Mutational Profile and Potential Molecular Therapeutic Targets of Pheochromocytoma

PurposePheochromocytoma/paraganglioma (PCC/PGL; collectively known as PPGL) can be driven by germline and somatic mutations in susceptibility genes. We aimed to investigate the mutation profile and clinical features of pathogenic genes in highly genetically heterogeneous PPGL and to preliminary explore molecular therapeutic targets in PPGL.MethodsWe established a panel of 260 genes, including susceptibility genes of PPGL and other important tumorigenic genes to sequence 107 PPGL tissues.ResultsOverall, 608 genomic mutations were identified in 107 PPGL tissues. Almost 57% of PPGL tissue samples exhibited pathogenic mutations, and the most frequently mutated gene was SDHB (15/107, 14%). SDHB and HRAS were the most commonly mutated genes in germline-mutated PPGL (25/107, 23%) and nongermline-mutated PPGL (36/107, 34%), respectively. In addition, novel pathogenic mutations were detected in sporadic PPGL. PPGL with mutations in the hypoxia pathway had an earlier onset and higher norepinephrine level than those in the kinase pathway. Receptor tyrosine kinase (RTK; 22%, 24/107), mitogen-activated protein kinase (MAPK; 14%, 15/107), and tyrosine kinase (TK; 2%, 2/107) pathways were the most frequently mutated pathways in PPGL.ConclusionOur results provided the genetic mutation profile in PPGL tissues. Genetic mutations in PPGL were mainly concentrated in the RTK, TK, and MAPK pathways, suggesting potential molecular therapeutic targets for PPGL

Review of solar energetic particle models

Solar Energetic Particle (SEP) events are interesting from a scientific perspective as they are the product of a broad set of physical processes from the corona out through the extent of the heliosphere, and provide insight into processes of particle acceleration and transport that are widely applicable in astrophysics. From the operations perspective, SEP events pose a radiation hazard for aviation, electronics in space, and human space exploration, in particular for missions outside of the Earth’s protective magnetosphere including to the Moon and Mars. Thus, it is critical to improve the scientific understanding of SEP events and use this understanding to develop and improve SEP forecasting capabilities to support operations. Many SEP models exist or are in development using a wide variety of approaches and with differing goals. These include computationally intensive physics-based models, fast and light empirical models, machine learning-based models, and mixed-model approaches. The aim of this paper is to summarize all of the SEP models currently developed in the scientific community, including a description of model approach, inputs and outputs, free parameters, and any published validations or comparisons with data.</p

Can China’s transfer payment in key ecological function areas reduce the carbon intensity? – Quasi – Natural experimental evidence from Jiangxi, China

Reducing carbon intensity while sustaining economic growth is a major challenge for China's ecological civilization construction in the context of global warming. China’s transfer payment policy in National Key Ecological Function areas plays a crucial role in promoting ecological improvement and reducing local carbon intensity. In this study, we examine the impact of transfer payment policies on carbon intensity in Jiangxi Province, a demonstration area for national ecological civilization, and we further investigate the carbon reduction mechanism and the spatial spillover effect of the policies. Results show the following: (1) the transfer payment policy in key ecological function areas has significantly reduced the carbon intensity, and the research conclusion is still valid after the robustness test; (2) the transfer payment policy in key ecological function areas reduces the carbon intensity by promoting the upgrading of industrial structure; (3) the transfer payment policy in key ecological function areas has a significant role in promoting the reduction of carbon intensity in this region and the adjacent regions. The findings highlight the significant promoting role of transfer payment policies in key ecological function zones on carbon emission reduction in both local and neighboring areas. It also underscores the importance of expanding policy coverage, establishing horizontal ecological compensation mechanisms, exploring multidimensional approaches to carbon reduction, and fostering cross-regional exchanges and cooperation. These insights provide valuable guidance for policymakers working towards effective and sustainable carbon emission reduction

The Evolution and Influencing Factors of Total Factor Productivity of Grain Production Environment: Evidence from Poyang Lake Basin, China

