Search Results (2,981)

Neuroblastoma (NB) is a solid tumor occurring in infancy and childhood. Its high-risk form has currently a survival rate <50%, despite aggressive treatments. This worrying scenario is worsened by drug-induced secondary tumorigenesis and the emergency of drug resistance, calling for the urgent development of new extra-genomic treatments. Triphenyl phosphonium salts (TPPs) are mitochondria-targeting compounds that exert anticancer effects, impair mitochondria functions, and damage DNA at the same time. Despite several biochemical applications, TPP-based bola-amphiphiles self-assembling nanoparticles (NPs) in water have never been tested as antitumor agents. Here, with the aim of developing new antitumor devices to also counteract resistant forms of HR-NB, the anticancer effects of a TPP-based bola-amphiphile molecule have been investigated in vitro for the first time. To this end, we considered the previously synthesized and characterized sterically hindered quaternary phosphonium salt (BPPB). It embodies both the characteristics of mitochondria-targeting compounds and those of bola-amphiphiles. The anticancer effects of BPPB were assessed against HTLA-230 human stage-IV NB cells and their counterpart, which is resistant to etoposide (ETO), doxorubicin (DOX), and many other therapeutics (HTLA-ER). Very low IC₅₀ values of 0.2 µM on HTLA-230 and 1.1 µM on HTLA-ER (538-fold lower than that of ETO) were already determined after 24 h of treatment. The very low cell viability observed after 24 h did not significantly differ from that observed for the longest exposure timing. The putative future inclusion of BPPB in a chemotherapeutic cocktail for HR-NB was assessed by investigating in vitro its cytotoxic effects against mammalian cell lines. These included monkey kidney cells (Cos-7, IC₅₀ = 4.9 µM), human hepatic cells (HepG2, IC₅₀ = 9.6 µM), a lung-derived fibroblast cell line (MRC-5, IC₅₀ = 2.8 µM), and red blood cells (RBCs, IC₅₀ = 14.9 µM). Appreciable to very high selectivity indexes (SIs) have been determined after 24 h treatments (SIs = 2.5–74.6), which provided evidence that both NB cell populations were already fully exterminated. These in vitro results pave the way for future investigations of BPPB on animal models and upon confirmation for the possible development of BPPB as a novel therapeutic to treat MDR HR-NB cells. Full article

Hyperlipidemia is a major risk factor for vascular lesions in diabetes mellitus and other metabolic disorders, although its basis remains poorly understood. One of the key pathogenetic events in this condition is mitochondrial dysfunction associated with the opening of the mitochondrial permeability transition (MPT) pore, a drop in the membrane potential, and ROS overproduction. Here, we investigated the effects of bongkrekic acid and carboxyatractyloside, a potent blocker and activator of the MPT pore opening, respectively, acting through direct interaction with the adenine nucleotide translocator, on the progression of mitochondrial dysfunction in mouse primary lung endothelial cells exposed to elevated levels of palmitic acid. Palmitate treatment (0.75 mM palmitate/BSA for 6 days) resulted in an 80% decrease in the viability index of endothelial cells, which was accompanied by mitochondrial depolarization, ROS hyperproduction, and increased colocalization of mitochondria with lysosomes. Bongkrekic acid (25 µM) attenuated palmitate-induced lipotoxicity and all the signs of mitochondrial damage, including increased spontaneous formation of the MPT pore. In contrast, carboxyatractyloside (10 μM) stimulated cell death and failed to prevent the progression of mitochondrial dysfunction under hyperlipidemic stress conditions. Silencing of gene expression of the predominate isoform ANT2, similar to the action of carboxyatractyloside, led to increased ROS generation and cell death under conditions of palmitate-induced lipotoxicity in a stably transfected HEK293T cell line. Altogether, these results suggest that targeted manipulation of the permeability transition pore through inhibition of ANT may represent an alternative approach to alleviate mitochondrial dysfunction and cell death in cell culture models of fatty acid overload. Full article

