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Abstract RNA N6-methyladenosine (m6A) regulators play essential roles in diverse biological processes, including immune responses. Mounting evidence suggests that their dysregulation is intricately linked to numerous diseases. However, the role of m6A-associated genes in carotid atherosclerosis and their relationship with aging and immune cells remain unclear. Analyze the expression profiles of m6A-related genes in carotid atherosclerosis-related datasets. Based on the expression patterns of m6A-related genes, perform consistent clustering analysis of carotid atherosclerosis samples and investigate associated immune cell infiltration patterns and aging characteristics. Develop an m6A prediction model specific to carotid atherosclerosis and analyze the relationships between immune cells infiltration and aging features. The m6A methylation modification level exhibited a substantial decrease in early-stage carotid atherosclerosis samples compared to late-stage carotid atherosclerosis samples. Subsequently, two distinct m6A subtypes were defined through consensus clustering analysis, with the lower m6A modification level group showing associations with heightened immune cell infiltration and increased expression of aging-related genes. A model composed of five m6A-related genes was formulated, and the results indicated that this model possesses effective predictive and therapeutic capabilities for carotid atherosclerosis. Furthermore, the downregulation of YTHDC1 expression resulted in elevated expression of inflammatory factors and a decrease in the expression of the aging-related gene RGN. Single-cell data analysis suggests that the reduced expression of YTHDC1 may decrease the degradation of inflammation-related factors in macrophages, leading to a highly inflammatory state in the carotid artery wall. Furthermore, the sustained release of inflammatory factors may increase the expression of the aging-related gene RGN in vascular smooth muscle cells, further exacerbating the progression of atherosclerosis. A reduced level of m6A methylation modification could enhance inflammation and expedite cellular aging, thereby contributing to the development of carotid atherosclerosis.

Object detection in drone-captured scenarios is a recent popular task. Due to the high flight altitude of unmanned aerial vehicle (UAV), the large variation of target scales, and the existence of dense occlusion of targets, in addition to the high requirements for real-time detection. To solve the above problems, we propose a real-time UAV small target detection algorithm based on improved ASFF-YOLOv5s. Based on the original YOLOv5s algorithm, the new shallow feature map is passed into the feature fusion network through multi-scale feature fusion to improve the extraction capability for small target features, and the Adaptively Spatial Feature Fusion (ASFF) is improved to improve the multi-scale information fusion capability. To obtain anchor frames for the VisDrone2021 dataset, we improve the K-means algorithm to obtain four different scales of anchor frames on each prediction layer. The Convolutional Block Attention Module (CBAM) is added in front of the backbone network and each prediction network layer to improve the capture capability of important features and suppress redundant features. Finally, to address the shortcomings of the original GIoU loss function, the SIoU loss function is used to accelerate the convergence of the model and improve accuracy. Extensive experiments conducted on the dataset VisDrone2021 show that the proposed model can detect a wide range of small targets in various challenging environments. At a detection rate of 70.4 FPS, the proposed model obtained a precision value of 32.55%, F1-score of 39.62%, and a mAP value of 38.03%, which improved 2.77, 3.98, and 5.1%, respectively, compared with the original algorithm, for the detection performance of small targets and to meet the task of real-time detection of UAV aerial images. The current work provides an effective method for real-time detection of small targets in UAV aerial photography in complex scenes, and can be extended to detect pedestrians, cars, etc. in urban security surveillance.

Ovarian cancer (OV) is characterized by high incidence and poor prognosis. Increasing evidence indicates that aberrant alternative splicing (AS) events are associated with the pathogenesis of cancer. We examined prognosis-related alternative splicing events and constructed a clinically applicable model to predict patients’ outcomes. Public database including The Cancer Genome Atlas (TCGA), TCGA SpliceSeq, and the Genomics of Drug Sensitivity in Cancer databases were used to detect the AS expression, immune cell infiltration and IC50. The prognosis-related AS model was constructed and validated by using Cox regression, LASSO regression, C-index, calibration plots, and ROC curves. A total of eight AS events (including FLT3LG|50942|AP) were selected to establish the prognosis-related AS model. Compared with high-risk group, low-risk group had a better outcome (P = 1.794e-06), was more sensitive to paclitaxel (P = 0.022), and higher proportions of plasma cells. We explored the upstream regulatory mechanisms of prognosis-related AS and found that two splicing factor and 156 tag single nucleotide polymorphisms may be involved in the regulation of prognosis-related AS. In order to assess patient prognosis more comprehensively, we constructed a clinically applicable model combining risk score and clinicopathological features, and the 1 -, and 3-year AUCs of the clinically applicable model were 0.812, and 0.726, which were 7.5% and 3.3% higher than that of the risk score. We constructed a prognostic signature for OV patients and comprehensively analysed the regulatory characteristics of the prognostic AS events in OV.

