Strong Electrochemiluminescence from MOF Accelerator Enriched Quantum Dots for Enhanced Sensing of Trace cTnI.

The development of a sensitive and practical electrochemiluminescence (ECL) bioassay relies on the use of ECL signal tags whose signal intensity is high and stable. In this work, strong ECL emission was achieved from metal organic framework (MOF) accelerator enriched quantum dots (CdTe), which were applied as an efficient ECL signal tag for trace biomarker detection. It is particularly noteworthy that a novel mechanism to drastically enhance the ECL intensity of CdTe is established because isoreticular metal organic framework-3 (IRMOF-3) with 2-amino terephthalic acid (2-NH2-BDC) as the organic ligand not only allows for loading a large amount of CdTe via the encapsulating effect and internal/external decoration but also functions as a novel coreactant accelerator for promoting the conversion of coreactant S2O82- into the sulfate radical anion (SO4•-), further boosting the ECL emission of CdTe. On the basis of the simple sandwich immunoreaction approach, cardiac troponin-I antigen (cTnI), a kind of biomarker related with myocardial infarction, was chosen as a detection model using an IRMOF-3-enriched CdTe labeled antibody as the signal probe. This immunosensor demonstrated desirable assay performance for cTnI with a wide response range from 1.1 fg mL-1 to 11 ng mL-1 and a very low detection limit (0.46 fg mL-1). This suggested that the IRMOF-3-enriched CdTe nanocomposite strategy can integrate the coreactant accelerator and luminophore to significantly enhance the ECL intensity and stability, providing a direction for promising ECL tag preparation with broad applications.

IFNa2 of triploid hybrid of gold fish and allotetraploid is an intracellular antiviral cytokine against SVCV and GCRV.

Sterile triploid hybrids (3n = 150) of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) display obviously improved disease resistance and much enhanced growth rate than their parents, which have been cultured widely in China. In this paper, one of the type I IFNs of triploid hybrid (3nIFNa2) has been cloned and characterized. The full-length cDNA of 3nIFNa2 gene consists of 715 nucleotides and the predicted 3nIFNa2 contains 183 amino acids. The transcription of 3nIFNa2 gene was detected in all the examined tissues of triploid hybrid and the mRNA level of 3nIFNa2 was obviously enhanced in response to SVCV and GCRV infection. 3nIFNa2 has been detected in the whole cell lysate of HEK293T cells transfected with plasmids expressing 3nIFNa2 but not in the supernatant media. EPC cells transfected with plasmid expressing 3nIFNa2 at 24 h before SVCV and GCRV infection showed obviously decreased cytopathic effect; and the virus titers in the supernatant media were much lower than those of the control cells. Glycosidase digestion analysis demonstrates that 3nIFNa2 is modified with N-linked glycosylation, which occurs on the asparagine (N) of residue 177 of this cytokine. The un-glycosylated mutant 3nIFNa2-N177Q shows the similar antiviral ability as that of 3nIFNa2, which suggests that the N-linked glycosylation does not contribute directly to its antiviral property. All the above data support the conclusion that 3nIFNa2 is an intracellular cytokine functioning importantly in host antiviral innate immunity.

IFNa of triploid hybrid of gold fish and allotetraploid is an antiviral cytokine against SVCV and GCRV.

Triploid hybrid of gold fish (Carassius auratus red var., ♀, 2n = 100) and allotetroploid (♂, 2n = 100) displays much improved disease resistance than its parents. In this paper, one of the type I IFNs of triploid hybrid (3nIFNa) has been cloned and characterized. The full-length cDNA of 3nIFNa consists of 740 nucleotides and the predicted 3nIFNa protein contains 183 amino acids. The mRNA transcription of 3nIFNa was detected in all the selected tissues of triploid hybrid and was obviously enhanced after SVCV or GCRV infection. bcIFNa was detected in both whole cell lysate and supernatant media of HEK293T cells transfected with plasmids expressing bcIFNa. It is interesting that the pre-matured 3nIFNa is modified with N-linked glycosylation, which is located within the N-terminal signal peptide. EPC cells showed much-decreased cytopathic effect when treated with 3nIFNa-containing media or transfected with plasmid expressing 3nIFNa at 24 h before SVCV or GCRV infection; and the virus titers in these cells were much lower than those of the control EPC cells. All the above data support the conclusion that 3nIFNa is a secreted cytokine functioning in host innate immune response against virus invasion.

The cellular isopeptidase T deubiquitinating enzyme regulates Kaposi's sarcoma-associated herpesvirus K7 degradation.

