LoC-SERS platform for rapid and sensitive detection of colorectal cancer protein biomarkers.

Colorectal cancer (CRC) remains a significant contributor to the global mortality rate, and a single biomarker cannot meet the specificity required for CRC screening. To this end, we developed a multiplexed, pump-free surface-enhanced Raman scattering (SERS) microfluidic chip (LoC-SERS) using a one-step recognition release mechanism; the aptamer-functionalized novel Au nanocrown array (AuNCA) was used as the detection element embedded in the detection zone of the platform for rapid and specific detection of protein markers in multiple samples simultaneously. Here, the corresponding aptamer specifically captured the protein marker, causing the complementary strand of the aptamer carrying the Raman signal molecule to be shed, reducing the SERS signal. Based on this platform, sensitive and specific detection of the target can be accomplished within 15 min with detection limits of 0.031 pg/mL (hnRNP A1) and 0.057 pg/mL (S100P). Meanwhile, the platform was consistent with ELISA results when used to test clinical. By substituting different aptamers, this platform can provide a new solution for the rapid and sensitive detection of protein markers, which has promising applications in future disease detection.

Aptamer-Based Functionalized SERS Biosensor for Rapid and Ultrasensitive Detection of Gastric Cancer-Related Biomarkers.

Background: Gastric cancer (GC) as is the second deadliest malignancy still lacks rapid, simple and economical detection and early clinical screening techniques. Surface-enhanced Raman spectroscopy (SERS) is a spectroscopic technique based on the surface plasmon resonance of precious metal nanoparticles, which can effectively detect low-abundance tumor markers. Combining SERS technology with sensors has high potential in the diagnosis and screening of GC. Methods: A novel Au/Si nano-umbrella array (Au/SiNUA) was prepared as a SERS substrate and the substrate was functionalized using the corresponding tumor marker aptamers for the detection of clinical biological samples using a one-step recognition release mechanism. Optimization of aptamer and complementary chain concentrations and detection time for optimal sensor preparation. Results: Au/SiNUA were tested to have good SERS enhancement activity. The proposed aptamer biosensor has good specificity and stability, with a low detection time of 18 min and a limit of detection (LOD) at the fM level, which is superior to most of the methods reported so far; and the accuracy of the clinical assay is comparable to that of the ELISA method. The expression levels of PDGF-B and thrombin in the serum of GC patients and healthy individuals can be effectively detected and differentiated. Conclusion: The ultrasensitive and specific aptamer biosensor is highly feasible for the diagnosis and screening of GC and has good application prospects.

BRD9 is an essential regulator of glycolysis that creates an epigenetic vulnerability in colon adenocarcinoma.

BACKGROUND: The intensive interplay between aberrant epigenetic events and metabolic remodeling represents one of the hallmarks of tumors, including colon cancer. The functions of Bromodomain Containing Protein BRD-9 in colon cancer remains indefinite. We aimed to identify the biological roles and clinical significance of BRD9 in colon cancer. METHODS: The univariate- and multi-variate Cox regression models were used to screen risk epigenetic regulators. Kaplan-Meier analysis and Pearson correlation analysis were used to assess clinical significance of BRD9. CCK-8 assays, colony formation assay, Transwell, and soft-agar assay were performed to determine the in vitro roles of BRD9. The oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) of colon cancer cells were evaluated by a Seahorse XF Extracellular Flux Analyzer. In vivo models and RT-qPCR, western blotting, and Chromatin Immunoprecipitation (ChIP) assay were conducted to explore the functional roles of BRD9 in COAD. RESULTS: In the study, we detected the expressions of 662 epigenetic regulators in COAD and identified a series of 42 hazard epigenetic factors with p < 0.05. Low-throughput MTT assays highlighted that BRD9 is an essential target, and targeting BRD9 could reduce significant decreases of cell growth. BRD9 overexpression could notably elevate proliferation and migration potentialities, whereas, BRD9 ablation abolished these effects. Mechanistically, functional enrichment analysis indicated the potential associations between BRD9 and glycolysis metabolism. In addition, BRD9 epigenetically coordinates the H3K27ac modifications on the promoter regions of ENO2 and ALDOC, inducing enhanced glycolysis activity. Lastly, I-BRD9 could significantly suppress the growth of colon cancer cells in vitro and in vivo. CONCLUSIONS: Together, our study revealed previously unidentified roles of BRD9 in colon cancer metabolism and tumor progression, indicating that BRD9 could be a valuable therapeutic target for COAD patients.

