Triglyceride-inflammation score established on account of random survival forest for predicting survival in patients with nasopharyngeal carcinoma: a retrospective study.

Objective: This study aimed to establish an effective prognostic model based on triglyceride and inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR), to predict overall survival (OS) in patients with nasopharyngeal carcinoma (NPC). Additionally, we aimed to explore the interaction and mediation between these biomarkers in their association with OS. Methods: A retrospective review was conducted on 259 NPC patients who had blood lipid markers, including triglyceride and total cholesterol, as well as parameters of peripheral blood cells measured before treatment. These patients were followed up for over 5 years, and randomly divided into a training set (n=155) and a validation set (n=104). The triglyceride-inflammation (TI) score was developed using the random survival forest (RSF) algorithm. Subsequently, a nomogram was created. The performance of the prognostic model was measured by the concordance index (C-index), time-dependent receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). The interaction and mediation between the biomarkers were further analyzed. Bioinformatics analysis based on the GEO dataset was used to investigate the association between triglyceride metabolism and immune cell infiltration. Results: The C-index of the TI score was 0.806 in the training set, 0.759 in the validation set, and 0.808 in the entire set. The area under the curve of time-dependent ROC of TI score in predicting survival at 1, 3, and 5 years were 0.741, 0.847, and 0.871 respectively in the training set, and 0.811, 0.837, and 0.758 in the validation set, then 0.771, 0.848, and 0.862 in the entire set, suggesting that TI score had excellent performance in predicting OS in NPC patients. Patients with stage T1-T2 or M0 had significantly lower TI scores, NLR, and PLR, and higher LMR compared to those with stage T3-T3 or M1, respectively. The nomogram, which integrated age, sex, clinical stage, and TI score, demonstrated good clinical usefulness and predictive ability, as evaluated by the DCA. Significant interactions were found between triglyceride and NLR and platelet, but triglyceride did not exhibit any medicating effects in the inflammatory markers. Additionally, NPC tissues with active triglyceride synthesis exhibited high immune cell infiltration. Conclusion: The TI score based on RSF represents a potential prognostic factor for NPC patients, offering convenience and economic advantages. The interaction between triglyceride and NLR may be attributed to the effect of triglyceride metabolism on immune response.

Integrating iron metabolism-related gene signature to evaluate prognosis and immune infiltration in nasopharyngeal carcinoma.

BACKGROUND: Dysregulation of iron metabolism has been shown to have significant implications for cancer development. We aimed to investigate the prognostic and immunological significance of iron metabolism-related genes (IMRGs) in nasopharyngeal carcinoma (NPC). METHODS: Multiple Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets were analyzed to identify key IMRGs associated with prognosis. Additionally, the immunological significance of IMRGs was explored. RESULTS: A novel risk model was established using the LASSO regression algorithm, incorporating three genes (TFRC, SLC39A14, and ATP6V0D1).This model categorized patients into low and high-risk groups, and Kaplan-Meier analysis revealed significantly shorter progression-free survival for the high-risk group (P < 0.0001). The prognostic model's accuracy was additionally confirmed by employing time-dependent Receiver Operating Characteristic (ROC) curves and conducting Decision Curve Analysis (DCA). High-risk patients were found to correlate with advanced clinical stages, specific tumor microenvironment subtypes, and distinct morphologies. ESTIMATE analysis demonstrated a significant inverse relationship between increased immune, stromal, and ESTIMATE scores and lowered risk score. Immune analysis indicated a negative correlation between high-risk score and the abundance of most tumor-infiltrating immune cells, including dendritic cells, CD8+ T cells, CD4+ T cells, and B cells. This correlation extended to immune checkpoint genes such as PDCD1, CTLA4, TIGIT, LAG3, and BTLA. The protein expression patterns of selected genes in clinical NPC samples were validated through immunohistochemistry. CONCLUSION: This study presents a prognostic model utilizing IMRGs in NPC, which could assist in assessing patient prognosis and provide insights into new therapeutic targets for NPC.

