Search Results (10,362)

In the tumor microenvironment, various immune and stromal cells, such as fibroblasts and vascular endothelial cells, contribute to tumor growth and progression by interacting with cancer cells. Tumor-associated macrophages (TAMs) have attracted attention as major players in the tumor microenvironment. The origin of TAMs is believed to be the infiltration of monocytes derived from bone marrow progenitor cells into tumor tissues and their differentiation into macrophages, whereas tissue-resident macrophages derived from yolk sacs have recently been reported. TAMs infiltrating tumor tissues act in a tumor-promoting manner through immunosuppression, angiogenesis, and the promotion of cancer cell invasion. Reflecting the nature of TAMs, increased TAM invasion and TAM-specific gene expression in tumor tissues may be the new biomarkers for cancer. Moreover, new therapeutic strategies targeting TAMs, such as transformation into immunostimulatory macrophages, suppression of TAM infiltration, and promotion of phagocytosis, are being investigated, and many clinical trials are underway. As the origin and function of TAMs are further elucidated, TAM-targeted therapy is expected to become a new option for the immunotherapy of various cancers, including oral cancers. Full article

Voltage-gated Na⁺ channels (Nav) are the molecular determinants of action potential initiation and propagation. Among the nine voltage-gated Na⁺ channel isoforms (Nav1.1–Nav1.9), Nav1.2 and Nav1.6 are of particular interest because of their developmental expression profile throughout the central nervous system (CNS) and their association with channelopathies. Although the α-subunit coded by each of the nine isoforms can sufficiently confer transient Na⁺ currents (I_Na), in vivo these channels are modulated by auxiliary proteins like intracellular fibroblast growth factor (iFGFs) through protein–protein interaction (PPI), and probes developed from iFGF/Nav PPI complexes have been shown to precisely modulate Nav channels. Previous studies identified ZL0177, a peptidomimetic derived from a short peptide sequence at the FGF14/Nav1.6 PPI interface, as a functional modulator of Nav1.6-mediated I_Na⁺. However, the isoform specificity, binding sites, and putative physiological impact of ZL0177 on neuronal excitability remain unexplored. Here, we used automated planar patch-clamp electrophysiology to assess ZL0177’s functional activity in cells stably expressing Nav1.2 or Nav1.6. While ZL0177 was found to suppress I_Na in both Nav1.2- and Nav1.6-expressing cells, ZL0177 elicited functionally divergent effects on channel kinetics that were isoform-specific and supported by differential docking of the compound to AlphaFold structures of the two channel isoforms. Computational modeling predicts that ZL0177 modulates Nav1.2 and Nav1.6 in an isoform-specific manner, eliciting phenotypically divergent effects on action potential discharge. Taken together, these results highlight the potential of PPI derivatives for isoform-specific regulation of Nav channels and the development of therapeutics for channelopathies. Full article

The scientific evaluation of the coordinated development level of the Yangtze River Delta Urban Agglomeration is crucial for promoting the localization of the Sustainable Development Goals (SDGs). This study, based on the SDGs framework, utilizes data from 41 prefecture-level cities in the Yangtze River Delta from 2013 to 2023 to establish a five-dimensional evaluation index system, covering urban–rural integration (SDG 10), scientific and technological innovation (SDG 9), infrastructure (SDG 9.1), ecological environment (SDG 13/14/15), and public services (SDG 3/4/11). By applying the coupling coordination degree model, kernel density estimation, and the standard deviation ellipse method, the study systematically assesses the regional coordinated development level and its spatio-temporal evolution patterns. The findings reveal that from 2013 to 2023, the development indices of the five subsystems showed a fluctuating upward trend, with significant disparities in growth rate and stability. The overall regional coordination degree continuously improved, and differences diminished, with the coupling degree and coupling coordination degree exhibiting a “polarization followed by an overall leap” pattern. The coupling coordination degree evolved in three stages: “imbalance in mutual feedback among elements, strengthening of coordination mechanisms, and deepening of policy innovation”, with spatial differentiation and clustered development coexisting. Spatially, the distribution center shifted through three phases: “policy-driven”, “market-regulated”, and “technology-led”, forming an axial reconstruction from northwest to southeast, ultimately establishing a multi-center coordinated development system. Full article