Abstract Continuing studies imply that m6A RNA modification is involved in the development of cervical cancer (CC), but lack strong support on recurrence and diagnosis prediction. In this research, a comprehensive analysis of 33 m6A regulators was performed to fulfill them. Here, we performed diagnostic and prognosis models and identified key regulators, respectively. Then the CC patients were separated into two clusters in accordance with 33 regulators, and participants in the cluster 1 had a worse prognosis. Subsequently, the m6AScore was calculated to quantify the m6A modification pattern based on regulators and we found that patients in cluster 1 had higher m6AScore. Afterwards, immune microenvironment, cell infiltration, escape analyses and tumor burden mutation analyses were executed, and results showed that m6AScore was correlated with them, but to a limited extent. Interestingly, HLAs and immune checkpoint expression, and immunophenoscore in patients with high-m6AScores were significantly lower than those in the low-m6AScore group. These suggested the m6AScores might be used to predict the feasibility of immunotherapy in patients. Results provided a distinctive perspective on m6A modification and theoretical basis for CC diagnosis, prognosis, clinical treatment strategies, and potential mechanism exploration.

Objectives The abnormal expression of immune-related genes (IRGs) plays an important role in the occurrence and progression of ovarian cancer (OC), which is the main cause of mortality among gynecological cancer patients. This study aims to establish a prognostic risk model and comprehensively analyze the relationship between OC risk score and prognosis, immune cell infiltration (ICI) and therapeutic sensitivity in OC. Methods We retrospectively evaluated the clinicopathological characteristics of consecutive OC patients in the Cancer Genome Atlas (TCGA) database. First, the prognostic risk model was constructed by bioinformatics methods. And then, we systematically assessed model robustness, and correlations between risk score and prognosis, and immune cell infiltration. The ICGC cohort was used to verify the prognostic risk model. Finally, we evaluated their value in the treatment of OC immunotherapy and chemotherapy. Results A total of 10 IRGs were identified to construct the prognostic risk model. Survival analysis revealed that patients in the low-risk group had a better prognosis ( P < .01), and the risk score might be considered an independent predictor for predicting the prognosis. In addition, risk scores and patient clinical information were used to construct clinical nomograms, improving the prediction’s precision. We also explored the relationship between the risk score and ICI, immunotherapy and drug sensitivity. Conclusions Collectively, we identified a novel ten IRGs signature that may be applied as a prognostic predictor of OC, thereby benefiting clinical decision-making and personalized treatment of patients.

Abstract Objective The aim of this study was to explore expression profiles of long noncoding RNA (lncRNA)‐messenger RNA (mRNA) in abdominal aortic aneurysm (AAA) patients. Further, we explored the mechanisms by which lncRNA SNHG5 modulates the function of vascular smooth muscle cells (VSMC) in AAA. Methods Human gene expression profile GSE57691 dataset, was retrieved from Gene Expression Omnibus database. The dataset included gene expression array data of 49 AAA patients and 10 control aortic specimens from organ donors. To explore the main roles of the biological network, differentially expressed lncRNA and mRNAs in the aortic aneurysm (AAA) and normal aortic specimens were determined. Differentially expressed lncRNA and mRNAs were then used to construct a competing endogenous RNA (ceRNA) network using Cytoscape software, and the five key lncRNA were identified. SNHG5 which was significantly downregulated in the AAA was chosen and analysis showed that it regulates mir‐205‐5p and SMAD4 by binding to mir‐205‐5p. Double luciferase reporter gene assays, RNA immunoprecipitation, and RNA knockdown studies were used to establish the relationship between SNHG5 and mir‐205‐5p. Apoptosis rate was determined using flow cytometry, whereas cell proliferation was evaluated using Edu, and 24 well Transwell assay. Western blot analysis was used to determine protein expression levels. Results The five differentially expressed lncRNAs were significantly correlated with 34 microRNAs and 112 mRNAs. mRNAs in the ceRNA network are implicated in protein binding, signal transduction, DNA and RNA transcription, development, and cell differentiation. SNHG5 was downregulated in the AAA and acts as a molecular sponge for mir‐205. Downregulation of SNHG5 induces expression of mir‐205‐5p. Increased mir‐205‐5p expression level inhibits SMAD4 production, thus inhibiting proliferation and migration and promotes apoptosis of smooth muscle cells. Conclusion Bioinformatics were used to explore molecular mechanism of AAA progression. The findings of this study show that lncRNA SNHG5 regulates proliferation and apoptosis of VSMC cells through modulation of the mir‐205‐5p/SMAD4 axis. Therefore, SNHG5 is a potential therapeutic target for AAA disease.

