Comprehensive analysis to identify a novel diagnostic marker of lung adenocarcinoma and its immune infiltration landscape

BackgroundLung cancer continues to be a problem faced by all of humanity. It is the cancer with the highest morbidity and mortality in the world, and the most common histological type of lung cancer is lung adenocarcinoma (LUAD), accounting for about 40% of lung malignant tumors. This study was conducted to discuss and explore the immune-related biomarkers and pathways during the development and progression of LUAD and their relationship with immunocyte infiltration.MethodsThe cohorts of data used in this study were downloaded from the Gene Expression Complex (GEO) database and the Cancer Genome Atlas Program (TCGA) database. Through the analysis of differential expression analysis, weighted gene co-expression network analysis (WGCNA), and least absolute shrinkage and selection operator(LASSO), selecting the module with the highest correlation with LUAD progression, and then the HUB gene was further determined. The Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were then used to study the function of these genes. Single-sample GSEA (ssGSEA) analysis was used to investigate the penetration of 28 immunocytes and their relationship with HUB genes. Finally, the receiver operating characteristic curve (ROC) was used to evaluate these HUB genes accurately to diagnose LUAD. In addition, additional cohorts were used for external validation. Based on the TCGA database, the effect of the HUB genes on the prognosis of LUAD patients was assessed using the Kaplan-Meier curve. The mRNA levels of some HUB genes in cancer cells and normal cells were analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).ResultsThe turquoise module with the highest correlation with LUAD was identified among the seven modules obtained with WGCNA. Three hundred fifty-four differential genes were chosen. After LASSO analysis, 12 HUB genes were chosen as candidate biomarkers for LUAD expression. According to the immune infiltration results, CD4 + T cells, B cells, and NK cells were high in LUAD sample tissue. The ROC curve showed that all 12 HUB genes had a high diagnostic value. Finally, the functional enrichment analysis suggested that the HUB gene is mainly related to inflammatory and immune responses. According to the RT-qPCR study, we found that the expression of DPYSL2, OCIAD2, and FABP4 in A549 was higher than BEAS-2B. The expression content of DPYSL2 was lower in H1299 than in BEAS-2B. However, the expression difference of FABP4 and OCIAD2 genes in H1299 lung cancer cells was insignificant, but both showed a trend of increase.ConclusionsThe mechanism of LUAD pathogenesis and progression is closely linked to T cells, B cells, and monocytes. 12 HUB genes(ADAMTS8, CD36, DPYSL2, FABP4, FGFR4, HBA2, OCIAD2, PARP1, PLEKHH2, STX11, TCF21, TNNC1) may participate in the progression of LUAD via immune-related signaling pathways

Genome-wide analysis of FRF gene family and functional identification of HvFRF9 under drought stress in barley

FHY3 and its homologous protein FAR1 are the founding members of FRS family. They exhibited diverse and powerful physiological functions during evolution, and participated in the response to multiple abiotic stresses. FRF genes are considered to be truncated FRS family proteins. They competed with FRS for DNA binding sites to regulate gene expression. However, only few studies are available on FRF genes in plants participating in the regulation of abiotic stress. With wide adaptability and high stress-resistance, barley is an excellent candidate for the identification of stress-resistance-related genes. In this study, 22 HvFRFs were detected in barley using bioinformatic analysis from whole genome. According to evolution and conserved motif analysis, the 22 HvFRFs could be divided into subfamilies I and II. Most promoters of subfamily I members contained abscisic acid and methyl jasmonate response elements; however, a large number promoters of subfamily II contained gibberellin and salicylic acid response elements. HvFRF9, one of the members of subfamily II, exhibited a expression advantage in different tissues, and it was most significantly upregulated under drought stress. In-situ PCR revealed that HvFRF9 is mainly expressed in the root epidermal cells, as well as xylem and phloem of roots and leaves, indicating that HvFRF9 may be related to absorption and transportation of water and nutrients. The results of subcellular localization indicated that HvFRF9 was mainly expressed in the nuclei of tobacco epidermal cells and protoplast of arabidopsis. Further, transgenic arabidopsis plants with HvFRF9 overexpression were generated to verify the role of HvFRF9 in drought resistance. Under drought stress, leaf chlorosis and wilting, MDA and O2− contents were significantly lower, meanwhile, fresh weight, root length, PRO content, and SOD, CAT and POD activities were significantly higher in HvFRF9-overexpressing arabidopsis plants than in wild-type plants. Therefore, overexpression of HvFRF9 could significantly enhance the drought resistance in arabidopsis. These results suggested that HvFRF9 may play a key role in drought resistance in barley by increasing the absorption and transportation of water and the activity of antioxidant enzymes. This study provided a theoretical basis for drought resistance in barley and provided new genes for drought resistance breeding

