Predicting potential lncRNA biomarkers for lung cancer and neuroblastoma based on an ensemble of a deep neural network and LightGBM.

Introduction: Lung cancer is one of the most frequent neoplasms worldwide with approximately 2.2 million new cases and 1.8 million deaths each year. The expression levels of programmed death ligand-1 (PDL1) demonstrate a complex association with lung cancer. Neuroblastoma is a high-risk malignant tumor and is mainly involved in childhood patients. Identification of new biomarkers for these two diseases can significantly promote their diagnosis and therapy. However, in vivo experiments to discover potential biomarkers are costly and laborious. Consequently, artificial intelligence technologies, especially machine learning methods, provide a powerful avenue to find new biomarkers for various diseases. Methods: We developed a machine learning-based method named LDAenDL to detect potential long noncoding RNA (lncRNA) biomarkers for lung cancer and neuroblastoma using an ensemble of a deep neural network and LightGBM. LDAenDL first computes the Gaussian kernel similarity and functional similarity of lncRNAs and the Gaussian kernel similarity and semantic similarity of diseases to obtain their similar networks. Next, LDAenDL combines a graph convolutional network, graph attention network, and convolutional neural network to learn the biological features of the lncRNAs and diseases based on their similarity networks. Third, these features are concatenated and fed to an ensemble model composed of a deep neural network and LightGBM to find new lncRNA-disease associations (LDAs). Finally, the proposed LDAenDL method is applied to identify possible lncRNA biomarkers associated with lung cancer and neuroblastoma. Results: The experimental results show that LDAenDL computed the best AUCs of 0.8701, 107 0.8953, and 0.9110 under cross-validation on lncRNAs, diseases, and lncRNA-disease pairs on Dataset 1, respectively, and 0.9490, 0.9157, and 0.9708 on Dataset 2, respectively. Furthermore, AUPRs of 0.8903, 0.9061, and 0.9166 under three cross-validations were obtained on Dataset 1, and 0.9582, 0.9122, and 0.9743 on Dataset 2. The results demonstrate that LDAenDL significantly outperformed the other four classical LDA prediction methods (i.e., SDLDA, LDNFSGB, IPCAF, and LDASR). Case studies demonstrate that CCDC26 and IFNG-AS1 may be new biomarkers of lung cancer, SNHG3 may associate with PDL1 for lung cancer, and HOTAIR and BDNF-AS may be potential biomarkers of neuroblastoma. Conclusion: We hope that the proposed LDAenDL method can help the development of targeted therapies for these two diseases.

Gene SH3BGRL3 regulates acute myeloid leukemia progression through circRNA_0010984 based on competitive endogenous RNA mechanism.

Introduction: Acute myeloid leukemia (AML) is a malignant proliferative disease affecting the bone marrow hematopoietic system and has a poor long-term outcome. Exploring genes that affect the malignant proliferation of AML cells can facilitate the accurate diagnosis and treatment of AML. Studies have confirmed that circular RNA (circRNA) is positively correlated with its linear gene expression. Therefore, by exploring the effect of SH3BGRL3 on the malignant proliferation of leukemia, we further studied the role of circRNA produced by its exon cyclization in the occurrence and development of tumors. Methods: Genes with protein-coding function obtained from the TCGA database. we detected the expression of SH3BGRL3 and circRNA_0010984 by real-time quantitative polymerase chain reaction (qRT-PCR). We synthesized plasmid vectors and carried out cell experiments, including cell proliferation, cell cycle and cell differentiation by cell transfection. We also studied the transfection plasmid vector (PLVX-SHRNA2-PURO) combined with a drug (daunorubicin) to observe the therapeutic effect. The miR-375 binding site of circRNA_0010984 was queried using the circinteractome databases, and the relationship was validated by RNA immunoprecipitation and Dual-luciferase reporter assay. Finally, a protein-protein interaction network was constructed with a STRING database. GO and KEGG functional enrichment identified mRNA-related functions and signaling pathways regulated by miR-375. Results: We identified the related gene SH3BGRL3 in AML and explored the circRNA_0010984 produced by its cyclization. It has a certain effect on the disease progression. In addition, we verified the function of circRNA_0010984. We found that circSH3BGRL3 knockdown specifically inhibited the proliferation of AML cell lines and blocked the cell cycle. We then discussed the related molecular biological mechanisms. CircSH3BGRL3 acts as an endogenous sponge for miR-375 to isolate miR-375 and inhibits its activity, increases the expression of its target YAP1, and ultimately activates the Hippo signaling pathway involved in malignant tumor proliferation. Discussion: We found that SH3BGRL3 and circRNA_0010984 are important to AML. circRNA_0010984 was significantly up-regulated in AML and promoted cell proliferation by regulating miR-375 through molecular sponge action.