PURPOSE: To understand the regulated degradation of KSHV K7. METHODS: Proteomic screen and immunofluoresence microscopy identified that K7 recruits polyubiquitin chains to membrane fractions; IP and GST pulldown verified the interaction between K7 and Iso T1; Protein stability assay and RQ-PCR demonstrated Iso T1 facilitates K7 degradation. RESULTS: The K7-containing membrane fraction contains a higher level of deubiquitinating (DUB) activity and K7 interacts with a cellular DUB, isopeptidase T1 (Iso T1). Mutational analyses revealed that the ubiquitin-associated domains of Iso T1 are necessary and sufficient to bind K7. Confocal microscopy and fractionation analyses indicated that K7 increases the membrane-associated Iso T1. Furthermore, the knockdown of IsoT1 by shRNA-mediated silencing greatly increased K7 ubiquitination even when proteasome activity was inhibited by lactacystin. CONCLUSIONS: IsoT1 disassembles of free ubiquitin chains to facilitate K7 degradation.

Identification and characterization of IKKε gene from grass carp Ctenopharyngodon idella.

IKKε is an IKK-related kinase implicated in antiviral immune response in higher vertebrates. To elucidate the function of IKKε in teleost fish, grass carp IKKε (gcIKKε) has been cloned and characterized in this paper. The full-length cDNA of gcIKKε is composed of 2529 nucleotides and encodes a polypeptide of 723 amino acids. The mRNA transcription of gcIKKε was constitutively detected in all the selected tissues and the gcIKKε mRNA level increased at 36 h after GCRV infection. Western blot data of both HEK293T cells and EPC cells demonstrated that gcIKKε was around 80 KDa; and immunofluorescence staining data of both NIH3T3 cells and EPC cells determined gcIKKε was a cytosolic protein. The mRNA level of gcIKKε in CIK cells was increased more than 150 times right after poly(I:C) treatment and PMA treatment triggered gcIKKε mRNA transcription in CIK cells more than 100 times. Over-expression of gcIKKε in EPC cells activated the promoter activity of both zebrafish IFN and fathead minnow IFN. gcIKKε mRNA transcription level in CIK cells was increased from 48 h post GCRV infection with different MOIs. All the data support the idea that gcIKKε is a novel teleost IκB kinase recruited in the IFN-mediated antiviral immunity of grass carp.

Clinical analysis of multiple primary gastrointestinal malignant tumors: A 10-year case review of a single-center.

BACKGROUND: Multiple primary malignant tumors (MPMTs) was first described by Billroth as early as 1889, with the first report published by Warren and Gates in 1932. Since then, numerous cases have been reported. A literature review of 1104269 patients with cancer revealed that the incidence of MPMTs ranged from 0.73 to 11.7%. In recent years, however, there has been a significant upward trend in the incidence of this phenomenon, which may be associated with many different factors, including the advancement of modern diagnostic procedures facilitating the examination and diagnosis of more MPMTs, increased exposure to chemotherapy and radiotherapy that exacerbate the risk of new malignant tumors in patients with cancer, and prolonged survival of patients with cancer allowing sufficient time for the development of new primary cancers. AIM: To analyze the incidence, clinical features, treatment factors, prevalence, and prognosis of patients with MPMTs in the gastrointestinal tract treated in a single center. Additionally, we analyzed the different tumor combinations, time interval between the occurrence of tumors, and staging. METHODS: This retrospective cohort study analyzed 8059 patients with pathologically confirmed gastrointestinal malignant tumors treated at the Gansu Province Hospital in Lanzhou, Gansu, China between June 2011 and June 2020. Of these, 85 patients had MPMTs. The clinical features, treatment factors, prevalence, and prognosis of this latter cohort were analyzed. RESULTS: The incidence of MPMTs in patients with gastrointestinal malignant tumors was 1.05% (85/8059), including 83 double primary malignant tumors and two triple primary malignant tumors of which 57 (67.06%) were synchronous MPMTs (SMPMTs) and 28 (32.94%) were metachronous MPMTs (MMPMTs). The most frequent associations were found between the rectum colon cancers within the SMPMT category and the gastric-colon cancers within the MMPMT category. For the MMPMTs, the median interval was 53 months. The overall 1-, 3- and 5-year survival rates from diagnosis of the first primary cancer were 91.36%, 65.41%, and 45.97%, respectively; those from diagnosis of the second primary cancer were 67.90%, 29.90%, and 17.37%, respectively. CONCLUSION: MPMTs in the gastrointestinal tract have a high incidence and poor prognosis. Thus, it is necessary to perform both gastroscopy and colonoscopy in patients with gastrointestinal tumors. Multidisciplinary comprehensive diagnosis and treatment may improve the diagnosis rate and treatment efficiency of MPMTs.

