Molecular mechanisms of macrophage immunomodulation mediated by Areca inflorescence polysaccharides based on RNA-seq analysis.

The elucidation of the immunomodulatory molecular mechanisms of polysaccharides has contributed to their further development and application. In this study, the effect of Areca inflorescence polysaccharide (AFP2a) on macrophage activation was confirmed and the detailed mechanisms were investigated based on a comprehensive transcriptional study and specific inhibitors. The results showed that AFP2a induced macrophage activation (M1 polarization), promoting macrophage proliferation, reactive oxygen species production, nitric oxide and cytokine release, and costimulatory molecule expression. RNA-seq analysis identified 5919 differentially expressed genes (DEGs). For DEGs, GO, KEGG, and Reactome enrichment analyses and PPI networks were conducted, elucidating that AFP2a activated macrophages mainly by triggering the Toll-like receptor cascade and corresponding adapter proteins (TIRAP and TRIF), thereby resulting in downstream NF-κB, TNF, and JAK-STAT signaling pathway expression. The inhibition assay revealed that TLR4 and TLR2 were essential for the recognition of AFP2a. This work provides an in-depth understanding of the immunoregulatory mechanism of AFP2a while offering a molecular basis for AFP2a to serve as a potential natural immunomodulator.

Identification and molecular docking of tyrosinase inhibitory peptides from allophycocyanin in Spirulina platensis.

BACKGROUND: Tyrosinase, a copper-containing metalloenzyme with catalytic activity, is widely found in mammals. It is the key rate-limiting enzyme that catalyzes melanin synthesis. For humans, tyrosinase is beneficial to the darkening of eyes and hair. However, excessive deposition of melanin in the skin can lead to dull skin color and lead to pigmentation. Therefore, many skin-whitening compounds have been developed to decrease tyrosinase activity. This study aimed to identify a new tyrosinase inhibitory peptide through enzymatic hydrolysis, in vitro activity verification, molecular docking, and molecular dynamics (MD) simulation. RESULTS: A tripeptide Asp-Glu-Arg (DER) was identified, with a '-CDOCKER_Energy' value of 121.26 Kcal mol-1 . DER has effective tyrosinase inhibitory activity. Research shows that its half maximal inhibitory concentration value is 1.04 ± 0.01 mmol L-1 . In addition, DER binds to tyrosinase residues His85, His244, His259, and Asn260, which are key residues that drive the interaction between the peptide and tyrosinase. Finally, through MD simulation, the conformational changes and structural stability of the complexes were further explored to verify and supplement the results of molecular docking. CONCLUSION: This experiment shows that DER can effectively inhibit tyrosinase activity. His244, His259, His260, and Asn260 are the critical residues that drive the interaction between the peptide and tyrosinase, and hydrogen bonding is an important force. DER from Spirulina has the potential to develop functional products with tyrosinase inhibition. © 2024 Society of Chemical Industry.

Phycobiliprotein Peptide Extracts from Arthrospira platensis Ameliorate Nonalcoholic Fatty Liver Disease by Modulating Hepatic Lipid Profile and Strengthening Fat Mobilization.

Arthrospira platensis phycobiliprotein peptide extracts (PPEs) exhibit potential mitigative effects on hepatic steatosis. However, the precise role of PPEs in addressing high-fat-induced nonalcoholic fatty liver disease (NAFLD), as well as the underlying mechanism, remains to be elucidated. In this study, NAFLD was induced in rats through a high-fat diet (HFD), and the rats were subsequently treated with PPEs for a duration of 10 weeks. The outcomes of this investigation demonstrate that PPE supplementation leads to a reduction in body weight gain, a decrease in the accumulation of lipid droplets within the liver tissues, alterations in hepatic lipid profile, regulation of lipolysis-related gene expression within white adipose tissues and modulation of intestinal metabolites. Notably, PPE supplementation exhibits a potential to alleviate liver damage by manipulating neutral lipid metabolism and phospholipid metabolism. Additionally, PPEs appear to enhance fat mobilization by up-regulating the gene expression levels of key factors such as HSL, TGL, UCP1 and UCP2. Furthermore, PPEs impact intestinal metabolites by reducing the levels of long-chain fatty acids while concurrently increasing the levels of short-chain fatty acids. The findings from this study unveil the potential of PPE intervention in ameliorating NAFLD through the modulation of hepatic lipid profile and the reinforcement of the fat mobilization of intestinal metabolites. Thus, PPEs exhibit noteworthy therapeutic effects in the context of NAFLD.