Choosing the most sustainable and ecologically stable soil tillage techniques requires dependence on long-term field trials, which are essential for successful interventions and evidence-based decision-making. This research evaluated several factors, including soil biological activity (CO₂ emission), soil chemical properties (pH (KCl), soil organic matter (SOM)), plant growth physiological indicators (Leaf Area Index (LAI), Soil and Plant Analysis Development (SPAD)), crop yield, and grain quality (Zeleny index, protein %, oil %, and gluten % content), under six soil cultivation methods that represent varying degrees of soil disturbance in a long-term (23 years) tillage experiment. Conventional tillage (ploughing (P)) and conservational tillage techniques (loosening (L), deep cultivation (DC), shallow cultivation (SC), disking (D), and no-till (NT)) were examined for three years (2022, 2023, and 2024) in a winter barley–soybean–winter wheat cropping system. Results indicate that tillage intensity has a differential influence on soil biological parameters, with minor variations in SPAD values across treatments. The findings show significant variations in CO₂ emissions, LAI values, and grain quality in certain years, likely due to the influence of P and L tillage treatments. The novelty of this study lies in determining that, although the short-term effects of soil tillage on crop physiological parameters and grain yield may be minimal under fluctuating climatic conditions, long-term tillage practices significantly influence existing disparities, underscoring the necessity for site-specific and climate-resilient tillage strategies in sustainable crop production. Full article

Optimizing the regional spatial pattern of land use and high-quality economic development requires an accurate understanding of the multifunctional evolution of land use. Based on remote sensing data and socio-economic data from 2000 to 2023, this study utilizes a land transfer matrix, an evaluation index system, an obstacle degree model, and regression analysis to deeply explore the spatial distribution characteristics and influencing factors of the production–living–ecological functions (PLEF) in the Yangtze River Economic Belt (YREB) over the 23-year period. The results show the following: ① the living function area of the YREB has increased by 22,400 km², while the production function area has decreased by 20,600 km², and the ecological function area has decreased by 1800 km². ② The production and living function spaces are characterized by high values in the eastern region and low values in the western region, and the ecological function space is characterized by high values in the western region and low values in the eastern region. ③ In the YREB, production function was the main obstacle to the PLEF between 2000 and 2023. ④ Population growth, economic development, agricultural technology, and agricultural efficiency are the main factors that influence the spatial and temporal evolution of the PLEF. This study suggests exploring an interactive compensation mechanism of the PLEF that combines the government and the market to form a differentiated development strategy. Full article

Hepatocellular carcinoma (HCC) remains a global health challenge due to molecular heterogeneity and frequent delayed diagnosis. This comprehensive review synthesizes recent immunohistochemistry (IHC) advancements for HCC diagnosis, prognostication, and therapeutic prediction. We systematically evaluate conventional markers, such as hepatocyte paraffin 1 (HepPar1), arginase-1 (Arg-1), and glypican-3 (GPC3), as well as emerging biomarkers, detailing their diagnostic sensitivities and specificities in HCC with varied tumor differentiation. Prognostic immunostaining markers, such as Ki-67 proliferation index and vascular endothelial growth factor (VEGF) overexpression, correlate with reduced 5-year survival, while novel immune checkpoint IHC markers (PD-L1 and CTLA-4) predict response to immunotherapy, particularly in advanced HCC. This work provides evidence-based recommendations for optimizing IHC utilization in clinical practice while identifying knowledge gaps in biomarker validation and standardization. Full article

