake can lead to growth retardation or disease. However, the specific molecular mechanisms through which vitamin A operates on pig skeletal muscle growth as well as muscle stem cell function remain unexplored. Therefore, in this study, we isolated the pig primary skeletal muscle stem cells (pMuSCs) and treated with retinoic acid (RA), the natural metabolite of vitamin A, and then examined the myogenic capacity of pMuSCs via immunostaining, real-time PCR, CCK8 and western-blot analysis. Unexpectedly, the RA caused a significant decrease in the proliferation and differentiation of pMuSCs. Mechanistically, the RA addition induced the activation of retinoic acid receptor gamma (RARγ), which inhibited the myogenesis through the blockage of protein translation of the master myogenic regulator myogenic differentiation 1 gene (MYOD). Specifically, RARγ inactivate AKT kinase (AKT) signalling and lead to dephosphorylation of eukaryotic translation initiation factor 4E binding protein 1 (eIF4EBP1), which in turn repress the eukaryotic translation initiation factor 4E (eIF4E) complex and block mRNA translation of MYOD. Inhibition of AKT could rescue the myogenic defects of RA-treated pMuSCs. Our findings revealed that retinoid acid signalling inhibits the skeletal muscle stem cell proliferation and differentiation in pigs. Therefore, the vitamin A supplement in the feedstuff should be cautiously optimized to avoid the potential adverse consequences on muscle development associated with the excessive levels of retinoic acid.

The emergence of sorafenib resistance has become a predominant impediment and formidable dilemma in the therapeutic approach for hepatocellular carcinoma (HCC). Although the approval of next-generation drugs as alternatives to sorafenib is a significant development, the concurrent use of inhibitors that target additional key molecular pathways remains an effective strategy to mitigate the acquisition of resistance. Here, we identified Glutathione S-Transferase Alpha 1 (GSTA1) as a critical modulator of sorafenib resistance (SR) in hepatocellular carcinoma (HCC) based on our findings from experiments conducted on recurrent liver cancer tissues, xenograft mouse models, organoids, and sorafenib-resistant cells. Elevated GSTA1 levels are strongly associated with adverse clinical prognoses. The knockout of GSTA1 reinstates sorafenib sensitivity, whereas its overexpression attenuates drug efficacy. Mechanistically, GSTA1 enhances the accumulation of lipid peroxides and suppresses ferroptosis by exerting its peroxidase function to regulate the SR. Notably, the upregulation of GSTA1 expression is mediated by the transcription factor CTNNB1 (β-catenin), resulting in the formation of a cytoplasmic complex between GSTA1 and CTNNB1. This complex facilitates the nuclear translocation of CTNNB1, establishing a positive feedback loop. The combined use of GSTA1 and CTNNB1 inhibitors demonstrated synergistic anti-tumour effects through the induction of ferroptosis both in vitro and in vivo. Our findings reveal a novel regulatory role of the GSTA1/CTNNB1 axis in ferroptosis, suggesting that targeting GSTA1 and CTNNB1 could be a promising strategy to circumvent sorafenib resistance in HCC.

With the increasing depth of coal seam mining in China, the consequences of coal and gas outburst accidents are becoming more and more serious, which poses a great threat to mine safety production. Tectonic coal is one of the main coal sample types prone to outburst, and the outburst law and phenomenon change obviously with the proportion of tectonic coal quality. In order to explore the thermodynamic mechanism of gas adsorption in structured coal with different mass ratios, PCT-C80 adsorption calorimeter was used to carry out gas isothermal adsorption and calorimetric test based on mixed coal samples, and the calculation models of adsorption enthalpy, Gibbs free energy and gas adsorption entropy were established from the thermodynamic point of view. Based on the test and calculation results, the relationships between adsorption capacity and adsorption heat, gas adsorption constant and the proportion of structural coal with different mass ratios are discussed respectively, and the variation laws of gas adsorption enthalpy, surface free energy and adsorption entropy of structural coal with different mass ratios are analyzed. The results show thatthe gas adsorption heat of structural coals with different mass ratios increases with the increase of adsorption capacity; The adsorption heat and adsorption constant A both increase first and then decrease with the increase of structural coal mass ratio, and the adsorption constant B shows the opposite change law. With the increase of the ratio of structural coal, the gas adsorption heat, adsorption enthalpy and adsorption entropy all increase at first and then decrease, and all reaching the maximum when the proportion of structural coal is 50%, while Gibbs free energy shows the opposite change law; According to the test results and fitting formula, the mathematical relationship between the thermodynamic parameters of gas adsorption and gas emission in mixed coal is summarized. Through the above research, the variation law of thermodynamic characteristic parameters of gas adsorption under the influence of structural coal ratio is obtained, and the thermodynamic action mechanism of mixed coal samples is revealed, which provides a certain theoretical basis for clarifying the mechanism of coal induction and gas outburst caused by mining disturbed structural coal.

Abstract Childhood stunting is a serious public health concern in Rwanda. Although stunting causes have been documented, we still lack a more in‐depth understanding of their local factors at a more detailed geographic level. We cross‐sectionally examined 615 height‐for‐age prevalence observations in the Northern Province of Rwanda, linked with their related covariates, to explore the spatial heterogeneity in the low height‐for‐age prevalence by fitting linear and non‐linear spatial regression models and explainable machine learning. Specifically, complemented with generalized additive models, we fitted the ordinary least squares (OLS), a standard geographically weighted regression (GWR), and multiscale geographically weighted regression (MGWR) models to characterize the imbalanced distribution of stunting risk factors and uncover the nonlinear effect of significant predictors, explaining the height‐for‐age variations. The results reveal that 27% of the children measured were stunted, and that likelihood was found to be higher in the districts of Musanze, Gakenke, and Gicumbi. The local MGWR model outperformed the ordinary GWR and OLS, with coefficients of determination of 0.89, 0.84, and 0.25, respectively. At specific ranges, the study shows that height‐for‐age decreases with an increase in the number of days a child was left alone, elevation, and rainfall. In contrast, land surface temperature is positively associated with height‐for‐age. However, variables like the normalized difference vegetation index, slope, soil fertility, and urbanicity exhibited bell‐shaped and U‐shaped non‐linear associations with the height‐for‐age prevalence. Identifying areas with the highest rates of stunting will help determine the most effective measures for reducing the burden of undernutrition.

Abstract Background Taxi drivers in a Chinese megacity are frequently exposed to traffic-related particulate matter (PM2.5) due to their job nature, busy road traffic, and urban density. A robust method to quantify dynamic population exposure to PM2.5 among taxi drivers is important for occupational risk prevention, however, it is limited by data availability. Methods This study proposed a rapid assessment of dynamic exposure to PM2.5 among drivers based on satellite-derived information, air quality data from monitoring stations, and GPS-based taxi trajectory data. An empirical study was conducted in Wuhan, China, to examine spatial and temporal variability of dynamic exposure and compare whether drivers’ exposure exceeded the World Health Organization (WHO) and China air quality guideline thresholds. Kernel density estimation was conducted to further explore the relationship between dynamic exposure and taxi drivers’ activities. Results The taxi drivers’ weekday and weekend 24-h PM2.5 exposure was 83.60 μg/m3 and 55.62 μg/m3 respectively, 3.4 and 2.2 times than the WHO’s recommended level of 25 µg/m3. Specifically, drivers with high PM2.5 exposure had a higher average trip distance and smaller activity areas. Although major transportation interchanges/terminals were the common activity hotspots for both taxi drivers with high and low exposure, activity hotspots of drivers with high exposure were mainly located in busy riverside commercial areas within historic and central districts bounded by the “Inner Ring Road”, while hotspots of drivers with low exposure were new commercial areas in the extended urbanized area bounded by the “Third Ring Road”. Conclusion These findings emphasized the need for air quality management and community planning to mitigate the potential health risks of taxi drivers.

