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PD-L1 is overexpressed in tumor cells and contributes to cancer immunoevasion. However, the role of the tumor cell-intrinsic PD-L1 in cancers remains unknown. Here we show that PD-L1 regulates lung cancer growth and progression by targeting the WIP and β-catenin signaling. Overexpression of PD-L1 promotes tumor cell growth, migration and invasion in lung cancer cells, whereas PD-L1 knockdown has the opposite effects. We have also identified WIP as a new downstream target of PD-L1 in lung cancer. PD-L1 positively modulates the expression of WIP. Knockdown of WIP also inhibits cell viability and colony formation, whereas PD-L1 overexpression can reverse this inhibition effects. In addition, PD-L1 can upregulate β-catenin by inhibiting its degradation through PI3K/Akt signaling pathway. Moreover, we show that in lung cancer cells β-catenin can bind to the WIP promoter and activate its transcription, which can be promoted by PD-L1 overexpression. The in vivo experiments in a human lung cancer mouse model have also confirmed the PD-L1-mediated promotion of tumor growth and progression through activating the WIP and β-catenin pathways. Furthermore, we demonstrate that PD-L1 expression is positively correlated with WIP in tumor tissues of human adenocarcinoma patients and the high expression of PD-L1 and WIP predicts poor prognosis. Collectively, our results provide new insights into understanding the pro-tumorigenic role of PD-L1 and its regulatory mechanism on WIP in lung cancer, and suggest that the PD-L1/Akt/β-catenin/WIP signaling axis may be a potential therapeutic target for lung cancers.

The Han River Basin, a critical water conservation and ecological barrier in Hubei Province, is intricately associated with the United Nations Sustainable Development Goals (SDGs). Research results show that vegetation cover changes are affected by multiple factors, and understanding the influences of climate change and human activities on vegetation is imperative for achieving sustainable development in the basin. Through quantitative assessment of vegetation changes in diverse landform regions, implementing adaptive ecological construction and environmental protection will foster the sustainable development of ecological civilization in the Han River Basin. This study utilizes MODIS13Q1 data and employs diverse analytical methods to investigate the characteristics of vegetation change and the interrelationships between climate change, meteorological factors, and vegetation cover in various geomorphological areas of the Han River Basin from 2000 to 2020. The results showed that (1) throughout the entire study period, the NDVI of the six types of geomorphological divisions in the Han River Basin exhibited a fluctuating upward trend, with the changes in the low-altitude hilly geomorphic regions being particularly noteworthy. (2) Within the study area, approximately 92.67% of vegetation coverage displayed an increasing trend, while 7.33% showed degradation, predominantly in plains and platforms. Notably, the area of continuous improvement (31.16%) outweighed the area of continuous degradation (3.05%), with low and middle-relief mountain areas demonstrating the most robust growth and sustainability. (3) Human agriculture activities and urbanization processes have emerged as the primary driving force behind vegetation changes in the Han River Basin. The responses of vegetation to climate change and human activities exhibited significant variations across diverse geomorphological regions. In areas characterized by vegetation improvement, the contribution rate of human activities to NDVI changes in different vegetation types surpassed 70%, with plain areas displaying the highest contribution rate at a remarkable 90%. In contrast, the plain and platform regions of the vegetation degradation area were significantly influenced by climate change. In future watershed ecological environment management, it is essential to not only recognize the dominant role of human activities in promoting the growth of mountain vegetation NDVI but also address the impact of climate change on the degradation of vegetation NDVI in plains and platforms. A comprehensive understanding of these factors is crucial for devising effective strategies to ensure sustainable development and ecological balance in the Han River Basin.

