Synthesis of Fluorescent and Water-Dispersed Germanium Nanoparticles and Their Cellular Imaging Applications

In recent years, Ge nanomaterials have aroused a great deal of attention because of their unique physical and chemical properties. However, the current synthesis methods bear some disadvantages, such as high reaction temperature, dangerous reagents, and inert atmospheres. In this paper, we developed a facile one-step route for preparing fluorescent and water-dispersed germanium nanoparticles (Ge NPs) by utilizing organogermanes as the precursor, operated at mild reactive conditions. The as-synthesized Ge NPs have an average diameter of 2.6 ± 0.5 nm and intense blue-green fluorescence (FL). Furthermore, the as-synthesized Ge NPs show remarkable water dispersibility, favorable biocompatibility, outstanding photostability, excellent storage stability, and low cytotoxicity. More importantly, these Ge NPs can act as a satisfactory FL probe and successfully be applied to cellular imaging of HeLa. The present study offers a simple and moderate strategy for the preparation of Ge NPs and expedites Ge NPs for bioimaging applications

Table_2_A novel pyroptosis gene expression-based risk score for survival in gastric cancer.xlsx

BackgroundGastric cancer (GC) is a highly heterogeneous disease, which makes treatment and prognosis prediction difficult. Pyroptosis plays a vital role in the development of GC and influence the prognosis of GC. Long non-coding RNAs (lncRNAs), as regulators of gene expressions, are among putative biomarkers and therapeutic targets. However, the importance of pyroptosis-associated lncRNAs is still unclear in predicting prognosis in gastric cancer.MethodsIn this study, the mRNA expression profiles and clinical data of GC patients were obtained from The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database. A pyroptosis-related lncRNA signature was constructed based on TCGA databases by using the Least Absolute Shrinkage and Selection Operator (LASSO) method Cox regression model. GC patients from the GSE62254 database cohort were used for validation. Univariate and multivariate Cox analyses were used to determine the independent predictors for OS. Gene set enrichment analyses were performed to explore the potential regulatory pathways. The immune cell infiltration level was analyzed via CIBERSORT.ResultsA four-pyroptosis-related lncRNA (ACVR2B-AS1, PRSS30P, ATP2B1-AS1, RMRP) signature was constructed using LASSO Cox regression analysis. GC patients were stratified into high- and low-risk groups, and patients in the high-risk group showed significant worse prognosis in TNM stage, gender, and age. The risk score was an independent predictor for OS by multivariate Cox analysis. Functional analysis indicated that the immune cell infiltrate was different between high- and low-risk groups.ConclusionThe pyroptosis-related lncRNA prognostic signature can be used for predicting prognosis in GC. Moreover, the novel signature might provide clinical therapeutic intervention for GC patients.</p

Table_1_A novel pyroptosis gene expression-based risk score for survival in gastric cancer.xlsx

BackgroundGastric cancer (GC) is a highly heterogeneous disease, which makes treatment and prognosis prediction difficult. Pyroptosis plays a vital role in the development of GC and influence the prognosis of GC. Long non-coding RNAs (lncRNAs), as regulators of gene expressions, are among putative biomarkers and therapeutic targets. However, the importance of pyroptosis-associated lncRNAs is still unclear in predicting prognosis in gastric cancer.MethodsIn this study, the mRNA expression profiles and clinical data of GC patients were obtained from The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database. A pyroptosis-related lncRNA signature was constructed based on TCGA databases by using the Least Absolute Shrinkage and Selection Operator (LASSO) method Cox regression model. GC patients from the GSE62254 database cohort were used for validation. Univariate and multivariate Cox analyses were used to determine the independent predictors for OS. Gene set enrichment analyses were performed to explore the potential regulatory pathways. The immune cell infiltration level was analyzed via CIBERSORT.ResultsA four-pyroptosis-related lncRNA (ACVR2B-AS1, PRSS30P, ATP2B1-AS1, RMRP) signature was constructed using LASSO Cox regression analysis. GC patients were stratified into high- and low-risk groups, and patients in the high-risk group showed significant worse prognosis in TNM stage, gender, and age. The risk score was an independent predictor for OS by multivariate Cox analysis. Functional analysis indicated that the immune cell infiltrate was different between high- and low-risk groups.ConclusionThe pyroptosis-related lncRNA prognostic signature can be used for predicting prognosis in GC. Moreover, the novel signature might provide clinical therapeutic intervention for GC patients.</p

Image_2_A novel pyroptosis gene expression-based risk score for survival in gastric cancer.tif

