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• GC cells-derived IL18 enhances the oncogenic activity of CAFs, which in turn facilitates the proliferation and growth of GC cells in vitro and in vivo. • Eupafolin disrupts crosstalk between GC cells and CAFs by directly binding to IL18RAP to destroy IL18 signaling activation. • Eupafolin prevents GC cells-derived IL18 from activating NF-κB and pro-carcinogenic cytokine release in CAFs, which is responsible for the suppression of activation of STAT3 signaling in GC cells triggered by CAFs. Cancer-associated fibroblasts (CAFs) are involved in the progression of gastric cancer (GC) as a critical component of the tumor microenvironment (TME), yet specific interventions remain limited. Natural products hold a promising application prospect in the field of anti-tumor in view of their high activity and ease of binding with biological macromolecules. However, the role of natural products in modulating the cross-talk between CAFs and GC cells has not been fully investigated. The aim of this study was to identify a potential therapeutic target in CAFs and then screen for natural small molecule drugs with anti-tumor activity against this target. Integrating bioinformatics analysis of public databases and experimental validation of human samples and cell lines to identify a candidate target in CAFs. Molecular docking and biolayer interferometry technique were utilized for screening potential natural small molecule drugs. The efficacy and underlying mechanisms of the candidates were explored in vitro and in vivo through techniques such as lentiviral infection, cell spheroids culture, immunoprecipitation and cells-derived xenografts. IL18 receptor accessory protein (IL18RAP) was found to be overexpressed in CAFs derived from GC tissues and facilitated the protumor function of CAFs on GC. Based on virtual screening and experimental validation, we identified a natural product, eupafolin, that interfered with IL18 signaling. Phenotyping studies confirmed that the proliferation, spheroids formation and tumorigenesis of GC cells facilitated by CAFs were greatly attenuated by eupafolin both in vitro and in vivo. Mechanistically, eupafolin impeded the formation of IL18 receptor (IL18R) complex by directly binding to IL18RAP, thus blocking IL18-mediated nuclear factor kappa B (NF-κB) activation and reduced the synthesis and secretion of IL6 in CAFs. As a consequence, it inactivated signal transducer and activator of transcription 3 (STAT3) in GC cells. This study provides new evidence that IL18 signaling regulates the cross-talk between GC cells and CAFs. And it highlights a novel pharmacological role of eupafolin in inhibiting IL18 signaling, thereby curbing the development of GC via modulating CAFs. GC cells-derived IL18 enhances the oncogenic activity of CAFs, which in turn facilitates the proliferation and growth of GC cells in vitro and in vivo, whereas the natural product eupafolin disrupts this interaction. Mechanistically, eupafolin prevents GC cells-derived IL18 from activating NF-κB and pro-carcinogenic cytokine release in CAFs by directly binding to IL18RAP, which is responsible for the suppression of activation of STAT3 signaling in GC cells triggered by CAFs. [Display omitted] [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has inflicted immense damage to countries, economies and societies worldwide. Authorized COVID-19 vaccines based on different platforms have been widely inoculated in adults, showing up to 100% immunogenicity with significant efficacy in preventing SARS-CoV-2 infections and the occurrence of severe COVID-19. It has also greatly slowed the evolution of SARS-CoV-2 variants, as shown in clinical trials and real-world evidence. However, the total dosage of COVID-19 vaccines for children is much smaller than that for adults due to limitations from parental concern of vaccine safety, presenting a potential obstacle in ending the COVID-19 pandemic. SARS-CoV-2 not only increases the risk of severe multisystem inflammatory syndrome (MIS-C) in children, but also negatively affects children's psychology and academics, indirectly hindering the maintenance and progress of normal social order. Therefore, this article examines the clinical manifestations of children infected with SARS-CoV-2, the status of vaccination against COVID-19 in children, vaccination-related adverse events, and the unique immune mechanisms of children. In particular, the necessity and challenges of vaccinating children against SARS-CoV-2 were highlighted from the perspectives of society and family. In summary, parental hesitancy is unnecessary as adverse events after COVID-19 vaccination have been proven to be infrequent, comprise of mild symptoms, and have a good prognosis. [ABSTRACT FROM AUTHOR]

• Identify changes in the center of gravity of the value of ecosystem services. • Ecosystem service value primarily driven by climate factors. • Study area contributes significant ecosystem services on a broader scale. The Yellow River Source Area (YRSA) functions as an ecological barrier within the Yellow River Basin, playing a significant role in providing indispensable ecosystem services. Analyzing the ecosystem service value (ESV) of YRSA holds great significance in establishing ecological protection awareness and promoting ecological actions. In this study, we reveal the spatial and temporal characteristics of ESV in YRSA from 2000 to 2020 based on the land use change and equivalent factor method, and explore the driving mechanisms behind ESV heterogeneity using geographical detector. The results showed that from 2000 to 2020, ESV in the YRSA increased significantly, with an average increase rate of 9.12 × 1021seJ/5a, showing a spatial distribution pattern of low in the northwest and high in the southeast, and this imbalance is gradually weakening. The average annual contribution of grassland ESV reached 45 %, followed by water bodies (23 %). Ecosystem services in the YRSA are mainly dominated by regulating services, among which hydrological regulating services are dominated, with an average annual contribution rate of more than 40 %. Supply and regulation, support and cultural services both form a strong correlation synergy. Climate factors are the main drivers of spatial heterogeneity in ESV, further illustrating the sensitivity of the YRSA to climate change. Moreover, our results accentuate the integral role of the YRSA in furnishing ESV to the broader Yellow River Basin, which provides a theoretical basis and reference for decision makers to assess the ecological security of the ecological barrier zones. [ABSTRACT FROM AUTHOR]

• Local Shannon diversity did not explain a significant amount of growth variation. • Individual growth responses to local spatial distribution varied among species. • Effects of size heterogeneity in tree height on tree growth depend on tree traits. • Forest structure is more vital than topography and soil resource for tree growth. Although diversity-ecosystem functioning relationships have been extensively studied, the impact of forest structure on productivity and the main drivers of this relationship remain unresolved. In addition to forest structure, local abiotic conditions affect tree growth, by influencing the diversity of soil properties, but their relative importance remains unclear. We analysed how tree size, local forest structure, topography, and soil resource availability affect plantation growth and their relative importance. We investigated 6117 living trees in 64 plots in Qinghai Province and analysed individual growth responses of the main local afforestation species using mixed-effect models. Results indicated that tree growth was affected by tree size, local forest structure, topography, and soil resource availability to different degrees. Individual growth responses to local forest structure varied among species, especially in relation to size heterogeneity and spatial distribution. Local species diversity did not show significant complementarity or facilitation, but intense competition have occurred between trees. Tree size was the most important predictor of tree growth, and local forest structure was more important than topography and soil resource availability. These findings call for implementing appropriate management measures based on species traits and paying attention to changes in the relative importance of biological and abiotic factors with forest succession. [ABSTRACT FROM AUTHOR]