The Hanjiang River Basin (HJRB) is an important water conservation and ecological barrier area for the South–North Water Transfer Central Project. The quantitative analysis of regional differences in vegetation changes and their main drivers is important for the monitoring of the ecological environment of the basin and formulation of ecological protection measures. Based on MODIS13Q1 data from 2000 to 2020, spatiotemporal variation characteristics of vegetation in the HJRB were analyzed using Theil–Sen + Mann–Kendall, the Hurst index, and correlation analysis. Then, we detected the drivers using an optimal parameter geographic detector. The results showed that from 2000 to 2020, the average NDVI value increased from 0.651 to 0.737, with a spatial distribution pattern of “high in the northwest and low in the southeast”, and 88.68% of the study area showed an increase in vegetation cover, while 5.80% showed a significant degradation. The positive persistence of future vegetation changes is stronger than the negative. It may show a slowdown or degradation trend, among which the vegetation restoration along the Han River and urbanized areas need to be strengthened. The factor detector indicated that the main factors influencing vegetation change were topography and climate, for which the most influential variables, respectively, were elevation (0.1979), landform (0.1720), slope (0.1647), and soil type (0.1094), with weaker influence from human activity factors. The interaction test results showed that the interaction of various geographic factors enhanced the explanatory power of vegetation changes and showed mainly nonlinear and two-factor enhancements. The dominant factor varies between sub-basins; for example, the interaction between wind speed and land use conversion was the dominant factor in the middle reaches of the HJRB; the dominant factor in the lower reaches of the HJRB was expressed as the interaction between land use conversion and temperature. Finally, the effects of the range or category of different drivers on vegetation growth were systematically analyzed. The results of the study contribute to the understanding of the dynamic changes of vegetation based on a comprehensive consideration of the interaction of topography, climate, and human activities, taking into account the totality and variability of the geographical environment, and provide a reference for the ecological restoration and rational use of vegetation resources in the HJRB.

Background Sepsis is a systemic inflammatory response which is frequently associated with acute lung injury (ALI). Activating transcription factor 3 (ATF3) promotes M2 polarization, however, the biological effects of ATF3 on macrophage polarization in sepsis remain undefined. Methods LPS-stimulated macrophages and a mouse model of cecal ligation and puncture (CLP)-induced sepsis were generated as in vitro and in vivo models, respectively. qRT-PCR and western blot were used to detect the expression of ATF3, ILF3, NEAT1 and other markers. The phenotypes of macrophages were monitored by flow cytometry, and cytokine secretion was measured by ELISA assay. The association between ILF3 and NEAT1 was validated by RIP and RNA pull-down assays. RNA stability assay was employed to assess NEAT1 stability. Bioinformatic analysis, luciferase reporter and ChIP assays were used to study the interaction between ATF3 and ILF3 promoter. Histological changes of lung tissues were assessed by H&E and IHC analysis. Apoptosis in lungs was monitored by TUNEL assay. Results ATF3 was downregulated, but ILF3 and NEAT1 were upregulated in PBMCs of septic patients, as well as in LPS-stimulated RAW264.7 cells. Overexpression of ATF3 or silencing of ILF3 promoted M2 polarization of RAW264.7 cells via regulating NEAT1. Mechanistically, ILF3 was required for the stabilization of NEAT1 through direct interaction, and ATF3 was a transcriptional repressor of ILF3. ATF3 facilitated M2 polarization in LPS-stimulated macrophages and CLP-induced septic lung injury via ILF3/NEAT1 axis. Conclusion ATF3 triggers M2 macrophage polarization to protect against the inflammatory injury of sepsis through ILF3/NEAT1 axis.

