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Background: To determine the role of N6-methyladenosine (m6A) modification in the tumor immune microenvironment (TIME), as well as their association with lung adenocarcinoma (LUAD). Methods: Consensus clustering was performed to identify the subgroups with distinct immune or m6A modification patterns using profiles from TCGA. A risk score model was constructed using least absolute shrinkage and selection operator regression and validated in two independent cohorts and LUAD tissue microarrays. For experimental validation, the regulation of METTL3/m6A axis in the expression of candidate genes by RIP-qPCR assay in A549 and H460 cell lines. Co-culture experiments with human T cells were performed to evaluate the impact of METTL3 on the enhancement of anti-tumor immunity through in vitro experiments. Results: We identified 282 m6A regulator genes and 955 immune-related genes, selecting seven key genes (SFTPC, CYP24A1, KRT6A, PTTG1, S100P, FAM83A, and ANLN) to develop a risk score model using Lasso regression. High-risk patients, determined by this model, exhibited poorer prognosis, increased immune infiltration, higher tumor mutational burden, more neoantigens, and elevated PD-L1 expression. These findings were validated by two independent databases and LUAD tissue microarrays. METTL3 was found to impact the mRNA expression of these genes, with METTL3 deficiency abolishing these interactions. Inhibition of METTL3 enhanced anti-tumor immunity, T cell activation, exhaustion, and infiltration in vitro. Conclusion: This risk score system shows promise for prognostic prediction and the development of personalized treatment strategies for LUAD patients. [ABSTRACT FROM AUTHOR]

Irritable bowel syndrome (IBS) is a common chronic functional bowel disorder and is strongly associated with an increased risk of depression and anxiety. The brain–gut axis plays an important role in the pathophysiologic changes in IBS, yet effective treatments for IBS are still lacking. Sinisan, originating from the Treatise on Typhoid Fever by the medical sage Zhang Zhongjing, is a classic formula in the Eight Methods of Traditional Chinese Medicine (TCM) that focuses on dispersing the liver and regulating the spleen, relieving depression and transmitting evils, and has been widely used in the treatment of liver-depression and spleen-deficiency, diarrhea, and related liver and stomach disorders. However, the therapeutic effect of sinisan in IBS has not been clarified. The aim of this study was to investigate the effects of sinisan on stress-induced intestinal dysfunction and depressive behavior in IBS mice. We established a diarrhea-predominant irritable bowel syndrome (IBS-D) mouse model using a 4% acetic acid enema combined with restraint stress, and analyzed the results using behavioral tests, relevant test kits, hematoxylin-eosin (HE) staining, immunofluorescence (IF), Western blot (WB), and quantitative fluorescence polymerase chain reaction (qRT-PCR). The results showed that sinisan administration significantly alleviated intestinal dysfunction and depressive-like behaviors in IBS-D mice, improved mild colonic inflammation and intestinal mucosal permeability, up-regulated the expression of tight junction proteins ZO-1 and occludin. Sinisan significantly alleviated intestinal dysfunction and depressive-like behaviors in IBS-D mice by decreasing the expression of TNF-α, promoting the expression of tight junction proteins (occludin, ZO-1) expression, and inhibiting the Tlr4/Myd88 signaling pathway, thereby attenuating the inflammatory response, protecting the intestinal barrier, and alleviating symptoms in the IBS-D mouse model. Taken together, sinisan may ameliorate intestinal inflammation and the intestinal barrier by regulating 5-HT expression and the Tlr4/Myd88 pathway, thereby alleviating stress-induced intestinal dysfunction and depressive behaviors in IBS-D mice. [ABSTRACT FROM AUTHOR]