The liver and kidneys are crucial for glucose homeostasis and are seriously damaged in diabetes. Cocoa and carob possess antidiabetic activity, but their hepatorenal protective effects, especially when combined with antidiabetic drugs, are unknown. The aim of this study is to investigate the effects of a cocoa–carob-supplemented diet (CC), either alone or in combination with metformin, on liver and kidney damage in Zucker diabetic fatty (ZDF) rats, a type 2 diabetes model. Male ZDF animals received a control or CC-supplemented diet, with or without metformin, and Zucker lean rats were fed the control diet. The CC-supplemented diet improved glucose tolerance and insulin resistance and alleviated functional and structural alterations in the diabetic liver and renal cortex. The CC-supplemented diet also ameliorated oxidative stress, downregulated apoptosis, and improved insulin signalling and glucose homeostasis. The combination of CC and metformin boosted several benefits as certain parameters related to morphological and structural alterations, apoptosis, oxidative stress, glucose homeostasis, and insulin resistance, were improved in comparison to animals receiving the CC-supplemented diet or metformin alone; these include the following: apoptotic index, Bax, hepatic insulin receptor or glutathione content, among others. These results demonstrate that the CC-supplemented diet alleviates the hepatorenal damage in type 2 diabetic ZDF rats, highlighting its potential alone or as an adjuvant therapy. Full article

In the process of roadway excavation in thick and hard coal seams with a hard roof, the instantaneous release of a large amount of elastic energy accumulated in coal and rock mass causes disasters. Especially under the action of tectonic stress, dynamic disasters of roadway-surrounding rock are extremely strong. Therefore, this paper takes the 110,505 roadway of the Yushuling Coal Mine as the engineering background. Aiming at the serious deformation of roadway-surrounding rock and the problem of strong mine pressure, the deformation mechanism of roadway-surrounding rock is studied by means of theoretical analysis, indoor experimentation, numerical simulation and field testing, and the surrounding rock control technology is proposed. Firstly, the results show that the stress field type of the Yushuling Coal Mine is a ${\sigma }_{Hv}$ type, the azimuth angle of the maximum horizontal principal stress is concentrated in 110.30°~114.12°, the dip angle is −33.04°~−3.43°, and the maximum horizontal principal stress is 1.94~2.76 times of the minimum horizontal principal stress. Secondly, the brittleness index of No. 5 is 0.62; the failure energy release of the surrounding rock compressive energy floor rock sample is up to 150,000 mv * ms. The more the cumulative number of rock samples, the greater the strength, and the more severe the damage. Thirdly, with the increase in tectonic stress, the stress of roadway-surrounding rock is asymmetrically distributed, and the plastic zone develops along the tendency. The maximum range of the plastic zone expands from 4.18 m to 10.19 m. Lastly, according to the deformation characteristics of roadway-surrounding rock, left side > roof > right side > floor, the surrounding rock control technology of ‘asymmetric anchor net cable support + borehole pressure relief’ is proposed, which realizes the effective control of roadway-surrounding rock deformation. Full article

Floods often cause significant damage to transportation infrastructure such as roads, railways, and bridges. This study identifies several topographic, environmental, and hydrological factors (slope, elevation, rainfall, land use and cover, distance from rivers, geology, topographic wetness index, and drainage density) influencing the safety of the railway infrastructure and uses multi-criteria analysis (MCA) alongside an analytical hierarchy process (AHP) to produce flood susceptibility maps within a geographic information system (GIS). The proposed methodology was applied to the catchment area of a railway track in southern Italy that was heavily affected by a destructive flood that occurred in the autumn of 2015. Two susceptibility maps were obtained, one based on static geophysical factors and another including triggering rainfall (dynamic). The results showed that large portions of the railway line are in a very highly susceptible zone. The flood susceptibility maps were found to be in good agreement with the post-disaster flood-induced infrastructural damage recorded along the railway, whilst the official inundation maps from competent authorities fail to supply information about flooding occurring along secondary tributaries and from direct rainfall. The reliable identification of sites susceptible to floods and damage may provide railway and environmental authorities with useful information for preparing disaster management action plans, risk analysis, and targeted infrastructure maintenance/monitoring programs, improving the resilience capacity of the railway network. The proposed approach may offer railway authorities a cost-effective strategy for rapidly screening flood susceptibility at regional/national levels and could also be applied to other types of linear transport infrastructures. Full article