Regional agricultural carbon balance studies are crucial for promoting coordinated development and achieving carbon neutrality. This research quantifies agricultural carbon emissions and sinks across 190 counties in the Beijing–Tianjin–Hebei (BTH) region from 2013 to 2022. The methodology involved the carbon emission factor approach and crop productivity models to assess the agricultural carbon balance. Furthermore, this study employed the carbon load model and the carbon output technical elasticity model to analyze the per-unit contribution of agricultural products and the carbon implications of augmented agricultural output. The findings reveal the following: (1) Total agricultural carbon emissions followed a fluctuating, inverted “U”-shaped trajectory, peaking in 2015. Emission reductions were primarily driven by decreases in agricultural energy consumption and land utilization, followed by crop cultivation. Conversely, agricultural net carbon sequestration and the carbon offset ratio show a fluctuating upward trend. (2) The agricultural carbon balance exhibits a distinct north–south differentiation. There has been a year-on-year reduction in carbon deficit counties, while the spatial aggregation of the carbon balance has become increasingly pronounced over time. (3) The marginal contribution of the agricultural carbon balance across the five primary agricultural zones positively correlates with the scale of agriculture and the prevailing crop cultivation regimes. Specifically, the Central Hebei Plain agricultural zone demonstrated the highest contribution, while the Daming agricultural zone exhibited the lowest. (4) Driven by the synergistic effect of internal and external factors, the BTH region has optimized its production elements. This has led to an elevated agricultural carbon balance and reduced inter-regional disparities. The region’s agricultural carbon balance demonstrates a favorable trajectory, suggesting sustainability under a low-carbon development paradigm. This study offers sustainability recommendations based on four pillars: establishing rigid production systems, enhancing compensation and trading mechanisms, optimizing industrial structures and integration strategies, and reinforcing regional coordination and incentive frameworks.

p53 is one of the most intensively studied tumor suppressors. It transcriptionally regulates a broad range of genes to modulate a series of cellular events, including DNA damage repair, cell cycle arrest, senescence, apoptosis, ferroptosis, autophagy, and metabolic remodeling, which are fundamental for both development and cancer. This review discusses the role of p53 in brain development, neural stem cell regulation and the mechanisms of inactivating p53 in gliomas. p53 null or p53 mutant mice show female biased exencephaly, potentially due to X chromosome inactivation failure and/or hormone-related gene expression. Oxidative cellular status, increased PI3K/Akt signaling, elevated ID1, and metabolism are all implicated in p53-loss induced neurogenesis. However, p53 has also been shown to promote neuronal differentiation. In addition, p53 mutations are frequently identified in brain tumors, especially glioblastomas. Mechanisms underlying p53 inactivation in brain tumor cells include disruption of p53 protein stability, gene expression and transactivation potential as well as p53 gene loss or mutation. Loss of p53 function and gain-of-function of mutant p53 are both implicated in brain development and tumor genesis. Further understanding of the role of p53 in the brain may provide therapeutic insights for brain developmental syndromes and cancer.

In the era of big data, advances in relevant technologies are profoundly impacting the field of real estate appraisal. Many scholars regard the integration of big data technology as an inevitable future trend in the real estate appraisal industry. In this paper, we summarize 124 studies investigating the use of big data technology to optimize real estate appraisal through the hedonic price model (HPM). We also list a variety of big data resources and key methods widely used in the real estate appraisal field. On this basis, the development of real estate appraisal moving forward is analyzed. The results obtained in the current studies are as follows: First, the big data resources currently applied to real estate appraisal include more than a dozen big data types from three data sources; the internet, remote sensing, and the Internet of things (IoT). Additionally, it was determined that web crawler technology represents the most important data acquisition method. Second, methods such as data pre-processing, spatial modeling, Geographic information system (GIS) spatial analysis, and the evolving machine learning methods with higher valuation accuracy were successfully introduced into the HPM due to the features of real estate big data. Finally, although the application of big data has greatly expanded the amount of available data and feature dimensions, this has caused a new problem: uneven data quality. Uneven data quality can reduce the accuracy of appraisal results, and, to date, insufficient attention has been paid to this issue. Future research should pay greater attention to the data integration of multi-source big data and absorb the applications developed in other disciplines. It is also important to combine various methods to form a new united evaluation model based on taking advantage of, and avoiding shortcomings to compensate for, the mechanism defects of a single model.