BackgroundGastric cancer (GC) is a highly heterogeneous disease, which makes treatment and prognosis prediction difficult. Pyroptosis plays a vital role in the development of GC and influence the prognosis of GC. Long non-coding RNAs (lncRNAs), as regulators of gene expressions, are among putative biomarkers and therapeutic targets. However, the importance of pyroptosis-associated lncRNAs is still unclear in predicting prognosis in gastric cancer.MethodsIn this study, the mRNA expression profiles and clinical data of GC patients were obtained from The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database. A pyroptosis-related lncRNA signature was constructed based on TCGA databases by using the Least Absolute Shrinkage and Selection Operator (LASSO) method Cox regression model. GC patients from the GSE62254 database cohort were used for validation. Univariate and multivariate Cox analyses were used to determine the independent predictors for OS. Gene set enrichment analyses were performed to explore the potential regulatory pathways. The immune cell infiltration level was analyzed via CIBERSORT.ResultsA four-pyroptosis-related lncRNA (ACVR2B-AS1, PRSS30P, ATP2B1-AS1, RMRP) signature was constructed using LASSO Cox regression analysis. GC patients were stratified into high- and low-risk groups, and patients in the high-risk group showed significant worse prognosis in TNM stage, gender, and age. The risk score was an independent predictor for OS by multivariate Cox analysis. Functional analysis indicated that the immune cell infiltrate was different between high- and low-risk groups.ConclusionThe pyroptosis-related lncRNA prognostic signature can be used for predicting prognosis in GC. Moreover, the novel signature might provide clinical therapeutic intervention for GC patients.</p

Image_1_A novel pyroptosis gene expression-based risk score for survival in gastric cancer.tif

BackgroundGastric cancer (GC) is a highly heterogeneous disease, which makes treatment and prognosis prediction difficult. Pyroptosis plays a vital role in the development of GC and influence the prognosis of GC. Long non-coding RNAs (lncRNAs), as regulators of gene expressions, are among putative biomarkers and therapeutic targets. However, the importance of pyroptosis-associated lncRNAs is still unclear in predicting prognosis in gastric cancer.MethodsIn this study, the mRNA expression profiles and clinical data of GC patients were obtained from The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database. A pyroptosis-related lncRNA signature was constructed based on TCGA databases by using the Least Absolute Shrinkage and Selection Operator (LASSO) method Cox regression model. GC patients from the GSE62254 database cohort were used for validation. Univariate and multivariate Cox analyses were used to determine the independent predictors for OS. Gene set enrichment analyses were performed to explore the potential regulatory pathways. The immune cell infiltration level was analyzed via CIBERSORT.ResultsA four-pyroptosis-related lncRNA (ACVR2B-AS1, PRSS30P, ATP2B1-AS1, RMRP) signature was constructed using LASSO Cox regression analysis. GC patients were stratified into high- and low-risk groups, and patients in the high-risk group showed significant worse prognosis in TNM stage, gender, and age. The risk score was an independent predictor for OS by multivariate Cox analysis. Functional analysis indicated that the immune cell infiltrate was different between high- and low-risk groups.ConclusionThe pyroptosis-related lncRNA prognostic signature can be used for predicting prognosis in GC. Moreover, the novel signature might provide clinical therapeutic intervention for GC patients.</p

Deoxycholic acid (DCA) confers an intestinal phenotype on esophageal squamous epithelium via induction of the stemness-associated reprogramming factors OCT4 and SOX2

<p>Barrett's esophagus (BE) is essentially a metaplasia in which the normal stratified squamous epithelium is replaced by columnar epithelium. This study focuses on the involvement of OCT4 and SOX2, 2 key cell-reprogramming factors, in the deoxycholic acid (DCA)-induced expression of the intestinal hallmarks Cdx2 and MUC2 using both in vivo and in vitro models. Up-regulated expression of OCT4 and down-regulated expression of SOX2 were observed in BE compared with normal esophagus and esophagitis. Consistent with the data in vivo, DCA induced time-dependent expression of OCT4 at both the mRNA and protein levels and decreased nuclear expression of SOX2 in Het-1A cells. Down-regulation of OCT4 expression by siRNA abrogated DCA-induced expression of Cdx2 and MUC2, whereas siRNA against SOX2 significantly upregulated the expression of both Cdx2 and MUC2. Our data indicate that both OCT4 and SOX2 play important roles in the development of BE triggered by bile acid reflux.</p

The Discovery and Hit-to-Lead Optimization of Tricyclic Sulfonamides as Potent and Efficacious Potentiators of Glycine Receptors

Current pain therapeutics suffer from undesirable psychotropic and sedative side effects, as well as abuse potential. Glycine receptors (GlyRs) are inhibitory ligand-gated ion channels expressed in nerves of the spinal dorsal horn, where their activation is believed to reduce transmission of painful stimuli. Herein, we describe the identification and hit-to-lead optimization of a novel class of tricyclic sulfonamides as allosteric GlyR potentiators. Initial optimization of high-throughput screening (HTS) hit <b>1</b> led to the identification of <b>3</b>, which demonstrated ex vivo potentiation of glycine-activated current in mouse dorsal horn neurons from spinal cord slices. Further improvement of potency and pharmacokinetics produced in vivo proof-of-concept tool molecule <b>20</b> (AM-1488), which reversed tactile allodynia in a mouse spared-nerve injury (SNI) model. Additional structural optimization provided highly potent potentiator <b>32</b> (AM-3607), which was cocrystallized with human GlyRα3_cryst to afford the first described potentiator-bound X-ray cocrystal structure within this class of ligand-gated ion channels (LGICs)