Dust storms have been an increasing concern in the Middle East. Severe drought events and human activities, particularly water and land management, have led to emerging dust sources in the last few decades. This study combines spatio-temporal maps of land susceptibility to dust storm incidence with agricultural land use change data to examine the link between farming patterns and dust storm generation in the Tigris and Euphrates Basin from 2000 to 2021. Farmland and bare ground trends depend heavily on water availability, affecting land susceptibility to dust storms. We observed a direct connection between cropping regimes and high land susceptibility to becoming a dust source. Our analysis found no significant correlation between low to intermediate dust storm source (DSS) susceptibility and bare ground trends. However, we found a positive correlation between highly susceptible land and areas where bare ground showed an increasing trend, including the lands that were abandoned for more than 50% of the study period. Among the farming patterns, i.e. single and double cropping, single cropping is more prone to DSS occurrence, underscoring the importance of year-round vegetation cover and effective water management. The disturbed lands, particularly those abandoned post-cropping, show higher susceptibility to DSS incidence. Between 2008 and 2012, dust sources and land susceptibility increased substantially, alongside a significant rise in bare ground, possibly due to severe drought. We highlight cases where changes in farming patterns and land abandonment contribute to the increased or decreased susceptibility of land to being a DSS, as well as consistent susceptibility in the cases where there is no land use change. Given the broad geographical scope of the study, this research underscores the need for further investigation, combining field measurements with remote sensing to obtain a more detailed picture of the link between farming patterns, land abandonment, and dust storms.

Many factors combine to influence the spatial distribution characteristics of overburden fracture during the increasingly intense mining process in coal mines. The characteristics of overburden fracture distribution has important significance in guiding the gas management in liberated layer mining. Several sets of two-dimensional physical similarity simulation experiments were carried out to investigated the distribution characteristics of overburden fracture network and the property parameters of the pressure relief gas storage and migration channels under different mining conditions (mining height, advancement speed, key layer upon layer and coal seam inclination). The topological network with geometric and fissure parameters was obtained. The topological transformation of the real stem system was simplified based on the theory of complex network evolution, and the evolution characteristics of the stem system structure and factor nodes of the transportation and storage channel was analyzed combined with the complex network characteristic parameters. The influencing factors of the overburden fissure network stem system was quantitatively described, and a matrix and model of the network structure of pressure relief gas transport and storage channel were established. The results indicated that, the development range, through degree, and fractal dimension of pressure relief gas migration and storge channel expand with the increase of mining height, key layer position, and coal seam dip angle. However, the development range shown a decreasing trend with the acceleration of advancing speed. The increase in mining height had the greatest impact on the amount of separation, with a 146.9% increase at 6 m mining height compared to 4 m. The variation in fracture density was mainly influenced by the dip angle of the coal seam, and was less influenced by the advancing speed. Arranging the boreholes in high-density areas (density > 4.7 pieces/m) can effectively act as a gas retention. The research results can further optimize the arrangement parameters of gas extraction boreholes under the influence of different factors, improve the efficiency of gas extraction, so as to ensure the safe and efficient recovery of the working face, which is of certain practical significance for the realization of accurate and green gas extraction.

In order to study the division method and fractal characteristics of the overburden gas slow permeability zone in up-dip fully mechanized face of inclined thick coal seam, based on the fractal theory and grey theory, the plane physical similarity simulation experiment was used to study the crack evolution law of the overburden gas slow permeability zone in up-dip fully mechanized face. The dynamic expansion law of the overburden gas slow permeability zone was obtained, and then the division method of the overburden gas slow permeability zone was constructed. The grey correlation analysis method was used to determine the maximum correlation degree between the horizontal direction (the advancing direction of the working face) and vertical direction (perpendicular to the upward direction of the coal seam floor) fractal dimensions of the overburden gas slow permeability zone and the separation amount, the fracture density and the stress concentration coefficient. The results show that the overburden gas slow permeability zone is initially formed after the first periodic weighting. After each periodic weighting, the caving angle on both sides of the overburden gas slow permeability zone decreases continuously and the width and height increase continuously. Specifically, from the initial formation of the slow permeability zone to the full development of the slow permeability zone, the caving angles of the open-off cut side and the working face side of the slow permeability zone are reduced from 68.3° and 76.2° to 44.7° and 53.5° respectively. The width and height of the slow permeability zone increased from 16.3 m and 19.2 m to 52.1 m and 38.4 m respectively. According to the established division criterion and process of the overburden gas slow permeability zone, combined with the grey correlation analysis method, it is obtained that the variation of fractal dimension along the horizontal and vertical directions of the overburden gas slow permeability zone has the strongest correlation with the variation of the separation amount (\begin{document}$ {r_1} $\end{document}=0.93,\begin{document}$ {r_1}^ * $\end{document}=0.91), and the accuracy of theoretical calculation is verified by experiments. Therefore, when the final hole (roadway) of pressure relief gas extraction borehole (roadway) is determined in the later stage, the boundary of the overburden gas slow permeability area can be judged by field observing the separation amount. The research results have certain guiding significance for accurate and efficient extraction of pressure relief gas in goaf.

The European spruce bark beetle is a major disturbance agent in Norway spruce forests in Europe, and with a changing climate it is predicted that damage will increase. To prevent the bark beetle population buildup, and to limit further spread during outbreaks, it is crucial to detect attacked trees early. In this study, we utilize Sentinel-2 data in combination with a risk map, created from geodata and forestry data, to detect trees predisposed to and attacked by the European spruce bark beetle. Random forest models were trained over two tiles (90 × 90 km) in southern Sweden for all dates with a sufficient number of cloud-free Sentinel-2 pixels during the period May–September in 2017 and 2018. The pixels were classified into attacked and healthy to study how detection accuracy changed with time after bark beetle swarming and to find which Sentinel-2 bands are more important for detecting bark beetle attacked trees. Random forest models were trained with (1) single-date data, (2) temporal features (1-year difference), (3) single-date and temporal features combined, and (4) Sentinel-2 data and a risk map combined. We also included a spatial variability metric. The results show that detection accuracy was high already before the trees were attacked in May 2018, indicating that the Sentinel-2 data detect predisposed trees and that the early signs of attack are low for trees at high risk of being attacked. For single-date models, the accuracy ranged from 63 to 79% and 84 to 94% for the two tiles. For temporal features, accuracy ranged from 65 to 81% and 81 to 92%. When the single-date and temporal features were combined, the accuracy ranged from 70 to 84% and 90 to 96% for the two tiles, and with the risk map included, the accuracy ranged from 83 to 91% and 92 to 97%, showing that remote sensing data and geodata can be combined to increase detection accuracy. The differences in accuracy between the two tiles indicate that local differences can influence accuracy, suggesting that geographically weighted methods should be applied. For the single-date models, the SWIR, red-edge, and blue bands were generally more important, and the SWIR bands were more important after the attack, suggesting that they are most suitable for detecting the early signs of a bark beetle attack. For the temporal features, the SWIR and blue bands were more important, and for the variability metric, the green band was generally more important.

