Self-calibration capabilities for flexible pressure sensors are greatly needed for fluid dynamic analysis, structure health monitoring and wearable sensing applications to compensate, in situ and in ...real time, for sensor drifts, nonlinearity effects, and hysteresis. Currently, very few self-calibrating pressure sensors can be found in the literature, let alone in flexible formats. This paper presents a flexible self-calibrating pressure sensor fabricated from a silicon-on-insulator wafer and bonded on a polyimide substrate. The sensor chip is made of four piezoresistors arranged in a Wheatstone bridge configuration on a pressure-sensitive membrane, integrated with a gold thin film-based reference cavity heater, and two thermistors. With a liquid-to-vapor thermopneumatic actuation system, the sensor can create precise in-cavity pressure for self-calibration. Compared with the previous work related to the single-phase air-only counterpart, testing of this two-phase sensor demonstrated that adding the water liquid-to-vapor phase change can improve the effective range of self-calibration from 3 psi to 9.5 psi without increasing the power consumption of the cavity micro-heater. The calibration time can be further improved to a few seconds with a pulsed heating power.
In this work, modulation by orexin-A of the release of glutamate and GABA from bipolar and amacrine cells respectively was studied by examining the effects of the neuropeptide on miniature excitatory ...postsynaptic currents (mEPSCs) and miniature inhibitory postsynaptic currents (mIPSCs) of rat retinal ganglion cells (GCs). Using RNAscope in situ hybridization in combination with immunohistochemistry, we showed positive signals for orexin receptor-1 (OX1R) mRNA in the bipolar cell terminals and those for orexin receptor-2 (OX2R) mRNA in the amacrine cell terminals. With whole-cell patch-clamp recordings in rat retinal slices, we demonstrated that application of orexin-A reduced the interevent interval of mEPSCs of GCs through OX1R. However, it increased the interevent interval of mIPSCs, mediated by GABAA receptors, through OX2R. Furthermore, orexin-A-induced reduction of mEPSC interevent interval was abolished by the application of PI-PLC inhibitors or PKC inhibitors. In contrast, orexin-A-induced increase of GABAergic mIPSC interevent interval was mimicked by 8-Br-cAMP or an adenylyl cyclase activator, but was eliminated by PKA antagonists. Finally, application of nimodipine, an L-type Ca2+ channel blocker, increased both mEPSC and mIPSC interevent interval, and co-application of orexin-A no longer changed the mEPSCs and mIPSCs. We conclude that orexin-A increases presynaptic glutamate release onto GCs by activating L-type Ca2+ channels in bipolar cells, a process that is mediated by an OX1R/PI-PLC/PKC signaling pathway. However, orexin-A decreases presynaptic GABA release onto GCs by inhibiting L-type Ca2+ channels in amacrine cells, a process that is mediated by an OX2R/cAMP-PKA signaling pathway.
•Orexin-A increases glutamate release onto GCs from BCs, acting via presynaptic OX1R.•This modulation is mediated by activation of PI-PLC/PKC signaling pathway in BCs.•Orexin-A suppresses GABA release onto GCs from amacrine cells via presynaptic OX2R.•Activation of cAMP-PKA signaling pathway mediates this type of modulation.•L-type Ca2+ channels are involved in the orexin effects on synaptic transmission to GCs.
Recent industry trends toward more complex and interconnected systems have increased the demand for more reliable pressure sensors. By integrating a microactuator with a pressure sensor, the sensor ...can self-calibrate, eliminating the complexities and costs associated with traditional sensor calibration methods to ensure reliability. The present work is focused on furthering understanding and improving the thermal performance of a thermopneumatic actuated self-calibrating pressure sensor. A transient numerical model was developed in ANSYS and was calibrated using experimental testing data. The numerical model provided insights into the sensor's performance not previously observed in experimental testing. Furthermore, the model was utilized for two design studies. First, it was found that a substrate with low thermal conductivity and high thermal diffusivity is ideal for both the sensor's efficiency and a faster transient response time. The second design study showed that decreasing the size of the sealed reference cavity lowers power consumption and transient response time. The study also showed that reducing the cavity base dimension has a greater effect on lowering power consumption and response time. Overall, the present work increases understanding of the self-calibrating pressure sensor and provides insight into potential design improvements, moving closer to optimized self-calibrating pressure sensors.