Due to limited land resources, it is necessary to balance urban economic development and efficient land use. Clarifying the relationship between the two is crucial to improving both economic efficiency and land use efficiency. Considering the undesirable output of urban land use, this paper adopts a super efficiency SBM model to quantify the urban land use efficiency (ULUE) of the Beijing–Tianjin–Hebei (BTH) region from 1999 to 2019, and analyzes the relationship between ULUE and economic development level (EDL) by combining the Tapio model and the environmental Kuznets curve (EKC) model. The results show the following: (1) During the study period, the ULUE showed a fluctuating upward trend on the temporal scale, with the lowest and highest inflection points occurring in 2002 and 2018, respectively, and a distribution pattern of “high in the southeast and low in the northwest” on the spatial scale. (2) The decoupling relationship between ULUE and EDL showed repeated fluctuations between decoupling and coupling states on the temporal scale, but the overall showed a transition trend from decoupling state to coupling state. On the spatial scale, from north to south, there were a strong decoupling state (SDS), weak decoupling state (WDS), strong decoupling state (SDS), and weak decoupling state (WDS) in order, showing a regular interval repetition distribution pattern. (3) The relationship between ULUE and EDL showed an EKC “U-shaped” curve, that is, ULUE decreases first and then increases with the increases in EDL. The results of this study can provide a reference for the coordinated and sustainable development of the BTH region.

Obesity and type 2 diabetes are national and worldwide epidemics. Because currently available antiobesity and antidiabetic drugs have limited efficacy and/or safety concerns, identifying new medicinal agents, such as ginsenoside Rb1 (Rb1) as reported here, offers exciting possibilities for future development of successful antiobesity and antidiabetic therapies. Changes in feeding behavior after acute intraperitoneal administration of Rb1 and the effects of intraperitoneal Rb1 for 4 weeks on body weight, energy expenditure, and glucose tolerance in high-fat diet (HFD)-induced obese rats were assessed. We also examined the effects of Rb1 on signaling pathways and neuropeptides in the hypothalamus. Acute intraperitoneal Rb1 dose-dependently suppressed food intake without eliciting signs of toxicity. This inhibitory effect on feeding may be mediated by central mechanisms because Rb1 stimulated c-Fos expression in brain areas involved in energy homeostasis. Consistent with this, Rb1 activated the phosphatidylinositol 3-kinase/Akt signaling pathway and inhibited NPY gene expression in the hypothalamus. Four-week administration of Rb1 significantly reduced food intake, body weight gain, and body fat content and increased energy expenditure in HFD-induced obese rats. Rb1 also significantly decreased fasting blood glucose and improved glucose tolerance, and these effects were greater than those observed in pair-fed rats, suggesting that although Rb1's antihyperglycemic effect is partially attributable to reduced food intake and body weight; there may be additional effects of Rb1 on glucose homeostasis. These results identify Rb1 as an antiobesity and antihyperglycemic agent.

Nerve growth factor receptor (NGFR, CD271, or p75NTR) is highly expressed in melanoma-initiating cells (MICs) and is critical for their proliferation and tumorigenesis, and yet the underlying mechanism(s) remain incompletely understood. We previously showed that NGFR inhibits p53 activity in a negative feedback manner in various cancer cells. Here we report that this feedback inhibition of p53 by NGFR plays an essential role in maintaining the sphere formation (stem-like phenotype) and proliferation of MICs, and in promoting MIC-derived melanoma growth in vivo. Knockdown of NGFR markedly reduced the size and number of spheroid formation of melanoma cells, which can be rescued by ectopically expressed NGFR. This reduction was also reversed by depleting p53. Consistently, knockdown of NGFR led to the suppression of MIC-derived xenograft tumor growth by inducing the p53 pathway. These results demonstrate that the NGFR-p53 feedback loop is essential for maintaining MIC stem-like phenotype and MIC-derived tumorigenesis, and further validates NGFR as a potential target for developing a molecule-based therapy against melanoma.