Hybridization and divergent climatic preferences drive divergence of two allopatric Gentiana species on the Qinghai-Tibet Plateau.

BACKGROUND AND AIMS: Exploring how species diverge is vital for understanding the drivers of speciation. Factors such as geographical separation and ecological selection, hybridization, polyploidization and shifts in mating system are all major mechanisms of plant speciation, but their contributions to divergence are rarely well understood. Here we test these mechanisms in two plant species, Gentiana lhassica and G. hoae, with the goal of understanding recent allopatric species divergence on the Qinghai-Tibet Plateau (QTP). METHODS: We performed Bayesian clustering, phylogenetic analysis and estimates of hybridization using 561 302 nuclear genomic single nucleotide polymorphisms (SNPs). We performed redundancy analysis, and identified and annotated species-specific SNPs (ssSNPs) to explore the association between climatic preference and genetic divergence. We also estimated genome sizes using flow cytometry to test for overlooked polyploidy. KEY RESULTS: Genomic evidence confirms that G. lhassica and G. hoae are closely related but distinct species, while genome size estimates show divergence occurred without polyploidy. Gentiana hoae has significantly higher average FIS values than G. lhassica. Population clustering based on genomic SNPs shows no signature of recent hybridization, but each species is characterized by a distinct history of hybridization with congeners that has shaped genome-wide variation. Gentiana lhassica has captured the chloroplast and experienced introgression with a divergent gentian species, while G. hoae has experienced recurrent hybridization with related taxa. Species distribution modelling suggested range overlap in the Last Interglacial Period, while redundancy analysis showed that precipitation and temperature are the major climatic differences explaining the separation of the species. The species differ by 2993 ssSNPs, with genome annotation showing missense variants in genes involved in stress resistance. CONCLUSIONS: This study suggests that the distinctiveness of these species on the QTP is driven by a combination of hybridization, geographical isolation, mating system differences and evolution of divergent climatic preferences.

Microbial remediation of oil-contaminated shorelines: a review.

Frequent marine oil spills have led to increasingly serious oil pollution along shorelines. Microbial remediation has become a research hotspot of intertidal oil pollution remediation because of its high efficiency, low cost, environmental friendliness, and simple operation. Many microorganisms are able to convert oil pollutants into non-toxic substances through their growth and metabolism. Microorganisms use enzymes' catalytic activities to degrade oil pollutants. However, microbial remediation efficiency is affected by the properties of the oil pollutants, microbial community, and environmental conditions. Feasible field microbial remediation technologies for oil spill pollution in the shorelines mainly include the addition of high-efficiency oil degrading bacteria (immobilized bacteria), nutrients, biosurfactants, and enzymes. Limitations to the field application of microbial remediation technology mainly include slow start-up, rapid failure, long remediation time, and uncontrolled environmental impact. Improving the environmental adaptability of microbial remediation technology and developing sustainable microbial remediation technology will be the focus of future research. The feasibility of microbial remediation techniques should also be evaluated comprehensively.

Structural characterization of polysaccharide fractions in areca (Areca catechu L.) inflorescence and study of its immunological enhancement activity in vitro and in vivo.

To obtain the structure-function relationship of the polysaccharides derived from areca (Areca catechu L.) inflorescences in the aspect of its immunomodulatory ability, the plant-based polysaccharide was isolated and purified on column chromatography. The purity, primary structure and immune activity of four polysaccharide fractions (AFP, AFP1, AFP2 and AFP2a) were characterized comprehensively. The main chain of AFP2a was confirmed to be composed of â†’ 3,6)-ß-D-Galp-(1→, with branch chains linked to the O-3 position on the main chain. The immunomodulatory activity of the polysaccharides was evaluated using the RAW264.7 cells and immunosuppression mice model. It was observed that AFP2a enabled greater NO release (49.72 µmol/L) than other fractions, significantly promoted the phagocytic activity of macrophages, and improved splenocyte proliferation and T lymphocyte phenotype in mice. The present results may shine a light on a new research direction in immunoenhancers and provide a theoretical foundation for the development and application of areca inflorescence.

