Phosphatidylinositol glycan anchor biosynthesis, class C is a prognostic biomarker and correlates with immune infiltrates in hepatocellular carcinoma.

Background and aims: The exact function of Phosphatidylinositol Glycan Anchor Biosynthesis, Class C (PIGC) gene has yet to be elucidated. In the study, we attempted to clarify the correlations of PIGC to prognosis and tumor-infiltrating lymphocytes in hepatocellular carcinoma (HCC). Methods: PIGC expression was analyzed via the Oncomine database, Gene Expression Profiling Interactive Analysis, Hepatocellular carcinoma data base, Human Protein Atlas database and Tumor Immune Estimation Resource (TIMER). We showed the correlation of PIGC with the clinical characteristics using UALCAN. We evaluated the influence of PIGC on clinical prognosis using Kaplan-Meier plotter databases. And co-expressed genes with PIGC and its regulators were identified using LinkedOmics. The correlations between PIGC and cancer immune infiltrates were investigated via TIMER. We analyzed the drug sensitivity and immunotherapy response via R package. Results: PIGC was found up-regulated in tumor tissues in multiple HCC cohorts, also increased in HCC patient with different clinical characteristics. High PIGC expression was associated with poorer overall survival. PIGC expression showed a strong positive association with the expression of ACBD6, a strong negative association with AGXT212. The cell components and distribution in treatment and non-treatment of HCC patients were quite distinct, which may reveal the relationship between the immunotherapy with tumor microenvironment. Notably, PIGC expression was positively correlated with infiltrating levels of immune cells. Conclusion: These findings suggest that PIGC is correlated with prognosis and immune infiltrating in HCC, which can be used as a prognostic biomarker for determining prognosis, laying a foundation for further study of the immune regulatory role of PIGC in HCC.

Construction of a Pyroptosis-Related Genes Signature to Improve the Prognostic Prediction and Therapeutic Drugs Selection in Patients with Pancreatic Cancer.

Background: Effective prognostic assessment and appropriate drug selection are important for the clinical management of pancreatic cancer (PaC). Here, we aimed to establish a pyroptosis-associated genes (PRGs) signature to predict the prognostic outcomes of PaC and guide clinical drug therapy. Methods: We identified the differentially expressed PRGs between pancreatic adenocarcinoma (n = 178) and control pancreas samples (n = 171) obtained from different databases, and performed Lasso and Cox regression analysis to create a prognosis signature. Kaplan-Meier (K-M) survival curves and time-dependent receiver operating characteristics were further constructed to assess the utility of the risk model. The International Cancer Genome Consortium (ICGC) PACA-AU cohort (n = 95) was used as a validation dataset to examine the validity of this prognostic model. The correlations of risk score (RS) with clinical features, immune cell infiltration, tumor mutation burden and half-maximal inhibitory concentrations (IC50) of chemotherapeutic drugs were analyzed, and the expression levels of PRGs in cell lines were detected. Results: A prognostic signature was constructed, which consisted of 4 PRGs (AIM2, IL18, GSMDC and PLCG1). K-M analysis demonstrated a remarkable difference in overall survival (OS) time between low-risk (LR) and high-risk (HR) groups (P < 0.001). The RS contributed to the progression of PaC, and could be a significant independent factor for prognostic prediction. The validation of the ICGC cohort confirmed the effectiveness of the proposed signature. The patients with a HR score in the TCGA cohort had higher tumor mutation burden and more sensitivity to paclitaxel, gemcitabine, 5-fluorouracil and cisplatin than those with a LR score. The differential expression levels of signature genes were verified in vitro. Conclusion: The PRGs signature can be applied for predicting the prognosis of PaC, and may provide useful information for selection of therapeutic drugs.

Heterogeneous epidemic modelling within an enclosed space and corresponding Bayesian estimation.

Since March 11th, 2020, COVID-19 has been a global pandemic for more than one years due to a long and infectious incubation period. This paper establishes a heterogeneous epidemic model that divides the incubation period into infectious and non-infectious and employs the Bayesian framework to model the 'Diamond Princess' enclosed space incident. The heterogeneity includes two different identities, two transmission methods, two different-size rooms, and six transmission stages. This model is also applicable to similar mixed structures, including closed schools, hospitals, and communities. As the COVID-19 pandemic continues, our mathematical modeling can provide management insights to the governments and policymakers on how the COVID-19 disease has spread and what prevention strategies still need to be taken.