Paired Box 5 (PAX5) Gene Has Diagnostic and Prognostic Potential in Nasopharyngeal Carcinoma.

Purpose: Paired Box 5 (PAX5) is a transcription factor that is widely associated with carcinogenesis. PAX5 can maintain Epstein-Barr virus (EBV) latency in B cells, while a close association exists between EBV infection and nasopharyngeal carcinoma (NPC). However, there are very few reports on the correlation between PAX5 and NPC development. The aim of this study was to investigate the role of PAX5 in NPC. Patients and Methods: The clinical value and prognostic significance of PAX5 in NPC and the association with PAX5 expression and immune cell infiltration were analyzed by multiple GEO datasets. In vivo and in vitro experiments including real-time PCR, Western blot, CCK-8 assay, and methylation sequencing were used to validate the results of bioinformatics analysis. Results: The expression of PAX5 was significantly reduced in NPC tissues, with the low expression being correlated with advanced clinical stage, low tumor mutation burden and immune activation, high relative expression of EBV, poor survival for NPC patients. PAX5 exhibited excellent diagnostic performance and had potential as a predictive factor for response to the immune checkpoint inhibitors therapy. Enrichment analysis suggested that the low expression of PAX5 was associated with the dysregulation of Hippo and Wnt signaling pathways. The promoter of PAX5 gene was hypermethylated in NPC tissues. Furthermore, the in vitro and in vivo experiments revealed that NPC tissue and cell lines had low mRNA expression levels of PAX5, the PAX5 promoter was hypermethylated in NPC cell lines, and PAX5 overexpression inhibited NPC cell proliferation and tumor growth in nude mice. Conclusion: PAX5 may be a tumor suppressor and serve as a novel potential diagnostic and prognostic marker for NPC.

Enhancing biosensing with fourfold amplification and self-powering capabilities: MoS2@C hollow nanorods-mediated DNA hexahedral framework architecture for amol-level liver cancer tumor marker detection.

Two-dimensional carbon-coated molybdenum disulfide (MoS2@C) hollow nanorods are combined with nucleic acid signal amplification strategies and DNA hexahedral nanoframework to construct a novel self-powered biosensing platform for ultra-sensitive dual-mode detection of tumor suppressor microRNA-199a. The nanomaterial is applied on carbon cloth and then modified with glucose oxidase or using as bioanode. A large number of double helix DNA chains are produced on bicathode by nucleic acid technologies including 3D DNA walker, hybrid chain reaction and DNA hexahedral nanoframework to adsorb methylene blue, producing high EOCV signal. Methylene blue also is reduced and an increased RGB Blue value is observed. For microRNA-199a detection, the assay shows a extensive linear range of 0.0001-100 pM with a low detection limit of 4.94 amol/L (S/N = 3). The method has been applied to the detection of actual serum samples, providing a novel method for the accurate and sensitive detection of tumor markers.

Hepatic transcriptome analysis provides new insights into ghrelin regulation of the liver in Nile tilapia (Oreochromis niloticus).

Ghrelin is a growth-promoting hormone produced by the gastrointestinal tract that plays a crucial role through the ghrelin-growth hormone secretagogue receptor (GHS-R) and growth hormone/insulin-like growth factor-1 (GH/IGF-1) axes. To explore the effect of ghrelin on the transcriptomic profile of tilapia liver, the hepatic transcriptome of tilapia was sequenced for two groups, including saline-injected control (CL) and ghrelin-injected (GL; 2 µg/g body weight) tilapia. The transcriptome of livers from the two groups was sequenced using an Illumina HiSeqTM 2000 platform and yielded approximately 310.53 million raw reads. Subsequently, approximately 308.51 million clean reads were obtained from the total raw reads using in-house Perl scripts. Approximately 92.36% clean reads were mapped to the Nile tilapia genome using RSEM. Using the DESeq package, 250 differentially expressed genes (DEGs) were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed enrichment of two pathways related to RNA transcription (ribosome biogenesis in eukaryotes pathway and RNA transport pathway), with a total of 14 functional DEGs. ATP-binding and muscle contraction terms were identified as enriched using Gene Ontology (GO), yielding a total of 28 DEGs. Finally, real-time quantitative PCR (RT-qPCR) was used to confirm the accuracy of the transcriptomic results. The results of RT-qPCR were highly consistent with the RNA-seq, indicating that results of RNA-seq were valid. The differences in gene expression between the groups indicated that ghrelin-injection altered energy metabolism and RNA transcription in the tilapia liver, which provides new information to help promote the growth of tilapia.