Neuroprotection by Nrf2 via modulating microglial phenotype and phagocytosis after intracerebral hemorrhage.

Activated microglia are divided into pro-inflammatory and anti-inflammatory functional states. In anti-inflammatory state, activated microglia contribute to phagocytosis, neural repair and anti-inflammation. Nrf2 as a major endogenous regulator in hematoma clearance after intracerebral hemorrhage (ICH) has received much attention. This study aims to investigate the mechanism underlying Nrf2-mediated regulation of microglial phenotype and phagocytosis in hematoma clearance after ICH. In vitro experiments, BV-2 cells were assigned to normal group and administration group (Nrf2-siRNA, Nrf2 agonists Monascin and Xuezhikang). In vivo experiments, mice were divided into 5 groups: sham, ICH + vehicle, ICH + Nrf2-/-, ICH + Monascin and ICH + Xuezhikang. In vitro and in vivo, 72 h after administration of Monascin and Xuezhikang, the expression of Nrf2, inflammatory-associated factors such as Trem1, TNF-α and CD80, anti-inflammatory, neural repair and phagocytic associated factors such as Trem2, CD206 and BDNF were analyzed by the Western blot method. In vitro, fluorescent latex beads or erythrocytes were uptaken by BV-2 cells in order to study microglial phagocytic ability. In vivo, hemoglobin levels reflect the hematoma volume. In this study, Nrf2 agonists (Monascin and Xuezhikang) upregulated the expression of Trem2, CD206 and BDNF while decreased the expression of Trem1, TNF-α and CD80 both in vivo and in vitro. At the same time, after Monascin and Xuezhikang treatment, the phagocytic capacity of microglia increased in vitro, neurological deficits improved and hematoma volume lessened in vivo. These results were reversed in the Nrf2-siRNA or the Nrf2-/- mice. All these results indicated that Nrf2 enhanced hematoma clearance and neural repair, improved neurological outcomes through enhancing microglial phagocytosis and alleviating neuroinflammation.

A fungus (Trametes pubescens) resists cadmium toxicity by rewiring nitrogen metabolism and enhancing energy metabolism.

As a primary goal, cadmium (Cd) is a heavy metal pollutant that is readily adsorbed and retained in rice, and it becomes a serious threat to food safety and human health. Fungi have attracted interest for their ability to remove heavy metals from the environment, although the underlying mechanisms of how fungi defend against Cd toxicity are still unclear. In this study, a Cd-resistant fungus Trametes pubescens (T. pubescens) was investigated. Pot experiments of rice seedlings colonized with T. pubescens showed that their coculture could significantly enhance rice seedling growth and reduce Cd accumulation in rice tissues. Furthermore, integrated transcriptomic and metabolomic analyses were used to explore how T. pubescens would reprogram its metabolic network against reactive oxygen species (ROS) caused by Cd toxicity. Based on multi-omic data mining results, we postulated that under Cd stress, T. pubescens was able to upregulate both the mitogen-activated protein kinase (MAPK) and phosphatidylinositol signaling pathways, which enhanced the nitrogen flow from amino acids metabolism through glutaminolysis to α-ketoglutarate (α-KG), one of the entering points of tricarboxylic acid (TCA) cycle within mitochondria; it thus increased the production of energy equivalents, adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide phosphate (NADPH) for T. pubescens to resist oxidative damage. This study can enable a better understanding of the metabolic rewiring of T. pubescens under Cd stress, and it can also provide a promising potential to prevent the rice paddy fields from Cd toxicity and enhance food safety.

Between allopatry and secondary contact: differentiation and hybridization among three sympatric Gentiana species in the Qinghai-Tibet Plateau.