Identifying the intervention mechanisms of polydatin in hyperuricemia model rats by using UHPLC-Q-Exactive Orbitrap mass spectroscopy metabonomic approach.

Introduction: Polydatin is a biologically active compound found in mulberries, grapes, and Polygonum cuspidatum, and it has uric acid-lowering effects. However, its urate-lowering effects and the molecular mechanisms underlying its function require further study. Methods: In this study, a hyperuricemic rat model was established to assess the effects of polydatin on uric acid levels. The body weight, serum biochemical indicators, and histopathological parameters of the rats were evaluated. A UHPLC-Q-Exactive Orbitrap mass spectrometry-based metabolomics approach was applied to explore the potential mechanisms of action after polydatin treatment. Results: The results showed a trend of recovery in biochemical indicators after polydatin administration. In addition, polydatin could alleviate damage to the liver and kidneys. Untargeted metabolomics analysis revealed clear differences between hyperuricemic rats and the control group. Fourteen potential biomarkers were identified in the model group using principal component analysis and orthogonal partial least squares discriminant analysis. These differential metabolites are involved in amino acid, lipid, and energy metabolism. Of all the metabolites, the levels of L-phenylalanine, L-leucine, O-butanoylcarnitine, and dihydroxyacetone phosphate decreased, and the levels of L-tyrosine, sphinganine, and phytosphingosine significantly increased in hyperuricemic rats. After the administration of polydatin, the 14 differential metabolites could be inverted to varying degrees by regulating the perturbed metabolic pathway. Conclusion: This study has the potential to enhance our understanding of the mechanisms of hyperuricemia and demonstrate that polydatin is a promising potential adjuvant for lowering uric acid levels and alleviating hyperuricemia-related diseases.

Protopanaxadiol manipulates gut microbiota to promote bone marrow hematopoiesis and enhance immunity in cyclophosphamide-induced immunosuppression mice.

Protopanaxadiol (PPD) has potential immunomodulatory effects, but the underlying mechanism remains unclear. Here, we explored the potential roles of gut microbiota in the immunity regulation mechanisms of PPD using a cyclophosphamide (CTX)-induced immunosuppression mouse model. Our results showed that a medium dose of PPD (PPD-M, 50 mg/kg) effectively ameliorated the immunosuppression induced by CTX treatment by promoting bone marrow hematopoiesis, increasing the number of splenic T lymphocytes and regulating the secretion of serum immunoglobulins and cytokines. Meanwhile, PPD-M protected against CTX-induced gut microbiota dysbiosis by increasing the relative abundance of Lactobacillus, Oscillospirales, Turicibacter, Coldextribacter, Lachnospiraceae, Dubosiella, and Alloprevotella and reducing the relative abundance of Escherichia-Shigella. Importantly, PPD-M lost the ability to promote bone marrow hematopoiesis and enhance immunity when the gut microbiota was depleted by broad-spectrum antibiotics. Moreover, PPD-M promoted the production of microbiota-derived immune-enhancing metabolites including cucurbitacin C, l-gulonolactone, ceramide, DG, prostaglandin E2 ethanolamide, palmitoyl glucuronide, 9R,10S-epoxy-stearic acid, and 9'-carboxy-gamma-chromanol. KEGG topology analysis showed that the PPD-M treatment significantly enriched the sphingolipid metabolic pathway with ceramide as a main metabolite. Our findings reveal that PPD enhances immunity by manipulating gut microbiota and has the potential to be used as an immunomodulator in cancer chemotherapy.