In this paper, a MEMS piezoresistive ultrathin silicon membrane-based strain sensor is presented. The sensor's ability to capture an acoustic emission signal is demonstrated using a Hsu-Nielsen ...source, and shows comparable frequency content to a commercial piezoceramic ultrasonic transducer. To the authors' knowledge, this makes the developed sensor the first known piezoresistive strain sensor which is capable of recording low-energy acoustic emissions. The improvements to the nondestructive evaluation and structural health monitoring arise from the sensor's low minimum detectable strain and wide-frequency bandwidth, which are generated from the improved fabrication process that permits crystalline semiconductor membranes and advanced polymers to be co-processed, thus enabling a dual-use application of both acoustic emission and static strain sensing. The sensor's ability to document quasi-static bending is also demonstrated and compared with an ultrasonic transducer, which provides no significant response. This dual-use application is proposed to effectively combine the uses of both strain and ultrasonic transducer sensor types within one sensor, making it a novel and useful method for nondestructive evaluations. The potential benefits include an enhanced sensitivity, a reduced sensor size, a lower cost, and a reduced instrumentation complexity.
Abstract
DNA methylation is an important epigenetic mechanism for regulating gene expression. Aberrant DNA methylation has been observed in various human diseases, including cancer. Single-nucleotide ...polymorphisms can contribute to tumor initiation, progression and prognosis by influencing DNA methylation, and DNA methylation quantitative trait loci (meQTL) have been identified in physiological and pathological contexts. However, no database has been developed to systematically analyze meQTLs across multiple cancer types. Here, we present Pancan-meQTL, a database to comprehensively provide meQTLs across 23 cancer types from The Cancer Genome Atlas by integrating genome-wide genotype and DNA methylation data. In total, we identified 8 028 964 cis-meQTLs and 965 050 trans-meQTLs. Among these, 23 432 meQTLs are associated with patient overall survival times. Furthermore, we identified 2 214 458 meQTLs that overlap with known loci identified through genome-wide association studies. Pancan-meQTL provides a user-friendly web interface (http://bioinfo.life.hust.edu.cn/Pancan-meQTL/) that is convenient for browsing, searching and downloading data of interest. This database is a valuable resource for investigating the roles of genetics and epigenetics in cancer.
Human cancer cell lines are fundamental models for cancer research and therapeutic strategy development. However, there is no characterization of circular RNAs (circRNAs) in a large number of cancer ...cell lines.
Here, we apply four circRNA identification algorithms to heuristically characterize the expression landscape of circRNAs across ~ 1000 human cancer cell lines from CCLE polyA-enriched RNA-seq data. By using integrative analysis and experimental approaches, we explore the expression landscape, biogenesis, functional consequences, and drug response of circRNAs across different cancer lineages.
We revealed highly lineage-specific expression patterns of circRNAs, suggesting that circRNAs may be powerful diagnostic and/or prognostic markers in cancer treatment. We also identified key genes involved in circRNA biogenesis and confirmed that TGF-β signaling may promote biogenesis of circRNAs. Strikingly, we showed that clinically actionable genes are more likely to generate circRNAs, potentially due to the enrichment of RNA-binding protein (RBP) binding sites. Among these, circMYC can promote cell proliferation. We observed strong association between the expression of circRNAs and the response to drugs, especially those targeting chromatin histone acetylation. Finally, we developed a user-friendly data portal, CircRNAs in cancer cell lines (CircRiC, https://hanlab.uth.edu/cRic ), to benefit the biomedical research community.
Our study provides the characterization of circRNAs in cancer cell lines and explored the potential mechanism of circRNA biogenesis as well as its therapeutic implications. We also provide a data portal to facilitate the related biomedical researches.
This multicenter observational study aimed to determine whether dyslipidemia or obesity contributes more significantly to unfavorable clinical outcomes in patients experiencing a first-ever ischemic ...stroke (IS).
The study employed a machine learning predictive model to investigate associations among body mass index (BMI), body fat percentage (BFP), high-density lipoprotein (HDL), triglycerides (TG), and total cholesterol (TC) with adverse outcomes in IS patients. Extensive real-world clinical data was utilized, and risk factors significantly linked to adverse outcomes were identified through multivariate analysis, propensity score matching (PSM), and regression discontinuity design (RDD) techniques. Furthermore, these findings were validated via a nationwide multicenter prospective cohort study.
