Urchin-Shaped Au-Ag@Pt Sensor Integrated Lateral Flow Immunoassay for Multimodal Detection and Specific Discrimination of Clinical Multiple Bacterial Infections.

A new lateral flow immunoassay strip (LFIA) combining sensitive detection and identification of multiple bacteria remains a huge challenge. In this study, we first developed multifunctional urchin-shaped Au-Ag@Pt nanoparticles (UAA@P NPs) with a unique combination of colorimetric-SERS-photothermal-catalytic (CM/SERS/PT/CL) properties and integrated them with LFIA for multiplexed detection and specific discrimination of pathogenic bacteria in blood samples. Unlike the conventional LFIA that relied on antibody (Ab), this novel LFIA introduced 4-mercaptophenylboronic acid (4-MPBA) as an ideal Ab replacer that was functionalized on UAA@P NPs (UAA@P/M NPs) with outstanding binding and enrichment capacities toward bacteria. Taking Staphylococcus aureus (S. aureus) as model bacteria, the limit of detection (LOD) was 3 CFU/mL for SERS-LFIA, 27 CFU/mL for PT-LFIA, and 18 CFU/mL for CL-LFIA, three of which were over 330-fold, 37-fold, and 55-fold more sensitive than ordinary visual CM-LFIA, respectively. Besides, this SERS-LFIA is capable of identifying three types of bacterial spiked blood samples (E. coli, S. aureus, and P. aeruginosa) effectively according to specific bacterial Raman "fingerprints" by partial least-squares-discriminant analysis (PLS-DA). More importantly, this LFIA was successfully applied to blood samples with satisfactory recoveries from 90.3% to 108.8% and capable of identifying the infected patients (N = 4) from healthy subjects (N = 2) with great accuracy. Overall, the multimodal LFIA incorporates bacteria discrimination and quantitative detection, offering an avenue for early warning and diagnosis of bacterial infection.

High Expression of COA6 Is Related to Unfavorable Prognosis and Enhanced Oxidative Phosphorylation in Lung Adenocarcinoma.

Mitochondrial metabolism plays an important role in the occurrence and development of cancers. Cytochrome C oxidase assembly factor six (COA6) is essential in mitochondrial metabolism. However, the role of COA6 in lung adenocarcinoma (LUAD) remains unknown. Here we report that the expression of COA6 mRNA and protein were upregulated in LUAD tissues compared with lung normal tissues. We found that COA6 had high sensitivity and specificity to distinguish LUAD tissues from normal lung tissues shown by a receiver operating characteristic (ROC) curve. In addition, our univariate and multivariate Cox regression analysis indicated that COA6 was an independent unfavorable prognostic factor for LUAD patients. Furthermore, our survival analysis and nomogram showed that a high expression of COA6 mRNA was related to the short overall survival (OS) of LUAD patients. Notably, our weighted correlation network analysis (WGCNA) and functional enrichment analysis revealed that COA6 may participate in the development of LUAD by affecting mitochondrial oxidative phosphorylation (OXPHOS). Importantly, we demonstrated that depletion of COA6 could decrease the mitochondrial membrane potential (MMP), nicotinamide adenine dinucleotide (NAD) + hydrogen (H) (NADH), and adenosine triphosphate (ATP) production in LUAD cells (A549 and H1975), hence inhibiting the proliferation of these cells in vitro. Together, our study strongly suggests that COA6 is significantly associated with the prognosis and OXPHOS in LUAD. Hence, COA6 is highly likely a novel prognostic biomarker and therapeutic target of LUAD.

Histone modifications in neurodifferentiation of embryonic stem cells.

Post-translational modifications of histone proteins regulate a long cascade of downstream cellular activities, including transcription and replication. Cellular lineage differentiation involves large-scale intracellular signaling and extracellular context. In particular, histone modifications play instructive and programmatic roles in central nervous system development. Deciphering functions of histone could offer feasible molecular strategies for neural diseases caused by histone modifications. Here, we review recent advances of in vitro and in vivo studies on histone modifications in neural differentiation.

Jmjd6 regulates ES cell homeostasis and enhances reprogramming efficiency.

Jmjd6 is a conserved nuclear protein which possesses histone arginine demethylation and lysyl hydroxylase activity. Previous studies have revealed that Jmjd6 is essential for cell differentiation and embryo development. However, the role of Jmjd6 in mammalian ES cell identity and reprogramming has been unclear. Here we report that depletion of Jmjd6 not only results in downregulation of pluripotency genes but also is implicated in apoptosis, glycolysis, cell cycle and protein hydroxylation. We also revealed the reduction of BrdU incorporation in Jmjd6 depleted cells. Reprogramming efficiency of MEFs can be enhanced with Jmjd6 overexpression while the efficiency was reduced upon Jmjd6 depletion. Together, these results suggest that Jmjd6 can regulate ES cell homeostasis and enhance somatic cell reprogramming.

Npac Is A Co-factor of Histone H3K36me3 and Regulates Transcriptional Elongation in Mouse Embryonic Stem Cells.

Chromatin modification contributes to pluripotency maintenance in embryonic stem cells (ESCs). However, the related mechanisms remain obscure. Here, we show that Npac, a "reader" of histone H3 lysine 36 trimethylation (H3K36me3), is required to maintain mouse ESC (mESC) pluripotency since knockdown of Npac causes mESC differentiation. Depletion of Npac in mouse embryonic fibroblasts (MEFs) inhibits reprogramming efficiency. Furthermore, our chromatin immunoprecipitation followed by sequencing (ChIP-seq) results of Npac reveal that Npac co-localizes with histone H3K36me3 in gene bodies of actively transcribed genes in mESCs. Interestingly, we find that Npac interacts with positive transcription elongation factor b (p-TEFb), Ser2-phosphorylated RNA Pol II (RNA Pol II Ser2P), and Ser5-phosphorylated RNA Pol II (RNA Pol II Ser5P). Furthermore, depletion of Npac disrupts transcriptional elongation of the pluripotency genes Nanog and Rif1. Taken together, we propose that Npac is essential for the transcriptional elongation of pluripotency genes by recruiting p-TEFb and interacting with RNA Pol II Ser2P and Ser5P.

PATZ1 (MAZR) Co-occupies Genomic Sites With p53 and Inhibits Liver Cancer Cell Proliferation via Regulating p27.

Liver cancer is the third most common cause of cancer death in the world. POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1/MAZR) is a transcription factor associated with various cancers. However, the role of PATZ1 in cancer progression remains controversial largely due to lack of genome-wide studies. Here we report that PATZ1 regulates cell proliferation by directly regulating CDKN1B (p27) in hepatocellular carcinoma cells. Our PATZ1 ChIP-seq and gene expression microarray analyses revealed that PATZ1 is strongly related to cancer signatures and cellular proliferation. We further discovered that PATZ1 depletion led to an increased rate of colony formation, elevated Ki-67 expression and greater S phase entry. Importantly, the increased cancer cell proliferation was accompanied with suppressed expression of the cyclin-dependent kinase inhibitor CDKN1B. Consistently, we found that PATZ1 binds to the genomic loci flanking the transcriptional start site of CDKN1B and positively regulates its transcription. Notably, we demonstrated that PATZ1 is a p53 partner and p53 is essential for CDKN1B regulation. In conclusion, our study provides novel mechanistic insights into the inhibitory role of PATZ1 in liver cancer progression, thereby yielding a promising therapeutic intervention to alleviate tumor burden.