KIF11 manipulates SREBP2-dependent mevalonate cross talk to promote tumor progression in pancreatic ductal adenocarcinoma.

Cholesterol metabolism is highly correlated with risks of pancreatic ductal adenocarcinoma (PDAC). Nevertheless, the underlying mechanisms of activation of cholesterol biogenesis remain inconclusive. KIF11 is a key component of the bipolar spindle and expresses highly in various malignancies. However, its functional role in PDAC tumorigenesis is still unclear. This study aims to elucidate the oncogenic functions of KIF11 in stimulating cholesterol metabolism, thereby driving PDAC progression. We utilized bioinformatics analysis to identify that KIF11 expressed highly in tumor samples versus paired normal tissues and high KIF11 correlated with high clinical stages of patients. Patients with high KIF11 had worse survival outcomes relative to those with low KIF11. Gene set enrichment analysis (GSEA) revealed that KIF11 correlated intensively with the mevalonate (MVA) metabolic pathway. Positive associations were observed between KIF11 and MVA-signature (HMGCR, FDFT1, SQLE, and MSMO1). KIF11 could elevate the free cholesterol content of PDAC cells and targeting MVA inhibited the in vitro growth of KIF11-overexpressing cells. Mechanistically, we found KIF11 could interact with SREBP2, the master regulator of MVA. High KIF11 could increase SREBP2 proteins, but not alter their mRNA levels. KIF11 could attenuate the ubiquitination-mediated degradation of SREBP2, thereby enhancing its stability and accumulation. Accordingly, KIF11 stimulated the expressions of MVA-signature and free cholesterol contents depending on SREBP2. In addition, KIF11 depended on SREBP2 to promote cell growth, migration, stemness, and colony formation abilities. The subcutaneous xenograft models indicated that targeting MVA biogenesis (atorvastatin) is effective to restrict the in vivo growth of KIF11high PDAC. Taken together, our study identified that KIF11 could activate the MVA cross talk to drive PDAC progression and inhibiting the KIF11/MVA axis provided a therapeutic vulnerability in the treatment of PDAC.

The complete mitochondrial genome of Dysgonia stuposa (Lepidoptera: Erebidae) and phylogenetic relationships within Noctuoidea.

To determine the Dysgonia stuposa mitochondrial genome (mitogenome) structure and to clarify its phylogenetic position, the entire mitogenome of D. stuposa was sequenced and annotated. The D. stuposa mitogenome is 15,721 bp in size and contains 37 genes (protein-coding genes, transfer RNA genes, ribosomal RNA genes) usually found in lepidopteran mitogenomes. The newly sequenced mitogenome contained some common features reported in other Erebidae species, e.g., an A+T biased nucleotide composition and a non-canonical start codon for cox1 (CGA). Like other insect mitogenomes, the D. stuposa mitogenome had a conserved sequence 'ATACTAA' in an intergenic spacer between trnS2 and nad1, and a motif 'ATAGA' followed by a 20 bp poly-T stretch in the A+T rich region. Phylogenetic analyses supported D. stuposa as part of the Erebidae family and reconfirmed the monophyly of the subfamilies Arctiinae, Catocalinae and Lymantriinae within Erebidae.

Giant solitary fibrous tumor arising from greater omentum.

Extrathoracic solitary fibrous tumors (SFTs) have been described at almost every anatomic location of human body, but reports of SFT in the abdominal cavity are rare. We herein present a rare case of SFT originating from greater omentum. Computed tomography revealed a 15.8 cm × 21.0 cm solid mass located at superior aspect of stomach. Open laparotomy confirmed its mesenchymal origin. Microscopically, its tissue was composed of non-organized and spindle-shaped cells exhibiting atypical nuclei, which were divided up by branching vessel and collagen bundles. Immunohistochemical staining showed that this tumor was negative for CD117, CD99, CD68, cytokeratin, calretinin, desmin, epithelial membrane antigen, F8 and S-100, but positive for CD34, bcl-2, α-smooth muscle actin and vimentin. The patient presented no evidence of recurrence during follow-up. SFT arising from abdominal cavity can be diagnosed by histological findings and immunohistochemical markers, especially for CD34 and bcl-2 positive cases.