The fracture structure is complex and irregular, which has a decisive influence on the migration and storage of pressure-relief gas in overlying strata. During the advancing process of the fully mechanized mining face in the high-gas thick-coal seam, in order to determine the impact of dynamic change of intersection and fusion of the gas transport and storage area on the gas occurrence, and the gas transport and storage law in the overlying strata under different advancing speeds, the two-dimensional physical similarity simulation was conducted to analyze the fracture distribution characteristics of the overlying strata and the geometric change law of the gas transport-storage area, and explore the change characteristics of the gas transport-storage area with the periodic weighting under different advancing speeds. Additionally, taking the advancing speed of the working face as a key parameter, the quantitative characterization model of the propulsion speed effect of the gas transport-storage area was established, and the symmetrical periodic construction mechanism of the gas transport-storage area under the influence of the advancing speed was revealed. The results show that the inner and outer boundaries and the boundary between the gas transport area and storage area are located in the mutation areas of the fracture openness and through degree respectively. With the increase of the advancing speed, the boundary of the transport-storage area is reduced from the middle of the goaf to both sides. As the working face advances, the gas storage area gradually transits into a migration area, and the two areas cross and fuse with each other. During the whole process, the transport-storage area is in the cycle of “construction-destruction-construction”, and finally form a complete symmetrical elliptical parabolic banded overburden fracture field. The change of fracture entropy increases first and then decreases with the advance of the working face, and the change of fracture rate increases and decreases twice with the advance of the working face respectively, indicating that the gas migration area and the storage area show the dynamic change of “initial formation-cross fusion-regional separation and expansion” with the advance of the working face. In addition, based on the theory of mining-induced fracture elliptic paraboloid zone, the quantitative characterization model of propulsion speed effect of gas transport-storage zone was constructed, and the boundary and state determination process of gas transport-storage zone was established. The cross-fusion evolution mechanism and symmetric periodic construction mechanism of gas transport-storage area under the influence of advancing speed were revealed, which provide a guidance for studying the distribution of pressure-relief gas in goaf and realizing the directional and accurate extraction of gas enrichment zone.

Alterations in cellular metabolism are important hallmarks of glioblastoma(GBM). Metabolic reprogramming is a critical feature as it meets the higher nutritional demand of tumor cells, including proliferation, growth, and survival. Many genes, proteins, and metabolites associated with GBM metabolism reprogramming have been found to be aberrantly expressed, which may provide potential targets for cancer treatment. Therefore, it is becoming increasingly important to explore the role of internal and external factors in metabolic regulation in order to identify more precise therapeutic targets and diagnostic markers for GBM. In this review, we define the metabolic characteristics of GBM, investigate metabolic specificities such as targetable vulnerabilities and therapeutic resistance, as well as present current efforts to target GBM metabolism to improve the standard of care.

A solid (coal) - gas (CH4) - liquid (surfactant) three-phase interaction system model is established based on the Grand Canonical Monte Carlo (GCMC) and Molecular Dynamics (MD) methods. The effects of the nanoparticle composite cationic surfactant CTAB, anionic surfactant SDBS and nonionic surfactant VAEO8 on CH4 adsorption/desorption and diffusion in coal are investigated from the aspects of adsorption configuration, adsorption amount, interaction energy, relative concentration distribution and diffusion coefficient. The results show that the surfactants and nanoparticles are imbibed into coal pores, occupying the adsorption sites of CH4 on the coal surface under the wetting effect and electrostatic action. In the absence of nanoparticles, the anionic surfactant SDBS enhances the hydrophilicity of coal and has the best effect on promoting CH4 desorption. Whereas the cationic surfactant CTAB and nonionic surfactant VAEO8 enhance the hydrophobicity of coal, resulting in a weaker CH4 desorption capacity. Nanoparticles and surfactants act synergistically in reducing solid-liquid interfacial tension, so nanoparticle composite surfactants are better than surfactants without nanoparticles in promoting CH4 desorption. After adding nanoparticles, the electrostatic force and interaction energy of the system are all increased. The CH4 diffusion coefficient in the raw coal system > the CH4 diffusion coefficient in surfactant coal system > the CH4 diffusion coefficient in coal system with nanoparticles composite surfactant. Overall, the mechanism of the influence of nanoparticle composite different types of surfactants on CH4 adsorption and diffusion is clarified from the microscopic point of view, and the study provides a theoretical basis for optimizing fracturing fluid system to improve coalbed methane recovery.

In order to study the dip angle effect on the evolution law of the target area for pressure relief gas drainage in inclined thick coal seams, the physical similarity simulation test and theoretical analysis were combined to study the fracture evolution in the target area under different coal seam dip angles. The evolution law of broken fracture’s width, the area proportion of bed-separated fracture, and the fractal dimension of fracture with the change of coal seam dip angle in the target area were obtained, and then the coal seam dip angle effect model of the targeted area evolution was established. The results showed that the broken fracture’s width presented the distribution characteristics that the boundary area on both sides of the goaf was greater than that in the middle, and the low horizon was greater than that in the higher horizon. What’s more, the broken fracture’s width was strongly affected by the hinged beam. With the increase of the coal seam dip angle (0° < 15° < 30°), the broken fracture’s width in the upper region of the first layer of hinged beam is significantly reduced compared with that in the lower region, which is only 52.8%, 64.3%, and 71.1%, respectively. The area proportion of bed-separated fracture in the dominant gas migration channel zone was the largest at the bottom, followed by the top, and the smallest in the middle. The fractal dimension of overlying fractures decreased first and then increased as a whole. The fracture evolution laws were obviously different on both sides of the layer where the hinged beam of the first layer and the minimum fractal dimension of the fracture were located. Therefore, the dominant channel belt of gas migration was divided into low-layer target areas, middle-layer target areas, and high-layer target areas according to the level of the spatial horizon. Finally, based on the theory of mining fracture ellipse belts and the dominant gas migration channel zone at the working face side, the mathematical equation of the target area in inclined thick coal seams was established considering the coal seam dip angle, and the basis for selection of pressure relief gas drainage methods in the targeted area was formed. It provided a reference for optimizing the parameters of pressure relief gas drainage in an inclined, thick coal seam working face.

Interannual variations in the end of the growing season (EOS) play a crucial role in assessing carbon and energy cycling within grassland ecosystems. Previous studies have often fixed the trend breakpoint in autumn phenology around the year 2000 to examine the response of the vegetation EOS to long-term climate change. However, the asymmetry of climate change and the diversity of grass species may lead to spatial disparities in EOS trend breakpoints, but little research has been done to quantify their characteristics and underlying climatic driving mechanisms. Focusing on the period from 1982 to 2015, this study extracts EOS data from six different grassland subregions in China to identify EOS trend breakpoints, and then investigates the associated climatic driving mechanisms. The results highlight the presence of significant breakpoints in the EOS trend within 54.1% of China's grasslands. Prior to 1997, the grassland EOS trend exhibited a pronounced delay, with a rate of 0.29 days per year (P

Abstract Background Despite progress in developing wound care strategies, there is currently no treatment that promotes the self-tissue repair capabilities. H2 has been shown to effectively protect cells and tissues from oxidative and inflammatory damage. While comprehensive effects and how H2 functions in wound healing remains unknown, especially for the link between H2 and extracellular matrix (ECM) deposition and epidermal stem cells (EpSCs) activation. Methods Here, we established a cutaneous aseptic wound model and applied a high concentration of H2 (66% H2) in a treatment chamber. Molecular mechanisms and the effects of healing were evaluated by gene functional enrichment analysis, digital spatial profiler analysis, blood perfusion/oxygen detection assay, in vitro tube formation assay, enzyme-linked immunosorbent assay, immunofluorescent staining, non-targeted metabonomic analysis, flow cytometry, transmission electron microscope, and live-cell imaging. Results We revealed that a high concentration of H2 (66% H2) greatly increased the healing rate (3 times higher than the control group) on day 11 post-wounding. The effect was not dependent on O2 or anti-reactive oxygen species functions. Histological and cellular experiments proved the fast re-epithelialization in the H2 group. ECM components early (3 days post-wounding) deposition were found in the H2 group of the proximal wound, especially for the dermal col-I, epidermal col-III, and dermis-epidermis-junction col-XVII. H2 accelerated early autologous EpSCs proliferation (1–2 days in advance) and then differentiation into myoepithelial cells. These epidermal myoepithelial cells could further contribute to ECM deposition. Other beneficial outcomes include sustained moist healing, greater vascularization, less T-helper-1 and T-helper-17 cell-related systemic inflammation, and better tissue remodelling. Conclusion We have discovered a novel pattern of wound healing induced by molecular hydrogen treatment. This is the first time to reveal the direct link between H2 and ECM deposition and EpSCs activation. These H2-induced multiple advantages in healing may be related to the enhancement of cell viability in various cells and the maintenance of mitochondrial functions at a basic level in the biological processes of life.

