Novel defined N7-methylguanosine modification-related lncRNAs for predicting the prognosis of laryngeal squamous cell carcinoma

Objective:Through integrated bioinformatics analysis,the goal of this work was to find new,characterised N7-methylguanosine modification-related long non-coding RNAs(m7G-lncRNAs)that might be used to predict the prognosis of laryngeal squamous cell carcinoma(LSCC).Methods:The clinical data and LSCC gene expression data for the current investigation were initially retrieved from the TCGA database&sanitised.Then,using co-expression analysis of m7G-associated mRNAs&lncRNAs&differential expression analysis(DEA)among LSCC&normal sample categories,we discovered lncRNAs that were connected to m7G.The prognosis prediction model was built for the training category using univariate&multivariate COX regression&LASSO regression analyses,&the model’s efficacy was checked against the test category data.In addition,we conducted DEA of prognostic m7G-lncRNAs among LSCC&normal sample categories&compiled a list of co-expression networks&the structure of prognosis m7G-lncRNAs.To compare the prognoses for individuals with LSCC in the high-&low-risk categories in the prognosis prediction model,survival and risk assessments were also carried out.Finally,we created a nomogram to accurately forecast the outcomes of LSCC patients&created receiver operating characteristic(ROC)curves to assess the prognosis prediction model’s predictive capability.Results:Using co-expression network analysis&differential expression analysis,we discovered 774 m7G-lncRNAs and 551 DEm7G-lncRNAs,respectively.We then constructed a prognosis prediction model for six m7G-lncRNAs(FLG−AS1,RHOA−IT1,AC020913.3,AC027307.2,AC010973.2 and AC010789.1),identified 32 DEPm7G-lncRNAs,analyzed the correlation between 32 DEPm7G-lncRNAs and 13 DEPm7G-mRNAs,and performed survival analyses and risk analyses of the prognosis prediction model to assess the prognostic performance of LSCC patients.By displaying ROC curves and a nomogram,we finally checked the prognosis prediction model's accuracy.Conclusion:By creating novel predictive lncRNA signatures for clinical diagnosis&therapy,our findings will contribute to understanding the pathogenetic process of LSCC.

Long non-coding RNA GATA6-AS1 is mediated by N6-methyladenosine methylation and inhibits the proliferation and metastasis of gastric cancer

BACKGROUND Through experimental research on the biological function of GATA6-AS1,it was confirmed that GATA6-AS1 can inhibit the proliferation,invasion,and migration of gastric cancer cells,suggesting that GATA6-AS1 plays a role as an anti-oncogene in the occurrence and development of gastric cancer.Further experi-ments confirmed that the overexpression of fat mass and obesity-associated protein(FTO)inhibited the expression of GATA6-AS1,thereby promoting the occurrence and development of gastric cancer.AIM To investigate the effects of GATA6-AS1 on the proliferation,invasion and migration of gastric cancer cells and its mechanism of action.METHODS We used bioinformatics methods to analyze the Cancer Genome Atlas(https://portal.gdc.cancer.gov/.The Cancer Genome Atlas)and download expression data for GATA6-AS1 in gastric cancer tissue and normal tissue.We also constructed a GATA6-AS1 lentivirus overexpression vector which was transfected into gastric cancer cells to investigate its effects on proliferation,migration and invasion,and thereby clarify the expression of GATA6-AS1 in gastric cancer and its biological role in the genesis and development of gastric cancer.Next,we used a database(http://starbase.sysu.edu.cn/starbase2/)to analysis GATA6-AS1 whether by m6A methylation modify regulation and predict the methyltransferases that may methylate GATA6-AS1.Furthermore,RNA immunoprecipitation experiments confirmed that GATA6-AS1 was able to bind to the m6A methylation modification enzyme.These data allowed us to clarify the ability of m6A methylase to influence the action of GATA6-AS1 and its role in the occurrence and development of gastric cancer.RESULTS Low expression levels of GATA6-AS1 were detected in gastric cancer.We also determined the effects of GATA6-AS1 overexpression on the biological function of gastric cancer cells.GATA6-AS1 had strong binding ability with the m6A demethylase FTO,which was expressed at high levels in gastric cancer and negatively correlated with the expression of GATA6-AS1.Following transfection with siRNA to knock down the expression of FTO,the expression levels of GATA6-AS1 were up-regulated.Finally,the proliferation,migration and invasion of gastric cancer cells were all inhibited following the knockdown of FTO expression.CONCLUSION During the occurrence and development of gastric cancer,the overexpression of FTO may inhibit the expression of GATA6-AS1,thus promoting the proliferation and metastasis of gastric cancer.

