Potential Prognostic Value and Mechanism of Stromal-Immune Signature in Tumor Microenvironment for Stomach Adenocarcinoma

Stomach adenocarcinoma (STAD) is one of the most common malignancies. But the molecular mechanism is unknown. In this study, we downloaded the transcriptional profiles and clinical data of 344 STAD and 30 normal samples from The Cancer Genome Atlas (TCGA) database. Stromal and immune scores of STAD were calculated by the Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) algorithm, and association of stromal/immune scores with tumor differentiation/T/N/M stage and survival was investigated. The differentially expressed genes (DEGs) between high and low score groups (based on media) were identified, and prognostic genes over-/underexpressed in both STAD and stromal/immune signature were retrieved. Furthermore, proportions of 22 infiltrating immune cells for the cohort from TCGA were estimated by the Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm, and association of 22 immune cells with tumor differentiation/T/N/M stage and survival was investigated. Next, coexpression analysis of 22 immune cells and intersection genes over-/underexpressed in both STAD and stromal signature was conducted. We found high stromal and immune scores and macrophage infiltration predicting poor tumor differentiation and severe local invasion, obtained a list of prognostic genes based on stromal-immune signature, and explored the interaction of collagen, chemokines such as CXCL9, CXCL10, and CXCL11, and macrophage through coexpression analysis and may provide novel prognostic biomarkers and immunotherapeutic targets for STAD

Metabolomics and transcriptomics of embryonic livers reveal hypoxia adaptation of Tibetan chickens

Abstract Background Exploring the hypoxia adaptation mechanism of Tibetan chicken is of great significance for revealing the survival law of Tibetan chicken and plateau animal husbandry production. To investigate the hypoxia adaptation of Tibetan chickens (TBCs), an integrative metabolomic-transcriptomic analysis of the liver on day 18 of embryonic development was performed. Dwarf laying chickens (DLCs), a lowland breed, were used as a control. Results A total of 1,908 metabolites were identified in both TBCs and DLCs. Energy metabolism and amino acid metabolism related differentially regulated metabolites (DRMs) were significantly enriched under hypoxia. Important metabolic pathways including the TCA cycle and arginine and proline metabolism were screened; PCK1, SUCLA2, and CPS1 were found to be altered under hypoxic conditions. In addition, integrated analysis suggested potential differences in mitochondrial function, which may play a crucial role in the study of chicken oxygen adaptation. Conclusions These results suggest that hypoxia changed the gene expression and metabolic patterns of embryonic liver of TBCs compared to DLCs. Our study provides a basis for uncovering the molecular regulation mechanisms of hypoxia adaptation in TBCs with the potential application of hypoxia adaptation research for other animals living on the Qinghai-Tibet plateau, and may even contribute to the study of diseases caused by hypoxia

The Accordant Trend of Both Parameters (rgs Expression and cAMP Content) Follows the Pattern of Development of Fruiting Body in Volvariella volvacea

The formation of fruiting body in Volvariella volvacea is affected by endogenous genes and environmental factors. However, its regulation at a molecular level is still poorly understood. To study the genes involved in the formation of fruiting body, we cloned a new regulator of the G protein signaling (RGS) encoding gene (rgs) from V. volvacea. Phylogenetic analysis showed that RGS in V. volvacea and other basidiomycete RGS proteins from Schizophyllum commune and Coprinus cinereus belong to the same clade. In addition, we assayed intracellular cAMP content in the three developmental stages (mycelium, fruiting body primordia, and button). We also found that the expression of rgs was highly positively correlated to the content of intracellular cAMP during fruiting body formation. The conserved protein sequences and expression of rgs, together with high concent of cAMP at primordia tissue, suggested that rgs gene and cAMP may play a crucial role in fruiting body formation in V. volvacea.</p

Cloning and Expression Analysis of Vvlcc3, a Novel and Functional Laccase Gene Possibly Involved in Stipe Elongation