Lipid nanomaterials-based RNA therapy and cancer treatment

We summarize the most important advances in RNA delivery and nanomedicine. We describe lipid nanoparticle-based RNA therapeutics and the impacts on the development of novel drugs. The fundamental properties of the key RNA members are described. We introduced recent advances in the nanoparticles to deliver RNA to defined targets, with a focus on lipid nanoparticles (LNPs). We review recent advances in biomedical therapy based on RNA drug delivery and state-of-the-art RNA application platforms, including the treatment of different types of cancer. This review presents an overview of current LNPs based RNA therapies in cancer treatment and provides deep insight into the development of future nanomedicines sophisticatedly combining the unparalleled functions of RNA therapeutics and nanotechnology

Preparation and photoluminescence of yttrium hydroxide and yttrium oxide doped with europium nanowires

Abstract Single-crystalline Y(OH) 3 :Eu nanowires have been prepared by polymer-assisted hydrothermal method. The yields of the nanowires were higher than 95%. XRD patterns showed that the products were the hexagonal Y(OH) 3 structure

Exploring and comparing the anti‐obesity mechanisms of defatted rice bran total dietary fiber, insoluble dietary fiber, and soluble dietary fiber based on multi‐omics technologies

Abstract This study aimed to investigate the anti‐obesity mechanisms of rice bran total dietary fiber (RDF), rice bran insoluble DF (RIDF), and rice bran soluble DF (RSDF) from defatted rice bran. RDF, RIDF, and RSDF exhibited excellent anti‐obesity effects, mainly reflected in lipid adsorption in vitro, reduction of body weight, inhibition of adipose tissue accumulation, improvement of dyslipidemia, and repair of histopathological damage. More importantly, the analysis of multi‐omics results revealed that the regulation of intestinal microbiota, amino acid metabolism, and lipid metabolism were the critical pathways for the anti‐obesity effects of RDF, RIDF, and RSDF. However, RIDF was involved in lipid metabolism through alanine, aspartate, and glutamate metabolism and exhibited a more favorable regulatory effect on gut microbiota. In contrast, RSDF impacted metabolic pathways dominated by tryptophan and cholesterol metabolism and excelled in immune and inflammatory amelioration. RIDF and RSDF together constitute RDF, with the latter integrating the tendencies of RIDF and RSDF in terms of intestinal microbiota and hepatic gene expression. However, RDF exhibited significant differences in metabolic regulation compared to RIDF and RSDF, particularly concerning tryptophan metabolism. These findings demonstrated that RIDF and RSDF have distinct mechanisms in obesity management, and that both contributed differently to the anti‐obesity effect of RDF. This study provides experimental evidence for the development of different types of DF from defatted rice bran as personalized anti‐obesity dietary supplements. It also offers new insights for future precision nutrition interventions involving DF