Objective: To investigate the pharmacological action and mechanism of cholic acid derivatives in traditional Chinese medicine (TCM) based on the regulation of gene expression. Methods: Genome-wide gene expression profiles of Michigan Cancer Foundation-7 (MCF-7) cells treated with or without 4 cholic acid derivatives were detected by gene chip technology. Similarities in upregulated and downregulated genes were analyzed using the Connectivity Map (CMap) database. The affinity between cholic acid derivatives and the potential target was confirmed by molecular docking. The cholic acid derivative-regulated pathway enrichment analysis was performed by the STRING database, and the potential pathway was confirmed by in vitro experiments on MD Anderson-Metastatic Breast-231 (MDA-MB-231) cells. Results: Compared with the reference genome in the CMap database, the gene expression profiles of cholic acid derivatives were similar to those of antipsychotic, anticancer, anti-inflammatory, and anti-infective drugs. Among them, 4 derivatives were associated with antianxiety drugs, and molecular docking results showed that these compounds may act by binding to the ligand-binding site of gamma-aminobutyric acid (GABA) receptors. Moreover, the cytoskeletal pathway is one of the pathways enriched in the derivatives. Of them, ursodeoxycholic acid showed significant inhibitory activity on the cytoskeleton formation of MDA-MB-231 cells. Conclusion: The gene expression detection method, combined with CMap and pathway enrichment analysis, could be used to study the mechanism of the active ingredients of TCM. In addition, our research showed that cholic acid derivatives have a potential affinity for membrane receptors, where they can exert anxiolytic activity by modulating opioid receptor, GABA receptor, and dopamine receptor. Moreover, ursodeoxycholic and chenodeoxycholic acid inhibit cytoskeleton formation, probably by acting on membrane proteins to activate the corresponding cytoskeletal pathways.

As a novel antioxidant, a growing body of studies has documented the diverse biological effects of molecular hydrogen (H2) in a wide range of organisms, spanning animals, plants, and microorganisms. Although several possible mechanisms have been proposed, they cannot fully explain the extensive biological effects of H2. Mitochondria, known for ATP production, also play crucial roles in diverse cellular functions, including Ca2+ signaling, regulation of reactive oxygen species (ROS) generation, apoptosis, proliferation, and lipid transport, while their dysfunction is implicated in a broad spectrum of diseases, including cardiovascular disorders, neurodegenerative conditions, metabolic disorders, and cancer. This review aims to 1) summarize the experimental evidence on the impact of H2 on mitochondrial function; 2) provide an overview of the mitochondrial pathways underlying the biological effects of H2, and 3) discuss H2 metabolism in eukaryotic organisms and its relationship with mitochondria. Moreover, based on previous findings, this review proposes that H2 may regulate mitochondrial quality control through diverse pathways in response to varying degrees of mitochondrial damage. By combining the existing research evidence with an evolutionary perspective, this review emphasizes the potential hydrogenase activity in mitochondria of higher plants and animals. Finally, this review also addresses potential issues in the current mechanistic study and offers insights into future research directions, aiming to provide a reference for future studies on the mechanisms underlying the action of H2.

Abstract Background The study and synthesis of membrane organelles are becoming increasingly important, not only as simplified cellular models for corresponding molecular and metabolic studies but also for applications in synthetic biology of artificial cells and drug delivery vehicles. Lipid droplets (LDs) are central organelles in cellular lipid metabolism and are involved in almost all metabolic processes. Multiple studies have also demonstrated a high correlation between LDs and metabolic diseases. During these processes, LDs reveal a highly dynamic character, with their lipid fraction, protein composition and subcellular localisation constantly changing in response to metabolic demands. However, the molecular mechanisms underlying these functions have not been fully understood due to the limitations of cell biology approaches. Fortunately, developments in synthetic biology have provided a huge breakthrough for metabolism research, and methods for in vitro synthesis of LDs have been successfully established, with great advances in protein binding, lipid function, membrane dynamics and enzymatic reactions. Aims and methods In this review, we provide a comprehensive overview of the assembly and function of endogenous LDs, from the generation of lipid molecules to how they are assembled into LDs in the endoplasmic reticulum. In particular, we highlight two major classes of synthetic LD models for fabrication techniques and their recent advances in biology and explore their roles and challenges in achieving real applications of artificial LDs in the future.

Land use allocation (LUA) is of prime importance for the development of urban sustainability and resilience. Since the process of planning and managing land use requires balancing different conflicting social, economic, and environmental factors, it has become a complex and significant issue in urban planning worldwide. LUA is usually regarded as a spatial multi-objective optimization (MOO) problem in previous studies. In this paper, we develop an MOO approach for tackling the LUA problem, in which maximum economy, minimum carbon emissions, maximum accessibility, maximum integration, and maximum compactness are formulated as optimal objectives. To solve the MOO problem, an improved non-dominated sorting genetic algorithm III (NSGA-III) is proposed in terms of mutation and crossover operations by preserving the constraints on the sizes for each land use type. The proposed approach was applied to KaMavota district, Maputo City, Mozambique, to generate a proper land use plan. The results showed that the improved NSGA-III yielded better performance than the standard NSGA-III. The optimal solutions produced by the MOO approach provide good trade-offs between the conflicting objectives. This research is beneficial for policymakers and city planners by providing alternative land use allocation plans for urban sustainability and resilience.

PurposeLacrimal gland benign lymphoepithelial lesion (LGBLEL) is an IgG4-related disease of unknown etiology with a risk for malignant transformation. Estrogen is considered to be related to LGBLEL onset.MethodsSeventy-eight LGBLEL and 13 control clinical samples were collected and studied to determine the relationship between estrogen and its receptors and LGBLEL development.ResultsThe serological analysis revealed no significant differences in the levels of three estrogens be-tween the LGBLEL and control groups. However, immunohistochemical analyses indicated that the expression levels of ERβ and its downstream receptor RERG were relatively lower in LGBLEL samples than in control samples, with higher expression in the lacrimal gland and lower expression in the lymphocyte infiltration region. However, low expression of ERα was detected. The transcriptome sequence analysis revealed upregulated genes associated with LGBLEL enriched in lymphocyte proliferation and activation function; downregulated genes were enriched in epithelial and vascular proliferation functions. The key genes and gene networks were further analyzed. Interactions between B cells and epithelial cells were analyzed due to the identified involvement of leukocyte subsets and epithelial cells. B cell proliferation was found to potentially contribute to lacrimal gland apoptosis.ConclusionTherefore, the tissue-heterogeneous expression pattern of ERβ is potentially related to the clinical manifestations and progression of LGBLEL, although further investigations are required to confirm this finding.

Jin et al. investigate the underlying mechanisms of hepatic steatosis and show that Glutathione-S-transferase mu 2 (GSTM2), which is a drug metabolizing enzyme (DME), is upregulated in hepatic steatosis tissue from mice fed with a high fat diet. They show that GSTM2 is a negative regulator of hepatic steatosis via both detoxification/antioxidant and inhibition of ASK1-p38/JNK signalling, which sheds light on its potential as a therapeutic target.

