Search Results (6,584)

Osteogenesis–angiogenesis coupling, a dynamic and coordinated interaction between skeletal and vascular cells, is essential for fracture healing. However, the effects of these cell ratios and their interactions under microfluidic perfusion and paracrine signaling on osteogenesis–angiogenesis coupling have rarely been reported. In this study, dynamic and static models of osteogenesis–angiogenesis coupling were developed and the osteogenic and angiogenic effects of the two models were compared. Static co-cultures of MC3T3-E1 and bEnd.3 cells in Transwell inserts showed a cell ratio-dependent reciprocal relation: a ratio of 1:1 (MC3T3-E1:bEnd.3) favored osteogenesis, whereas a ratio of 2:1 (MC3T3-E1:bEnd.3) promoted angiogenesis. On that basis, we developed an osteogenesis–angiogenesis coupling chip based on microfluidic technology. The microfluidic perfusion within the chip further enhanced the mineralizing effect of osteoblasts and the angiogenic effect of endothelial cells, respectively, and increased the secretion of vascular endothelial growth factor (VEGF) and bone morphogenetic protein-2 (BMP-2) compared to the static Transwell insert model. The results suggest that the microfluidic chip enhanced the potential of osteogenesis–angiogenesis coupling mediated by paracrine signaling. Overall, the chip is not only a powerful model for understanding bone–vascular interaction but also a scalable platform for high-throughput drug screening and personalized therapy development for fractures. Full article

Prostate cancer (PCa) is a major global health concern, particularly in advanced stages where chemotherapy resistance and androgen-independent tumor growth reduce survival rates to below 30%. Toll-like receptor 3 (TLR3), regulated by tumor suppressor p53, is a promising therapeutic target due to its role in tumor cell apoptosis. However, chronic exposure to inorganic arsenic (iAs), a known carcinogen, has been linked to PCa progression and reduced TLR3 expression and activation by polyinosinic/polycytidylic acid (Poly(I/C)), a synthetic ligand used in PCa immunotherapy. Here, we demonstrate that chronic sodium arsenite (NaAsO) exposure increases p53 transcript and protein levels in immortalized prostate epithelial cells. Despite this, key p53 target genes, including TLR3, CDKN1A, and BAX, were significantly downregulated, indicating a transcriptionally inactive p53. Chromatin immunoprecipitation (ChIP) confirmed diminished p53 binding to TLR3 and CDKN1A promoters, while sequencing ruled out TP53 mutations. A bioinformatic analysis revealed elevated TP53 but reduced TLR3 and CDKN1A in prostate adenocarcinoma, suggesting that iAs-induced oxidative stress disrupts p53 function. These findings reveal a novel mechanism by which iAs promotes PCa progression through impaired p53 activity, highlighting the need to explore post-translational and epigenetic factors affecting p53. Restoring p53 transcriptional activity may offer a therapeutic strategy for PCa patients exposed to NaAsO. Full article

Apomorphine (APO), a dopamine agonist, activates nuclear factor erythroid 2-related factor 2 (Nrf2) and exerts antioxidant effects, making it a promising candidate for neuroprotection against oxidative stress. This study evaluated neuroplasticity-enhancing properties of newly synthesized APO derivatives, focusing on their ability to promote neurite outgrowth in PC12 cells under nerve growth factor (NGF) stimulation. D55, an APO derivative, retains the hydroxyl group at APO’s 11th position while substituting the 10th with an ethoxy group. D55 exhibited the highest potency (EC₅₀ = 0.5661 nM), significantly enhancing neurite outgrowth. APO demonstrated the highest efficacy (Emax ~10-fold increase), while edaravone (Eda) required higher concentrations (EC₅₀ = 22.5 nM) for moderate effects (Emax ~4-fold increase). D30, in which the 11th hydroxyl was replaced with a methoxy group, had no effect. Neurite outgrowth-promoting effects of APO, D55, and Eda were significantly attenuated by Nrf2 siRNA knockdown, confirming that their neuroplasticity effects are Nrf2-mediated. These findings confirm that D55 is a highly potent Nrf2-activating compound with strong neuroprotective potential, providing new insights into its therapeutic applications for neurodegenerative diseases associated with oxidative stress. Full article