BACKGROUND: Mountains of the world host a significant portion of all terrestrial biodiversity, and the region of the Qinghai-Tibet Plateau (QTP) stands as one of the most remarkable mountain regions on Earth.  Because many explosive radiations occurred there, the QTP is a natural laboratory which is ideal to investigate patterns and processes linked to speciation and diversification. Indeed, understanding how closely related and sympatric species diverged is vital to explore drivers fostering speciation, a topic only rarely investigated in the QTP. By combining genomic and environmental data, we explored the speciation process among three closely related and sympatric species, Gentiana hexaphylla, G. lawrencei and G. veitchiorum in the QTP region. RESULTS: Combining genome sizes and cytological data, our results showed that G. hexaphylla and G. veitchiorum are diploid, whereas G. lawrencei is tetraploid. Genetic clustering and phylogenetic reconstruction based on genomic SNPs indicated a clear divergence among the three species. Bayesian clustering, migrant, and D-statistic analyses all showed an obvious signature of hybridization among the three species, in particular between G. lawrencei and both G. hexaphylla and G. veitchiorum in almost all populations. Environmental variables related to precipitation and particularly temperature showed significant differences among the three gentians, and in fact a redundancy analysis confirmed that temperature and precipitation were the major climatic factors explaining the genetic differentiation among the three species. CONCLUSION: Our study suggested that ancient hybridization, polyploidization, geological isolation and the evolution of different climatic preferences were all likely to be involved in the divergence of the three Gentiana species, as may be the case for many other taxa in the QTP region.

Reconfiguration of Gut Microbiota and Reprogramming of Liver Metabolism with Phycobiliproteins Bioactive Peptides to Rehabilitate Obese Rats.

Phycobiliproteins (derived from Arthrospira platensis) bioactive peptide extracts (PPE) possess multiple pharmacological effects in the mitigation of human metabolic disorders. The role of PPE in the treatment of diet-induced obesity and the understanding of the underlying mechanism between the gut microbiome and metabolic blood circulation for obese patients remains poorly understood. In this study, we showed that PPE attenuated obesity by reducing body weight, and ameliorated glucose and lipid indexes in serum. In particular, PPE is postulated to mitigate liver steatosis and insulin resistance. On the other hand, dietary treatment with PPE was found to "reconfigure" the gut microbiota in the way that the abundances were elevated for Akkermansia_muciniphila, beneficial Lactobacillus and Romboutsia, SCFA-producing species Faecalibacterium prausnitzii, Lachnospiraceae_bacterium, Clostridiales_bacterium, probiotics Clostridium sp., Enterococcus faecium, and Lactobacillus_johnsonii, while the abundance of Firmicutes was reduced and that of Bacteroidetes was increased to reverse the imbalance of Firmicutes/Bacteroidetes ratio. Finally, the metabolomics of circulating serum using UHPLC-MS/MS illustrated that PPE supplementation indeed promoted lipid metabolism in obese rats. As summary, it was seen that PPE reprogrammed the cell metabolism to prevent the aggravation of obesity. Our findings strongly support that PPE can be regarded as a potential therapeutic dietary supplement for obesity.

The m7G-Related Long Noncoding RNA Signature Predicts Prognosis and Indicates Tumour Immune Infiltration in Colon Cancer.

With high morbidity and mortality, colon cancer (CC) is considered as one of the most often diagnosed cancers around the world. M7G-related lncRNA may provide a regulatory function in the formation of CC, but the principle of regulation is still unclear. The purpose of this research was to establish a novel signature that may be used to predict survival and tumour immunity in CC patients. Data about CC in TCGA was collected for analysis, coexpression analysis and univariate Cox analysis were used to screen prognostic m7G-related lncRNAs. A consensus clustering analysis based on prognostic m7G-related lncRNAs was applied, and a prognosis model based on least absolute shrinkage and selection operator (LASSO) regression analysis was established. Independent prognostic analysis, nomogram, PCA, clinicopathological correlation analysis, TMB, survival analysis, immune correlation analysis, qRT-PCR and clinical therapeutic compound prediction were also applied. 90 prognostic m7G-related lncRNAs were found, GO and KEGG analysis showed that prognostic m7G-related lncRNAs were mainly related to cell transcription and translation. The results of the consensus clustering analysis revealed substantial disparities in survival prognosis and tumour immune infiltration between two clusters. We built a risk model with 21 signature m7G-related lncRNAs, patients in the high-risk group had a considerably poorer prognosis than those in the low-risk group. Independent prognostic analysis confirmed that patients' prognosis was linked to their tumour stage and risk score. PCA, subgroups with distinct clinicopathological characteristics were studied for survival, multi-index ROC curve, c-index curve, the survival analysis of TMB, and model comparison tested the reliability of risk model. A tumour immunoassay revealed a substantial difference in immune infiltration between high-risk and low-risk individuals. Five chemicals were eliminated, and qRT-PCR indicated that the four lncRNAs were expressed differently. Overall, m7G-related lncRNA is closely related to colon cancer and the 21 signature lncRNAs risk model can efficiently evaluate the prognosis of CC patients, which has a possible positive consequence for the future diagnosis and therapy of CC.