High-efficiency genome editing of an extreme thermophile Thermus thermophilus using endogenous type I and type III CRISPR-Cas systems.

Thermus thermophilus is an attractive species in the bioindustry due to its valuable natural products, abundant thermophilic enzymes, and promising fermentation capacities. However, efficient and versatile genome editing tools are not available for this species. In this study, we developed an efficient genome editing tool for T. thermophilus HB27 based on its endogenous type I-B, I-C, and III-A/B CRISPR-Cas systems. First, we systematically characterized the DNA interference capabilities of the different types of the native CRISPR-Cas systems in T. thermophilus HB27. We found that genomic manipulations such as gene deletion, mutation, and in situ tagging could be easily implemented by a series of genome-editing plasmids carrying an artificial self-targeting mini-CRISPR and a donor DNA responsible for the recombinant recovery. We also compared the genome editing efficiency of different CRISPR-Cas systems and the editing plasmids with donor DNAs of different lengths. Additionally, we developed a reporter gene system for T. thermophilus based on a heat-stable ß-galactosidase gene TTP0042, and constructed an engineered strain with a high production capacity of superoxide dismutases by genome modification.

Integrated Analysis of FAM57A Expression and Its Potential Roles in Hepatocellular Carcinoma.

BACKGROUND: Family with sequence similarity 57 member A (FAM57A) is a membrane associated gene contributing to lung carcinogenesis. In hepatocellular carcinoma (HCC) and other cancers, whether FAM57A exerts similar roles has been rarely reported. Herein, the biological functions and clinical significance of FAM57A in HCC were explored. METHODS: Initially the differential expression of FAM57A between nontumor and HCC tissues was validated using a number of publicly accessible databases and immunohistochemistry (IHC). Then, the Kruskal-Wallis rank sum test or the Wilcoxon rank sum test as well as logistic regression were employed to analyze the association of FAM57A expression with clinical characteristics of HCC. The Cox regression and Kaplan-Meier analyses were conducted to assess the prognostic significance. Besides, with the coexpression analysis, Gene Ontology (GO), Gene Set Enrichment Analysis (GSEA), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, the molecular pathomechanisms that were mediated by FAM57A in HCC were elucidated. Furthermore, the correlations between FAM57A expression and tumor-infiltrating immune cells (TIICs) or immune checkpoint genes were analyzed. Finally, in vitro cell functional assay was carried out to preliminarily verify the role of FAM57A in HCC. RESULTS: FAM57A expression was demonstrated to be higher in HCC samples than in nontumor samples (all p-values <0.05), statistically correlated with clinicopathological characteristics (clinical stage, T stage, pathological grade), and inversely correlated to HCC patient survival. Univariate and multivariate Cox regression analyses showed that FAM57A expression could independently predict prognosis in HCC patients. Functional enrichment analyses further indicated that FAM57A was involved in multiple tumor-related pathways. FAM57A expression was positively correlated with TIICs, gene markers of TIICs, as well as immune checkpoint genes. Also, high expression of FAM57A predicted a poor prognosis for HCC based on immune cell subgroups. Functional assay of FAM57A knockdown significantly inhibited cell proliferation and induced cell apoptosis in HCC cells. CONCLUSIONS: Our results indicated that FAM57A could be used as a biomarker to predict the prognosis and immunotherapy response for HCC patients and might function as an oncogene to promote HCC progression.

High Expression Levels of SLC38A1 Are Correlated with Poor Prognosis and Defective Immune Infiltration in Hepatocellular Carcinoma.