In the derived cohort, a total of 45,162 patients diagnosed with IS were assessed, with 522 experiencing adverse outcomes. A multifactorial analysis incorporating PSM and RDD methods identified TG (adjusted odds ratio (OR) = 1.110; 95% confidence interval (CI): 1.041-1.183; P < 0.01) and TC (adjusted OR = 1.139; 95%CI: 1.039-1.248; P < 0.01) as risk factors. However, BMI, BFP, and HDL showed no significant effect. In the validation cohort, 1410 controls and 941 patients were enrolled, confirming that lipid levels are more strongly correlated with the prognosis of IS patients compared to obesity (TC, OR = 1.369; 95%CI: 1.069-1.754; P < 0.05; TG, OR = 1.332; 95%CI: 1.097-1.618; P < 0.01).
This study suggests that dyslipidemia has a more substantial impact on the prognosis of IS patients compared to obesity. This highlights the importance of prioritizing dyslipidemia management in the treatment and prevention of adverse outcomes in IS patients.
ADAR (Adenosine Deaminases Acting on RNA) proteins are a group of enzymes that play a vital role in RNA editing by converting adenosine to inosine in RNAs. This process is a frequent ...post-transcriptional event observed in metazoan transcripts. Recent studies indicate widespread dysregulation of ADAR-mediated RNA editing across many immune-related diseases, such as human cancer. We comprehensively review ADARs' function as pattern recognizers and their capability to contribute to mediating immune-related pathways. We also highlight the potential role of site-specific RNA editing in maintaining homeostasis and its relationship to various diseases, such as human cancers. More importantly, we summarize the latest cutting-edge computational approaches and data resources for predicting and analyzing RNA editing sites. Lastly, we cover the recent advancement in site-directed ADAR editing tool development. This review presents an up-to-date overview of ADAR-mediated RNA editing, how site-specific RNA editing could potentially impact disease pathology, and how they could be harnessed for therapeutic applications.
Autophagy is a major contributor to anti-cancer therapy resistance. Many efforts have been made to understand and overcome autophagy-mediated therapy resistance, but these efforts have been ...unsuccessful in clinical applications. In this study, we establish an autophagy signature to estimate tumor autophagy status. We then classify approximately 10,000 tumor samples across 33 cancer types from The Cancer Genome Atlas into autophagy score-high and autophagy score-low groups. We characterize the associations between multi-dimensional molecular features and tumor autophagy, and further analyse the effects of autophagy status on drug response. In contrast to the conventional view that the induction of autophagy serves as a key resistance mechanism during cancer therapy, our analysis reveals that autophagy induction may also sensitize cancer cells to anti-cancer drugs. We further experimentally validate this phenomenon for several anti-cancer drugs in vitro and in vivo, and reveal that autophagy inducers potentially sensitizes tumor cells to etoposide through downregulating the expression level of DDIT4. Our study provides a comprehensive landscape of molecular alterations associated with tumor autophagy and highlights an opportunity to leverage multi-omics analysis to utilize multiple drug sensitivity induced by autophagy.
Biofuel is a kind of sustainable, renewable and environment friendly energy. Lignocellulose from the stems of woody plants is the main raw material for "second generation biofuels". Lignin content ...limits fermentation yield and is therefore a major obstacle in biofuel production. Plant laccase plays an important role in the final step of lignin formation, which provides a new strategy for us to obtain ideal biofuels by regulating the expression of laccase genes to directly gain the desired lignin content or change the composition of lignin.
Multiple sequence alignment and phylogenetic analysis were used to classify
genes; sequence features of
were revealed by gene structure and motif composition analysis; gene duplication, interspecific collinearity and Ka/Ks analysis were conducted to identify ancient
; expression levels of
genes were measured by RNA-Seq data and qRT-PCR; domain analysis combine with cis-acting elements prediction together showed the potential function of
. Furthermore, Alphafold2 was used to simulate laccase 3D structures,
transgenic Populus stem transects were applied to fluorescence observation.
A comprehensive analysis of the
laccase gene (
) family was performed. Some ancient
genes such as
,
and
were identified. Gene structure and distribution of conserved motifs clearly showed sequence characteristics of each
. Combining published RNA-Seq data and qRT-PCR analysis, we revealed the expression pattern of
gene family. Prediction results of cis-acting elements show that
gene regulation was closely related to light. Through above analyses, we selected 5 laccases and used Alphafold2 to simulate protein 3D structures, results showed that
may be closely related to the lignification. Fluorescence observation of
transgenic
stem transects and qRT-PCR results confirmed our hypothesis again.
In this study, we fully analyzed the Populus trichocarpa laccase gene family and identified key laccase genes related to lignification. These findings not only provide new insights into the characteristics and functions of Populus laccase, but also give a new understanding of the broad prospects of plant laccase in lignocellulosic biofuel production.
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