Immunogenic-cell-killing and immunosuppression-inhibiting nanomedicine

Combining chemo-therapeutics with immune checkpoint inhibitors facilitates killing cancer cells and activating the immune system through inhibiting immune escape. However, their treatment effects remain limited due to the compromised accumulation of both drugs and inhibitors in certain tumor tissues. Herein, a new poly (acrylamide-co-acrylonitrile-co-vinylimidazole-co-bis(2-methacryloyl) oxyethyl disulfide) (PAAVB) polymer-based intelligent platform with controllable upper critical solution temperature (UCST) was used for the simultaneous delivery of paclitaxel (PTX) and curcumin (CUR). Additionally, a hyaluronic acid (HA) layer was coated on the surface of PAAVB NPs to target the CD44-overexpressed tumor cells. The proposed nanomedicine demonstrated a gratifying accumulation in tumor tissue and uptake by cancer cells. Then, the acidic microenvironment and high level of glutathione (GSH) in cancer cells could spontaneously decrease the UCST of polymer, leading to the disassembly of the NPs and rapid drug release at body temperature without extra-stimuli. Significantly, the released PTX and CUR could induce the immunogenic cell death (ICD) to promote adaptive anti-tumor immunogenicity and inhibit immunosuppression through suppressing the activity of indoleamine 2,3-dioxygenase 1 (IDO1) enzyme respectively. Therefore, the synergism of this intelligent nanomedicine can suppress primary breast tumor growth and inhibit their lung metastasis

Evaluation of Anti-Obesity Activity, Acute Toxicity, and Subacute Toxicity of Probiotic Dark Tea

Probiotic dark tea (PDT) is a novel kind of dark tea produced by fresh albino tea leaves and fermented with specific probiotics. Our study demonstrates that PDT can ameliorate high-fat diet-induced overweight and lipid metabolic disorders and shows no acute or subacute toxicity in Sprague-Dawley (SD) rats. Daily intragastric administration of 5% PDT infusion for 14 days caused no obvious effect on general physiological features and behaviors of rats. Oral administration of 1%, 2%, and 3% of PDT infusion for six weeks had no influence on the biochemistry and histopathology of rats’ organs and blood, as well as the body weight and ratios of organ/body weight. To investigate its anti-obesity activity, SD rats were randomly divided into four groups, treated with normal diet + water (Group I), high-fat diet + water (Group II), high-fat diet + 3% traditional dark tea infusion (Group III), high-fat diet + 3% PDT infusion (Group IV). After six weeks, the body weight, serum total triacylglycerol (TG) and serum total cholesterol (TC) levels of rats in Group II were significantly increased and the high-density lipoprotein cholesterol (HDL) levels were significantly decreased compared with those in the other three groups. Both traditional dark tea and PDT treatment effectively counteracted the adverse effect of a high-fat diet in SD rats. These results suggest that PDT could be applied for the prevention of obesity, which ameliorates overweight and lipid metabolic disorders and which shows no acute or subacute toxicity

An NIR photothermal-responsive hybrid hydrogel for enhanced wound healing

Moderately regulating vascularization and immune microenvironment of wound site is necessary to achieve scarless wound healing of the skin. Herein, we have prepared an angiogenesis-promoting and scar-preventing band-aid with a core-shell structure, that consists of MXene-loaded nanofibers (MNFs) as the core and dopamine-hyaluronic acid hydrogel (H) as the shell (MNFs@V–H@DA) to encapsulate a growth factor (vascular endothelial growth factor, VEGF, abbreviated as V) and H2S donor (diallyl trisulfide, DATS, abbreviated as DA). The continuous release of DA from this system produced H2S, which would successfully induce macrophages to polarize into M2-lile phenotype, regulating the immune microenvironment and inhibiting an excessive inflammatory response at the wound sites. It is conducive to the proliferation of skin cells, facilitating the wound healing. In addition, an appropriate amount of VEGF can be released from the MXene nanofibrous skeleton by adjusting the time of near-infrared (NIR) light exposure, preventing excessive neovascularization and extracellular matrix deposition at the wound sites. Collectively, this NIR photothermal-responsive band-aid achieved scarless wound healing through gradient-controlled vascularization and a related immune sequential reaction of damaged skin tissue