Solute Carrier Family 38 Member 1 (SLC38A1) is a principal transporter of glutamine and plays a crucial role in the transformation of neoplastic cells. However, the correlation between SLC38A1 expression, prognosis, and immune infiltration in hepatocellular carcinoma (HCC) has yet to be elucidated. We used two independent patient cohorts, namely, a Cancer Genome Atlas (TCGA) cohort and a Clinical Proteomic Tumor Analysis Consortium (CPTAC) cohort, to analyze the role of SLC38A1 in HCC at the mRNA and protein levels, respectively. In these two cohorts, SLC38A1 mRNA and protein expression levels were higher in HCC tissues than in adjacent nontumor tissues. Both SLC38A1 mRNA and protein expression were positively associated with clinicopathological characteristics (clinical stage, T stage, pathological grade, tumor size, and tumor thrombus), were negatively associated with survival, and were independent prognostic factors in HCC patients. Functional enrichment analyses further indicated that SLC38A1 was involved in multiple pathways related to amino acid metabolism, tumors, and immunity. High expression levels of SLC38A1 were inversely proportional to CD8+ T cells and directly proportional to macrophages M0, neutrophils, programmed cell death-1/programmed cell death ligand 1 (PD-1/PD-L1), and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). Moreover, we used immunohistochemical analysis of tissue samples and other online databases to further validate the expression levels and prognostic significance of SLC38A1 in HCC. Collectively, our study demonstrated that the upregulated expression of SLC38A1 was related to an unfavorable prognosis and defective immune infiltration in HCC.

Dissimilatory nitrate reduction and functional genes in two subtropical rivers, China.

Dissimilatory nitrate reduction processes, including denitrification, anaerobic ammonium oxidation (anammox), and dissimilatory nitrate reduction to ammonium (DNRA), are important pathways of nitrate transformation in the aquatic environments. In this study, we investigated potential rates of denitrification, anammox, and DNRA in the sediments of two subtropical rivers, Jinshui River and Qi River, with different intensities of human activities in their respective catchment, China. Our objectives were to assess the seasonality of dissimilatory nitrate reduction rates, quantify their respective contributions to nitrate reduction, and reveal the relationship between dissimilatory nitrate reduction rates, functional gene abundances, and physicochemicals in the river ecosystems. Our results showed higher rates of denitrification and anammox in the intensively disturbed areas in autumn and spring, and higher potential DNRA in the slightly disturbed areas in summer. Generally, denitrification, anammox, and DNRA were higher in summer, autumn, and spring, respectively. Relative contributions of nitrate reduction from denitrification, anammox, and DNRA were quite different in different seasons. Dissimilatory nitrate reduction rates and gene abundances correlated significantly with water temperature, dissolved organic carbon (DOC), sediment total organic carbon (SOC), NO3-, NH4+, DOC/NO3-, iron ions, and sulfide. Understanding dissimilatory nitrate reduction is essential for restoring nitrate reduction capacity and improving and sustaining ecohealth of the river ecosystems.

Identification of the molecular targets and mechanisms of compound mylabris capsules for hepatocellular carcinoma treatment through network pharmacology and bioinformatics analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese herbal formulas have been proven to exert an inhibitory effect on tumor. Compound mylabris capsules (CMC) has been used for treating cancer, especially hepatocellular carcinoma (HCC), for years in China. However, its therapeutic mechanisms on HCC remain unclear. AIM OF THE STUDY: This research aimed to elucidate the molecular targets and mechanisms of CMC for treating HCC. MATERIALS AND METHODS: First, the bioactive ingredients and potential targets of CMC, as well as HCC-related targets were retrieved from publicly available databases. Next, the overlapped genes between potential targets of CMC and HCC-related targets were determined using bioinformatics analysis. Then, networks of ingredient-target and gene-pathway were constructed. Finally, cell experiments were carried out to examine the effects of CMC-medicated serum on HCC and validate the core molecular targets. RESULTS: In total, 151 bioactive ingredients and 255 potential targets of CMC were selected, 982 differentially expressed genes of HCC were identified. Among them, 34 overlapped genes were finally selected. In addition, 20 pathways and 429 GO terms were significantly enriched. Protein-protein interaction and gene-pathway networks indicated that Cyclin B1(CCNB1) and Cyclin Dependent Kinase 1(CDK1) were the core gene targets for the treatment of CMC on HCC. Moreover, in vitro studies showed that CMC-medicated serum significantly inhibited the viability of HepG2 cells. Furthermore, CMC downregulated CCNB1 and CDK1 expressions and induced G2/M phase cell cycle arrest. CONCLUSIONS: CMC plays a therapeutic role in HCC via multi-component, -target and -pathway mechanisms, in which CCNB1 and CDK1 may be the core molecular targets. This study indicates that the integration of network pharmacology and bioinformatics analysis, followed by experimental validation, can serves as an effective tool for studying the therapeutic mechanisms of traditional Chinese medicine.