Learning Sequential and Structural Dependencies Between Nucleotides for RNA N6-Methyladenosine Site Identification

N6-methyladenosine(m6A)is an important RNA methylation modification involved in regulating diverse biological processes across multiple species.Hence,the identification of m6A modification sites provides valuable insight into the biological mechanisms of complex diseases at the post-transcriptional level.Although a variety of identification algorithms have been proposed recently,most of them capture the features of m6A modification sites by focusing on the sequential dependencies of nucleotides at different positions in RNA sequences,while ignoring the structural dependencies of nucleotides in their threedimensional structures.To overcome this issue,we propose a cross-species end-to-end deep learning model,namely CR-NSSD,which conduct a cross-domain representation learning process integrating nucleotide structural and sequential dependencies for RNA m6A site identification.Specifically,CR-NSSD first obtains the pre-coded representations of RNA sequences by incorporating the position information into single-nucleotide states with chaos game representation theory.It then constructs a crossdomain reconstruction encoder to learn the sequential and structural dependencies between nucleotides.By minimizing the reconstruction and binary cross-entropy losses,CR-NSSD is trained to complete the task of m6A site identification.Extensive experiments have demonstrated the promising performance of CR-NSSD by comparing it with several state-of-the-art m6A identification algorithms.Moreover,the results of cross-species prediction indicate that the integration of sequential and structural dependencies allows CR-NSSD to capture general features of m6A modification sites among different species,thus improving the accuracy of cross-species identification.

External-Strain-Induced Raman Scattering Modification in g-C3N4 Structures

Regulation of optical properties and electronic structure of graphitic carbon nitride （g-C3N4 ） via external strain has attracted much attention due to its potential in photocatalyst and electronic devices. However, the identifi- cation of g-C3N4 structure transformation induced by strain is greatly lacking. In this work, the Raman spectra of g-C3N4 with external strain are determined theoretically based on the density function theory. Deformation induced by external strain not only regulates the Raman mode positions but also leads to a I^aman mode split- ting, which can be ascribed to crystal symmetry destruction by strain engineering. Our results suggest the use of Raman scattering in structural identification in deformed 9-C3N4 structure.

Nanodrug enhances post-ablation immunotherapy of hepatocellular carcinoma via promoting dendritic cell maturation and antigen presentation

Thermal ablation(TA)as an effective method treating hepatocellular carcinoma(HCC)in clinics is facing great challenges of high recurrence and metastasis.Although immune-checkpoint blockade(ICB)-based immuno-therapy has shown potential to inhibit recurrence and metastasis,the combination strategy of ICB and thermal ablation has shown little progress in HCC treatments.The tremendous hurdle for combining ICB with thermal ablation lies with the insufficient antigen internalization and immaturity of tumor-infiltrating dendritic cells(TIDCs)which leads to an inferior immune response to distant tumor growth and metastasis.Herein,an antigen-capturing nanoplatform,whose surface was modified with mannose as a targeting ligand,was constructed for co-delivering tumor-associated antigens(TAAs)and m6A demethylases inhibitor(i.e.,fat mass and obesity asso-ciated gene(FTO)inhibitor)into TIDCs.In vivo results demonstrate that the intratumoral injection of nanodrug followed by HCC thermal ablation promotes dendritic cells(DCs)maturation,improves tumor infiltration of effector T cells and generates immune memory,which synergize with ICB treatment to inhibit the distant tumor growth and lung metastasis.Therefore,the antigen-capturing and FTO-inhibiting nanodrug holds potential to boost the ICB-based immunotherapy against HCC after thermal ablation.

