The Identification of Gamma-Glutamyl Hydrolase in Uterine Corpus Endometrial Carcinoma: a Predictive Model and Machine Learning.

BACKGROUND: Poor neoplastic differentiation contributes to the rapid progression of uterine corpus endometrial carcinoma (UCEC). Thus, it is essential to identify candidate genes, clarifying the carcinogenesis and progression of UCEC. METHODS: We screened genes that affect differentiation and prognosis in UCEC. Least absolute selection and shrinkage operator (LASSO) regression, univariate Cox, and multivariate Cox proportional risk regression analyses were performed to screen out γ-glutamyl hydrolase (GGH) as the candidate gene. The clinical value of GGH on prognosis was evaluated. The relationship between GGH and immune infiltration was assessed by CIBERSORT, EPIC, ssGSEA, unsupervised clustering and immunohistochemistry (IHC). Additionally, we investigated the effect of GGH knockdown in vitro. RESULTS: Among the GGH, CDKN2A, and SIX1 genes, the impact of GGH was predominant on immune infiltration in UCEC. A nomogram containing GGH and other clinical features showed good predictive performance via curve analysis (DCA). In the functional analysis, GGH affected differentiation, tumour proliferation, and immune regulation. The immunosuppressive components were enriched in the GGH-high group, with poor immunotherapy efficacy. The study suggests that GGH may influence the progression of UCEC by regulating the glycolytic process. CONCLUSIONS: GGH is closely associated with various immune cell infiltrations. Our study demonstrates the prognostic role of GGH in carcinogenesis in UCEC.

Development of a Bioluminescent Imaging Mouse Model for SARS-CoV-2 Infection Based on a Pseudovirus System.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains widely pandemic around the world. Animal models that are sensitive to the virus are therefore urgently needed to evaluate potential vaccines and antiviral agents; however, SARS-CoV-2 requires biosafety level 3 containment. To overcome this, we developed an animal model using the intranasal administration of SARS-CoV-2 pseudovirus. As the pseudovirus contains the firefly luciferase reporter gene, infected tissues and the viral load could be monitored by in vivo bioluminescent imaging. We used the model to evaluate the protective efficacy of monoclonal antibodies and the tissue tropism of different variants. The model may also be a useful tool for the safe and convenient preliminary evaluation of the protective efficacy of vaccine candidates against SARS-CoV-2, as well as the treatment efficacy of anti-viral drugs.

Berberine Attenuates Cell Motility via Inhibiting Inflammation-Mediated Lysyl Hydroxylase-2 and Glycolysis.

Lysyl hydroxylase-2 (LH2) involves in the hydroxylation of telopeptide lysine residues during collagen deposition. Recent studies indicate that interleukin (IL)-6 generated by the chronic inflammation disease may trigger the LH2 expression to accelerate cell motility. Berberine is the alkaloid derived from the traditional Chinese medicine Coptis chinensis, which displays potential anti-inflammatory activity in multiple diseases. The anti-inflammatory activity of berberine has been confirmed by reducing proinflammatory cytokines such as IL-6, IL-8, and IFN-γ. However, whether and how berberine inhibits cellular motility against metastatic spread in triple-negative breast cancer (TNBC) has not been demonstrated, and the underlying mechanism remains unclear. We investigated the effects of berberine on the inflammatory cytokine secretion, cell proliferation, and migration in vitro and further explored the effect of berberine on growth and metastasis in vivo. Berberine restrained TNBC cell proliferation, motility, and glycolysis process in a dose-dependent way. The secretion of IL-6 was abrogated by berberine in TNBC cells, and IL-6-stimulated cell migration was inhibited by berberine. Mechanistically, berberine remarkably suppressed LH2 expression at both mRNA and protein levels. LH2 depletion led to decreasing the antimotility effect of berberine, and this phenomenon was related to the suppressed glycolysis after LH2 inhibition. Conversely, ectopic restoration of LH2 could further increase the antimotility effect of berberine. Moreover, berberine was confirmed to inhibit cell growth and motility in vivo, and the expression of LH2 and glycolytic enzymes was also blocked by berberine in vivo. Collectively, this study indicated that berberine could be a promising therapeutic drug via regulating LH2 for TNBC.

Epigenetic association study uncovered H3K27 acetylation enhancers and dysregulated genes in high-fat-diet-induced nonalcoholic fatty liver disease in rats.