The biomass of rice at maturity serves as a vital indicator for assessing overall productivity, and its accurate estimation holds significant importance for ensuring food security and promoting sustainable agriculture. To improve the precision of current biomass estimation methods for mature rice, this study employed support vector regression to integrate RGB vegetation indices from rice canopy images with growth parameters, thereby developing a biomass estimation model. The model was validated by applying it to the experimental area. The results indicated that screening RGB vegetation indices and combining them with growth parameters enhanced estimation accuracy. Specifically, the model integrating RGB vegetation indices (g, RGBVI) with rice plant height and moisture content demonstrated high estimation accuracy (R² = 0.78, RMSE = 0.32 kg/m²). The absolute difference between the estimated and measured biomass values ranged from 0.15 to 0.39 kg/m². Additionally, the estimated biomass showed a strong correlation with yield (R² = 0.86), with a fitted equation of y = 0.04x + 0.59. These results suggest that the model is reliable for large-area estimation of mature rice biomass. However, the degree of rice maturity and the lodging phenomenon were identified as the primary factors influencing the precision of model application. Overall, integrating RGB vegetation indices of the rice canopy, obtained via UAV-based remote sensing technology, with growth parameters provides an effective method for estimating mature rice biomass and offers a valuable reference for efficient yield estimation. Full article

Pulmonary fibrosis (PF) is a chronic pulmonary disease characterized by excessive extracellular matrix (ECM) deposition, with cigarette smoking being a major risk factor and no effective treatment at present. Transforming growth factor beta 1 (TGF-β1) plays a key role in PF and regulating oxidative stress. This study investigated the effects and mechanisms of Artemisia rupestris L. ethanol extract (ER) on cigarette smoke (CS)-induced PF. We used pull-down and LC–MS analyses to screen and identify compounds that bind to TGF-β1 in ER. We demonstrated that ER inhibits CS-induced PF, lung inflammation, and oxidative stress, thereby improving pulmonary structural injury. The ER inhibits fibroblast activation and fibroblast-to-myofibroblast transition (FMT), reducing collagen deposition for the treatment of PF. We identified the active ingredient in ER that binds to TGF-β1, namely, Luteolin 7-glucuronide (LG). LG inhibits the TGF-β1 signaling pathway through targeted binding to TGF-β1, downregulates the expression of downstream proteins (including collagen I, α-SMA, MMP-2, and MMP-9), and inhibits fibronectin expression. It also inhibits fibroblast activation and FMT, enhances E-cadherin expression to promote fibroblast adhesion, and suppresses collagen deposition, alleviating PF. Based on these findings, we propose that LG might be a promising therapeutic drug candidate for treating PF. Full article

Modern cities are rapidly evolving in terms of urban morphology, driven by exponential population growth that accelerates the urbanisation process. The changes in land use have increased urban area and density, intensifying the urban heat island (UHI) effect, which poses one of the biggest threats to human health and well-being, especially in metropolitan regions. One of the most effective strategies to counter urban heat is the implementation of green infrastructure and the use of suitable building materials that help reduce heat stress. However, access to green spaces and the affordability of efficient building materials are not the same among citizens. This paper aims to identify the socio-economic characteristics of communities in Melbourne, Australia, that contribute to their vulnerability to urban heat under local conditions. This study employs remote sensing and geographical information systems (GIS) to conduct a macro-scale analysis, to investigate the correlation between urban heat patterns and socio-economic characteristics, taking into account factors such as vegetation cover, built-up areas, and land use types. The results from the satellite images and the geospatial data reveal that Deer Park, located in the western suburbs of Melbourne, has the highest land surface temperature (LST) at 32.54 °C, a UHI intensity of 1.84 °C, a normalised difference vegetation index (NDVI) of 0.11, and a normalised difference moisture index (NDMI) of −0.081. The LST and UHI intensity indicate a strong negative correlation with the NDVI (r = −0.42) and NDMI (r = −0.6). In contrast, the NDVI and NDMI have a positive correlation with the index of economic resources (IER) with r values of 0.29 and 0.24, indicating that the areas with better finance resources tend to have better vegetation coverage or plant health with less water stress, leading to lower LST and UHI intensity. This study helps to identify the most critical areas in the Greater Melbourne region that are vulnerable to the risk of urban heat and extreme heat events, providing insights for the local city councils to develop effective mitigation strategies and urban development policies that promote a more sustainable and liveable community. Full article