In the process of tunnel construction, problems such as high-stress rockburst, large deformation of soft rock, water inrush and mud gushing, secondary cracking of linings, blasting interference, man-made damage, and mechanical damage are often encountered. These pose a great challenge to the installation of monitoring equipment and line protection. In order to solve these problems, the 2# inclined shaft of Muzhailing Tunnel in the Gansu Province of China, which exists under high stress, water bearing, and bias conditions, was taken as the research object in this paper. By assembling a string, drilling grouting and sealing, and introducing multiple modes of protection, new fiber grating sensor group installation and line protection methods were proposed. The automatic continuous monitoring of the deep deformation of surrounding rock and the automatic continuous monitoring of steel arch stress were realized. The field monitoring results showed that: (1) the fiber grating displacement sensor group could be used to verify the authenticity of the surface displacement results monitored by the total station; (2) the NPR anchor cable coupling support effectively limited the large deformation of soft rock and the expansion of surrounding rock in a loose circle, and the range of the loose circle was stable at about 1 m; and (3) the main influence range of blasting was at a depth of 0~5 m in surrounding rock, and about 25 m away from the working face. In addition, to secure weak links in the steel arch due to the hardening phenomenon, a locking tube was set at the arch foot. In the support design, the fatigue life of the steel was found to be useful as the selection index for the steel arch frame to ensure the stability of the surrounding rock and the long-term safety of the tunnel. The present research adopted a robust method and integrates a variety of sensor technologies to provide a multifaceted view of the stresses and deformations encountered during the tunneling process, and the effective application of the above results could have certain research and reference value for the design and monitoring of high stress, water-bearing, and surrounding rock supports in tunnels. Full article

Fruit skin color and physical quality are important for customer acceptability and market value. Therefore, this study aimed to evaluate the effect of pneumatic defoliation on the fruit quality, coloration, and anthocyanin content of ‘Fuji’ apples. Apple trees were subjected to no defoliation (control) and defoliation at low (0.6 bar) and high (0.9 bar) air pressure 20 days before harvest at 1 km/h of tractor speed. High-defoliation treatment increased the leaf damage rate but did not significantly affect the defoliation rate compared to low-defoliation treatment. Additionally, photosynthetically active radiation and solar irradiance inside the tree canopies were highest in the high-defoliation group, followed by the low-defoliation and control groups. With the exception of higher firmness in the high-defoliation treatment, pneumatic defoliation treatments had little effect on fruit size and weight, titratable acidity, soluble solids content, the starch pattern index, and the sunburn incidence of fruit. Compared with that of the control group, both defoliation treatments significantly increased the a* and C values and decreased the h^o values of the fruit color. Moreover, both defoliation treatments significantly increased anthocyanin content and upregulated the anthocyanin biosynthesis genes (MdPAL, MdCHS, MdCHI, MdF3H, MdANS, MdANS, MdUFGT) and the transcription factor (MdMYB10). A Pearson′s correlation analysis also showed that anthocyanin production was strongly correlated with each of the anthocyanin biosynthesis genes, especially in the pneumatic defoliation treatments. Conclusively, the results show that pneumatic defoliation at low pressure bars could be an effective strategy for improving the red coloration of ‘Fuji’ apples. Full article