Artificial photoactive chlorophyll conjugated vanadium carbide nanostructure for synergistic photothermal/photodynamic therapy of cancer.

Optically active nanostructures consisting of organic compounds and metallic support have shown great promise in phototherapy due to their increased light absorption capacity and high energy conversion. Herein, we conjugated chlorophyll (Chl) to vanadium carbide (V2C) nanosheets for combined photodynamic/photothermal therapy (PDT/PTT), which reserves the advantages of each modality while minimizing the side effects to achieve an improved therapeutic effect. In this system, the Chl from Leptolyngbya JSC-1 extracts acted as an efficient light-harvest antenna in a wide NIR range and photosensitizers (PSs) for oxygen self-generation hypoxia-relief PDT. The available large surface of two-dimensional (2D) V2C showed high Chl loading efficiency, and the interaction between organic Chl and metallic V2C led to energy conversion efficiency high to 78%. Thus, the Chl/ V2C nanostructure showed advanced performance in vitro cell line killing and completely ablated tumors in vivo with 100% survival rate under a single NIR irradiation. Our results suggest that the artificial optical Chl/V2C nanostructure will benefit photocatalytic tumor eradication clinic application.

Comprehensive Analysis of Immune Infiltrates of Ferroptosis-Related Long Noncoding RNA and Prediction of Colon Cancer Patient Prognoses.

Ferroptosis is a newly defined mode of programmed oxidative cell death. Knowledge of ferroptosis-related long noncoding (lnc) RNA in the tumor immune microenvironment of colon cancer is lacking. We systematically analyzed the correlations between ferroptosis-related lncRNAs and the tumor microenvironment, immune cell infiltration, and patient prognosis for 379 colon cancer samples in the Cancer Genome Atlas (TCGA). Using consensus clustering, we divided the 379 colon cancer patients into two subgroups (clusters 1 and 2) based on the differentially expressed ferroptosis-related lncRNAs. Cluster 1 was preferentially associated with longer overall survival, upregulated immune checkpoint inhibitor expressions, higher immunoscores, higher stromal scores, higher estimated scores, and distinct immune cell infiltration. Cancer- and metabolism-related pathways were enriched by gene set enrichment analyses. We constructed a prognostic signature of 15 ferroptosis-related lncRNAs (ZEB1-AS1, LINC01011, AC005261.3, LINC01063, LINC02381, ELFN1-AS1, AC009283.1, LINC02361, AC105219.1, AC002310.1, AL590483.1, MIR4435-2HG, NKILA, AC021054.1, and AL450326.1) and divided the patients into the high- and low-risk-score groups. The signature was validated using TCGA training and testing cohorts. The risk signature was an independent prognostic factor for predicting survival and excellently predicted the prognoses of patients with colon cancer. Moreover, the risk signature was related to immune characteristics. Chemosensitivity analyses showed that low-risk-score patients were more sensitive to sorafenib. In summary, our work revealed the important role of ferroptosis-related lncRNAs in the tumor microenvironment and immune cell infiltration and may help determine personalized prognoses and treatment for patients with colon cancer.

Comprehensive Analysis of Pyroptosis-Related Long Noncoding RNA Immune Infiltration and Prediction of Prognosis in Patients with Colon Cancer.