Background: Reed canary grass has been identified as a suitable species for restoring plateau wetlands and understanding plant adaptation mechanisms in wetland environments. In this study, we subjected a reed canary grass cultivar 'Chuanxi' to waterlogging, salt, and combined stresses to investigate its phenotypic characteristics, physiological indices, and transcriptome changes under these conditions. Results: The results revealed that the growth rate was slower under salt stress than under waterlogging stress. The chlorophyll content and energy capture efficiency of the PS II reaction center decreased with prolonged exposure to each stress. Conversely, while the activities of enzymes associated with respiratory metabolism, as well as MDA, PRO, Na+, and K+-ATPase, increased. The formation of distinct aerenchyma was observed under waterlogging stress and combined stress. Transcriptome sequencing analysis identified 5,379, 4,169, and 14,993 DEGs under CK vs. W, CK vs. S, and CK vs. SW conditions, respectively. The WRKY was found to be the most abundant under waterlogging stress, whereas the MYB predominated under salt stress and combined stress. Glutathione metabolic pathways and Plant hormone signal transduction have also been found to play important roles in stress. Conclusion: By integrating phenotypic, physiological, anatomical, and transcriptomic, this research provides valuable insights into how reed canary grass responds to salt, waterlogging, and combined stresses. These findings may inform the ecological application of reed canary grass in high-altitude wetlands and for breeding purposes. [ABSTRACT FROM AUTHOR]

The alternative oxidase (AOX), a common terminal oxidase in the electron transfer chain (ETC) of plants, plays a crucial role in stress resilience and plant growth and development. Oat (Avena sativa), an important crop with high nutritional value, has not been comprehensively studied regarding the AsAOX gene family. Therefore, this study explored the responses and potential functions of the AsAOX gene family to various abiotic stresses and their potential evolutionary pathways. Additionally, we conducted a genome-wide analysis to explore the evolutionary conservation and divergence of AOX gene families among three Avena species (Avena sativa, Avena insularis, Avena longiglumis) and four Poaceae species (Avena sativa, Oryza sativa, Triticum aestivum, and Brachypodium distachyon). We identified 12 AsAOX, 9 AiAOX, and 4 AlAOX gene family members. Phylogenetic, motif, domain, gene structure, and selective pressure analyses revealed that most AsAOXs, AiAOXs, and AlAOXs are evolutionarily conserved. We also identified 16 AsAOX segmental duplication pairs, suggesting that segmental duplication may have contributed to the expansion of the AsAOX gene family, potentially preserving these genes through subfunctionalization. Chromosome polyploidization, gene structural variations, and gene fragment recombination likely contributed to the evolution and expansion of the AsAOX gene family as well. Additionally, we hypothesize that AsAOX2 may have potential function in resisting wounding and heat stresses, while AsAOX4 could be specifically involved in mitigating wounding stress. AsAOX11 might contribute to resistance against chromium and waterlogging stresses. AsAOX8 may have potential fuction in mitigating ABA-mediated stress. AsAOX12 and AsAOX5 are most likely to have potential function in mitigating salt and drought stresses, respectively. This study elucidates the potential evolutionary pathways of the AsAOXs gene family, explores their responses and potential functions to various abiotic stresses, identifies potential candidate genes for future functional studies, and facilitates molecular breeding applications in A. sativa. [ABSTRACT FROM AUTHOR]

Objective To establish a method that can be used to analyze the distribution of DNA base damage sites at the genome-wide level, and use this method to analyze the distribution pattern of DNA base damage hotspots in non-small cell lung cancer cell line A549. Methods Chromatin immunoprecipitation sequencing(ChIP-seq)was used to perform immunoaffinity separation of specific binding DNA fragments with apurinic/apyrimidinic endonuclease 1(APE1)and 8-oxoguanine DNA glycosylase 1(OGG1)in A549 cells for sequence identification, and bioinformatics analysis was carried out to study the whole genome DNA base damage hotspots distribution. Results The binding peaks of APE1 and OGG1 were mainly distributed in the gene promoter region, with proportions of 41.70% and 49.26% respectively. The peaks of APE1 and OGG1 located in the 2 000 bp region upstream of TSS, accounting for 38.80% and 39.80%, respectively. The binding peaks of APE1 and OGG1 were significantly correlated(r=0.636 3, P < 0.01). The number of APE1 and OGG1 associated genes with the same binding peak was 25 038, among which 641 were directly associated with tumorigenesis. Conclusion A genome-wide analysis method is established to analyze the distribution of DNA base damage sites. DNA base damage is not randomly distributed in lung cancer cells, but mainly distributed in gene regulatory region. Hot spots related to base damage repair protein binding may be closely associated with tumor genesis and tumor inflammatory microenvironment.