Esophageal squamous cell carcinoma (ESCC) is an environment-relevant malignancy with a high mortality. Nitrosamines, a class of nitrogen-containing environmental carcinogens, are widely suggested as a risk factor for ESCC. However, how nitrosamines affect metabolic regulation to promote ESCC tumorigenesis is largely unknown. In this study, the transition trajectory of serum metabolism in the course of ESCC induced by N-nitrosomethylbenzylamine (NMBA) in rats was depicted by an untargeted metabolomic analysis, and the potential molecular mechanisms were revealed. The results showed that the metabolic alteration in rats was slight at the basal cell hyperplasia (BCH) stage, while it became apparent when the esophageal lesion developed into dysplasia (DYS) or more serious conditions. Moreover, serum metabolism of severe dysplasia (S-DYS) showed more similar characteristics to that of carcinoma in situ (CIS) and invasive cancer (IC). Aberrant nicotinate (NA) and nicotinamide (NAM) metabolism, tryptophan (TRP) metabolism, and sphingolipid metabolism could be the key players favoring the malignant transformation of esophageal epithelium induced by NMBA. More particularly, NA and NAM metabolism in the precancerous stages and TRP metabolism in the cancerous stages were demonstrated to replenish NAD+ in different patterns. Furthermore, both the IDO1-KYN-AHR axis mediated by TRP metabolism and the SPHK1-S1P-S1PR1 axis by sphingolipid metabolism provided an impetus to create the pro-inflammatory yet immune-suppressive microenvironment to facilitate the esophageal tumorigenesis and progression. Together, these suggested that NMBA exerted its carcinogenicity via more than one pathway, which may act together to produce combination effects. Targeting these pathways may open up the possibility to attenuate NMBA-induced esophageal carcinogenesis. However, the interconnection between different metabolic pathways needs to be specified further. And the integrative and multi-level systematic research will be conducive to fully understanding the mechanisms of NMBA-induced ESCC.

Abstract Background Association mapping studies of quantitative trait loci (QTL) for canine hip dysplasia (CHD) can contribute to the understanding of the genetic background of this common and debilitating disease and might contribute to its genetic improvement. The power of association studies for CHD is limited by relatively small sample numbers for CHD records within countries, suggesting potential benefits of joining data across countries. However, this is complicated due to the use of different scoring systems across countries. In this study, we incorporated routinely assessed CHD records and genotype data of German Shepherd dogs from two countries (UK and Sweden) to perform genome-wide association studies (GWAS) within populations using different variations of CHD phenotypes. As phenotypes, dogs were either classified into cases and controls based on the Fédération Cynologique Internationale (FCI) five-level grading of the worst hip or the FCI grade was treated as an ordinal trait. In a subsequent meta-analysis, we added publicly available data from a Finnish population and performed the GWAS across all populations. Genetic associations for the CHD phenotypes were evaluated in a linear mixed model using 62,089 SNPs. Results Multiple SNPs with genome-wide significant and suggestive associations were detected in single-population GWAS and the meta-analysis. Few of these SNPs overlapped between populations or between single-population GWAS and the meta-analysis, suggesting that many CHD-related QTL are population-specific. More significant or suggestive SNPs were identified when FCI grades were used as phenotypes in comparison to the case-control approach. MED13 (Chr 9) and PLEKHA7 (Chr 21) emerged as novel positional candidate genes associated with hip dysplasia. Conclusions Our findings confirm the complex genetic nature of hip dysplasia in dogs, with multiple loci associated with the trait, most of which are population-specific. Routinely assessed CHD information collected across countries provide an opportunity to increase sample sizes and statistical power for association studies. While the lack of standardisation of CHD assessment schemes across countries poses a challenge, we showed that conversion of traits can be utilised to overcome this obstacle.