Risk of Esophageal Adenocarcinoma After Bariatric Surgery: A Meta-Analysis of Retrospective Studies.

PURPOSE: This study aims to systematically review and meta-analyze the evidence on the risk of esophageal adenocarcinoma (EAC) following metabolic and bariatric surgery (MBS). MATERIALS AND METHODS: A systematic literature search was conducted on the China National Knowledge Infrastructure (CNKI), Wanfang, EMBASE, MEDLINE, Web of Science, The Cochrane Library, and PubMed databases. Meta-analysis utilized odds ratios (ORs) and 95% confidence intervals (CIs) to analyze the correlation between MBS and the risk of EAC. Meta-analysis was performed using STATA software (version 12.0). RESULTS: Fourteen studies involving patients with obesity undergoing bariatric surgery and control groups receiving conventional treatment were included. The meta-analysis indicated a reduction in the overall incidence of esophageal cancer after bariatric surgery (OR = 0.69, 95% CI: 0.51-0.95, P = 0.022). Subgroup analysis results demonstrated a decreased risk of EAC in European patients with obesity undergoing MBS treatment (OR: 0.60, 95% CI: 0.38-0.95, P = 0.028). In studies with a sample size greater than or equal to 100,000 patients, the risk of EAC in patients with obesity undergoing MBS was significantly lower than the non-surgery group (OR: 0.59, 95% CI: 0.42-0.83, P = 0.003). Articles published before 2020 and those published in 2020 or earlier showed a significant difference in the incidence of EAC between the surgery and non-surgery groups (OR: 0.57, 95% CI: 0.43-0.75, P < 0.001). The risk of EAC in patients with obesity with a follow-up time of less than 5 years was statistically significant (OR: 0.46, 95% CI: 0.25-0.82, P = 0.009). CONCLUSION: Our meta-analysis results suggest a reduced risk of esophageal cancer in patients with obesity after bariatric surgery. PROSPERO REGISTRATION: CRD 42024505177.

Hessian Regularized [Formula: see text]-Nonnegative Matrix Factorization and Deep Learning for miRNA-Disease Associations Prediction.

Since the identification of microRNAs (miRNAs), empirical research has demonstrated their crucial involvement in the functioning of organisms. Investigating miRNAs significantly bolsters efforts related to averting, diagnosing, and treating intricate human maladies. Yet, exploring every conceivable miRNA-disease association consumes significant resources and time within conventional wet experiments. On the computational front, forecasting potential miRNA-disease connections serves as a valuable source of preliminary insights for medical investigators. As a result, we have developed a novel matrix factorization model known as Hessian-regularized [Formula: see text] nonnegative matrix factorization in combination with deep learning for predicting associations between miRNAs and diseases, denoted as [Formula: see text]-NMF-DF. In particular, we introduce a novel iterative fusion approach to integrate all similarities. This method effectively diminishes the sparsity of the initial miRNA-disease associations matrix. Additionally, we devise a mixed model framework that utilizes deep learning, matrix decomposition, and singular value decomposition to capture and depict the intricate nonlinear features of miRNA and disease. The prediction performance of the six matrix factorization methods is improved by comparison and analysis, similarity matrix fusion, data preprocessing, and parameter adjustment. The AUC and AUPR obtained by the new matrix factorization model under fivefold cross validation are comparative or better with other matrix factorization models. Finally, we select three diseases including lung tumor, bladder tumor and breast tumor for case analysis, and further extend the matrix factorization model based on deep learning. The results show that the hybrid algorithm combining matrix factorization with deep learning proposed in this paper can predict miRNAs related to different diseases with high accuracy.

SQSTM1/p62 promotes the progression of gastric cancer through epithelial-mesenchymal transition.

Background: SQSTM1/p62 is an autophagy-related receptor protein that participates in regulating tumorigenesis and multiple signaling pathways. Gastric cancer (GC) is a common tumor in the digestive tract and continues to pose a significant threat to human health. Therefore, this study aims to investigate the impact of p62 on gastric cancer. Methods: Immunohistochemistry and Western blotting were employed to assess the expression level of the p62 protein in gastric cancer tissues and its correlation with prognosis. Subsequently, in vitro cell experiments were conducted to determine the role of p62 in gastric cancer cell proliferation, migration, and metastasis. Result: The expression of p62 in gastric cancer tissues was significantly higher than in normal tissues. The expression of p62 was positively correlated with poor prognosis in gastric cancer patients. In vitro cell experiments indicated that p62 promotes gastric cancer cell proliferation and migration. Mechanistically, elevated p62 expression induced epithelial-mesenchymal transition (EMT), leading to upregulation of E-cadherin and downregulation of N-cadherin and vimentin. Conclusion: This study provides novel and robust evidence for the mechanism by which elevated p62 expression promotes the progression of gastric cancer. It offers promising therapeutic targets for anti-tumor treatment strategies in gastric cancer patients.