Background: Extra virgin olive oil is a fundamental component of the Mediterranean diet. It contains several molecules that sustain human well-being by modulating cellular metabolism and exerting antioxidant, anti-inflammatory, and anti-ageing effects to protect normal tissues, and it can exert anti-angiogenic and pro-apoptotic effects on cancer cells. Metabolites found in different parts of the olive tree, including leaves, also possess properties that might help in cancer prevention and promote wellness in aging. Olive mill wastewater (OMWW), a liquid residue produced during olive oil extraction, represents an environmental issue. However, it is rich in phytochemicals with potential beneficial properties. Dietary supplements based on OMWW can be produced for nutritional supplementation with advantages to the ecology. Purpose: This work aims to measure hematochemical, anthropometric, and metabolomic parameters in volunteers taking an OMWW dietary supplement, Oliphenolia^® (OMWW-OL). Methods: The supplementation of OMWW-OL 25 mL twice daily for 30 days was tested on a pilot cohort of volunteers with characteristics close to metabolic syndrome. Hematochemical, anthropometric, serum biomarkers and serum metabolomic parameters were analyzed before the intervention, at 30 days, and 30 days after stopping consumption. Results: A total of 29 volunteers were enrolled, and 23 completed the study. The participants’ parameters at baseline were measured, and then twice daily at 30 days of treatment and 30 days after assumption discontinuation. Although treatment was with an olive derivative, their weight did not increase. Their body mass index, instead of augmenting, slightly decreased, particularly in the women. Also, hydration increased, especially in the women, while blood pressure, glycemia, and insulin decreased. Cholesterol, high-density lipoproteins, and triglycerides were stable, and LDL levels decreased, while vitamin D levels, alongside calcium, perceptibly increased. Albumin also increased. All the values were in support of an equilibrium, with no damaging effects. By mass spectrometry analysis, we also found favorable changes in the vitamin D/histamine and homocysteine/methionine ratios, an increase in a new metabolite of unknown formula, and the vitamin D/unknown metabolite ratio. Conclusions: Supplementation of OMWW-OL has no detrimental effects and might imply the beneficial modulation of several biological parameters. Although this is a small pilot study, with limited potency, it preliminarily suggests that the OMWW extract use could be potentially valuable for people at risk of metabolic syndrome. Some of these parameters could also be relevant in supporting healthy ageing and in cancer prevention. Full article

To implement the geographical and future climate adaptation of building moisture design for building projects, practitioners need efficient tools, such as precalculated climate indices to assess climate loads. Among them, the Frost Decay Exposure Index (FDEI) describes the risk of freezing damage for clay bricks in facades. Previously, the FDEI has been calculated for 12 locations in Norway using 1961–1990 measurements. The purpose of this study is both updating the FDEI values with new climate data and future scenarios and assessing how such indices may be suitable as a climate adaptation tool in building moisture safety design. The validity of FDEI as an expression of frost decay potential is outside the scope of this study. Historical data from the last normal period as well as future estimated climate data based on 10 different climate models forced by two emission scenarios (representative concentration pathways 4.5 and 8.5) have been analyzed. The results indicate an overall decline in FDEI values on average, due to increased winter temperatures leading to fewer freezing events. Further, the variability between climate models and scenarios necessitates explicit uncertainty evaluations, as single climate model calculations may result in misleading conclusions due to high variability between models. Full article

The Pavement Condition Index (PCI) is a prevalent metric for assessing the condition of rigid pavements. The PCI calculation involves evaluating 19 types of damage. This study aims to analyze how different types of damage impact the PCI calculation and the impact of the performance of prediction models of PCI by reducing the number of evaluated damages. The Municipality of León, Gto., Mexico, provided a dataset of 5271 records. We evaluated five different decision-tree models to predict the PCI value. The Extra Trees model, which exhibited the best performance, was used to assess the feature importance of each type of damage, revealing their relative impacts on PCI predictions. To explore the potential for reducing the complexity of the PCI evaluation, we applied Sequential Forward Search and Brute Force Search techniques to analyze the performance of models with various feature combinations. Our findings indicate no significant statistical difference in terms of Mean Absolute Error (MAE) and the coefficient of determination (R²) between models trained with 13 features compared to those trained with all 17 features. For instance, a model using only eight damages achieved an MAE of 4.35 and an R² of 0.89, comparable to the 3.56 MAE and 0.92 R² obtained with a model using all 17 features. These results suggest that omitting some damages from the PCI calculation has a minimal impact on prediction accuracy but can substantially reduce the evaluation’s time and cost. In addition, knowing the most significant damages opens up the possibility of automating the evaluation of PCI using artificial intelligence. Full article