Abstract Background To rummage autophagy-related prognostic, diagnostic, and therapeutic biomarkers in cervical cancer (CC). Methods The RNA-sequence and clinical information were from the TCGA and GTEx databases. We operated Cox regression to determine signatures related to overall survival (OS) and recurrence-free survival (RFS) respectively. The diagnostic and therapeutic effectiveness of prognostic biomarkers were further explored. Results We identified nine (VAMP7, MTMR14, ATG4D, KLHL24, TP73, NAMPT, CD46, HGS, ATG4C) and three risk signatures (SERPINA1, HSPB8, SUPT20H) with prognostic values for OS and RFS respectively. Six risk signatures (ATG4C, ATG4D, CD46, TP73, SERPINA1, HSPB8) were selected for qPCR. We screened five prognostic signatures(ATG4C, CD46, HSPB8, MTMR14, NAMPT) with diagnostic function through the GEO database. Correlation between our models and treatment targets certificated the prognostic score provided a reference for precision medicine. Conclusions We constructed OS and RFS prognostic models in CC. Autophagy-related risk signatures might serve as diagnostic and therapeutic biomarkers.

Health risks caused by crucial environmental carcinogens N-nitrosamines triggered ubiquitous attention. As the liver exerted vital function through metabolic process, lipid metabolism disorders have been confirmed as potential drivers for toxicological effects, and the mechanisms of lipid regulation related to hepatotoxicity induced by N-nitrosamines remained largely unclear. In this study, we comprehensively explored the disturbance of hepatic lipid homeostasis in mice induced by nitrosamines. The results implied that nitrosamines exposure induced hepatotoxicity accompanied by liver injury, inflammatory infiltration, and hepatic edema. Lipidomics profiling analysis indicated the decreased levels of phosphatidic acids (PA), phosphatidylcholines (PC), phosphatidylethanolamines (PE), lyso-phosphatidylcholines (LPC), lyso-phosphatidylethanolamines (LPE), diacylglycerols (DAG) and triacylglycerols (TAG), the elevation of ceramides (Cer) and decomposition of free fatty acids (FFA) in high-dose nitrosamines exposure group. Importantly, nitrosamines exposure promoted fatty acid oxidation (FAO) by facilitating fatty acid uptake and decomposition, together with the upregulation of genes associated with FAO accompanied by the activation of inflammatory cytokines TNF-α, IL-1β and NLRP3. Furthermore, fatty acid translocase CD36-mediated fatty acid oxidation was correlated with the enhancement of oxidative stress in the liver caused by nitrosamines exposure. Overall, our results contributed to the new strategies to interpret the early toxic effects of nitrosamines exposure.

Abstract Objective To screen for immune genes that play a major role in Kawasaki disease and to investigate the pathogenesis of Kawasaki disease through bioinformatics analysis. Methods Kawasaki disease‐related datasets GSE18606, GSE68004, and GSE73461 were downloaded from the Gene Expression Omnibus database. Three microarrays were integrated and standardized to include 173 Kawasaki disease samples and 101 normal samples. The samples were analyzed using CIBERSORT to obtain the infiltration of 22 immune cells and analyze the differential immune cells in the samples and correlations. The distribution of the samples was analyzed using principal component analysis (PCA). Immune‐related genes were downloaded, extracted from the screened samples and analyzed for differential analysis (different expression genes [DEG]) and weighted gene co‐expression network analysis (WGCNA). We constructed coexpression networks, and used the cytohobbe tool in Cytoscape to analyze the coexpression networks and select the immune genes that played a key role in them. Results Immune cell infiltration analysis showed that B cells naive, T cells CD8, natural killer (NK) cells activated, and so forth were highly expressed in normal samples. T cells CD4 memory activated, monocytes, neutrophils, and so forth were highly expressed in Kawasaki disease samples. PCA results showed a significant difference in the distribution of normal and Kawasaki disease samples. From the screened samples, 97 upregulated and 103 downregulated immune‐related genes were extracted. WGCNA analysis of DEG yielded 10 gene modules, of which the three most relevant to Kawasaki disease were red, yellow, and gray modules. They were associated with cytokine regulation, T‐cell activation, presentation of T‐cell receptor signaling pathways, and NK cell‐mediated cytotoxicity. CXCL8, CCL5, CCR7, CXCR3, and CCR1 were identified as key genes by constructing a coexpression network. Conclusion Our study shows that we can distinguish normal samples from Kawasaki disease samples based on the infiltration of immune cells, and that CXCL8, CCL5, CCR7, CXCR3, and CCR1 may play important roles in the development of Kawasaki disease.