Abstract Molecular hydrogen (H2) has emerged as a new therapeutic option in several diseases and is widely adopted by healthy people. However, molecular data to support therapeutic functions attributed to the biological activities of H2 remain elusive. Here, using transcriptomic and metabolomic approaches coupled with biochemistry and micro-CT technics, we evaluated the effect of long-term (6 months) and daily use of H2 on liver function. Rats exposed 2 h daily to H2 either by drinking HRW (H2 dissolved in H2O) or by breathing 4% H2 gas showed reduced lipogenesis and enhanced lipolysis in the liver, which was associated with apparent loss of visceral fat and brown adipose tissue together with a reduced level of serum lipids. Both transcripts and metabolites enriched in H2-treated rats revealed alteration of amino acid metabolism pathways and activation of purine nucleotides and carbohydrate biosynthesis pathways. Analysis of the interaction network of genes and metabolites and correlation tests revealed that NADP is the central regulator of H2 induced metabolic alterations in the liver, which was further confirmed by an increase in the level of components of metabolic pathways that require NADP as substrate. Evidence of immune response regulation activity was also observed in response to exposure to H2. This work is the first to provide metabolomic and transcriptomic data to uncover molecular targets for the effect of prolonged molecular hydrogen treatment on liver metabolism.

As found in the health studies literature, the levels of climate association between epidemiological diseases have been found to vary across regions. Therefore, it seems reasonable to allow for the possibility that relationships might vary spatially within regions. We implemented the geographically weighted random forest (GWRF) machine learning method to analyze ecological disease patterns caused by spatially non-stationary processes using a malaria incidence dataset for Rwanda. We first compared the geographically weighted regression (WGR), the global random forest (GRF), and the geographically weighted random forest (GWRF) to examine the spatial non-stationarity in the non-linear relationships between malaria incidence and their risk factors. We used the Gaussian areal kriging model to disaggregate the malaria incidence at the local administrative cell level to understand the relationships at a fine scale since the model goodness of fit was not satisfactory to explain malaria incidence due to the limited number of sample values. Our results show that in terms of the coefficients of determination and prediction accuracy, the geographical random forest model performs better than the GWR and the global random forest model. The coefficients of determination of the geographically weighted regression (R2), the global RF (R2), and the GWRF (R2) were 4.74, 0.76, and 0.79, respectively. The GWRF algorithm achieves the best result and reveals that risk factors (rainfall, land surface temperature, elevation, and air temperature) have a strong non-linear relationship with the spatial distribution of malaria incidence rates, which could have implications for supporting local initiatives for malaria elimination in Rwanda.

The low-gas permeability area of a fully mechanized up-dip working face was quantitatively studied using a physical similarity simulation test and theoretical analysis under varying dip angles of rock strata. Based on the theory of fractal geometry, this study obtained the fractal dimensions of the low-gas permeability area, the boundary area of the low-gas permeability region, and various layer areas of the low-gas permeability area by increasing the dip angle of rock strata. The findings reveal that the goaf’s high penetration area moved from a symmetrical shape to an asymmetrical one as the dip angle of rock strata increased. The high penetration area on the open-off cut side is notably larger than that on the working face side, due to the effects of advancement at the working face. In the goaf, the lateral length of the cavity decreases as the rock strata’s dip angle increases, while the longitudinal width expands and then contracts until it vanishes because of sliding. In the goaf, the lateral length of the cavity decreases as the rock strata’s dip angle increases, while the longitudinal width expands and then contracts until it vanishes because of sliding. In the goaf, the lateral length of the cavity decreases as the rock strata’s dip angle increases, while the longitudinal width expands and then contracts until it vanishes because of sliding. Moreover, the low-gas permeability area has a larger fractal dimension. The fractal dimension of the area with low gas permeability steadily decreased as periodic weighting emerged, ultimately reaching values of 1.24, 1.27, and 1.34. Moreover, the area’s fractal dimension was greater on the open-off cut side in comparison to the working face side. As the distance from the rock strata floor decreased, the fractal dimension of the area with low gas permeability increased. According to the gradient evolution law, the low-gas permeability area may be divided from bottom to top into three areas: strongly disturbed, moderately disturbed, and lowly disturbed. Based on the theory of mining fissure elliptic paraboloid zones and experimental findings, a mathematical model has been developed to analyze the fractal characteristics of low-gas permeability areas that are influenced by the rock strata’s dip angle. Finally, this study established a dependable theoretical foundation for precisely examining the development of cracks in the area of low gas permeability and identifying the storage and transportation region of pressure relief gas, which is affected by various dip angles of rock strata. It also offered assistance in constructing a precise gas extraction mechanism for pressure relief.

For decades, tissue regeneration has been a challenging issue in scientific modeling and human practices. Although many conventional therapies are already used to treat burns, muscle injuries, bone defects, and hair follicle injuries, there remains an urgent need for better healing effects in skin, bone, and other unique tissues. Recent advances in three-dimensional (3D) printing and real-time monitoring technologies have enabled the creation of tissue-like membranes and the provision of an appropriate microenvironment. Using tissue engineering methods incorporating 3D printing technologies and biomaterials for the extracellular matrix (ECM) containing scaffolds can be used to construct a precisely distributed artificial membrane. Moreover, advances in smart sensors have facilitated the development of tissue regeneration. Various smart sensors may monitor the recovery of the wound process in different aspects, and some may spontaneously give feedback to the wound sites by releasing biological factors. The combination of the detection of smart sensors and individualized membrane design in the healing process shows enormous potential for wound dressings. Here, we provide an overview of the advantages of 3D printing and conventional therapies in tissue engineering. We also shed light on different types of 3D printing technology, biomaterials, and sensors to describe effective methods for use in skin and other tissue regeneration, highlighting their strengths and limitations. Finally, we highlight the value of 3D bioengineered membranes in various fields, including the modeling of disease, organ-on-a-chip, and drug development.

Abstract Lipid droplet (LD), a multi-functional organelle, is found in most eukaryotic cells. LDs participate in the regulation of many cellular processes including proliferation, stress, and apoptosis. Previous studies showed the athlete’s paradox that trained athletes accumulate LDs in their skeletal muscle. However, the impact of LDs on skeletal muscle and myogenesis is not clear. We discovered that C2C12 myoblast cells containing more LDs formed more multinucleated muscle fibers. We also discovered that LDs promoted cell migration and fusion by promoting actin-filaments remodeling. Mechanistically, two LD-proteins, Acyl-CoA synthetase long chain family member 3 (ACSL3) and lysophosphatidylcholine acyltransferase 1 (LPCAT1), medicated the recruitment of actinin proteins which contributed to actin-filaments formation on the surface of LDs. During remodeling, the actinin proteins on LDs surface translocated to actin-filaments via ARF1/COPI vesicles. Our study demonstrate LDs contribute to cell differentiation, which lead to new insight into the LD function.

The heterogeneous and highly plastic cell populations of macrophages are important mediators of cellular responses during all stages of wound healing, especially in the inflammatory stage. Molecular hydrogen (H2), which has potent antioxidant and anti-inflammatory effects, has been shown to promote M2 polarization in injury and disease. However, more in vivo time series studies of the role of M1-to-M2 polarization in wound healing are needed. In the current study, we performed time series experiments on a dorsal full-thickness skin defect mouse model in the inflammatory stage to examine the effects of H2 inhalation. Our results revealed that H2 could promote very early M1-to-M2 polarization (on days 2–3 post wounding, 2–3 days earlier than in conventional wound healing), without disturbing the functions of the M1 phenotype. Time series analysis of the transcriptome, blood cell counts, and multiple cytokines further indicated that peripheral blood monocytes were a source of H2-induced M2 macrophages and that the functions of H2 in macrophage polarization were not only dependent on its antioxidant effects. Therefore, we believe that H2 could reduce inflammation in wound care by shifting early macrophage polarization in clinical settings.