N6-methyladenosine modified LINC00901 promotes pancreatic cancer progression through IGF2BP2/MYC axis

Accumulating evidence indicates that RNA methylation at N6-methyladenosine(m6A)plays an important regulatory role in gene expression and aberrant mRNA m6A modification is often associated with a variety of cancers.However,little is known whether and how m6A-modification impacts long non-coding RNA(lncRNA)and lncRNA-mediated tumorigenesis,particularly in pancreatic ductal adenocarcinoma(PDAC).In the present study,we report that a previously uncharacterized lncRNA,LINC00901,promotes pancreatic cancer cell growth and invasion and moreover,LINC00901 is subject to m6A modification which regulates its expression.In this regard,YTHDF1 serves as a reader for the m6A modified LINC00901 and downregulates the LINC00901 level.Notably,two conserved m6A sites in LINC00901 are critical to the recognition of LINC00901 by YTHDF1.Finally,RNA sequencing(RNA-seq)and gene function analysis revealed that LINC00901 positively regulates MYC through upregulation of IGF2BP2,a known RNA binding protein that can enhance MYC mRNA stability.Together,our results suggest that there is a LINC00901-IGF2BP2-MYC axis through which LINC00901 promotes PDAC progression in an m6A dependent manner.

Lingguizhugan Decoction, a Chinese herbal formula, improves insulin resistance in overweight/obese subjects with non-alcoholic fatty liver disease: a translational approach

Lingguizhugan Decoction(LGZG)has been investigated in basic studies,with satisfactory effects on insulin resistance in non-alcoholic fatty liver disease(NAFLD).This translational approach aimed to explore the effect and underlying mechanism of LGZG in clinical setting.A randomized,double-blinded,placebo-controlled trial was performed.A total of 243 eligible participants with NAFLD were equally allocated to receive LGZG(two groups:standard dose and low dose)or placebo for 12 weeks on the basis of lifestyle modifications.The primary efficacy variable was homeostasis model assessment of insulin resistance(HOMA-IR).Analyses were performed in two populations in accordance with body mass index(BMI;overweight/obese,BMI 24 kg/m^(2);lean,BMI<24 kg/m^(2)).For overweight/obese participants,low-dose LGZG significantly decreased their HOMA-IR level compared with placebo(0.19(1.47)versus 0.08(1.99),P=0.038).For lean subjects,neither dose of LGZG showed a superior effect compared with placebo.Methylated DNA immunoprecipitation sequencing and real-time qPCR found that the DNA N6-methyladenine modification levels of protein phosphatase 1 regulatory subunit 3A(PPP1R3A)and autophagy related 3(ATG3)significantly increased after LGZG intervention in overweight/obese population.Low-dose LGZG effectively improved insulin resistance in overweight/obese subjects with NAFLD.The underlying mechanism may be related to the regulation of DNA N6-methyladenine modification of PPP1R3A and ATG3.Lean subjects may not be a targeted population for LGZG.

Highly enhanced visible-light photocatalytic NOx purification and conversion pathway on self-structurally modified g-C-3N4 nanosheets

The unmodified graphitic carbon nitride(g-C_3N_4) suffers from low photocatalytic activity because of the unfavourable structure.In the present work,we reported a simple self-structural modification strategy to optimize the microstructure of g-C_3N_4 and obtained graphene-like g-C_3N_4 nanosheets with porous structure.In contrast to traditional thermal pyrolysis preparation of g-C_3N_4,the present thermal condensation was improved via pyrolysis of thiourea in an alumina crucible without a cover,followed by secondary heat treatment.The popcorn-like formation and layer-by-layer thermal exfoliation of graphene-like porous g-C_3N_4 was proposed to explain the formation mechanism.The photocatalytic removal performance of both NO and NO_2 with the graphene-like porous g-C_3N_4 for was significantly enhanced by selfstructural modification.Trapping experiments and in-situ diffuse reflectance infrared fourier transform spectroscopy(DRIFTS) measurement were conducted to detect the active species during photocatalysis and the conversion pathway of g-C_3N_4 photocatalysis for NO_x purification was revealed.The photocatalytic activity of graphene-like porous g-C_3N_4 was highly enhanced due to the improved charge separation and increased oxidation capacity of the ·O_2^- radicals and holes.This work could not only provide a novel self-structural modification for design of highly efficient photocatalysts,but also offer new insights into the mechanistic understanding of g-C_3N_4 photocatalysis.