BackgroundPrimary tumor of the inferior vena cava is a rare tumor, which arises from the smooth muscle of vascular walls. Surgery appears the only curative treatment. However, the optimal surgical methods and surgical management are not well-studied. In this article, we reviewed the successful treatment experience of patients in our center who had resection of primary tumor of the inferior vena cava and reviewed the relevant literature.MethodsFour cases of patients who undergoing initial resection of primary tumors of the inferior vena cava from September 2017 to August 2021 in the Second Affiliated Hospital of Nanchang University were screened and followed up. They were discussed and cases reported in this field were reviewed.ResultsAmong the four patients, three of them were female. The median age of the disease is 53.75 years (range 45–60 years). After surgical treatment, tumors were removed in all patients, and some patients had reconstruction of inferior vena cava. There were no disease-specific deaths, no serious complications, and no recurrence during follow-up in these cases.ConclusionsCareful preoperative examination, correct surgical treatment methods, and multidisciplinary collaboration can lead to safe and successful operations, which improve the survival rate of patients.

Ovarian cancer (OC), one of the most common malignancies of the female reproductive system, is characterized by high incidence and poor prognosis. Tumor mutation burden (TMB), as an important biomarker that can represent the degree of tumor mutation, is emerging as a key indicator for predicting the efficacy of tumor immunotherapy. In our study, the gene expression profiles of OC were downloaded from TCGA and GEO databases. Subsequently, we analyzed the prognostic value of TMB in OC and found that a higher TMB score was significantly associated with a better prognosis (p = 0.004). According to the median score of TMB, 9 key TMB related immune prognostic genes were selected by LASSO regression for constructing a TMB associated immune risk score (TMB-IRS) signature, which can effectively predict the prognosis of OC patients (HR = 2.32, 95% CI = 1.68–3.32; AUC = 0.754). Interestingly, TMB-IRS is also closely related to the level of immune cell infiltration and immune checkpoint molecules (PD1, PD-L1, CTLA4, PD-L2) in OC. Furthermore, the nomogram combined with TMB-IRS and a variety of clinicopathological features can more comprehensively evaluate the prognosis of patients. In conclusion, we explored the relationship between TMB and prognosis and validated the TMB-IRS signature based on TMB score in an independent database (HR = 1.60, 95% CI = 1.13–2.27; AUC = 0.639), which may serve as a novel biomarker for predicting OC prognosis as well as possible therapeutic targets.

Fanconi anemia (FA) pathway is a typical and multienzyme-regulated DNA damage repairer that influences the occurrence and development of disease including cancers. Few comprehensive analyses were reported about the role of FA-related genes (FARGs) and their prognostic values in cancers. In this study, a comprehensive pan-cancer analysis on 79 FARGs was performed. According to the correlation analyses between HPV integration sites and FARGs, we found that FARGs played specific and critical roles in HPV-related cancers, especially in cervical cancer (CC). Based on this, a FARGs-associated prognostic risk score (FPS) model was constructed, and subsequently a nomogram model containing the FPS was developed with a good accuracy for CC overall survival (OS) and recurrence-free survival (RFS) outcome prediction. We also used the similar expression pattern of FARGs by consensus clustering analysis to separate the patients into three subgroups that exhibited significant differential OS but not RFS. Moreover, differential expressed genes (DEGs) between the two risk groups or three clusters were identified and immune pathways as well as cell adhesion processes were determined by functional enrichment analysis. Results indicated that FARGs might promote occurrence and development of CC by regulating the immune cells’ infiltration and cell adhesion. In addition, through the machine learning models containing decision tree, random forest, naïve bayes, and support vector machine models, screening of important variables on CC prognosis, we finally determined that ZBTB32 and CENPS were the main elements affecting CC OS, while PALB2 and BRCA2 were for RFS. Kaplan-Meier analysis revealed that bivariate prediction of CC outcome was reliable. Our study systematically analyzed the prognostic prediction values of FARGs and demonstrated their potential mechanism in CC aggressiveness. Results provided perspective in FA pathway-associated modification and theoretical basis for CC clinical treatments.