Aortic aneurysms (AAs), the dilation or widening of the aorta, lead to dissection or rupture with high morbidity and mortality if untreated. AA displays gender disparities in its prevalence, progression and outcomes, with women having worse outcomes and faster aneurysm growth. However, current guidelines do not address gender dimorphism, emphasizing the urgent need for personalized treatment strategies and further research. Perivascular adipose tissue (PVAT), a unique type of fat surrounding blood vessels, plays a critical role in maintaining vasomotor tone and vascular homeostasis, with dysfunction associated with chronic inflammation and vessel-wall remodeling. Indeed, PVAT dysfunction promotes the development of aortic aneurysms, with hormonal and biomechanical factors exacerbating the pathological vascular microenvironment. The sexually dimorphic characteristics of PVAT include morphological, immunological, and hormonally mediated differences. Thus, targeting PVAT-mediated mechanisms may be a promising option for the (gender-specific) therapeutic management of cardiovascular pathologies. This review examines the emerging importance of PVAT in vascular health, its potential therapeutic implications for AA, and identifies gaps in the current state of research. Full article

Biodentine, a tricalcium silicate cement, has emerged as a retrograde root-end filling material to promote periapical lesion (PL) healing after apicoectomy. However, its underlying mechanisms remain unclear. This study tested the hypothesis that Biodentine stimulates the osteogenic differentiation of mesenchymal stromal cells (MSCs) derived from PLs. The Biodentine extract (B-Ex) was prepared by incubating polymerized Biodentine in RPMI medium (0.2 g/mL) for three days at 37 °C. B-Ex, containing both released microparticles and soluble components, was incubated with PL-MSCs cultured in either a basal MSC medium or suboptimal osteogenic medium. Osteogenic differentiation was assessed by Alizarin Red staining and the expression of 20 osteoblastogenesis-related genes. Non-cytotoxic concentrations of B-Ex stimulated the proliferation of PL-MSCs and induced their osteogenic differentiation in a dose-dependent manner, with a significantly enhanced effect in suboptimal osteogenic medium. B-Ex upregulated most early and late osteoblastic genes. However, the differentiation process was prolonged, as indicated by the delayed expression of wingless-type MMTV integration site family member 2 (WNT2), bone gamma-carboxyglutamate protein (BGLAP), bone morphogenic protein-2 (BMP-2), growth hormone receptor (GHR), and FOS-like 2, AP-1 transcription factor subunit (FOSL2), compared with their expression under optimal osteogenic conditions. The stimulatory effect of B-Ex was primarily calcium dependent, as it was reduced by 85% when B-Ex was treated with the calcium-chelating agent EGTA. In conclusion, Biodentine promotes the osteogenic differentiation of PL-MSCs in a calcium-dependent manner, supporting its stimulatory role in periapical healing. Full article

This study investigates the decoupling relationship between industrial carbon emissions and economic development in the Beibu Gulf City Cluster based on panel data from 2005 to 2022. It also uses the Tapio decoupling model to assess the degree of decoupling and synergy in Guangdong, Guangxi, and Hainan and combines it with the logarithmic mean differential index (LMDI) decomposition model to study the driving factors affecting industrial carbon emissions. The study indicates that the industrial carbon emissions of the Beibu Gulf City Cluster increases from 71.42 MT in 2005 to 108.29 MT in 2022 but peaks in 2020 and changes from weak decoupling to strong decoupling; the synergistic relationship among Guangdong, Guangxi, and Hainan will evolve from poor to favorable. The LMDI decomposition results show that the economic scale and population scale effects increase 157.05 MT and 11.67 MT of carbon emissions in the study period, while the optimization of energy structure and energy intensity reduces 117.26 MT and 19.60 MT of carbon emissions, respectively, and the industrial development of many cities in the Beibu Gulf region gradually decouples economic growth and carbon emissions after 2021. Based on this, this study proposes targeted measures to reduce carbon emissions from industrial production in the Beibu Gulf City Cluster, which is of constructive significance for promoting sustainable industrial development in the region. Full article

Background: Crossbreeding strategies that combine the growth performance of Western pig breeds with the meat quality traits of Chinese indigenous breeds have garnered considerable interest. Duroc pigs are known for their high growth efficiency but have relatively low intramuscular fat (IMF) content. In contrast, native breeds like the Diannan Small-Eared pig exhibit superior pork quality with higher IMF levels. This study aimed to compare the muscle growth characteristics and molecular mechanisms between Duroc × Landrace × Yorkshire (DLY) and Duroc × Berkshire × Diannan Small-Eared (DBD) pigs. Methods: The longissimus dorsi tissue of 210-day-old DLY and DBD pigs was collected for analysis. HE staining assessed muscle fiber characteristics, IMF content was measured, and ELISA quantified muscle-derived growth and development-related factors. Transcriptome sequencing was conducted, followed by differential gene expression analysis, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein–protein interaction (PPI) analyses. Functional validation of key genes was performed in C2C12 cells. Results: DBD pigs exhibited significantly larger muscle fiber diameter and higher IMF content compared to DLY pigs. IGF1 and GH levels were elevated in DBD pigs. Transcriptome analysis identified 185 upregulated and 102 downregulated genes, with enrichment in pathways including PI3K-Akt, MAPK, FoxO, and cGMP-PKG signaling. ACSL1 and FABP3 were functionally validated, showing promotion of differentiation and inhibition of proliferation in C2C12 cells. Conclusions: DBD pigs exhibit superior muscle growth traits and higher IMF content compared to DLY pigs. ACSL1 and FABP3 may serve as key regulators of muscle development in pigs. Full article