Aim: To evaluate the regulatory landscape underlying the active enhancer marked by H3K27ac in high-fat diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) in rats. Materials & methods: H3K27ac chromatin immunoprecipitation and high-throughput RNA sequencing to construct regulatory profiles and transcriptome of liver from NAFLD rat model induced by HFD. De novo motif analysis for differential H3K27ac peaks. Functional enrichment, Kyoto Encyclopedia of Genes and Genomes pathway and protein-protein interaction network were examined for differential peak-genes. The mechanism was further verified by western blot, chromatin immunoprecipitation-quantitative PCR and real-time PCR. Results: A total of 1831 differential H3K27ac peaks were identified significantly correlating with transcription factors and target genes (CYP8B1, PLA2G12B, SLC27A5, CYP7A1 and APOC3) involved in lipid and energy homeostasis. Conclusion: Altered acetylation induced by HFD leads to the dysregulation of gene expression, further elucidating the epigenetic mechanism in the etiology of NAFLD.

What is this summary about? Nonalcoholic fatty liver disease (NAFLD) is a typical metabolic disease, which is becoming the most common liver disease in the world. Despite its high prevalence and morbidity, there is currently no effective diagnostic or approved therapy, and the molecular mechanisms for NAFLD have not been fully clarified, especially for epigenetics. Herein, we focused on histone modification and investigated the impact of active enhancer to explore the epigenetic regulation of NAFLD, seeking new targets for the prevention and treatment of the disease. What were the results? We identified the alteration of H3K27 acetylation and differential gene expression, enriched potential transcription-factor binding motifs and highlighted the hub risk genes of CYP8B1, PLA2G12B, SLC27A5, CYP7A1 and APOC3 in a NAFLD rat model. What do the results mean? This work emphasized the vital roles of histone modification of H3K27ac in a high-fat-diet-induced NAFLD model, which could regulate the expression of key genes and transcription factor binding motifs, and H3K27ac induced the formation of NAFLD. Targeting the H3K27ac modification, dysregulated target genes and enriched pathways may be of great importance for NAFLD prediction and prevention, and serve as a valuable resource for genome-wide studies of epigenomic regulation in lipid metabolic disease.

Effect of mechanochemical activation of natural phosphorite structure as well as phosphorus solubility.

Mechanochemical treatment of phosphate rock is considered as an effective and ecologically clean way of treating the medium- and low-grade phosphorite which could be used as fertilizer instead of the high-grade phosphorite. In order to investigate the effects of different milling times on the mechanochemically activated phosphorite (lower total phosphorus content) by more efficient milling equipment with enhanced milling speed, phosphorus solubility in citric acid and structural characteristics of natural and mechanochemically activated phosphorite from Yichang, China were studied using scanning electron microscope, infrared spectroscopy and X-ray diffraction. Phosphorus solubility in citric acid increased proportionately with the milling time until 30 min (57.51%), but then gradually reached an equilibrium with the maximum (59.03%) in 50 min. These changes were mainly manifested in considerably reduced particle size, decreased crystallinity and increased structural defects of phosphorite due to substitution of PO43- with CO32- and the incorporation of OH-. With the incorporation of CO32- and OH-, the non-activated carbonate-fluorapatite (type B) was transformed into a mixture of carbonate-fluorapatite, hydroxyapatite, fluorocarbon hydroxyapatite and/or carbonate apatite, respectively during the process of mechanochemical activation. As a result of the structural and phase transformations after mechanochemical activation, phosphorus solubility remarkably increased.

[The Study of Organic Nitrogen Uptake by Soil Microorganisms Using Gas Chromatography-Mass Spectrometry and Double Isotope Labeling Technique].

The direct absorption and utilization of low-molecular weight organic nitrogen (N) by soil microbial is a new subject in the research of microbial N nutrition. The study used gas chromatography-mass spectrometry to trace dual-labeled (13C, 15N) glycine from the soil solution and microorganisms. The results showed that glycine added to the soil was quickly taken up by soil microorganisms, with the half-life of glycine being 2.9 h. Withthe incubation of 4 h, the maximum amount of dual-labeled glycine in the microbial biomass was measured (equivalent to 10% of glycine added), indicating that added glycine was absorbed as intact molecular by soil microorganisms. The single labeled-Keto acid was detected in soil solution and in the microorganisms (decomposed production by double labeled glycine), but the content is extremely low, suggesting that added glycine mainly served as carbon (C) source for soil microbial life activities. This study demonstrated that compound specific stable dual labeled isotope analysis combined with chloroform fumigation technique was an effective method for detecting the low-molecular organic N utilized by soil microorganisms.