Background Abdominal aortic aneurysm (AAA) is a complex vascular disease involving expansion of the abdominal aorta. Extracellular matrix (ECM) degradation is crucial to AAA pathogenesis, however, the specific molecular mechanism remains unclear. This study aimed to investigate differentially expressed circular RNAs (DEcircRNAs) involved in ECM degradation of AAA. Methods Transcriptome sequencing was used to analyze the DEcircRNAs between the AAA tissues and normal tissues. The expression of circRNAs in tissues and cells was validated using quantitative reverse transcription PCR (RT-qPCR). Overexpression of circRNAs in vascular smooth muscle cells (VSMCs) treated with angiotensin II (Ang II) was employed to explore its effect on ECM degradation of AAA. Bioinformatic technology, luciferase reporter gene assay, RT-qPCR, and rescue experiment were employed to evaluate the regulatory mechanism of circRNA. Results We identified 65 DEcircRNAs in AAA tissues compared with normal abdominal aortic tissues, including 30 up-regulated and 35 down-regulated circRNAs, which were mainly involved in inflammation and ECM-related functions and pathways. Moreover, circRBM33 was significantly increased in AAA tissues and Ang II-induced VSMCs compared with control samples. Overexpression of circRBM33 increased the expression of ECM-related molecule matrix metalloproteinase-2 and reduced the tissue inhibitor of matrix metalloproteinases-1 expression. Mechanistically, miR-4268 targeted binding to circRBM33 and inhibited the luciferase activity of circRBM33. Overexpression of circRBM33 induced the expression of EPH receptor B2 (EPHB2), and this effect was countered by miR-4268 mimics. Conclusions Overall, our data suggest that circRBM33 might be involved in AAA progression by regulating ECM degradation via the miR-4268/EPHB2 axis.

Copper (Cu) pollution in water and agricultural soil has always been a worldwide concern. This research aims to investigate the health effects of copper exposure on Caenorhabditis elegans (C. elegans) under the existing environmental quality standards (1 mg/L and 2 mg/L) via lifespan, reproduction, biological markers and transcriptome analysis. The results showed that copper of these two environmental standards shorten the lifespan of nematodes, reduced the brood size, reduced the frequency of pharyngeal pumps and prolonged defecation time as aging-related behaviors, and increased the levels of aging-related markers ROS, MDA and H2O2. There was a certain effect trend for the two exposure concentrations. Further, the possible molecular mechanism of copper-induced aging and reproductive effects on C. elegans was explored. Differential gene expression analysis was performed, and 2332 genes (567 up- and 1765 down-regulated genes) in the 1 mg/L group, 2449 DEGs (724 up- and 1725 down-regulated genes) in the 2 mg/L group in response to copper treatment. The top 20 regulated genes were vit (vit-1, vit-3, vit-4) genes, col genes (col-35, col-72, col-114, col-123, col-164, col-183, col-185), eea-1, him-18 and grl-20, which suggested that cuticle collagen synthesis and yolk expression were disrupted by copper. Analysis of KEGG pathway showed copper exposure widely affects longevity regulation pathways, thereby promoting aging. In summary, the sequencing results extensively and deeply reveal the health hazards of environmentally relevant doses of copper exposure to C. elegans, and behavioral testing verified that copper promoted aging of C. elegans.

Esophageal cancer (EC) is the seventh most common tumor in the world, ranking the sixth leading cause of cancer death, with a 5-year survival rate of 15-25%. Therefore, reliable prognostic biomarkers are needed to effectively predict the prognosis of EC. In this study, the gene profile information of the EC cohort served as a training set, which was derived from TCGA and Immport databases. GO and KEGG enrichment analysis was performed on the differential genes in normal and tumor groups of EC. The immune genes in differentially expressed genes (DEGs) were further obtained for univariate and multivariate Cox and Lasso regression analysis, and 6 independent immune genes (S100A3, STC2, HSPA6, CCL25, GPER1, and OSM) associated with prognosis were obtained to establish an immune risk score signature (IRSS). The signature was validated using head and neck cancers (HNSC) and gastric cancer (GC)in upper gastrointestinal malignancies as validation sets. The Kaplan-Meier results showed that the prognosis of the high-risk group was significantly favorable than that of the low-risk group in both the training set (P < 0.001; HR = 3.68, 95% CI = 2.14−6.35) and the validation set (P = 0.010; HR = 1.43, 95% CI = 1.09−1.88). A nomogram combining multiple clinical information and IRSS was more effective than a single independent prognostic factor in predicting outcome. This study explored the potential link between immunity and EC, and established and validated prognostic biomarkers that can effectively predict the prognosis of EC, HNSC and GC based on six immune genes.