Monitoring pollution of PM2.5 on walkable roads is important for resident health in high-density cities. Due to the spatiotemporal resolution limitations of aerosol optical depth observation, fixed-point monitoring, or traditional mobile measurement instruments, the microscale PM2.5 distribution in the walking environment cannot be fully estimated at the fine scale. In this article, by the integration of mobile measurement data, OpenStreetMap (OSM) data, Landsat images, and other multisource data in land-use regression (LUR) models, a novel framework is proposed to estimate and map PM2.5 distribution in a typical microscale walkable environment of the high-density city Hong Kong. First, the PM2.5 data on the typical walking paths were collected by the handheld mobile measuring instruments, to be selected as the dependent variables. Second, geographic prediction factors calculated by Google Street View, OSM data, Landsat images, and other multisource data were further selected as independent variables. Then, these dependent and independent variables were put into the LUR models to estimate the PM2.5 concentration on sidewalks, footbridges, and footpaths in the microscale walkable environment. The proposed models showed high performance relative to those in similar studies (adj R2, 0.593 to 0.615 [sidewalks]; 0.641 to 0.682 [footpaths]; 0.783 to 0.797 [footbridges]). This article is beneficial for mapping PM2.5 concentration in the microscale walking environment and the identification of hot spots of air pollution, thereby helping people avoid the PM2.5 hotspots and indicating a healthier walking path.

Ferroptosis is a newly defined programmed cell death, which by its mechanism differs from other programmed cell death processes such as apoptosis, necrosis, and autophagy. It has a unique morphology and biological properties that antioxidants and iron-chelating agents can regulate. Ferroptosis has the characteristics of iron ion deposition and dependence on lipid peroxidation. It can affect the progression of many cancers, including liver cancer, by inducing an intracellular iron-dependent accumulation of reactive oxygen species, providing new possibilities for cancer treatment. At present, great progress has been made in exploring the molecular mechanism of ferroptosis. In this review, we summarize the characteristics, mechanisms, and regulatory factors of ferroptosis in detail, discuss the progress of ferroptosis research in liver cancer, and provide directions and new ideas for the treatment of hepatocellular carcinoma.

The collected dataset derives from the laboratory testing of bentonite clay investigated as a stabilization technology for the unbound layers of road pavements. The effect of two kinds of bentonite (calcium based and sodium based) are assessed on two aggregate types commonly used as road construction materials. The investigation program, performed by means of repeated load triaxial tests, encompasses the different combinations of bentonite and aggregate types; two replicate specimens are tested dried for each condition. Considering the global need for ensuring well-performing road infrastructures while employing environmentally sound construction technologies, this dataset documenting the potential of bentonite clays used as road stabilizers can be of interest for several road stakeholders.

Oxidative stress and chronic inflammation have been implicated in the pathophysiology of metabolic diseases, including diabetes mellitus (DM), metabolic syndrome (MS), fatty liver (FL), atherosclerosis (AS), and obesity. Molecular hydrogen (H2) has long been considered a physiologically inert gas. In the last two decades, accumulating evidence from pre-clinical and clinical studies has indicated that H2 may act as an antioxidant to exert therapeutic and preventive effects on various disorders, including metabolic diseases. However, the mechanisms underlying the action of H2 remain unclear. The purpose of this review was to (1) provide an overview of the current research on the potential effects of H2 on metabolic diseases; (2) discuss the possible mechanisms underlying these effects, including the canonical anti-oxidative, anti-inflammatory, and anti-apoptotic effects, as well as suppression of ER stress, activation of autophagy, improvement of mitochondrial function, regulation of gut microbiota, and other possible mechanisms. The potential target molecules of H2 will also be discussed. With more high-quality clinical trials and in-depth mechanism research, it is believed that H2 will eventually be applied to clinical practice in the future, to benefit more patients with metabolic disease.

Several technologies are currently available to stabilize the unbound layers of road pavements. The use of these solutions, often manufactured by means of chemical processes, is steadily increasing worldwide. As an alternative natural resource, the use of bentonite represents a valid option when it comes to road stabilization and its application in this context is still relatively unexplored. This study characterises the use of calcium based bentonite and sodium based bentonite to stabilize a typical road base layer. Considering two types of aggregates with different geological origin, the laboratory investigation is performed on dry specimens by means of repeated load triaxial tests, which assess the enhancement in stiffness and resistance to permanent deformation. The findings show that both the investigated types of bentonite are suitable for road stabilization. Even if negligible from a road engineering standpoint, the performance stemming from calcium bentonite was slightly better than the one pertaining to sodium bentonite when it came to the increase in resilient modulus.

The transport of eroded soil to rivers changes the nutrient cycles of river ecosystems and has significant impacts on the regional eco-environment and human health. The Loess Plateau, a leading vegetation restoration region in China and the world, has experienced severe soil erosion and nutrient loss, however, the extent to which vegetation restoration prevents soil erosion export (to rivers) and it caused nutrient loss is unknown. To evaluate the effects of the first stage of the Grain for Green Project (GFGP) on the Loess Plateau (started in 1999 and ended in 2013), we analyzed the vegetation change trends and quantified the effects of GFGP on soil erosion export (to rivers) and it caused nutrient loss by considering soil erosion processes. The results were as follows: (1) in the first half of study period (from 1982 to 1998), the vegetation cover changed little, but after the implementation of the first stage of the GFGP (from 1999 to 2013), the vegetation cover of 75.0% of the study area showed a significant increase; (2) The proportion of eroded areas decreased from 41.8 to 26.7% as a result of the GFGP, and the erosion intensity lessened in most regions; the implementation significantly reduce the soil nutrient loss; (3) at the county level, soil erosion export could be avoided significantly by the increasing of vegetation greenness in the study area (R = −0.49). These results illustrate the relationships among changes in vegetation cover, soil erosion and nutrient export, which could provide a reference for local government for making ecology-relative policies.

Wetlands are important modulators of atmospheric greenhouse gas (GHGs) concentrations. However, little is known about the magnitudes and spatiotemporal patterns of GHGs fluxes in wetlands on the Qinghai-Tibetan Plateau (QTP), the world’s largest and highest plateau. In this study, we measured soil temperature and the fluxes of carbon dioxide (CO2) and methane (CH4) in an alpine wetland on the QTP from April 2017 to April 2019 by the static chamber method, and from January 2017 to December 2017 by the eddy covariance (EC) method. The CO2 and CH4 emission measurements from both methods showed different relationships to soil temperature at different timescales (annual and seasonal). Based on such relationship patterns and soil temperature data (1960–2017), we extrapolated the CO2 and CH4 emissions of study site for the past 57 years: the mean CO2 emission rate was 1096.59 mg C m–2 h–1 on different measurement methods and timescales, with the range of the mean emission rate from 421.17 to 1754.99 mg C m–2 h–1, while the mean CH4 emission rate was 32.99 mg C m–2 h–1, with the ranges of the mean emission rate from 16.95 to 46.25 mg C m–2 h–1. The estimated regional CO2 and CH4 emissions from permanent wetlands on the QTP were 94.29 and 2.37 Tg C year–1, respectively. These results indicate that uncertainties caused by measuring method and timescale should be fully considered when extrapolating wetland GHGs fluxes from local sites to the regional level. Moreover, the results of global warming potential showed that CO2 dominates the GHG balance of wetlands on the QTP.

Traffic flow information is of great importance for transport planning and related research. The conventional methods of automated data collection, such as annual average daily traffic (AADT) data, are often restricted by limited installation, while the state-of-the-art sensing technologies (e.g., GPS) only reflect some types of traffic flow (e.g., taxi and bus). Complete coverage of traffic flow is still lacking, thus demanding a rigorous estimation model. Most studies dedicated to estimating the traffic flow of the entire road network rely on single to only a few properties of the road network and the results may not be promising. This paper presents an idea of integrating five topological measures and road length to estimate traffic flow based on a multiple regression approach. An empirical study in Hong Kong has been conducted with three types of traffic datasets, namely floating car, public transport route, and AADT. Six measures, namely degree, betweenness, closeness, page rank, clustering coefficient, and road length, are used for traffic flow estimation. It is found that each measure correlates differently for the three types of traffic data. Multiple regression approach is then conducted, including multiple linear regression and random forest. The results show that a combination of various topological and geometrical measures has proved to have a better performance in estimating traffic flow than that of a single measure. This paper is especially helpful for transport planners to estimate traffic flow based on correlation available but limited flow data with road network characteristics.