This study aimed to examine the effect of adding volcanic slag to soil on the growth, yield, and quality of cucumbers. It also analyzed the changes in the physicochemical properties of the rhizosphere soil, as well as the diversity and structural changes of the bacterial community present in the soil of the cucumber plants. This study used conventional fertilization and cultivation techniques and set up five treatments: HS500, HS1000, HS1500, and HS2000 (representing 500, 1000, 1500, and 2000 kg/ha of volcanic slag added per 667 sq.m in the cultivation trough, respectively), and control (CK; representing 0 kg of added volcanic slag). The Illumina MiSeq System was used to analyze the soil microbial community. The findings revealed that the HS1000 treatment had the most significant promoting effect on increasing cucumber yield, whereas the HS2000 treatment exhibited no significant change compared with the CK treatment. The HS500, HS1000, and HS1500 treatments increased the yield by 12.89%, 24.28%, and 19.56%, respectively, compared with the CK treatment. The HS1000 treatment increased the soluble sugar, vitamin C, and soluble solid contents by 12.39%, 17.57%, and 24.33%, respectively, compared with the CK treatment. The organic matter, total nitrogen, alkali-hydrolyzable nitrogen, nitrate nitrogen, ammonium nitrogen (NH4+-N), available potassium (AK), and available phosphorus (AP) contents in the rhizosphere soil of cucumber plants were the highest under the HS1000 treatment. The alpha diversity analysis revealed that the Chao1, Shannon, and ACE indexes reached the highest under the HS1000 treatment, which were significantly higher than the CK treatment. In contrast, the Simpson index and coverage had no significant changes between treatments. The dominant phyla in each treatment were Proteobacteria, Actinobacteria, and Acidobacteria, among others. The redundancy analysis of soil physicochemical properties and 15 bacterial genera of interest revealed that the available phosphorus, available potassium, and NH4+-N contents were the primary factors influencing the bacterial community in cucumber rhizosphere soil. Full article

The inefficient irrigation strategy is an important factor affecting the yield and water productivity of tomatoes in greenhouses, seriously hindering the development of the cultivation industry. While the impact of irrigation level on tomato growth and yield has been extensively studied, irrigation interval, another crucial component of irrigation schedule, as well as their interaction, remain poorly explored. There were four irrigation levels (W1: 125% ET_c, W2: 100% ET_c, W3: 75% ET_c, and W4: 50% ET_c; ET_c represented crop evapotranspiration) and three irrigation intervals (D1: 4-day interval, D2: 7-day interval, and D3: 10-day interval), aiming to explore the effects of different irrigation intervals and levels on the performance of tomatoes. Here, we showed that the moderate increases in irrigation level and interval promoted root growth, improved nitrogen uptake and distribution, and enhanced plant height, stem diameter, leaf area index, and aboveground biomass, thereby promoting the net photosynthetic rate of plants and fruit yield. The fruit quality indicators of total soluble solids, vitamin C, and soluble sugar decreased with increasing irrigation level but increased with decreasing irrigation interval. Higher irrigation levels increased tomato water consumption and resulted in lower water-nitrogen use efficiency. Overall, compared with W2D2 and W2D3, the yield of W2D1 increased by 8.0% and 26.1%, respectively, and the water productivity increased by 5.7% and 19.3%, respectively, and the soluble sugar increased by 7.1% and 17.5%, respectively. In addition, nitrogen uptake in tomato organs increased and then decreased with the increase of irrigation level, while it consistently increased with decreasing irrigation interval. At the harvest period, the nitrogen uptake in plant organs followed the order of fruit > leaf > stem. Taken together, W2D1 (100% ET_c and 4-day interval) is the recommended irrigation strategy for this experiment, which can provide a theoretical basis and technical support for the sustainable production strategy of greenhouse drip irrigation tomatoes. Full article