The total factor productivity (hereafter TFP) of grain production is important to achieve balanced development, while environmental factors are an important part of TEP. In order to explore the characteristics and patterns of the temporal and spatial evolution of the environmental total factor productivity (hereafter ETFP), the Malmquist-Luerberger index, and the spatial autoregressive panel (SAR panel) model were adopted to analyze the evolutionary rules and the influencing factors of ETFP. In this study, we took Poyang Lake, one of China’s main grain production areas, as a study area, and carried out empirical research based on grain production statistical data. The results show that: (1) ETFP shows a growth trend with the increase of grain production from 2001 to 2017, and a great potential for improvement exists. Moreover, from the perspective of time sequence evolution and decomposition of ETFP, which belongs to the dual-track driver of environmental technical efficiency and environmental technological progress, relevant technologies play an important role in promoting the improvement of TEFP; (2) Given that the objective conditions of gain production remain unchanged, the fact that the urbanization rate and average annual rainfall have a negative effect on ETFP, the explanatory variables such as the business scale per worker, the proportion of grain growing population, industrial agglomeration, the proportion of grain sown area and the average annual temperature all play a positive role. Among the variables, the business scale per worker and the proportion of grain growing population significantly affect ETFP at the 1% level. The average annual rainfall, industrial agglomeration and the proportion of grain sown area significantly affect the ETFP at the 5% level. The average annual temperature significantly affects the ETFP at the 10% level

Modulation of the p38 MAPK Pathway by Anisomycin Promotes Ferroptosis of Hepatocellular Carcinoma through Phosphorylation of H3S10

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor worldwide. Ferroptosis is emerging as an effective target for tumor treatment as it has been shown to potentiate cell death in some malignancies. However, it remains unclear whether histone phosphorylation events, an epigenetic mechanism that regulates transcriptional expression, are involved in ferroptosis. Our study found that supplementation with anisomycin, an agonist of p38 mitogen-activated protein kinase (MAPK), induced ferroptosis in HCC cells, and the phosphorylation of histone H3 on serine 10 (p-H3S10) was participated in anisomycin-induced ferroptosis. To investigate the anticancer effects of anisomycin-activated p38 MAPK in HCC, we analyzed cell viability, colony formation, cell death, and cell migration in Hep3B and HCCLM3 cells. The results showed that anisomycin could significantly suppress HCC cell colony formation and migration and induce HCC cell death. The hallmarks of ferroptosis, such as abnormal accumulation of iron and elevated levels of lipid peroxidation and malondialdehyde, were detected to confirm the ability of anisomycin to promote ferroptosis. Furthermore, coincubation with SB203580, an inhibitor of activated p38 MAPK, partially rescued anisomycin-induced ferroptosis. And the levels of p-p38 MAPK and p-H3S10 were successively increased by anisomycin treatment. The relationship between p-H3S10 and ferroptosis was revealed by ChIP sequencing. The reverse transcription PCR and immunofluorescence results showed that NCOA4 was upregulated both in mRNA and protein levels after anisomycin treatment. And by C11-BODIPY staining, we found that anisomycin-induced lipid reactive oxygen species was reduced after NCOA4 knockdown. In conclusion, the anisomycin-activated p38 MAPK promoted ferroptosis of HCC cells through H3S10 phosphorylation

Review of Solar Energetic Particle Models

Solar Energetic Particles (SEP) events are interesting from a scientific perspective as they are the product of a broad set of physical processes from the corona out through the extent of the heliosphere, and provide insight into processes of particle acceleration and transport that are widely applicable in astrophysics. From the operations perspective, SEP events pose a radiation hazard for aviation, electronics in space, and human space exploration, in particular for missions outside of the Earth’s protective magnetosphere including to the Moon and Mars. Thus, it is critical to imific understanding of SEP events and use this understanding to develop and improve SEP forecasting capabilities to support operations. Many SEP models exist or are in development using a wide variety of approaches and with differing goals. These include computationally intensive physics-based models, fast and light empirical models, machine learning-based models, and mixed-model approaches. The aim of this paper is to summarize all of the SEP models currently developed in the scientific community, including a description of model approach, inputs and outputs, free parameters, and any published validations or comparisons with data