Abstract Background Benign Lymphoepithelial Lesion (BLEL) is a rare disease observed in the adult population. Despite the growing numbers of people suffering from BLEL, the etiology and mechanisms underlying its pathogenesis remain unknown. Methods In the present study, we used gene and cytokines expression profiling, western blot and immunohistochemistry to get further insight into the cellular and molecular mechanisms involved in the pathogenesis of BLEL of the lacrimal gland. Results The results showed that Macrophage Migration Inhibitory Factor (MIF) was the most highly expressed cytokine in BLEL, and its expression positively correlated with the expression of Th2 and Th17 cells cytokines. MIF was found to regulate biological functions and pathways involved in BLEL pathogenesis, such as proliferation, resistance to apoptosis, MAPK and PI3K/Akt pathways. We also found that MIF promotes fibrosis in BLEL by inducing BLEL fibroblast differentiation into myofibroblasts as well as the synthesis and the deposit of extracellular matrix in BLEL tissues. Conclusions Our findings demonstrate the contribution of MIF to the pathogenesis of BLEL of the lacrimal gland and suggested MIF as a promising therapeutic target for its treatment.

Environmental exposure of people plays an important role in assessing the quality of human life. The most existing methods that estimate the environmental exposure either focus on the individual level or do not consider human mobility. This paper adopts a vector field generated from the observed locations of human activities to model the environmental exposure at the population level. An improved vector-field-generation method was developed by considering people’s decision-making factors, and we proposed two indicators, i.e., the total exposure indicator (TEI) and the average exposure indicator (AEI), to assess various social groups’ environmental exposure. A case study about the risky environmental exposure of coronavirus disease 2019 (COVID-19) was conducted in Guangzhou, China. Over 900 participants with various socioeconomic backgrounds were involved in the questionnaire, and the survey-based activity locations were extracted to generate the vector field using the improved method. COVID-19 pandemic exposure (or risk) was estimated for different social groups. The findings show that people in the low-income group have an 8% to 10% higher risk than those in the high-income group. This new method of vector field may benefit geographers and urban researchers, as it provides opportunities to integrate human activities into the metrics of pandemic risk, spatial justice, and other environmental exposures.

Lipid droplets (LDs) play an important role in the regulation of cellular stress. This suggests LDs can be applied as safe and effective biomaterials to alleviate cellular stress and lipotoxicity. Here, we constructed a convenient method to generate stable and pure artificial lipid droplets (aLDs). aLDs can maintain their biological function by incubating LD-associated proteins or organelles in vitro. It was validated that perilipin-coated aLDs could be uptaken by cells, significantly reducing hydrogen peroxide-induced reactive oxidative species (ROS) and alleviating cellular lipotoxicity caused by excess fatty acid. Our work demonstrated a direct role of LDs in regulating cellular stress levels, providing methods and potential value for future research and medical applications of LDs.

Landslides often cause significant casualties and economic losses, and therefore landslide susceptibility mapping (LSM) has become increasingly urgent and important. The potential of deep learning (DL) like convolutional neural networks (CNN) based on landslide causative factors has not been fully explored yet. The main target of this study is the investigation of a GIS-based LSM in Zanjan, Iran and to explore the most important causative factor of landslides in the case study area. Different machine learning (ML) methods have been employed and compared to select the best results in the case study area. The CNN is compared with four ML algorithms, including random forest (RF), artificial neural network (ANN), support vector machine (SVM), and logistic regression (LR). To do so, sixteen landslide causative factors have been extracted and their related spatial layers have been prepared. Then, the algorithms were trained with related landslide and non-landslide points. The results illustrate that the five ML algorithms performed suitably (precision = 82.43–85.6%, AUC = 0.934–0.967). The RF algorithm achieves the best result, while the CNN, SVM, the ANN, and the LR have the best results after RF, respectively, in this case study. Moreover, variable importance analysis results indicate that slope and topographic curvature contribute more to the prediction. The results would be beneficial to planning strategies for landslide risk management.

Summary: Voltage-gated calcium channels are exquisitely Ca2+ selective, conferred primarily by four conserved pore-loop glutamate residues contributing to the selectivity filter. There has been little previous work directly measuring whether the trafficking of calcium channels requires their ability to bind Ca2+ in the selectivity filter or to conduct Ca2+. Here, we examine trafficking of neuronal CaV2.1 and 2.2 channels with mutations in their selectivity filter and find reduced trafficking to the cell surface in cell lines. Furthermore, in hippocampal neurons, there is reduced trafficking to the somatic plasma membrane, into neurites, and to presynaptic terminals. However, the CaV2.2 selectivity filter mutants are still influenced by auxiliary α2δ subunits and, albeit to a reduced extent, by β subunits, indicating the channels are not grossly misfolded. Our results indicate that Ca2+ binding in the pore of CaV2 channels may promote their correct trafficking, in combination with auxiliary subunits. Furthermore, physiological studies utilizing selectivity filter mutant CaV channels should be interpreted with caution. : Meyer et al. examine whether selectivity filtering mutations in CaV2 channels, preventing inward Ba2+ currents, would reduce trafficking. Pore-mutant channels show strongly reduced cell-surface expression in cell lines and neurons, but still require β and α2δ subunits and thus are not grossly misfolded. Keywords: N-type, P/Q-type, calcium channel, selectivity filter, α2δ subunit, β subunit, divalent cation, permeation, trafficking, calcium currents

Forest carbon density is an important indicator for evaluating forest carbon sink capacities. Accurate carbon density estimation is the basis for studying the response mechanisms of forest ecosystems to global climate change. Airborne light detection and ranging (LiDAR) technology can acquire the vertical structure parameters of forests with a higher precision and penetration ability than traditional optical remote sensing. Combining top of canopy height model (TCH) and allometry models, this paper constructed two prediction models of aboveground carbon density (ACD) with 94 square plots in northwestern China: one model is plot-averaged height-based power model and the other is plot-averaged daisy-chain model. The correlation coefficients (R2) were 0.6725 and 0.6761, which are significantly higher than the correlation coefficients of the traditional percentile model (R2 = 0.5910). In addition, the correlation between TCH and ACD was significantly better than that between plot-averaged height (AvgH) and ACD, and Lorey’s height (LorH) had no significant correlation with ACD. We also found that plot-level basal area (BA) was a dominant factor in ACD prediction, with a correlation coefficient reaching 0.9182, but this subject requires field investigation. The two models proposed in this study provide a simple and easy approach for estimating ACD in coniferous forests, which can replace the traditional LiDAR percentile method completely.

Dynamic global vegetation models (DGVMs) suffer insufficiencies in tracking biochemical cycles and ecosystem fluxes. One important reason for these insufficiencies is that DGVMs use fixed parameters (mostly traits) to distinguish attributes and functions of plant functional types (PFTs); however, these traits vary under different climatic conditions. Therefore, it is urgent to quantify trait covariations, including those among specific leaf area (SLA), area-based leaf nitrogen (Narea), and leaf area index (LAI) (in 580 species across 218 sites in this study), and explore new classification methods that can be applied to model vegetation dynamics under future climate change scenarios. We use a redundancy analysis (RDA) to derive trait–climate relationships and employ a Gaussian mixture model (GMM) to project vegetation distributions under different climate scenarios. The results show that (1) the three climatic variables, mean annual temperature (MAT), mean annual precipitation (MAP), and monthly photosynthetically active radiation (mPAR) could capture 65% of the covariations of three functional traits; (2) tropical, subtropical and temperate forest complexes expand while boreal forest, temperate steppe, temperate scrub and tundra shrink under future climate change scenarios; and (3) the GMM classification based on trait covariations should be a powerful candidate for building new generation of DGVM, especially predicting the response of vegetation to future climate changes. This study provides a promising route toward developing reliable, robust and realistic vegetation models and can address a series of limitations in current models.