Salt–alkaline stress is one of the most stressful occurrences, causing negative effects on plant development and agricultural yield. Identifying and utilizing genes that affect alkaline tolerance is an excellent approach to accelerate breeding processes and meet the needs for remediating saline–alkaline soil. Here, we employed a mapping population of 176 recombinant inbred lines (RILs) produced from a cross between alkali-tolerant Longdao5 and alkali-sensitive Zhongyouzao8 to identify the quantitative trait loci (QTLs) determining alkali tolerance at the seedling stage. For the evaluation of alkali tolerance, the recovered seedling’s average alkali tolerance index (ATI), root number (RN), root length (RL), seedling dry weight (SW), root dry weight (RW), and seedling height (SH) were assessed, together with their relative alkaline damage rate. Under alkaline stress, the ATI was substantially negative connected with the root number, seedling height, seedling dry weight, and root dry weight; however, it was considerably positive correlated with the relative alkaline damage rate of the root number and root dry weight. A total of 13 QTLs for the root number, root length, seedling height, seedling dry weight, root dry weight, and alkali tolerance index under alkaline stress were identified, which were distributed across chromosomes 1, 2, 3, 4, 5, 7, and 8. All of these QTLs formed two QTL clusters for alkali tolerance on chromosome 5 and chromosome 7, designated AT5 and AT7, respectively. Nine QTLs were identified for the relative alkaline damage rate of the root number, root length, seedling height, seedling dry weight, and root dry weight under alkali stress. These QTLs were located on chromosome 2, 4, 6, 7, 8, 9, and 12. In conclusion, these findings further strengthen our knowledge about rice’s genetic mechanisms for alkaline tolerance. This research offers clues to accelerate breeding programs for new alkaline-tolerance rice varieties. Full article

The Pendjari Biosphere Reserve is one of the protected areas of Benin where biodiversity conservation policies intertwine with the economic development of local populations. It is located in the Atacora region in northern Benin, which has a high prevalence of poverty and food insecurity among households. Agriculture and livestock farming are the primary activities of the local communities in the villages surrounding the reserve. However, wild animals sometimes cause damage to people’s fields or livestock. To deal with the damage caused by wild animals, local populations have developed several mitigation measures that may not be effective, leading them into a vulnerable situation. Vulnerability is often associated with the impacts of natural disasters and their management, anticipation, and recovery. In the context of human–wildlife conflict, vulnerability refers to the level of risk farmers face from issues such as crop raiding, livestock depredation, and human injury caused by wildlife, as well as farmers’ ability to cope with such damage. To assess the vulnerability of households, we used the Livelihood Vulnerability Index (LVI). Data were collected from July to December 2019 through questionnaires and interviews. We surveyed 320 households to collect data on their socio-demographics, livelihoods, social networks, natural capital, food and water security, and the incidence and severity of human–wildlife conflicts. The results showed that farmers around the Pendjari Biosphere Reserve are highly sensitive to human–wildlife conflicts, with a low adaptive capacity, revealing their vulnerability. More precisely, farmers are vulnerable in terms of major components of the LVI such as water, food, social networks, and livelihoods. Conservation policies are expected to pay more attention to local populations’ vulnerability to human–wildlife conflicts in order to improve their tolerance towards wildlife and guarantee the success of conservation efforts. Full article

In the ecological context of global climate change, ensuring the stable carbon sequestration capacity of forest ecosystems, which is among the most important components of terrestrial ecosystems, is crucial. Forest fires are disasters that often burn vegetation and damage forest ecosystems. Accurate recognition of firegrounds is essential to analyze global carbon emissions and carbon flux, as well as to discover the contribution of climate change to the succession of forest ecosystems. The common recognition of firegrounds relies on remote sensing data, such as optical data, which have difficulty describing the characteristics of vertical structural damage to post-fire vegetation, whereas airborne LiDAR is incapable of large-scale observations and has high costs. The new generation of satellite-based photon counting radar ICESat-2/ATLAS (Advanced Topographic Laser Altimeter System, ATLAS) data has the advantages of large-scale observations and low cost. The ATLAS data were used in this study to extract three significant parameters, namely general, canopy, and topographical parameters, to construct a recognition index system for firegrounds based on vertical structure parameters, such as the essential canopy, based on machine learning of the random forest (RF) and extreme gradient boosting (XGBoost) classifiers. Furthermore, the spatio-temporal parameters are more accurate, and widespread use scalability was explored. The results show that the canopy type contributed 79% and 69% of the RF and XGBoost classifiers, respectively, which indicates the feasibility of using ICESat-2/ATLAS vertical structure parameters to identify firegrounds. The overall accuracy of the XGBoost classifier was slightly greater than that of the RF classifier according to 10-fold cross-validation, and all the evaluation metrics were greater than 0.8 after the independent sample test under different spatial and temporal conditions, implying the potential of ICESat-2/ATLAS for accurate fireground recognition. This study demonstrates the feasibility of ATLAS vertical structure parameters in identifying firegrounds and provides a novel and effective way to recognize firegrounds based on different spatial–temporal vertical structure information. This research reveals the feasibility of accurately identifying fireground based on parameters of ATLAS vertical structure by systematic analysis and comparison. It is also of practical significance for economical and effective precise recognition of large-scale firegrounds and contributes guidance for forest ecological restoration. Full article