Colon cancer (CC) is one of the most prevalent malignant tumours of the alimentary canal. It is unclear whether pyroptosis-related lncRNA expression is correlated with CC prognosis. We discovered 20 pyroptosis-related lncRNAs that were expressed differently in CC and normal colon tissues in our investigation. Based on differentially expressed genes (DEGs), we grouped all CC patients into two categories (Clusters 1 and 2). Cluster 1 was shown to be connected with a higher overall survival rate, upregulated expression of immune checkpoints, higher immunoscores, higher estimated scores, and immune cell infiltration. Using data from the Cancer Genome Atlas (TCGA), to create a multigene signature, the predictive significance of each lncRNA linked with pyroptosis for survival was assessed. A 9-lncRNA signature was established using the least absolute shrinkage and selection operator (LASSO) Cox regression method, and all CC patients in the TCGA cohort were classified into low-risk or high-risk groups. The low-risk CC patients had a much greater chance of survival than those in the high-risk group. The risk score is an independent prognostic indicator for predicting survival. In addition, risk characteristics are linked to immune characteristics. In summary, pyroptosis-related lncRNAs can be used to predict CC prognosis and participate in tumour immunity.

Multiple amplified microRNAs monitoring in living cells based on fluorescence quenching of Mo2B and hybridization chain reaction.

Imaging intracellular microRNAs (miRNAs) demonstrated an essential role in exposing their biological and pathological functions. However, the detection of sequence-specific miRNAs in living cells remains a key challenge. Herein, a facile amplified multiple intracellular miRNAs imaging platform was constructed based on Mo2B nanosheets (NSs) fluorescence (FL) quenching and hybridization chain reaction (HCR). The Mo2B NSs demonstrated strong interaction with the hairpin probes (HPs), ssDNA loop, and excellent multiple FL dyes quenching performance, achieving ultralow background signal. After transfection, the HPs recognized specific targets miRNAs, the corresponding HCR was triggered to produce tremendous DNA-miRNA duplex helixes, which dissociated from the surface of the Mo2B NSs to produce strong FL for miRNAs detection. It realized to image multiple miRNAs biomarkers in different cells to discriminate cancer cells from normal cells owing to the excellent sensitivity, and the regulated expression change of miRNAs in cancer cells was also successfully monitored. The facile and versatile Mo2B-based FL quenching platform open an avenue to profile miRNAs expression pattern in living cells, and has great applications in miRNAs based biological and biomedical research.

Alpha-terpineol grafted acetylated lentinan as an anti-bacterial adhesion agent.

Biomedical implants-associated bacterial infections have become a major threat to human health. Therefore, it is meaningful to develop new antibacterial strategies to solve this problem. In this study, we conjugated acetylated lentinan (AceLNT) with α-terpineol (AceLNT-g-α-ter), a highly effective natural antibacterial compound, to constitute a novel AceLNT-g-α-ter membrane (AceLNT-g-α-terM). Compared with AceLNT membrane (AceLNTM), the adhesion amount of E. coli and P. aeruginosa in AceLNT-g-α-terM decreased by 80% and 85% after 7 d incubation in fluid bacterial medium. Moreover, the number of E. coli and P. aeruginosa biofilm on AceLNT-g-α-terM surface decreased by 70% and 71%. At the meanwhile, α-terpineol grafting modification of AceLNT had limited effect on its stimulating activity on macrophages and had no more cytotoxicity. In summary, our study firstly confirmed that AceLNT-g-α-terM could effectively inhibit gram-negative bacteria adhesion and biofilm formation, and provided a novel strategy for preventing infection of biomedical implants.

Green synthesis and characterization of Fe3O4 nanoparticles using Chlorella-K01 extract for potential enhancement of plant growth stimulating and antifungal activity.