Superior performance of a graphdiyne self-powered biosensor with exonuclease III-assisted signal amplification for sensitive detection of microRNAs.

Graphdiyne (GDY) is an sp and sp2 co-hydrocarbon allotrope whose particular structure endows it with many fascinating properties, including abundant chemical bonds, high conjugation, natural pores, high carrier mobility, high conductivity and stability, etc. In this work, two-dimensional graphdiyne is prepared as an electrode substrate material coupling with an exonuclease III-assisted amplification strategy to construct a superior-performance self-powered biosensor based on enzymatic biofuel cells for highly sensitive detection of the tumour marker miRNA-21. Glucose oxidase (GOD) is first immobilized on the GDY/AuNP composite to prepare a bioconjugate. GDY/AuNP modified carbon cloth is used as an enzyme biofuel cell electrode, which is then modified with bilirubin oxidase as a biocathode. The bioconjugate binds to GOD through specific binding to the bioanode. When miRNA-21 is present, specific recognition by exonuclease III in the system results in cleavage of the capture probe, and miRNA-21 is recovered and involved in the cycle. The target miRNA-21 then causes corresponding changes in the open-circuit voltage of the self-powered system. Based on this, a sensitive detection method was constructed, within the scope from 0.1 fM to 0.1 nM with a shallow detection limit of 55.2 aM (S/N = 3). The new approach triumphantly has been used to detect miRNA-21 in serum, which provides a compelling new way for early diagnosis of related cancers.

The Correlations among Circulating Tumor Cells, Epstein-Barr Virus Status, and Epidemiology in Patients with Nasopharyngeal Carcinoma.

BACKGROUND: Studies have shown that circulating tumor cells (CTCs) can be detected in nasopharyngeal carcinoma (NPC). However, the relationship between CTCs and tumor stage is still controversial. This study aims to investigate the correlations among CTCs, Epstein-Barr virus (EBV) status, clinicopathologic features, and epidemiological risk factors in patients with NPC. METHODS: Three hundred and thirty primary NPC patients with complete clinical data and epidemiology information were collected. Analysis of CTCs was performed using the CTCBIOPSY system. The plasma EBV DNA load was detected by quantitative real-time PCR. Detection of VCA-IgA and EA-IgA antibodies titers was conducted by immunoenzymatic assay. EBNA1-IgA and Zta-IgA were measured using an enzyme-linked immunosorbent assay. RESULTS: The presence of CTCs was associated with high EBV DNA load (p < 0.05). The positive rate of CTCs was correlated with T and M classifications of NPC (T: 13.2% vs. 22.9%; M: 17.9% vs. 34.8%, p < 0.05). Compared with never and former smokers, current smokers exhibited a higher positive rate of EBNA1-IgA (83.3% and 81.0% vs. 92.5%, p < 0.05); the patients with pack-years of smoking ≥ 15 displayed a significantly higher positive rate of EBNA1-IgA than those with pack-years of smoking < 15 (98.0% and 92.5% vs. 81.0%, p < 0.05). CONCLUSIONS: CTCs positivity was closely associated with tumor burden and distant metastasis of NPC. Smoking status and smoking cumulative dose of NPC patients might be correlated with EBV activation.