Angus cattle have made remarkable contributions to the livestock industry worldwide as a commercial meat-type breed. Some evidence supported that Angus cattle with different coat colors have different feed-to-meat ratios, and the genetic basis of their coat color is inconclusive. Here, genome-wide association study was performed to investigate the genetic divergence of black and red Angus cattle with 63 public genome sequencing data. General linear model analysis was used to identify genomic regions with potential candidate variant/genes that contribute to coat color and feed conversion rate. Results showed that six single nucleotide polymorphisms (SNPs) and two insertion–deletions, which were annotated in five genes (ZCCHC14, ANKRD11, FANCA, MC1R, and LOC532875 [AFG3-like protein 1]), considerably diverged between black and red Angus cattle. The strongest associated loci, namely, missense mutation CHIR18_14705671 (c.296T > C) and frameshift mutation CHIR18_12999497 (c.310G>-), were located in MC1R. Three consecutive strongly associated SNPs were also identified and located in FANCA, which is widely involved in the Fanconi anemia pathway. Several SNPs of highly associated SNPs was notably enriched in ZCCHC14 and ANKRD11, which are related to myofiber growth and muscle development. This study provides a basis for the use of potential genetic markers to be used in future breeding programs to improve cattle selection in terms of coat color and meat phenotype. This study is also helpful to understand the hereditary basis of different coat colors and meat phenotypes. However, the putative candidate genes or markers identified in this study require further investigation to confirm their phenotypic causality and potential effective genetic relationships.

The BVA/KC (British Veterinary Association/Kennel Club) and FCI (Fédération Cynologique Internationale) are the main screening schemes used to evaluate the status of canine hip dysplasia (HD) in Europe. Jointly utilizing HD records from both BVA/KC and FCI schemes could improve the reliability of genetic evaluation within and across countries. In this study, HD scores for German shepherd dogs (GSDs) in the UK (using the BVA/KC scheme) and Sweden (using the FCI scheme) were used to investigate how to better operate joint genetic evaluations across the two schemes. It was shown that under a bivariate model, which regarded BVA/KC and FCI scores as different traits, the estimated genetic correlations between the UK and Swedish GSD populations were the same when using BVA/KC total or worse hip scores and for single-country or joint analysis of both the UK and Swedish populations. Under a univariate model that converted BVA/KC scores into FCI scores, the predictability of estimated breeding values was slightly improved by performing a joint analysis.

Objective This study compared the meat quality, muscle fiber characteristics, and fatty acids between Jinjiang yellow cattle (JJ) and F1 Simmental×Jinjiang yellow cattle (SJ) which were offered the same diet. Methods Six JJ and six SJ individuals were reared and fattened from 10 to 26 months of age. After feeding, the highrib (HR), ribeye (RB), and tenderloin (TL) samples were taken from the carcass for meat quality evaluations. Results The results showed that growth performance of SJ was higher than that of JJ (higher live weight and average daily gain), and the hot carcass weight of SJ was higher than that of JJ (p

Abstract Previously, we have identified single nucleotide polymorphisms (SNPs) rs7958904 and rs4759314 in long non-coding RNA HOX transcript antisense RNA (HOTAIR) were significantly associated with risk of colorectal and gastric cancer, respectively. Here, we aimed to investigate the association between HOTAIR SNPs and cervical cancer (CC) susceptibility. A total of 1209 cases and 1348 controls were enrolled for association study and genotyped with TaqMan allelic discrimination method. The Cancer Genome Atlas (TCGA) database was utilized for in vivo analysis of allele-specific HOTAIR expression. MTT assay was employed for evaluation of allele-specific cell proliferation. The rs7958904 CC genotype was related to an increased risk of cervical cancer compared with the GG/GC genotypes (OR = 1.57, 95% CI = 1.10–2.25). TCGA database showed the CC tissues with rs7958904 CC genotype had higher HOTAIR expression than those with GG genotype (P = 0.046). MTT assay demonstrated a growth-promoting role of rs7958904 C allele on CC cells. Further functional studies on the effect of rs7958904 on biological behavior of CC cells are needed to confirm and extend our findings. In conclusion, HOTAIR rs7958904 might influence CC susceptibility through modulation of CC cell proliferation, and could serve as a diagnostic biomarker.

BACKGROUND: Apurinic/apyrimidinic endonuclease 1 (APE1) has a central role in the repair of apurinic apyrimidic sites through both its endonuclease and its phosphodiesterase activities. A common APE1 polymorphism, T1349G (rs3136820), was previously shown to be associated with the risk of cancers. OBJECTIVE: We hypothesized that the APE1 T1349G polymorphism is also associated with risk of gastric cancer. METHODS: In a hospital-based case-control study of 338 case patients with newly diagnosed gastric cancer and 362 cancer-free controls frequency-matched by age and sex, we genotyped the T1349G polymorphism and assessed its associations with risk of gastric cancer. RESULTS: Compared with the APE1 TT genotype, individuals with the variant TG/GG genotypes had a significantly increased risk of gastric cancer (odds ratio = 1.69, 95% confidence interval = 1.19-2.40), which was more pronounced among subgroups of aged ≤ 60 years, male, ever smokers, and ever drinkers. Further analyses revealed that the variant genotypes were associated with an increased risk for diffuse-type, low depth of tumor infiltration (T1 and T2), and lymph node metastasis gastric cancer. CONCLUSIONS: The APE1 T1349G polymorphism may be a marker for the development of gastric cancer in the Chinese population. Larger studies are required to validate these findings in diverse populations.