Zinc deficiency is one of the most widespread nutritional problems, affecting nearly one-third of the world population. In addition, it is known that zinc deficiency not only reduces crop yield but also its quality. The effect of different methods of zinc application on the growth, yield, and quality of safflower seeds under regular irrigation and interruption of irrigation from flowering to harvest (82 and 80 DAS in the first and second years, respectively) was evaluated. Zinc sulfate was applied in both soil and foliar methods. The zinc sulfate treatments include no zinc sulfate, soil application of 20, 40, and 60 kg ha⁻¹ at the planting stage; spraying 2.5, 5, and 7.5 g L⁻¹ in the rosette stage; and spraying 2.5, 5, and 7.5 g L⁻¹ in the flowering stage. The end-season drought caused a decrease in the chlorophyll index, leaf area index, relative water content, plant height, yield components, biological yield, seed yield, harvest index, seed oil content, oil harvest index, and seed element content compared to regular irrigation. The decrease in yield occurred with a decrease in the capitol number and diameter, seed number per capitol, and 1000-seed weight. The severity of the damage of the end-season drought stress in the second year was higher than in the first year due to the higher temperatures and the decrease in the rainfall. In both years, the application of zinc sulfate in different ways had an increasing effect on the studied traits in both normal and stress conditions. The application of zinc sulfate reduced the negative effects of unfavorable environmental conditions and improved the yield and nitrogen, phosphorus, potassium, zinc, and iron element content in the seed. In both application methods of zinc sulfate, the increment in the zinc sulfate concentration decreased the seed phosphorus content. However, the phosphorous content was more than that of the treatment of non-zinc application. The application of zinc increased the biological, seed, and oil yield of the treated plants, but the seed and oil yield were more affected. This effect was shown in the seed and oil harvest index increment. Under regular irrigation, higher concentrations of zinc sulfate enhanced plant performance, but under stress conditions, medium and lower concentrations were more effective. The highest 1000-seed weight and potassium and zinc content were obtained by spraying zinc sulfate at 5 g L⁻¹ in the flowering stage under normal irrigation conditions. A comparison of the two methods of applying zinc sulfate showed that foliar spraying was more effective than soil application in improving the seed yield. The soil application is more effective on biological yield than seed yield. Full article

The black soil region of Northeast China is the largest commercial grain production base in China, accounting for about 25% of the total in China. In this region, the water erosion is prominent, which seriously threatens China’s food security. It is of great significance to effectively identify the erosion-prone points for the prevention and control of soil erosion on the slope of the black soil region in Northeast China. This article takes the Tongshuang small watershed (Heilongjiang Province in China) as an example, which is dominated by hilly landforms with mainly black soil and terraces planted with corn and soybeans. Based on the 2.5 cm resolution Digital Elevation Model (DEM) reconstructed by unmanned aerial vehicles (UAVs), we explore the optimal resolution for hydrological simulation research on sloping farmland in the black soil region of Northeast China and explore the critical water depth at which erosion damage occurs in ridges on this basis. The results show that the following: (1) Compared with the 2 m resolution DEM, the interpretation accuracy of field roads, wasteland, damaged points, ridges and cultivated land at the 0.2 m resolution is increased by 4.55–27.94%, which is the best resolution in the study region. (2) When the water depth is between 0.335 and 0.359 m, there is a potential erosion risk of ridges. When the average water depth per unit length is between 0.0040 and 0.0045, the ridge is in the critical range for its breaking, and when the average water depth per unit length is less than the critical range, ridge erosion damage occurs. (3) When local erosion damage occurs, the connectivity will change abruptly, and the remarkable change in the index of connectivity (IC) can provide a reference for predicting erosion damage. Full article