As the cornerstone of terrestrial ecosystems, forests have faced mounting challenges due to escalating human activities, jeopardizing their vital ecological functions and even their existence. It has become an important issue to explore how to promote harmonious coexistence of man and nature, or even to improve the forest ecological function (FEF) through human activities. Thus, in this study, we select the Yellow River Basin (YRB) in China as a typical region. Firstly, we assess the FEF at the county level and reveal their spatial distribution and agglomeration characteristics on the basis of the data from the Ninth National Forest Inventory of China. Then, using multiple linear regression (MLR) and geographically weighted regression (GWR) modeling, we further explore the overall impacts of different human activities on FEF and their spatial differences, respectively. Our findings underscored a moderate deficiency in the county-level FEF in the YRB, with pronounced positive spatial agglomerations. The high–high areas are primarily clustered in the southern and central mountainous areas, whereas low–low areas are distributed in the upstream warm temperate steppe and desert-grassland regions. Human activities exert substantial impacts on FEF, with distinct spatial heterogeneity in the coefficient and significance levels. The trend analysis indicates that FEF is more sensitive to the increase in living land, population density and forest protection in the east–west direction. And in the north–south direction, FEF is more easily affected by agricultural development, population growth and urbanization. This study verifies that natural factors dominate FEF in those regions where human activities are quite scarce, and also reveals that due to the inter-constraint or counteract effects among different human activities, FEF may still ultimately depend on the natural endowments in some populated regions. We point out the core human activity factors affecting FEF after excluding the interference from natural conditions. And we recommend that policymakers prioritize sustainable development strategies that mitigate the adverse impacts of human activities on forest ecosystems while promoting conservation efforts tailored to the unique characteristics of each region. Full article

Background: Follicle stimulating hormone (FSH) is key regulator for follicular development, differentiation, and maturation, and the effects involve various intra follicular factors, such as members of the forkhead box O (FOXO) subfamily. However, the specific role and mechanism of FOXO3 and FOXO4 in growth and development of hen follicles by affecting granulosa cell (GC) division and FSH response function are still unclear. Method: This study selected GCs from 6–8 mm chicken follicles, and immunofluorescence and Western blot methods were used to detect FSH-induced FOXO3/4 phosphorylation and nuclear exclusion. Quantitative real-time PCR and flow cytometry were used to investigate the regulatory effects of FSH-induced FOXO3/4 phosphorylation and nuclear exclusion on follicular GC proliferation, differentiation, and apoptosis. Results: This study found that the level of p-FOXO3/4 protein significantly increased in cells treated with FSH for 12 h, while the expression level of non-phosphorylated FOXO3/4 significantly decreased. After co-treatment with 10 ng/mL Leptomycin B (LMB), FOXO3/4 phosphorylation was effectively prevented. The immunofluorescence results showed that FOXO3 and FOXO4 were originally distributed in the GC nucleus and cytoplasm, whereas they were almost accumulated in cytoplasm when treated with FSH for 12 h. Conversely, FOXO3/4 nuclear translocation was blocked by LMB. Moreover, RT-qPCR and flow cytometry results showed that FSH treatment significantly increased proliferation and differentiation of cells but significantly reduced GCs apoptosis. However, LMB also eliminated these stimulating or inhibitory effects on cell proliferation. Conclusion: These findings provide new evidence that FSH-induced FOXO3/4 nuclear exclusion promotes GCs proliferation and reduces GCs apoptosis during hen follicular development. Full article

The digital economy has become an important engine for global economic development by promoting optimal resource allocation and advancing industrial restructuring. Based on the panel data from 279 prefecture-level cities in China from 2012 to 2021, this paper constructs the spatial association networks of urban digital economy using a modified gravity model and analyzes the complex network characteristics and driving factors of urban digital economy growth by the social network analysis methods and the Quadratic Assignment Procedure (QAP). This study finds that (1) the level of urban digital economy in China shows a rising trend year by year and displays an uneven spatial distribution. (2) Spatial association networks of urban digital economy are relatively well-connected, with increasing density and stability of spatial associations, yet some hierarchical structure remains, and overall connectivity still needs to be improved. (3) Most cities in the east region occupy the core positions within the complex network, significantly influencing the overall complex network through a “siphon effect”, while cities in the central region play more of a “bridge” role in the spatial association network. In contrast, cities in the northwest, northeast, and southwest regions are situated on the periphery of this spatial association network. (4) The economic development level, informatization level, technological innovation, urbanization level, industrial structure, and human capital contribute to the formation of the spatial association network of the digital economy. Based on these conclusions, specific policy implications for the future development of the spatial association network of the urban digital economy are proposed. Full article