Integrated bioinformatics investigation of adenylyl cyclase family co-expression network in bladder cancer followed by preliminary validation of member 2 (ADCY2) in tumorigenesis and prognosis.

Background: The adenylyl cyclase (ADCY) gene family encodes enzymes responsible for the synthesis of cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP), which comprises nine transmembrane isoforms (ADCYs 1-9). Although ADCYs correlate with intracellular signalling and tumorigenesis in different malignancies, their roles in bladder cancer remain unclear. Methods: Utilizing the bladder urothelial carcinoma (BLCA) dataset from The Cancer Genome Atlas (TCGA), we employed the R package 'limma' to identify differential genes. Subsequent correlation analysis with corresponding clinical data was conducted. Prognostic significance of ADCY family genes was assessed through survival analysis. Univariate and multivariate Cox regression determined ADCY2 as a potential independent risk factor for BLCA. Validation was performed using immunohistochemistry results from independent cohorts. Additionally, we delved into the mechanism of genetic variations, methylation modifications, and signalling pathways of ADCY family genes. Evaluation of their role in the immune microenvironment was achieved through R packages single-sample gene set enrichment analysis (ssGSEA), CIBERPORT, and ESTIMATE. Results: Cases of bladder cancer were retrieved from TCGA, and the transcriptionally differentially expressed members of ADCY were identified (members 2, 4, and 5). Genomic alteration, epigenomic modification, clinicopathological characteristics and clinical survival were systematically investigated. A co-expression network was established based on the intersection of correlated genes, which was centred around ADCY2, ADCY4, and ADCY5. Enrichment analysis revealed that correlated genes were involved in epithelial-mesenchymal transition (EMT). The ADCY2 was selected as the most representative biomarker for prognosis in bladder cancer. Bladder tumour with higher ADCY2 expression had higher prognostic risk and worse survival outcomes. Moreover, ADCY2 was correlated with classic immune checkpoints, and a better responsiveness to immunotherapy was exhibited in high-expression subsets. To ameliorate universality of the conclusion, our study also included several real-world cohorts into the preliminary validation, using datasets from the Gene Expression Omnibus (GEO; GSE13507), tissue microarray (TMA) with 80 bladder cancer inclusion and clinical trial IMvigor210, which were associated with immunotherapy sensitivity, prognosis, and common biomarker presentation. Conclusions: Our study reveals that ADCY family has prognostic value in patients with bladder cancer; the ADCY2 is a prominent prognostic biomarker. The bioinformatics analyses and validation provide direction for further functional and mechanistic studies on the screened members of ADCY family.

Fascin 1 promoted the growth and migration of non-small cell lung cancer cells by activating YAP/TEAD signaling.

Fascin 1 (Fascin actin-bundling protein 1) is an actin-binding protein. Although several studies have reported the dysregulation of Fascin 1 in non-small cell lung cancer (NSCLC), its functions in the progression of NSCLC and the related molecular mechanism were not fully understood. In this study, the expression of Fascin 1 in NSCLC tissues was determined using quantitative PCR (qPCR), and the roles of Fascin 1 in the progression of NSCLC were investigated. It was found that both the messenger RNA (mRNA) level and the protein level of Fascin 1 were upregulated in NSCLC tissues. Forced expression of Fascin 1 promoted the growth and migration of NSCLC cells, while knocking down the expression of Fascin 1 inhibited the growth, migration, and tumorigenesis of NSCLC cells. Mechanism studies showed that Fascin 1 increased the transcriptional activity of the YAP/TEAD (Yes-associated protein/TEA domain transcriptional factor) complex, and knocking down the expression of Fascin 1 attenuated the expression of target genes downstream the YAP/TEAD complex. In addition, MST1 interacted with Fascin 1. Taken together, Fascin 1 plays an oncogenic role in NSCLC by activating the transcriptional activity of the YAP/TEAD complex.

Geological disaster survey based on Curvelet transform with borehole Ground Penetrating Radar in Tonglushan old mine site.