Establishment of fin cell lines and their use to study the immune gene expression in cyprinid fishes with different ploidy in rhabdovirus infection.

Triploid hybrid (3n = 150) of red crucian carp (♀, 2n = 100) and allotetraploid (♂, 4n = 200) display improved disease resistance and stress resistance than their parents. In order to elucidate their innate immune mechanisms, three novel cell lines from the caudal fin of red crucian carp, triploid hybrid and allotetraploid (named 2nFC, 3nFC and 4nFC accordingly) were established and characterized respectively. 2nFC, 3nFC and 4nFC showed fibroblast-like morphology and characteristics. They have been subcultured for more than 100 passages since the initial primary culture. Viral infection experiments showed that 2nFC, 3nFC and 4nFC were susceptible to spring viraemia of carp virus (SVCV) infection. Intriguingly, 3nFC performed the stronger resistance ability against SVCV than 2nFC and 4nFC, which indicated that 2nFC, 3nFC and 4nFC might be used as the suitable in vitro models for exploring and analyzing the differences among these three cyprinid fishes in antiviral innate immune mechanisms. Based on this, we analyzed the transcriptome profile of 2nFC, 3nFC and 4nFC in the context of SVCV infection. The KEGG enrichment analysis showed that the differentially expressed genes (DEGs) were primarily enriched to immune-related signaling pathways. However, some signaling pathways against viral infection were activated remarkably in 2nFC and 3nFC but not in 4nFC. Overall, the establishment of 2nFC, 3nFC and 4nFC provided us a suitable platform to elucidate the innate immunity of fishes with different ploidy and clear genetic relationship.

Alterations in vitamin D signaling pathway in gastric cancer progression: a study of vitamin D receptor expression in human normal, premalignant, and malignant gastric tissue.

Amount of studies in cells and animal models have proved vitamin D has multifarious antitumor effects. However, epidemiological studies showed inconsistent result on gastric cancer. The antitumor role is mainly mediated by the vitamin D receptor (VDR). Our hypothesis is that VDR may be abnormally (poorly) expressed in gastric cancer tissue. Present study is aimed at discovering and analyzing VDR expression in a series of human gastric tissues, including normal, premalignant, and malignant gastric tissue, and correlated VDR to the clinicopathological parameters of gastric cancer patients. VDR expression was detected by immunohistochemistry. The χ(2) test was used to analyze the VDR expression as well as the relationship between VDR and the clinicopathological factors of gastric cancer patients. Compared with normal (82.61%) and premalignant tissues (73.64%), VDR was lower expressed in cancer tissues (57.61%), with a statistically significant difference (P = 0.001). Among cancer tissues, VDR was higher expressed in well and moderate differentiated tissues contrasted with tissues with poor differentiation, and higher expressed in small tumors (< 5 cm) compared with large tumors (≥ 5 cm), with a statistically significant difference respectively (P = 0.016, P = 0.009). A decline linear trend appeared when analyzing the statistical difference of VDR expression among normal, premalignant, and malignant gastric tissues. VDR expression has been on the decline from the premalignant stage, finally low expressed in gastric cancer tissues, especial in poorly differentiated tissues. VDR could be a potential prognostic factor for patients with gastric cancer.

Synchronous double primary gastric and endometrial cancer: a case report and literature review.

Multiple primary malignant neoplasms (MPMN) are two or more malignancies in an individual without any relationship between the tumors. In recent years, increasing number of cases were reported. However, Synchronous double primary gastric and endometrial cancer are relatively rare to be reported. Here we present a rare case of synchronous double cancer involving the stomach and endometrium, which is resected simultaneously and received six times chemo. After reviewing lots of literatures at home and abroad, we discuss the risk factors, the diagnostic criteria, the treatment modalities and the prognosis of these rare MPMN. Although a number of risk factors have been proposed in a mass of literatures, but the mechanism of MPMN is still unclear. We didn't discover a detailed explanation for the mechanism of MPMN from our patient. Therefore, further research should focus on the etiology and mechanism of MPMN.