Intrauterine growth restriction (IUGR) severely hinders the development of the livestock industry and impacts economic efficiency. MicroRNAs (miRNAs) participate in the epigenetic regulation of animal growth and development. Using IUGR pigs as a model, this study analyzed transcriptomic data from IUGR piglets to investigate the miRNA-mRNA regulatory network in their testes. Compared with NBW pigs, IUGR pigs exhibited reduced testicular volume, decreased weight, and abnormal testicular development. A total of 4945 differentially expressed mRNAs and 53 differentially expressed miRNAs were identified in IUGR testicular tissues, including 1748 downregulated and 3197 upregulated mRNAs, as well as 41 upregulated and 12 downregulated miRNAs. The integrated analysis of differentially expressed genes, miRNA target genes, and the miRNA-mRNA network revealed that IUGR may impair testicular development by disrupting cell cycle progression and apoptotic pathways, thereby hindering normal testicular cell growth. Furthermore, analysis of the miRNA-mRNA network indicated that miRNAs such as ssc-miR-23a, ssc-miR-29c, ssc-miR-193a-3p, and ssc-miR-574-3p could serve as potential marker miRNAs for IUGR testes, while YWHAZ, YWHAB, and PPP2CA may function as core target genes within this regulatory network. In conclusion, this study enhances our understanding of male reproduction in IUGR pigs and provides a theoretical foundation for preventing and treating IUGR-induced male reproductive disorders. Full article

Germplasm resources embody the genetic diversity of plants and form the foundation for breeding and the ongoing improvement of elite cultivars. The establishment of germplasm banks, along with their systematic evaluation, constitutes a critical step toward the conservation, sustainable use, and innovative utilization of these resources. Liriodendron, a rare and endangered tree genus with species distributed in both East Asia and North America, holds considerable ecological, ornamental, and economic significance. However, a standardized evaluation system for Liriodendron germplasm remains unavailable. In this study, 297 Liriodendron germplasm accessions were comprehensively evaluated using 34 phenotypic traits and whole-genome resequencing data. Substantial variation was observed in most phenotypic traits, with significant correlations identified among several characteristics. Cluster analysis based on phenotypic data grouped the accessions into three distinct clusters, each exhibiting unique distribution patterns. This classification was further supported by principal component analysis (PCA), which effectively captured the underlying variation among accessions. These phenotypic groupings demonstrated high consistency with subsequent population structure analysis based on SNP markers (K = 3). Notably, several key traits exhibited significant divergence (p < 0.05) among distinct genetic clusters, thereby validating the coordinated association between phenotypic variation and molecular markers. Genetic diversity and population structure were assessed using 4204 high-quality single-nucleotide polymorphism (SNP) markers obtained through stringent filtering. The results indicated that the Liriodendron sino-americanum displayed the highest genetic diversity, with an expected heterozygosity (He) of 0.18 and a polymorphic information content (PIC) of 0.14. In addition, both hierarchical clustering and PCA revealed clear population differentiation among the accessions. Association analysis between three phenotypic traits (DBH, annual height increment, and branch number) and SNPs identified 25 highly significant SNP loci (p < 0.01). Of particular interest, the branch number-associated locus SNP_17_69375264 (p = 1.03 × 10⁻⁵) demonstrated the strongest association, highlighting distinct genetic regulation patterns among different growth traits. A minimal set of 13 core SNP markers was subsequently used to construct unique DNA fingerprints for all 297 accessions. In conclusion, this study systematically characterized phenotypic traits in Liriodendron, identified high-quality and core SNPs, and established correlations between key phenotypic and molecular markers. These achievements enabled differential analysis and genetic diversity assessment of Liriodendron germplasm, along with the construction of DNA fingerprint profiles. The results provide crucial theoretical basis and technical support for germplasm conservation, accurate identification, and utilization of Liriodendron resources, while offering significant practical value for variety selection, reproduction and commercial applications of this species. Full article

Organic agriculture is a production system based on environmentally friendly practices that promote the conservation of natural resources, biodiversity, and the production of high-quality food. Its tenets are linked to the concept of sustainable development, which integrates environmental, social, and economic goals. In the face of global competition and changes in food systems, studying their competitiveness of organic agriculture is essential. It is key to assessing its potential for long-term development and competition with conventional agriculture. The purpose of this study is to identify and assess the spatial differentiation in the competitiveness of organic agriculture in EU countries. This study assessed the level of input and output competitiveness of organic agriculture in selected EU countries using the author’s synthetic taxonomic indicators consisting of several sub-variables. The competitiveness of organic farming in twenty-three countries (Cyprus, Latvia, Portugal, and Finland were not included due to a lack of statistical data) was analysed using one of the linear ordering methods, i.e., a non-pattern method with a system of fixed weights. The research has shown significant spatial differentiation in both the input competitiveness and the outcome competitiveness of organic agriculture in EU countries. In 2023, Estonia had the highest level of input competitiveness, followed by Austria, the Czech Republic, and Sweden. In 2023, Estonia had the highest synthetic indicator of outcome competitiveness, followed by The Netherlands and Denmark. In addition, an assessment was made of changes in EU organic agriculture in 2014–2023 by analysing the direction and dynamics of changes in selected measures of the development potential of organic agriculture in all member states (27 countries). This sector is characterised by high growth dynamics, including both the area under cultivation and the number of producers and processors of organic food. This study identified several important measures to support the development of organic farming (especially in countries where this type of activity is relatively less competitive) through targeted support mechanisms, such as policy and regulatory measures, financing, agricultural training and advisory services, scientific research, encouraging cooperation, and stimulating demand for organic products. Full article