Volvariella volvacea, usually harvested in its egg stage, is one of the most popular mushrooms in Asia. The rapid transition from the egg stage to elongation stage, during which the stipe stretches to almost full length leads to the opening of the cap and rupture of the universal veil, and is considered to be one of the main factors that negatively impacts the yield and value of V. volvacea. Stipe elongation is a common phenomenon in mushrooms; however, the mechanisms, genes and regulation involved in stipe elongation are still poorly understood. In order to study the genes related to the stipe elongation, we analyzed the transcription of laccase genes in stipe tissue of V. volvacea, as some laccases have been suggested to be involved in stipe elongation in Flammulina velutipes. Based on transcription patterns, the expression of Vvlcc3 was found to be the highest among the 11 laccase genes. Moreover, phylogenetic analysis showed that VvLCC3 has a high degree of identity with other basidiomycete laccases. Therefore, we selected and cloned a laccase gene, named Vvlcc3, a cDNA from V. volvacea, and expressed the cDNA in Pichia pastoris. The presence of the laccase signature L1-L4 on the deduced protein sequence indicates that the gene encodes a laccase. Phylogenetic analysis showed that VvLCC3 clusters with Coprinopsis cinerea laccases. The ability to catalyze ABTS (2,2’-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) oxidation proved that the product of the Vvlcc3 gene was a functional laccase. We also found that the expression of the Vvlcc3 gene in V. volvacea increased during button stage to the elongation stage; it reached its peak in the elongation stage, and then decreased in the maturation stage, which was similar to the trend in the expression of Fv-lac3 and Fv-lac5 in F. velutipes stipe tissue. The similar trend in expression level of these laccase genes of F. velutipes suggested that this gene could be involved in stipe elongation in V. volvacea

The lead time and geographical variations of Baidu Search Index in the early warning of COVID-19

Abstract Internet search data was a useful tool in the pre-warning of COVID-19. However, the lead time and indicators may change over time and space with the new variants appear and massive nucleic acid testing. Since Omicron appeared in late 2021, we collected the daily number of cases and Baidu Search Index (BSI) of seven search terms from 1 January to 30 April, 2022 in 12 provinces/prefectures to explore the variation in China. Two search peaks of “COVID-19 epidemic”, “Novel Coronavirus” and “COVID-19” can be observed. One in January, which showed 3 days lead time in Henan and Tianjin. Another on early March, which occurred 0–28 days ahead of the local epidemic but the lead time had spatial variation. It was 4 weeks in Shanghai, 2 weeks in Henan and 5–8 days in Jilin Province, Jilin and Changchun Prefecture. But it was only 1–3 days in Tianjin, Quanzhou Prefecture, Fujian Province and 0 day in Shenzhen, Shandong Province, Qingdao and Yanbian Prefecture. The BSI was high correlated (rs:0.70–0.93) to the number of cases with consistent epidemiological change trend. The lead time of BSI had spatial and temporal variation and was close related to the strength of nucleic acid testing. The case detection ability should be strengthened when perceiving BSI increase

Disease burden of prostate cancer from 2014 to 2019 in the United States: estimation from the Global Burden of Disease Study 2019 and Medical Expenditure Panel Survey

OBJECTIVES The aim of this study was to evaluate the disease burden of prostate cancer (PC) and assess key influencing factors associated with the disease expenditures of PC in the United States. METHODS The total deaths, incidence, prevalence, and disability-adjusted life-years of PC were obtained from the Global Burden of Disease Study 2019. The Medical Expenditure Panel Survey was used to estimate healthcare expenditures and productivity loss and to investigate patterns of payment and use of healthcare resources in the United States. A multivariable logistic regression model was conducted to identify key factors influencing expenditures. RESULTS For patients aged 50 and older, the burden for all age groups showed a modest increase over the 6-year period. Annual medical expenditures were estimated to range from US$24.8 billion to US$39.2 billion from 2014 to 2019. The annual loss in productivity for patients was approximately US$1,200. The top 3 major components of medical costs were hospital inpatient stays, prescription medicines, and office-based visits. Medicare was the largest source of payments for survivors. In terms of drug consumption, genitourinary tract agents (57.0%) and antineoplastics (18.6%) were the main therapeutic drugs. High medical expenditures were positively associated with age (p=0.005), having private health insurance (p=0.016), more comorbidities, not currently smoking (p=0.001), and patient self-perception of fair/poor health status (p<0.001). CONCLUSIONS From 2014 to 2019, the national real-world data of PC revealed that the disease burden in the United States continued to increase, which was partly related to patient characteristics