Research on an Off-Chip Microvalve for Pneumatic Control in Microfluidic Chips

A compact, rapid, and portable off-chip pneumatic control valve is significant for the miniaturization and integration of external pneumatic systems for microfluidic chips. In this work, an off-chip microvalve with a high-speed electromagnetic switch actuator and a polydimethylsiloxane (PDMS) material valve body has been designed to be easily encapsulated, simulated using MATLAB/Simulink software, and tested in a micromixer. Multi-physical coupling mathematical models are developed based on the elastic deformation force of the valve membrane, the driving force of the valve core, and the fluid force in the microchannel. Two single microvalves are used to form a three-way microvalve, which can control the air pressure in a pneumatic microchannel on the microfluidic chip. The relationship between the flow–duty cycle, the flow–pressure difference of the single electromagnetic microvalve, and the load pressure of the three-way microvalve is simulated and analyzed. Sample mixing performance controlled by the proposed off-chip three-way microvalve was tested to evaluate the pneumatic control capability, and the results show that the undertaking can fully satisfy the needs of a pneumatic microfluidic chip for most applications

Prognostic value of Kinesin‐4 family genes mRNA expression in early‐stage pancreatic ductal adenocarcinoma patients after pancreaticoduodenectomy

Abstract Background The aim of this study was to investigate the potential prognostic value of Kinesin‐4 family genes mRNA expression in early‐stage pancreatic ductal adenocarcinoma (PDAC) patients after pancreaticoduodenectomy. Methods Kaplan‐Meier survival analysis method with log‐rank test and Cox proportional hazards regression analysis were performed to figure out the association between Kinesin‐4 family genes expression and PDAC patients overall survival time. Joint‐effect survival analysis and stratified survival analysis were carried out to assess the prognosis prediction value of prognosis‐related gene. Nomogram was constructed for the individualized prognosis prediction. In addition, we had used the gene set enrichment analysis and genome‐wide co‐expression analysis to further explore the potential mechanism. Results KIF21A expression level was significantly associated with PDAC patient clinical prognosis outcome and patient with a high expression of KIF21A would have a shorter overall survival time. The prognosis prediction significance of KIF21A was well validated by the joint‐effect survival analysis, stratified survival analysis, and nomogram. Meanwhile, the gene set enrichment analysis and genome‐wide co‐expression analysis revealed that KIF21A might involve in DNA damage and repair, transcription and translation process, post‐translation protein modification, cell cycle, carcinogensis genes and pathways. Conclusions Our current research demonstrated that KIF21A could serve as a potential prognostic biomarker for patient with early‐stage PDAC after pancreaticoduodenectomy

High-throughput telomere length measurement at nucleotide resolution using the PacBio high fidelity sequencing platform

There exist challenges in quantifying the length of individual telomeres at single nucleotide resolution. Here the authors report a method to capture telomeres and accurately analyse their length in human cell lines and patient peripheral blood leukocyte samples using single-molecule real-time sequencing

HoxC5 and miR-615-3p target newly evolved genomic regions to repress hTERT and inhibit tumorigenesis

The repression of telomerase activity during cellular differentiation promotes replicative aging and functions as a physiological barrier for tumorigenesis in long-lived mammals, including humans. However, the underlying mechanisms remain largely unclear. Here we describe how miR-615-3p represses hTERT expression. mir-615-3p is located in an intron of the HOXC5 gene, a member of the highly conserved homeobox family of transcription factors controlling embryogenesis and development. Unexpectedly, we found that HoxC5 also represses hTERT expression by disrupting the long-range interaction between hTERT promoter and its distal enhancer. The 3′UTR of hTERT and its upstream enhancer region are well conserved in long-lived primates. Both mir-615-3p and HOXC5 are activated upon differentiation, which constitute a feed-forward loop that coordinates transcriptional and post-transcriptional repression of hTERT during cellular differentiation. Deregulation of HOXC5 and mir-615-3p expression may contribute to the activation of hTERT in human cancers.NRF (Natl Research Foundation, S’pore)MOE (Min. of Education, S’pore)Published versio

Genomic and epigenomic <i>EBF1</i> alterations modulate<i> TERT</i> expression in gastric cancer

Transcriptional reactivation of telomerase catalytic subunit (TERT) is a frequent hallmark of cancer, occurring in 90% of human malignancies. However, specific mechanisms driving TERT reactivation remain obscure for many tumor types and in particular gastric cancer (GC), a leading cause of global cancer mortality. Here, through comprehensive genomic and epigenomic analysis of primary GCs and GC cell lines, we identified the transcription factor early B cell factor 1 (EBF1) as a TERT transcriptional repressor and inactivation of EBF1 function as a major cause of TERT upregulation. Abolishment of EBF1 function occurs through 3 distinct (epi)genomic mechanisms. First, EBF1 is epigenetically silenced via DNA methyltransferase, polycomb-repressive complex 2 (PRC2), and histone deacetylase activity in GCs. Second, recurrent, somatic, and heterozygous EBF1 DNA-binding domain mutations result in the production of dominant-negative EBF1 isoforms. Third, more rarely, genomic deletions and rearrangements proximal to the TERT promoter remobilize or abolish EBF1-binding sites, derepressing TERT and leading to high TERT expression. EBF1 is also functionally required for various malignant phenotypes in vitro and in vivo, highlighting its importance for GC development. These results indicate that multimodal genomic and epigenomic alterations underpin TERT reactivation in GC, converging on transcriptional repressors such as EBF1

Genomic and epigenomic EBF1 alterations modulate TERT expression in gastric cancer

Transcriptional reactivation of telomerase catalytic subunit (TERT) is a frequent hallmark of cancer, occurring in 90% of human malignancies. However, specific mechanisms driving TERT reactivation remain obscure for many tumor types and in particular gastric cancer (GC), a leading cause of global cancer mortality. Here, through comprehensive genomic and epigenomic analysis of primary GCs and GC cell lines, we identified the transcription factor early B cell factor 1 (EBF1) as a TERT transcriptional repressor and inactivation of EBF1 function as a major cause of TERT upregulation. Abolishment of EBF1 function occurs through 3 distinct (epi)genomic mechanisms. First, EBF1 is epigenetically silenced via DNA methyltransferase, polycomb-repressive complex 2 (PRC2), and histone deacetylase activity in GCs. Second, recurrent, somatic, and heterozygous EBF1 DNA-binding domain mutations result in the production of dominant-negative EBF1 isoforms. Third, more rarely, genomic deletions and rearrangements proximal to the TERT promoter remobilize or abolish EBF1-binding sites, derepressing TERT and leading to high TERT expression. EBF1 is also functionally required for various malignant phenotypes in vitro and in vivo, highlighting its importance for GC development. These results indicate that multimodal genomic and epigenomic alterations underpin TERT reactivation in GC, converging on transcriptional repressors such as EBF1