Statins Are Associated with Improved Survival of Patients with Gastric Cancer: A Systematic Review and Meta-Analysis.

Statins are associated with gastric cancer (GC) risk. The present study aimed to clarify the efficacy of statins on the overall survival (OS) benefits in patients with GC. Publications were retrieved from PubMed, Embase, and the Cochrane Library as of April 2022. Data from the eligible cohort, case-control studies, and randomized control trials (RCTs) were extracted for the meta-analysis. Hazard ratio (HR) and 95% confidence intervals (CI) were used to assess the association between statins users and OS in GC patients. Subgroup analysis was performed based on the study design (prospective vs. retrospective). A total of 6 studies encompassing 5693 GC patients were included. Statins added to the standard treatment prolonged the patient's OS outcome (HR (95% CI): 0.72 (0.53-0.97), p = 0.032; I 2 = 88.0%, p heterogeneity < 0.001). A prospective study did not find any statistically significant difference in OS between statins users vs. nonstatin users (HR (95% CI): 0.92 (0.68-1.26), p = 0.614; I 2 = 11.7%, p heterogeneity = 0.322), whereas the retrospective studies showed prolonged OS in statins users (HR (95% CI): 0.63 (0.42-0.961), p = 0.032; I 2 = 94.6%, p heterogeneity < 0.001). Statin users had significantly improved OS compared to nonstatin users in GC treatment. This long-term survival benefit was only observed in the pooled analysis of retrospective studies but not in prospective studies.

Mental health of new undergraduate students before and after COVID-19 in China.

The purpose of this study was to examine the changes in severity of anxiety and depression symptoms, stress and sleeping quality after three months of mass quarantine for COVID-19 among undergraduate fresh students compared to their pre-COVID-19 measures. We used participants from the Chinese Undergraduate Cohort (CUC), a national prospective longitudinal study to examine the changes in anxiety and depression symptoms severity, stress and sleep quality after being under mass quarantine for three months. Wilcoxon matched pair signed-rank test was used to compare the lifestyle indicators. Severity of anxiety, depression symptoms, stress and sleep quality were compared with Wilcoxon signed-rank test. We used generalized estimating equation (GEE) to further quantify the change in mental health indicators and sleep quality after the COVID-19 mass quarantine compared to baseline. This study found that there was no deterioration in mental health status among Chinese new undergraduate students in 2020 after COVID-19 mass quarantine compared with the baseline measures in 2019. There was an improvement in sleep quality and anxiety symptoms. After adjusting for age, sex, exercise habit, time spent on mobile gadgets, and time spent outdoors, year 2020 was significantly associated with severity of depression symptoms in males (OR:1.52. 95%CI:1.05-2.20, p-value = 0.027). Year 2020 was significantly associated with the improvement of sleeping quality in total (OR:0.45, 95%CI:0.38-0.52, p < 0.001) and in all the subgroups. This longitudinal study found no deterioration in mental health status among Chinese new undergraduate students after three months of mass quarantine for COVID-19.

Genomic Sequence Analysis of Bombyx mori Nucleopolyhedrovirus Isolated from Yunnan Sericulture Region, China.

The blood pathogens of grasserie caused by Bombyx mori nucleopolyhedrovirus BmNPV have a serious impact on the sericulture industry. To understand the genetic status of BmNPV endemic strains in the Yunnan sericulture region, the structure and complete genome sequence of BmNPV isolated from Baoshan city of Yunnan Province were described and compared to known strains. The BmNPV-Baoshan isolate was a nucleopolyhedrovirus parasitized in silkworm larvae. Its genome has 128, 452 bp with a G + C content of 40.4%. Phylogenetic analysis clustered the virus with China BmNPV isolates; BmNPV-Baoshan was closely related to BomaNPV-S1 (both strains originated from the same ancestor). BmNPV-Baoshan strain has bro-b gene deletion, hr1 missing 4 repeat units of 30-bp palindrome structure compared to BmNPV-T3 strain. The aim of this study was to elucidate the evolution of the virus further and provide insights for the protection of virus-induced hematologic sepsis.

Role of platelet infiltration as independent prognostic marker for gastric adenocarcinomas.