Objective: The aim of this study was to explore expression profiles of long noncoding RNA (lncRNA)-messenger RNA (mRNA) in abdominal aortic aneurysm (AAA) patients. Further, we explored the mechanisms by which lncRNA SNHG5 modulates the function of vascular smooth muscle cells (VSMC) in AAA. Methods: Human gene expression profile GSE57691 dataset, was retrieved from Gene Expression Omnibus database. The dataset included gene expression array data of 49 AAA patients and 10 control aortic specimens from organ donors. To explore the main roles of the biological network, differentially expressed lncRNA and mRNAs in the aortic aneurysm (AAA) and normal aortic specimens were determined. Differentially expressed lncRNA and mRNAs were then used to construct a competing endogenous RNA (ceRNA) network using Cytoscape software, and the five key lncRNA were identified. SNHG5 which was significantly downregulated in the AAA was chosen and analysis showed that it regulates mir-205-5p and SMAD4 by binding to mir-205-5p. Double luciferase reporter gene assays, RNA immunoprecipitation, and RNA knockdown studies were used to establish the relationship between SNHG5 and mir-205-5p. Apoptosis rate was determined using flow cytometry, whereas cell proliferation was evaluated using Edu, and 24 well Transwell assay. Western blot analysis was used to determine protein expression levels. Results: The five differentially expressed lncRNAs were significantly correlated with 34 microRNAs and 112 mRNAs. mRNAs in the ceRNA network are implicated in protein binding, signal transduction, DNA and RNA transcription, development, and cell differentiation. SNHG5 was downregulated in the AAA and acts as a molecular sponge for mir-205. Downregulation of SNHG5 induces expression of mir-205-5p. Increased mir-205-5p expression level inhibits SMAD4 production, thus inhibiting proliferation and migration and promotes apoptosis of smooth muscle cells. Conclusion: Bioinformatics were used to explore molecular mechanism of AAA progression. The findings of this study show that lncRNA SNHG5 regulates proliferation and apoptosis of VSMC cells through modulation of the mir-205-5p/SMAD4 axis. Therefore, SNHG5 is a potential therapeutic target for AAA disease. [ABSTRACT FROM AUTHOR]

Background: Abdominal aortic aneurysm (AAA) is a complex vascular disease involving expansion of the abdominal aorta. Extracellular matrix (ECM) degradation is crucial to AAA pathogenesis, however, the specific molecular mechanism remains unclear. This study aimed to investigate differentially expressed circular RNAs (DEcircRNAs) involved in ECM degradation of AAA. Methods: Transcriptome sequencing was used to analyze the DEcircRNAs between the AAA tissues and normal tissues. The expression of circRNAs in tissues and cells was validated using quantitative reverse transcription PCR (RT-qPCR). Overexpression of circRNAs in vascular smooth muscle cells (VSMCs) treated with angiotensin II (Ang II) was employed to explore its effect on ECM degradation of AAA. Bioinformatic technology, luciferase reporter gene assay, RT-qPCR, and rescue experiment were employed to evaluate the regulatory mechanism of circRNA. Results: We identified 65 DEcircRNAs in AAA tissues compared with normal abdominal aortic tissues, including 30 up-regulated and 35 down-regulated circRNAs, which were mainly involved in inflammation and ECM-related functions and pathways. Moreover, circRBM33 was significantly increased in AAA tissues and Ang II-induced VSMCs compared with control samples. Overexpression of circRBM33 increased the expression of ECM-related molecule matrix metalloproteinase-2 and reduced the tissue inhibitor of matrix metalloproteinases-1 expression. Mechanistically, miR-4268 targeted binding to circRBM33 and inhibited the luciferase activity of circRBM33. Overexpression of circRBM33 induced the expression of EPH receptor B2 (EPHB2), and this effect was countered by miR-4268 mimics. Conclusions: Overall, our data suggest that circRBM33 might be involved in AAA progression by regulating ECM degradation via the miR-4268/EPHB2 axis. [ABSTRACT FROM AUTHOR]