Metabolic reprogramming in the tumor microenvironment: unleashing T cell stemness for enhanced cancer immunotherapy

T cells play a pivotal role in the immune system by distinguishing between various harmful pathogens and cancerous cells within the human body and initiating an immune response. Within the tumor microenvironment (TME), immune effector T cells encounter both immunosuppressive cells and factors that hinder their functionality. Additionally, they endure robust and persistent antigenic stimulation, often leading to exhaustion and apoptosis. However, the stemness of T cells, characterized by their ability to survive and self-renew over extended periods, represents a primary target in immune checkpoint therapies such as anti-PD-1 therapy. T cell stemness encompasses specific memory T cell subsets and progenitor-exhausted T cells with stem cell-like properties. Therefore, understanding the impact of the TME on T cell stemness, including factors like K+, lactate, and H+, holds significant importance and can facilitate the mitigation of terminal T-cell depletion, the identification of potential resilient biomarkers or therapeutic targets resistant to immune checkpoint therapies, and ultimately lead to sustained anti-tumor effects. Thus, it offers a novel perspective for advancing tumor immunotherapy

Spatial Heterogeneity of Farmland Abandonment in the Sichuan Province, China

Urbanization and regional geomorphological and agricultural conditions have caused rural hollowing out and a large number of farms to be abandoned, which is a big obstacle to food security and rural industrial development. Sichuan Province is representative of national major grain producing areas and high-quality cultivated protected land in China. This paper reveals the spatial heterogeneity of farmland abandonment in the Sichuan Province. In total, 455 random sample plots were investigated to explore spatial heterogeneity of abandoned farmland in Sichuan Province. In each sample plot, farmland and abandoned farmland patches were mapped. The rate of paddy field abandonment (RPFA), the rate of non-irrigated farmland abandonment (RNFA), and the rate of farmland abandonment (RFA) were calculated as indicators of farmland abandonment. Our results reveal the spatial heterogeneity of abandoned farmland in Sichuan Province, and the clustering characteristics of spatial cold- and hot spots of the RFA. The findings from this study may have importance in rural infrastructure construction and the implementation of a rural revitalization strategy, as well as in making policies to curb abandonment of farmland. The spatial heterogeneity of farmland abandonment revealed in this study may contribute to sustaining food security and farmland protection in China

Ecosystem services balance and its influencing factors detection in China: A case study in Chengdu-Chongqing urban agglomerations

Rapid urbanization in China’s urban agglomerations has severely disrupted the relationship between supply and demand for ecosystem services (ESs). Exploring the spatial and temporal variation characteristics of ESs balance and its driving mechanisms is crucial for the high-quality development of urban agglomerations. However, few studies have explored the pattern of ESs balance and its driving mechanisms at multiple scales in urban agglomerations, which constrains the formulation of regional ecological protection and land use policies. In this study, we attempted to characterize the ESs balance pattern and its spatio-temporal variation from 2000 to 2020 at multiple scales in the Chengdu-Chongqing urban agglomerations (CCUA), using ESs matrix and hotspot analysis tools. We then introduced the optimal parametric geographic detector to detect the formation mechanism of the spatial differentiation pattern of ESs balance. The results show that the overall ESs supply index for CCUA was greater than the demand index. The ESs were in short supply in Chengdu and Chongqing. The pattern of ESs balance had significant scale dependence. The hot spots of the ESs balance index were mainly in the western, southern, and eastern mountainous regions, while the cold spots were concentrated in urban areas of Chengdu and Chongqing, with significant differences in characteristics at different scales. The spatial distribution of the ESs balance was mainly affected by the forest land proportion, slope, normalized difference vegetation index (NDVI), elevation, cultivated land proportion, and temperature. The interaction of natural, land use, and socio-economic factors significantly enhanced the spatial differentiation of ESs balance. The interaction of different types of factors highlights the importance of topography, NDVI, cultivated land, forest land, and population. The results of this study can provide scientific references for the sustainable management of ESs and the construction of ecological civilization in CCUA

Grouting Treatment of Water and Mud Inrush in Fully Weathered Granite Tunnel: A Case Study

When mountain tunnel passes through completely weathered granite strata, water and mud inrush is easy to occur, causing casualties and economic losses. Grouting is a common and effective treatment method for water and mud inrush disaster. The current existing researches focus on theoretical analysis, numerical simulation, and laboratory test, and the researches based on the field of engineering application are few. Based on the fully weathered granite tunnel of Junchang tunnel in Guangxi, this paper studies the grouting treatment of water and mud disaster in the fully weathered granite tunnel. This paper first introduces the geological and hydrological conditions of Junchang tunnel in order to understand the causes of water inrush and mud inrush. Then, the treatment method of full-section curtain grouting is introduced. During the grouting, the combination of exploration and injection is adopted. According to different hydrological conditions, different kinds of grouting materials are adopted. After grouting is completed, Transient Electromagnetic Methods, water inflow analysis, borehole investigation, and P-Q-T method are used to evaluate the grouting effect. According to the reaction of the detection results, the weak part of grouting can be supplemented to improve the grouting quality. The results show that the curtain grouting is effective for the treatment of water-mud inrush disaster in the fully weathered granite tunnel. This study provides a reference for the treatment of water and mud inrush in other similar tunnels

Dietary Supplementation of 25-Hydroxyvitamin D3 Improves Growth Performance, Antioxidant Capacity and Immune Function in Weaned Piglets

This study was conducted to evaluate the effects of 25-hydroxyvitamin D3 (25(OH)VD3) and Vitamin D3 (VD3) supplemented in the diet of weaned piglets on their growth performance, bone quality, intestinal integrity, immune function and antioxidant capacity. A total of 192 weaned piglets were allocated into four groups and they were fed a control diet containing 2000 IU VD3 (negative control, NC), NC + 100 ppm colistin sulfate (positive control, PC), NC + 2000 IU VD3 (VD3) and NC + 2000 IU 25(OH)VD3 (25(OH)VD3). The results showed that 25(OH)VD3 improved the growth performance, bone quality and antioxidase activity of piglets compared with the other groups. Meanwhile, 25(OH)VD3 up-regulated ileal mRNA expressions of tight junction proteins and host defense peptides. The VD3 group had an increased intestinal sIgA content and mRNA expression of pBD-1 compared with the NC group. Both groups of VD3 and 25(OH)VD3 altered the microbial β-diversity compared with the NC group, and 25(OH)VD3 increased ileal concentrations of acetate and butyrate. In conclusion, our findings indicated that a regular dosage of 2000 IU VD3 in the weaned piglets’ diet did not achieve optimal antioxidant capacity and immune function. 25(OH)VD3 had better growth performance than VD3 at the same inclusion level, which is associated with the improved intestinal integrity and antioxidant capacity