Soil salinization is a significant obstacle to improving natural grasslands, also affecting farmland productivity. The main distribution area of high salinity soils is primarily located in western China, with a significant presence in the Qinghai–Tibet Plateau (QTP). Siberian wildrye (Elymus sibiricus L.) has been widely used in ecological restoration and reseeding in the QTP, due to its strong salt and alkali resistance. To comprehensively evaluate its salt tolerance and to screen salt-tolerant and salt-sensitive germplasm resources, 50 wild E. sibiricus accessions were assessed through the measurement of several physiological parameters. These included the relative water content (RWC); relative electrical conductivity (REC); malondialdehyde content (MDA); proline content (Pro); and Na+/K+ ratio after 14 days of salt stress treatment (200 mmol L−1 NaCl). Through principal component analysis (PCA) based on both material sources and physiological indexing, it was found that the salt damage score (SDS) and RWC had a strong positive correlation (p < 0.05), in opposition to other indices. The positive indicators were REC, Pro, Na+/K+, and MDA, and the negative indicators were RWC and SDS. Ultimately, by combining the results of the conventional membership function analysis and the weighted membership function analysis based on major components, three salt-tolerant accessions—including XJ013-28, NM021-13 and XJ012-17—and four salt-sensitive accessions, including XZ008-20, QH013-8, XZ009-20, and QH005-35, were screened out. These results could be effectively used to assess the effects of salt stress on Siberian wildrye and its related species. This study provides a reference for the discovery and breeding of salt-tolerant cultivars among the Elymus species. [ABSTRACT FROM AUTHOR]

Orchardgrass (Dactylis glomerata L.) is highly tolerant of shade, cold, and overwintering, making it an ideal species for grassland ecological restoration and livestock production. However, the genetic diversity of orchardgrass may be threatened by climate change. Using a Maximum Entropy (MaxEnt) model with the BCC-CSM2-MR global climate database and the Harmonized World Soil Database, we projected the current and future distribution of orchardgrass suitable areas globally. The predicted ecological thresholds for vital environmental factors were determined to be a temperature seasonality range of 411.50–1034.37 °C, a mean diurnal range of −0.88–10.69 °C, a maximum temperature of the warmest month of 22.21–35.45 °C, and precipitation of the coldest quarter of 116.56–825.40 mm. A range of AUC values from 0.914 to 0.922, indicating the accuracy of the prediction model. Our results indicate that the total area of current suitable habitats for orchardgrass was estimated to be 2133.01 × 104 km2, it is dispersed unevenly over six continents. Additionally, the suitable areas of habitats increased in higher latitudes while decreasing in lower latitudes as greenhouse gas emissions increased. Therefore, efforts should be made to save places in the southern hemisphere that are in danger of becoming unsuitable, with the possibility of using northern America, China, and Europe in the future for conservation and extensive farming. [ABSTRACT FROM AUTHOR]

The mutation of tumor suppressor gene liver kinase B1 (LKB1) has a prevalence of about 20% in non–small cell lung cancer (NSCLC). LKB1‐mutant lung cancer is characterized by enhanced aggressiveness and immune escape and is associated with poor prognosis. Therefore, it is urgent to develop effective therapeutic methods for LKB1‐mutant NSCLC. Recently, apatinib, a VEGFR‐TKI, was found to significantly improve the outcome of LKB1‐mutant NSCLC, but the mechanism is not completely clear. In this study, AMP‐activated protein kinase (AMPK), the crucial downstream kinase of LKB1 was excavated as the potential target of apatinib. Biochemical experiments verified that apatinib is a direct AMPK activator. Moreover, clinically available VEGFR‐TKIs were found to regulate AMPK differently: Apatinib and anlotinib can directly activate AMPK, while axitinib and sunitinib can directly inhibit AMPK. Activation of AMPK by apatinib leads to the phosphorylation of acetyl‐CoA carboxylase (ACC) and inhibition of de novo fatty acid synthesis (FAsyn), which is upregulated in LKB1‐null cancers. Moreover, the killing effect of apatinib was obviously enhanced under delipidated condition, and the combination of exogenous FA restriction with apatinib treatment can be a promising method for treating LKB1‐mutant NSCLC. This study discovered AMPK as an important off‐target of apatinib and elucidated different effects of this cluster of VEGFR‐TKIs on AMPK. This finding can be the basis for the accurate and combined application of these drugs in clinic and highlights that the subset of VEGFR‐TKIs including apatinib and anlotinib are potentially valuable in the treatment of LKB1‐mutant NSCLC. [ABSTRACT FROM AUTHOR]