The purpose of this research was to determine the efficacy of iron oxide nanoparticles (Fe3O4-NPs) using microalgal products as a plant growth stimulant and antifungal agent. The work was conducted with the phyco-synthesis and characterization of Fe3O4-NPs using 0.1 M ferric/ferrous chloride solution (2:1 ratio; 65 °C) with aqueous extract of the green microalga Chlorella K01. Protein, carbohydrate and polyphenol contents of Chlorella K01 extract were measured. The synthesized microalgal Fe3O4-NPs made a significant contribution to the germination and vigor index of rice, maize, mustard, green grams, and watermelons. Fe3O4-NPs also exhibited antifungal activity against Fusarium oxysporum, Fusarium tricinctum, Fusarium maniliforme, Rhizoctonia solani, and Phythium sp. Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) scanning electron microscopy (SEM), transmission electron microscopy (TEM), particle size analysers (PSA), and zeta potential (ZP) measurements were used to characterize these green fabricated magnetite NPs. FTIR analysis showed that the synergy of microalgal proteins, carbohydrtates and polyphenols is responsible for the biofabrication of iron nanoparticles. A spheroid dispersion of biosynthesized Fe3O4-NPs with an average diameter of 76.5 nm was produced in the synthetic process.

Identification of a Tumor Microenvironment-Related Gene Signature Indicative of Disease Prognosis and Treatment Response in Colon Cancer.

BACKGROUND: The tumor microenvironment (TME) is associated with disease outcomes and treatment response in colon cancer. Here, we constructed a TME-related gene signature that is prognosis of disease survival and may predict response to immunotherapy in colon cancer. METHODS: We calculated immune and stromal scores for 385 colon cancer samples from The Cancer Genome Atlas (TCGA) database using the ESTIMATE algorithm. We identified nine TME-related prognostic genes using Cox regression analysis. We evaluated associations between protein expression, extent of immune cell infiltrate, and patient survival. We calculated risk scores and built a clinical predictive model for the TME-related gene signature. Receiver operating characteristic (ROC) curves were generated to assess the predictive power of the signature. We estimated the half-maximal inhibitory concentration (IC50) of chemotherapeutic drugs in patients using the pRRophetic algorithm. The expression of immune checkpoint genes was evaluated. RESULTS: High immune and stromal scores are significantly associated with poor overall survival (p < 0.05). We identified 773 differential TME-related prognostic genes associated with survival; these genes were enriched in immune-related pathways. Nine key prognostic genes were identified and were used to construct a TME-related prognostic signature: CADM3, LEP, CD1B, PDE1B, CCL22, ABI3BP, IGLON5, SELE, and TGFB1. This signature identified a high-risk group with worse survival outcomes, based on Kaplan-Meier analysis. A nomogram composed of clinicopathological factors and risk score exhibited good accuracy. Drug sensitivity analysis identified no difference in sensitivity between the high-risk and low-risk groups. High-risk patients had higher expression of PD-1, PDL-1, and CTLA-4 and lower expression of LAG-3 and VSIR. Infiltration of dendritic cells was higher in the high-risk group. CONCLUSIONS: We identified a novel prognostic TME-related gene expression signature in colon cancer. Stratification of patients based on this gene signature could be used to improve outcomes and guide better therapy for colon cancer patients.

Identification of Ferroptosis-Related Long Noncoding RNA and Construction of a Novel Prognostic Signature for Gastric Cancer.

BACKGROUND: Gastric cancer is the most common malignant tumor of the digestive system. It has a poor prognosis and is clinically challenging to treat. Ferroptosis is a newly defined mode of programmed cell death. The roles and prognostic value of ferroptosis-related long noncoding RNAs (lncRNAs) in gastric cancer remain unknown. RESULTS: In the current study, 20 ferroptosis-related lncRNAs were identified via univariate Cox analysis, least absolute shrinkage, and selection operator Cox regression analysis and used to construct a prognostic signature and classify gastric cancer patients into high-risk and low-risk groups. The signature was validated using TCGA training and testing cohorts. The risk signature was an independent prognostic indicator of survival and accurately predicted the prognoses of patients with gastric cancer. It was also associated with immune cell infiltration. Gene set enrichment analysis was used to investigate underlying mechanisms that the 20 ferroptosis-related lncRNAs were involved in. Chemosensitivity and immune checkpoint inhibitor analyses indicated that high-risk patients were more sensitive to the immune checkpoint inhibitor programmed cell death protein 1. CONCLUSIONS: The important role of ferroptosis-related lncRNAs in immune infiltration identified in the current study may assist the determination of personalized prognoses and treatments in patients with gastric cancer. These 20 lncRNAs can be used as the diagnostic and prognostic markers for gastric cancer.