Background: Clear cell renal cell carcinoma with rhabdoid features (ccRCC-R) is a highly aggressive variant of renal cell carcinoma that carries a poor prognosis and limited treatment options. Methods: To better define the clinicopathologic and molecular landscape of ccRCC-R, we conducted an integrated clinicopathologic and molecular study of 17 tumors of ccRCC-R, utilizing comprehensive histomorphologic evaluation, immunohistochemistry, and targeted next-generation sequencing (NGS). Results: Histologically, all tumors demonstrated classic clear cell renal cell carcinoma morphology with focal to extensive rhabdoid differentiation, characterized by eccentrically located nuclei, prominent nucleoli, abundant eosinophilic cytoplasm, and paranuclear intracytoplasmic inclusion. Architectural alterations, including solid/sheet-like, alveolar/trabecular, and pseudopapillary growth patterns, were frequently observed. Immunohistochemically, tumors commonly exhibited loss of PAX8 and Claudin4 expression, preserved cytokeratin AE1/AE3 staining, and diffuse membranous CAIX expression. Frequent loss of SMARCA2 with retained SMARCA4 supported aberrations in chromatin remodeling. Unsupervised hierarchical clustering based on pathway-specific somatic mutations identified four distinct molecular subgroups defined by recurrent alterations in (1) DNA damage repair (DDR) genes, (2) chromatin remodeling genes, (3) PI3K/AKT/mTOR signaling components, and (4) MAPK pathway genes. Clinicopathologic correlation revealed that each subgroup was associated with unique biological characteristics and suggested distinct therapeutic vulnerabilities. Conclusions: Our findings underscore the molecular heterogeneity of ccRCC-R and support the utility of pathway-based stratification for guiding precision oncology approaches and biomarker-informed clinical trial design. Full article

To systematically elucidate the chronological patterns of embryonic development and morphological changes in the larval and juvenile stages of Silurus glanis, and provide fundamental biological insights into this species, in this study, fertilized eggs were obtained through artificial spawning induction technology. After removing adhesiveness from fertilized eggs using trypsin, a detailed developmental study was conducted. The study systematically analyzed the chronological sequence of embryonic development and the morphological change patterns of larval and juvenile fish. The results showed the following: The fertilized eggs of S. glanis are yellow, spherical, and sticky, and the stickiness allows eggs to attach to spawning substrates, enhancing hatching success. The egg diameter after water absorption was (2.88 ± 0.13) mm. The embryonic development took 47 h and 55 min, with a total accumulated temperature of 1245.56 h degrees Celsius, the developmental process includes seven stages and twenty-six periods, namely the zygophase stage, cleavage stage, blastula stage, gastrula stage, neurula stage, organogenesis stage, and hatching stage. At a temperature of (26.0 ± 0.9) °C, the hatched individuals went through the pre-yolk sac larval stage, late larval stage, juvenile fry stage, and juvenile stage. In the pre-yolk sac larval stage, otoliths appeared in the bilateral otic vesicles, a pair of barbel primordia emerged under the mandible, a short and thin straight intestine formed in the abdominal cavity, and the oral fissure first appeared. In the late larval stage, the fin rays were initially formed, the intestine became thicker and longer, the oral fissure, anus, and cloaca were formed, and the larvae could float and start feeding on exogenous food. In the juvenile fry stage, the differentiation of various organs was basically complete, the nostrils became larger, and both the anal fin and caudal fin had dark black markings. In the juvenile stage, the maxillary barbels elongated, the mucus layer thickened on the body and back, the abdomen is light white, and it had the external morphological characteristics of an adult fish. By measuring and calculating the total length, body length, body height, and head length of S. glanis larvae and juveniles (0–40 days), the results showed that the growth characteristics conformed to the following fish growth formula: TL = 0.0141x² + 0.8096x + 8.2421 (R² = 0.9916), where x denotes days after hatching. This study has preliminarily mastered the chronological patterns of the embryonic development, growth, and formation of the morphological characteristics in larval and juvenile S. glanis, providing scientific data and laying a theoretical foundation for the division of early developmental stages, reproduction, hatching, and fry cultivation. Full article