[Structure Characteristics and Driving Variables of Epilithic Algae Community in Lhasa River Basin of Qinghai-Tibet Plateau].

In order to explore the characteristics and driving factors of the epilithic algae community in the middle and lower reaches of the Lhasa River, epilithic algae was collected and identified in September 2019, the species composition and spatial distribution were analyzed, and the key environmental factors affecting the epilithic algae community were identified through redundancy analysis. The results indicated that 31 genera of epilithic algae belonging to six phyla were identified, and the average cell density of the epilithic algae was 1.92×106 cells·m-2. The number of species and cell density of the diatom phylum were the largest at each sampling point. The species number and cell density of the epilithic algae were significantly different between the main stream and tributaries. The main stream and tributaries contained relatively small differences in the dominant algae genera, which were Gomphonema, Fragilaria, Cymbella, and Planktolyngbya in the main stream and Gomphonema, Fragilaria, Cymbella, and Oscillatoria in the tributaries. The redundancy analysis revealed that temperature, pH, and dissolved oxygen were the main driving factors affecting the community structure of the dominant genus in the main stream, while HCO3- and flow velocity controlled the community structure of the dominant genus in the tributaries. This study provides basic data and the theoretical basis for the conservation of aquatic ecosystems and water quality management in the middle and lower reaches of the Lhasa River.

Construction of Z-scheme Ag/In2S3/ZnO nanorods composite photocatalysts for degradation of 4-nitrophenol.

Herein, Ag/In2S3/ZnO nanorods (NRs) composite photocatalysts were successfully prepared via simple methods. Significantly, hydroxyl radical active substances were found in the electron spin resonance tests of In2S3/ZnO NRs and Ag/In2S3/ZnO NRs, which indicates that the oxidation reaction that oxidizes water or hydroxide ions into hydroxyl radicals occurs on the valence band of ZnO NRs. It suggests that Z-scheme heterojunction was successfully constructed. In the photocatalytic experiments of degrading 4-nitrophenol (PNP), the Ag/In2S3/ZnO NRs composite exhibits higher photocatalytic activity than ZnO NRs, In2S3, Ag/ZnO NRs and In2S3/ZnO NRs. The characteristic peak of PNP disappears completely in 50 min. The enhanced photocatalytic performance can be attributed to the formation of Z-scheme heterojunction between ZnO NRs and In2S3. In addition, local surface plasmon resonance of Ag and Schottky junction formed between Ag and In2S3 also promote the photocatalytic activity.

Aminoglycoside Antibiotics Inhibit Mycobacteriophage Infection.

Antibiotic resistance is becoming the biggest threat to global health. At the same time, phage therapy is witnessing a return of interest. The therapeutic use of bacteriophages that infect and kill bacteria is a suitable strategy to combat antibiotic resistance. Furthermore, bacteriophages are increasingly used in combination with standard antibiotics against drug-resistant pathogens. Interestingly, we found that the engineered mycobacteriophage phAE159 and natural phage D29 cannot infect the Mycobacterium tuberculosis in the presence of kanamycin, hygromycin or streptomycin, but the phage infection was not affected in the presence of spectinomycin. Based on a series of studies and structural analysis of the above four aminoglycoside antibiotics, it could be speculated that the amino sugar group of aminoglycoside might selectively inhibit mycobacteriophage DNA replication. Our discovery that broad-spectrum antibiotics inhibit phage infection is of great value. This study will provide guidance for people to combine phage and antibiotics to treat M. tuberculosis.

Raman Spectroscopy of Oxide-Embedded and Ligand-Stabilized Silicon Nanocrystals.

Oxide-embedded and oxide-free alkyl-terminated silicon (Si) nanocrystals with diameters ranging from 3 nm to greater than 10 nm were studied by Raman spectroscopy. For ligand-passivated nanocrystals, the zone center Raman-active mode of diamond cubic Si shifted to lower frequency with decreasing size, accompanied by asymmetric peak broadening, as extensively reported in the literature. The size dependence of the Raman peak shifts, however, was significantly more pronounced than previously reported or predicted by the RWL (Richter, Wang, and Ley) and bond polarizability models. In contrast, Raman peak shifts for oxide-embedded nanocrystals were significantly less pronounced as a result of the stress induced by the matrix.