The integrated energy system can realize the complementary advantages of multiple energy sources and effectively solve the problem of low integrated energy efficiency of traditional energy systems. Carrying out research on the interactive scenarios and mechanisms of the energy supply and use modules of the integrated energy system is conducive to promoting the development of clean energy and promoting the indepth integration of energy Internet and distributed energy technology, smart grid technology, and energy storage technology. First, it summarizes the scenarios of the energy supply and use modules of the integrated energy system, and analyzes the interaction mechanism and paths of the energy supply and use modules of the integrated energy system on this basis.

Sugarcane bagasse (SCB) was modified by steam explosion pretreatment at 190 °C for 10 min and 210 °C for 5 min using green liquor (GL) combined with hydrogen peroxide (GL-H2O2) and ethanol (GL-Ethanol) for simultaneous saccharification and fermentation (SSF)-based ethanol production. The results showed that 85.02% and 100% of hemicelluloses were solubilized by steam explosion pretreatment at 190 °C for 10 min and 210 °C for 5 min, respectively. Moreover, 20.08% and 73.77% of the lignin was removed through GL-H2O2 and GL-Ethanol pretreatments, respectively. The steam explosion pretreatments greatly improved the specific surface area of the SCB and led to the highest ethanol yield of 92.20% at 190 °C for 10 min and 93.19% of 210 °C for 5 min, respectively. In addition, the ethanol yield reached 72.58% for the GL-Ethanol pretreatment, and about 70% of active lignin could be recovered from the pretreatment liquid. When the GL-H2O2 pretreatment was used, the maximum ethanol yield of 20.92% was achieved.

A combination of steam explosion (SE) and chemical pretreatments, such as acid sulfite (AS), alkali (AL), and alkaline sulfite (ALS), were evaluated using bamboo. Low pressure steam explosion at 1.25 MPa for 4 min was first applied to the bamboo. Then, the pretreated bamboo was delignified using three chemical pretreatments. Enzymatic hydrolysis was also compared among the pretreated bamboo samples. It was found that SE-ALS could be a potential method for bamboo pretreatment, which led to the reduction of lignin from 25.15% to 1.74% at 165 °C for 2 h in 5% (w/v) Na2SO3 and 0.7% (w/v) NaOH; however, little cellulose was solubilized during ALS pretreatment. A maximum glucose yield of 99.35% was achieved during the enzymatic hydrolysis process when combined with the SE-ALS pretreatment. The SE-ALS method resulted in a lower degree of lignin condensation and increased delignification compared to the SE-AS method. In addition, the SE-ALS pretreatment protected carbohydrates from degradation better than the SE-AL methods.

The enzyme-assisted aqueous extraction of oil from wet microalgae was employed to avoid the energy consumption of a dewatering process. In this paper, oil-rich microalgae Scenedesmus sp. G4 was hydrolyzed by enzyme mixtures for oil extraction. The results showed that the algae concentration had the greatest influence on yield of extracted oil, and the temperature and the ratio of enzyme mixtures affected the results as follows: the maximum yield of oil extracted from Scenedesmus sp. G4 reached 86.1% under optimal conditions with an algae concentration at 2.5 g/L, temperature 30/50 °C, pH 3.5/4.5 and a cellulase:pectinase:hemicellulase ratio of 1:1:1 or 1:2:1 (w/w/w). The results also indicated that the enzyme mixtures had a significant impact on the integrity of microalgae cells and the crystallization index increased from 30.7% to around 36.0% after enzymatic hydrolysis treatment. The cell wall of Scenedesmus sp. G4 has a high content of cellulose Iα and low crystallization, which is beneficial to the oil extraction by the enzyme-assisted hydrolysis method.

Public transport plays an important role in developing sustainable cities. A better understanding of how different public transit modes (bus, metro, and taxi) interact with each other will provide better sustainable strategies to transport and urban planners. However, most existing studies are either limited to small-scale surveys or focused on the identification of general interaction patterns during times of regular traffic. Transient demographic changes in a city (i.e., many people moving out and in) can lead to significant changes in such interaction patterns and provide a useful context for better investigating the changes in these patterns. Despite that, little has been done to explore how such interaction patterns change and how they are linked to the built environment from the perspective of transient demographic changes using urban big data. In this paper, the tap-in-tap-out smart card data of bus/metro and taxi GPS trajectory data before and after the Chinese Spring Festival in Shenzhen, China, are used to explore such interaction patterns. A time-series clustering method and an elasticity change index (ECI) are adopted to detect the changing transit mode patterns and the underlying dynamics. The findings indicate that the interactions between different transit modes vary over space and time and are competitive or complementary in different parts of the city. Both ordinary least-squares (OLS) and geographically weighted regression (GWR) models with built environment variables are used to reveal the impact of changes in different transit modes on ECIs and their linkage with the built environment. The results of this study will contribute to the planning and design of multi-modal transport services.

A simple and high-throughput assay to detect fungicide resistance is required for large-scale monitoring of the emergence of resistant strains of Botrytis cinerea. Using suspension array technology performed on a Bio-Plex 200 System, we developed a single-tube allele-specific primer extension (ASPE) assay that can simultaneously detect eight alleles in one reaction. These eight alleles include E198 and 198A of the β-Tubulin gene (BenA), H272 and 272Y of the Succinate dehydrogenase iron–sulfur subunit gene (SdhB), I365 and 365S of the putative osmosensor histidine kinase gene (BcOS1), and F412 and 412S of the 3-ketoreductase gene (erg27). This assay was first established and optimized with eight plasmid templates containing the DNA sequence variants BenA-E198, BenA-198A, SdhB-H272, SdhB-272Y, BcOS1-I365, BcOS1-365S, erg27-F412, and erg27-412S. Results indicated that none of the probes showed cross-reactivity with one another. The minimum limit of detection for these genotypes was one copy per test. Four mutant plasmids were mixed with 10 ng/μL wild-type genomic DNA in different ratios. Detection sensitivity of mutant loci was 0.45% for BenA-E198A, BcOS1-I365S, and erg27-F412S, and was 4.5% for SdhB-H272Y. A minimum quantity of 0.1 ng of genomic DNA was necessary to obtain reliable results. This is the first reported assay that can simultaneously detect mutations in BenA, SdhB, BcOS1, and erg27.

Tectonic coal is a kind of soft coal that is generated during tectonic movement. Gas outbursts usually occur in seams containing both virgin coal and tectonic coal. To reveal the adsorption characteristics of this type of coal seam (containing both virgin coal and tectonic coal), both tectonic coal and virgin coal were collected from the same longwall face and a series of laboratory tests were conducted, including coal sorption tests and pore specific surface measurements. Both the tectonic coal and virgin coal were crushed into coal powder (0.18⁻0.25 mm) for the coal sorption tests. In these laboratory tests, different mass ratios between tectonic coal and virgin coal were tested. We found that with the increase of the percentage of tectonic coal, the adsorption volume showed a rising trend, reached its maximum value, and then decreased. The specific surface areas of the mixed coal samples had the same evolution trends as those of the adsorption volume. From the laboratory tests, we found that when the mass ratio of virgin coal to tectonic coal was 1:1, both the adsorption volume and the specific surface areas reached their maximum values. Due to the percentage variation of the tectonic coal in the panel with the advancement of the longwall face, when the tectonic coal accounted for 50% of the total coal, the gas content would rise. Thus, proper measures should be adopted for outburst hazards control. The mathematical model between the change of specific surface area and the stress and strain of pore expansion before and after gas adsorption was established, and the relationship between the change of pore structure and gas emission before and after gas adsorption was obtained. It provides a theoretical basis for further research on coal and gas outburst mechanisms.