The increasing demographic aging of society is a great challenge to the healthcare sector and raises the socio-economic burden. Therefore, elucidating the mechanisms of aging and developing safe effective anti-aging products to prolong people’s healthy lifespan are paramount nowadays. Panax ginseng has been highly regarded since ancient times for its ability to enhance health and prolong life. However, its main active substances of anti-aging and their mechanisms are not fully understood. In this research, Caenorhabditis elegans was used as a model organism to explore and confirm the key active substances from Panax ginseng and the mechanisms that exert anti-aging effects. Various ginsenoside compounds were evaluated based on longevity, anti-stress, physiological function, etc. Ginsenoside Re, which has powerful anti-aging activity, was screened. In the follow-up trials, transcriptomics and RT-qPCR techniques were used to investigate the mechanism of Re in exerting its anti-aging properties. Differential genes were enriched in the Insulin/Insulin-like Growth Factor-1 Signaling (IIS) pathway, the neuropeptide signaling pathway, and lipid metabolism. A significant increase in the expression levels of daf-16, sgk-1, skn-1, hsf-1, hsp-16.2, sod-3, gst-4, fil-2, lips-11, cyp-35A4, and aex-2 genes, and a significant decrease in the expression levels of daf-2, age-1, and akt-2 genes were verified. These suggest that ginsenoside Re exerts its life-extending influence by regulating lipid metabolism and the IIS pathway. Full article