BACKGROUND: In recent years, the relationship between malignant tumors and platelets has been paid more attention. The increase of platelets is an independent risk factor for the poor prognosis of some malignant tumors. METHODS: This study retrospectively analyzed the clinical and pathological data of 114 patients with initial gastric cancer from August 2005 to August 2018 in Shandong Provincial Hospital. Single-factor and multifactor survival analysis were used to evaluate the effect of platelet elevation on postoperative survival. The gastric cancer tissues of the Jinan Central Hospital and its matched paracancerous tissues were collected. The expression of platelets in tissues was detected by immunofluorescence technique. Different numbers of platelets were co-cultured with MKN-45 cells, CCK-8 assay and transwell assay were performed, and the expression of epithelial-mesenchymal transition-related proteins was detected. RESULTS: Platelet count was independent factors affecting prognosis. The stratified analysis showed that there was a statistically significant difference in the 5-year survival rate between the platelet-increase group and the normal platelet group in the TNM stages I-II. The expression of platelets in gastric cancer tissues was higher than that in adjacent tissues. The results of CCK-8 and transwell showed that platelets significantly enhanced the proliferation and metastasis capability of MKN-45 cells in a concentration-dependent manner. After co-culture, the expression level of E-cadherin protein in MKN-45 cells decreased, and the protein expression levels of N-cadherin, vimentin, and VEGFA increased. CONCLUSION: Platelet elevation is closely related to the occurrence, development, and metastasis of gastric cancer, and platelet count can be used as a prognostic indicator for malignant tumors.

Analytical comparison between two hematological analyzer systems: Mindray BC-5180 vs Sysmex XN-1000.

BACKGROUND: To compare the Mindray BC-5180 and Sysmex XN-1000 instruments by analyzing the results of complete blood count in the external quality assessment in Shandong Province in 2018. METHODS: In the external quality assessment, 10 batches of quality control materials were issued throughout the year. The test items were WBC, RBC, Hb, PLT, and HCT. The laboratories using Mindray BC-5180 and Sysmex XN-1000 were screened, and the results were analyzed by t test, Passing-Bablok regression analysis, and Bland-Altman analysis. RESULTS: Thirty-six laboratories using Mindray BC-5180 instruments and thirty-six laboratories using Sysmex XN-1000 instruments were screened, and the average difference between the two instruments results is not significant (P > 0.05, t test). Passing-Bablok regression analysis showed that the 95% confidence interval of the regression equation interception of each test item included 0, and the 95% confidence interval of the slope contained 1, r > 0.98, which showed that the correlation is good. The Bland-Altman analysis showed that both instruments had more than 95% of the points within the 95% consistency limit (WBC97.2%, RBC95.6%, PLT97.2%, Hb96.7%, HCT97.5%). Within the consistency limit, the absolute value of the difference between the Mindray BC-5180 instrument and the Sysmex XN-1000 instrument is WBC 0.14%, RBC 0.26%, PLT 2.7%, and Hb 1.9%. HCT is 0.69%, and the difference is clinically acceptable. CONCLUSION: It can be considered that the two instruments have good correlation and consistency, and the two instruments can replace each other.

[The up-regulated expression of LAIR-1 in tumor patients PBMC].

AIM: To investigate the expression of LAIR-1 in patients with tumors and the function of LAIR-1 in anticancer immunity. METHODS: A sandwich ELISA was employed to detect the serum sLAIR-1 from tumor patients and healthy individuals. The expression of LAIR-1 in CD4+ T cells, CD8+ T cells, NK cells and B cells isolated from the peripheral blood of cancer patients was examined by fluorescence staining and flow cytometry. RESULTS: The level of serum sLAIR-1 in tumor patients was higher than that in healthy individuals [4.6+/-3.2 microg/L vs 3.9+/-3.0 microg/L, P<0.05]. NK cells, CD4+ T cells and CD8+ T cells expressed the up-regulated LAIR-1. The ratio of CD4/CD8 in lung cancer patients decreased significantly while the percentage of B cells in cancer patients increased greatly compared with healthy individuals. CONCLUSION: The expression of LAIR-1 is up-regulated in tumor patients, which may contribute to cancer immune escape.