A polygenic risk score for nasopharyngeal carcinoma shows potential for risk stratification and personalized screening.

Polygenic risk scores (PRS) have the potential to identify individuals at risk of diseases, optimizing treatment, and predicting survival outcomes. Here, we construct and validate a genome-wide association study (GWAS) derived PRS for nasopharyngeal carcinoma (NPC), using a multi-center study of six populations (6 059 NPC cases and 7 582 controls), and evaluate its utility in a nested case-control study. We show that the PRS enables effective identification of NPC high-risk individuals (AUC = 0.65) and improves the risk prediction with the PRS incremental deciles in each population (Ptrend ranging from 2.79 × 10-7 to 4.79 × 10-44). By incorporating the PRS into EBV-serology-based NPC screening, the test's positive predictive value (PPV) is increased from an average of 4.84% to 8.38% and 11.91% in the top 10% and 5% PRS, respectively. In summary, the GWAS-derived PRS, together with the EBV test, significantly improves NPC risk stratification and informs personalized screening.

Chromosome-level assembly of the Hypophthalmichthys molitrix (Cypriniformes: Cyprinidae) genome provides insights into its ecological adaptation.

Hypophthalmichthys molitrix (silver carp) is phytoplanktivorous and is an economically and ecologically important fish species. As a well-known invasive species, a number of factors associated with the ecological adaptations of this species are largely unknown. Here, we present a chromosomal-level assembly of the species based on the PacBio Sequel II platform and Hi-C scaffolding technology. Based on the high-quality genome sequences and previous genome sequencing projects, a number of genes that were probably subject to positive selection reside in the genome of H. molitrix, and the last common ancestors of H. molitrix and H. nobilis were identified. Some of these genes may partially explain the mechanisms of H. molitrix for surviving damage due to toxic algae. Demographic history estimation suggests that the effective population size (EPS) of the species may have constantly increased along with the uplift of the Qinghai-Tibet Plateau, started to decline when quaternary glaciation started, and further declined during the Younger Dryas Period. Moreover, the introgression from H. nobilis to H. molitrix in North America was corroborated based on the whole-genome sequencing data, and the proportion of introgressed regions was estimated to be approximately 5.8%. Based on the high-quality assembly, the possible mechanisms by which H. molitrix adapts to its endemic and invaded locations were profiled.

Polyamidoamine dendrimer-functionalized carbon nanotubes-mediated GFP gene transfection for HeLa cells: effects of different types of carbon nanotubes.

Three types of functionalized carbon nanotubes (f-CNTs), polyamidoamine (PAMAM) dendrimer-functionalized single and multi-walled CNTs (MWCNT-PAMAM-1, MWCNT-PAMAM-2, and SWCNT-PAMAM-3), were prepared by covalent linkage approach. The micro-morphologies of the three f-CNTs and the interaction of MWCNT-PAMAM-2 with HeLa cells were characterized by transmission electron microscopy (TEM). The free amine groups on the surface of the three types of CNTs-PAMAM hybrids were quantitatively analyzed. Their cytotoxicity and transfection efficiency of plasmid DNA of enhanced green fluorescent protein (pEGFP-N1) to HeLa cells were investigated in detail. The results suggest that although all three types of CNTs-PAMAM hybrids can deliver pEGFP-N1 into HeLa cells and the exogenous GFP gene has been successfully expressed, MWCNT-PAMAM-2 with shorter length and larger amount of free amine groups on its surface possesses higher transfection efficiency (6.79%), being about 3.0 and 1.7 times as large as those of MWCNT-PAMAM-1 (2.24%) and SWCNT-PAMAM-3 (4.08%), respectively; their cytotoxicity to HeLa cells decrease following the sequence of SWCNT-PAMAM-3 > MWCNT-PAMAM-2 > MWCNT-PAMAM-1. These results may be useful for understanding the effects of the chemical/physical properties of f-CNTs on their gene transfection efficiency and cytotoxicity, allowing for construction of promising CNT-based intracellular delivery vectors for gene therapy.