The germination and elongation of maize in the early growth stage are closely related to the elongation of the mesocotyl, which is one of the earlier parts that are able to sense external temperature, except for the coleoptile. And, low-temperature (LT) stress can significantly influence the survival and growth of maize seedlings. In addition, the brassinosteroids (BRs) have also been applied to alleviate the damage suffered by various plants in LT in recent years. However, the interaction relationship among LT, BRs, and sugar remains unclear. Therefore, we examined the changing relationships among the contents of glucose, sucrose, and starch, as well as the changes in differentially expressed genes (DEGs) in the starch and sucrose metabolism and glycolysis/gluconeogenesis pathways. Herein, compared to CK (0 μM 24-epibrassinolide (EBR) application at 25 °C), the contents of glucose and sucrose all increased by 0.26, 0.47, and 0.70 mg g⁻¹ FW and 0.80, 0.30, and 0.61 mg g⁻¹ FW, respectively, under the CKE (2.0 μM 24-epibrassinolide (EBR) application at 25 °C), LT (0 μM 24-epibrassinolide (EBR) application at 10 °C), and LTE (2.0 μM 24-epibrassinolide (EBR) application at 10 °C) treatments, but the contents of starch decreased under LT and LTE treatments by −0.54% and −0.20%, compared to CK. This suggested that not only did the sugar signaling and metabolism play key roles in regulating LT tolerance but the application of EBR can also alleviate the damage caused by LT by regulating the sugar accumulation level. Meanwhile, 108 DEGs in the starch and sucrose metabolism pathway and 65 DEGs in the glycolysis pathway were identified at the transcriptome level. The common Zm00001d042146 in both pathways is always down-regulated, and the down-regulation multiple when EBR is added is less than the LT. In addition, key genes such as Zm00001d021598, Zm00001d034017, and Zm00001d029091, were all differentially expressed under LT, and the expression multiples decreased when EBR was added. In conclusion, our results provide new insights into the molecular mechanism by which exogenous application of EBR enhances the low-temperature tolerance of maize seedlings. The germination and elongation of maize in the early growth stage are closely related to the elongation of the mesocotyl, which is one of the first parts to sense external temperature, aside from the coleoptile. Low-temperature (LT, 10~15 °C) stress can significantly affect the survival and growth of maize seedlings. Additionally, brassinosteroids (BRs) have been used in recent years to help alleviate damage caused by LT in various plants. However, the interaction among LT, BRs, and sugar remains unclear. Therefore, we examined the relationships among the contents of glucose, sucrose, and starch, along with the changes in differentially expressed genes (DEGs) involved in starch and sucrose metabolism and glycolysis/gluconeogenesis pathways. Compared to CK (0 μM 24-epibrassinolide (EBR) application at 25 °C), the contents of glucose and sucrose increased by 0.26, 0.47, and 0.70 mg g⁻¹ FW and 0.80, 0.30, and 0.61 mg g⁻¹ FW, respectively, under the CKE (2.0 μM 24-epibrassinolide (EBR) application at 25 °C), LT (0 μM 24-epibrassinolide (EBR) application at 10 °C), and LTE (2.0 μM 24-epibrassinolide (EBR) application at 10 °C) treatments. However, starch contents decreased under LT and LTE treatments, by −20.54% and −0.20%, respectively, compared to CK. This suggests that sugar signaling and metabolism play key roles in regulating LT tolerance, and the application of EBR may alleviate LT damage by regulating sugar accumulation levels. Furthermore, 108 DEGs were identified in the starch and sucrose metabolism pathways, along with 23 in glycolysis, with 65 DEGs at the transcriptome level. The common Zm00001d042146 (hexokinase-3) in both pathways is usually down-regulated, and the degree of down-regulation when EBR is added is less than under LT alone. Additionally, key genes such as Zm00001d021598 (glucan endo-1,3-beta-glucosidase 3), Zm00001d034017 (uncharacterized LOC541703), and Zm00001d029091 (sucrose synthase 2) were differentially expressed under LT, with their expression levels decreasing further when EBR was added. In conclusion, our results provide a new direction into the molecular mechanisms by which exogenous EBR application enhances low-temperature tolerance in maize seedlings. Full article

The rapid growth of global urbanisation has resulted in significant environmental pollution, with urban water pollution emerging as a critical factor in comprehensive urban development. The present study employs panel data from 268 Chinese cities between 2013 and 2022, utilising entropy weighting and a two-effect fixed-effects model to empirically analyse how urban water pollution control promotes comprehensive urban development. The research findings reveal that water pollution control significantly promotes comprehensive urban development, but there are differences across urban regions and scales, with greater effectiveness observed in central and western regions and medium-sized and small cities. This paper also highlights that water pollution control can promote urban development by optimising industrial structure and proposes that governments should formulate regionally differentiated water pollution control policies, establish a ‘Regional Water Environment Governance and Industrial Transformation Coordination Centre,’ and implement the ‘River and Lake Chief System+’ policy. Full article

Karst regions, characterized by thin soil layers, severe rocky desertification, and fragile vegetation, hold significant scientific value for achieving China’s “dual-carbon” goals. This study focuses on Zhijin County in Guizhou Province, integrating provincial carbon density data with forest resource inventory data. By constructing a model to adjust aboveground forest carbon density (AGC) estimation parameters and utilizing the InVEST model alongside hotspot analysis, the research systematically examines the spatiotemporal heterogeneity of carbon storage from 2000 to 2020. These findings provide actionable strategies for enhancing carbon sequestration efficiency in ecologically fragile regions, supporting China’s “dual-carbon” policy goals. Key findings include: (1) Carbon storage exhibits a “growth-turning point” two-phase pattern, increasing by 0.46% from 2000 to 2015 but decreasing by 3.31% in 2020 due to construction land expansion. (2) There are significant differences in carbon storage among ecological engineering projects, with the highest carbon storage found in the “Grain-for-Green Program” project area and the lowest in the “National Rocky Desertification Control Program” area. (3) Elevation is the primary controlling factor for carbon storage, with rocky desertification showing notable spatial differentiation. This study provides theoretical support for the precise regulation of ecological programs and the development of high-precision carbon storage models in karst regions. Full article