Tonglushan old mine site located in Huangshi City, China, is very famous in the world. However, some of the ruins had suffered from geological disasters such as local deformation, surface cracking, in recent years. Structural abnormalities of rock-mass in deep underground were surveyed with borehole ground penetrating radar (GPR) to find out whether there were any mined galleries or mined-out areas below the ruins. With both the multiresolution analysis and sub-band directional of Curvelet transform, the feature information of targets' GPR signals were studied on Curvelet transform domain. Heterogeneity of geotechnical media and clutter jamming of complicated background of GPR signals could be conquered well, and the singularity characteristic information of typical rock mass signals could be extracted. Random noise had be removed by thresholding combined with Curvelet and the statistical characteristics of wanted signals and the noise, then direct wave suppression and the spatial distribution feature extraction could obtain a better result by making use of Curvelet transform directional. GprMax numerical modeling and analyzing of the sample data have verified the feasibility and effectiveness of our method. It is important and applicable for the analyzing of the geological structure and the disaster development about the Tonglushan old mine site.

Direct fabrication of homogeneous microfluidic channels embedded in fused silica using a femtosecond laser.

We demonstrate direct fabrication of homogeneous microfluidic channels embedded in fused silica by femtosecond laser direct writing, followed by wet chemical etching and glass drawing. In addition, the glass drawing process significantly reduces the inner surface roughness of the fabricated channels, and centimeter-level microfluidic channels with an aspect ratio above 1000 can be realized.

Electro-optic integration of embedded electrodes and waveguides in LiNbO3 using a femtosecond laser.

We describe the fabrication of a Mach-Zehnder optical modulator in LiNbO(3) by femtosecond laser micromachining, which is composed of optical waveguides inscripted by a femtosecond laser and embedded microelectrodes subsequently fabricated using femtosecond laser ablation and selective electroless plating. A half-wave voltage close to 19 V is achieved at a wavelength of 632.8 nm with an interaction length of 2.6 mm. This simple and cost-effective technique opens up new opportunities for fabricating integrated electro-optic devices.

Fabrication of microfluidic optical waveguides on glass chips with femtosecond laser pulses.

We describe the fabrication of microfluidic channel structures on the surface of a borosilicate glass slide by femtosecond laser direct writing for optical waveguide application. Liquid with a variable refractive index is fed into the microchannel, serving as the core of the waveguide. We demonstrate that either a multimode or a single-mode waveguide can be achieved by controlling the refractive index of the liquid.

Selective metallization on insulator surfaces with femtosecond laser pulses.

We report selective metallization on surfaces of insulators (glass slides and lithium niobate crystal) based on femtosecond laser modification combined with electroless plating. The process is mainly composed of four steps: (1) formation of silver nitrate thin films on the surfaces of glass or crystal substrates; (2) generation of silver particles in the irradiated area by femtosecond laser direct writing; (3) removal of unirradiated silver nitrate films; and (4) selective electroless plating in the modified area. We discuss the mechanism of selective metallization on the insulators. Moreover, we investigate the electrical and adhesive properties of the copper microstructures patterned on the insulator surfaces, showing great potential of integrating electrical functions into lab-on-a-chip devices.

[Probing R6G single molecules by surface-enhanced resonance Raman scattering].

R6G was incubated in three kinds of silver colloid with different low concentrations, and its surface-enhanced resonance Raman scattering (SERRS) was studied with a confocal microscopy system. Each sample exhibited different spectrum character. At the single-molecule level the SERRS-spectra were recorded in 10(-13) mol x L(-1) dye colloidal solution. Some spectral inhomogeneous behavior was recorded such as spectral diffusion, intensity fluctuation of vibrational lines and spectral polarization, and even on/off blinking and splitting of some lines within the spectrum of one molecule. Polarization of excitation light and background subtraction of signal have an important influence on the SERRS spectra detection of single-molecule, which was analyzed in the present paper.