Efficient assembly of multi-walled carbon nanotube-CdSe/ZnS quantum dot hybrids with high biocompatibility and fluorescence property.

CdSe/ZnS core-shell quantum dots (QDs) were efficiently tethered onto polyamidoamine dendrimer-modified multi-walled carbon nanotubes (MWCNTs) by covalent linkage and mercapto-mediated assembly. The obtained MWCNT-QD hybrids were both photophysically and morphologically characterized. The QDs are well-distributed on single nanotube surface in high density and the assembly of QDs onto MWCNTs does not change the fluorescence emission wavelength of QDs but significantly decreases the emission density. Cytotoxicity of MWCNT-QD hybrids to HeLa cells and their fluorescence property in living cell system were evaluated in detail. The hybrids show a little effect on cell viability even at very high concentration (100 µg mL(-1)). Moreover, they possess intense red fluorescence signal under optical fluorescence microscopy and good fluorescence stability over 72-h exposure in living cell system.

[Diagnostic value of serum Cystatin C in renal function impairments in children with viral encephalitis].

OBJECTIVE: To study the value of serum Cystatin C (Cyst C) in the evaluation of glomerular filtration function in children with viral encephalitis. METHODS: Serum levels of Cyst C, urea nitrogen (BUN) and creatinine (Cr) were measured in 92 children with viral encephalitis and in 50 healthy children as a control group. According to glomerular filtration rate (GFR), the encephalitis group was subdivided into normal renal function, renal insufficiency in the compensatory or decompensatory stage, and renal failure /end-stage groups. RESULTS: Serum levels of Cyst C, BUN and Cr in the encephalitis group increased and GFR decreased significantly compared with those in the control group (P<0.01). With the decline of renal function, GFR decreased and serum levels of Cyst C, BUN and Cr increased gradually. Serum levels of Cyst C and GFR were significantly different among the encephaitis subgroups (P<0.01). For serum levels of BUN and Cr, there were significant differences among the subgroups except between the normal renal function and the compensatory renal insufficiency groups. Serum Cyst C level was positively correlated with serum BUN and Cr levels, and negatively correlated with GFR. CONCLUSIONS: The children with viral encephalitis have different degrees of renal impairments. Cyst C appears to be superior to BUN and Cr as a marker for the evaluation of glomerular filtration function. Measurement of serum Cyst C levels is very valuable in renal function monitoring in children with viral encephalitis.

Improved GFP gene transfection mediated by polyamidoamine dendrimer-functionalized multi-walled carbon nanotubes with high biocompatibility.

The multi-walled carbon nanotubes (MWCNTs)-polyamidoamine (PAMAM) hybrid was prepared by covalent linkage approach, and characterized by transmission electron microscopy, Fourier transform infrared spectroscopy and ultraviolet-visible spectrometry. The PAMAM dendrimers were present on the surface of MWCNTs in high density, and the MWCNT-PAMAM hybrid exhibited good dispersibility and stability in aqueous solution. The interaction between MWCNT-PAMAM with plasmid DNA of enhanced green fluorescence protein (pEGFP-N1), intracellular trafficking of the hybrid, transfection performance and cytotoxicity to HeLa cells were evaluated in detail. We found that the MWCNT-PAMAM hybrid possessed good pEGFP-N1 immobilization ability and could efficiently delivery GFP gene into cultured HeLa cells. The surface modification of MWCNTs with PAMAM improved the transfection efficiency 2.4 and 0.9 times, and simultaneously decreased cytotoxicity by about 38%, as compared with mixed acid-treated MWCNTs and pure PAMAM dendrimers. The MWCNT-PAMAM hybrid can be considered as a new carrier for the delivery of biomolecules into mammalian cells. Therefore, this novel system may have good potential applications in biology and therapy, including gene delivery systems.