Stress Detection of Conical Frustum Windows in Submersibles Based on Polarization Imaging.

Stress detection of the conical frustum window is a very important issue to ensure the safety of deep manned submersibles. In this paper, we propose a method based on polarization imaging to evaluate the stress accumulation and recovery in the conical frustum window. An experimental setup of Mueller matrix polarimetry is built, and the samples are made by referring to the typical conical frustum windows in submersibles. By pressurizing different pressures on the samples, we can find the changes of their Mueller matrix images and further derived polarization parameters. The results show that the polarization parameters can characterize the stress transfer process and the elastic-plastic transformation process of the window under different pressurization pressures. We also use a two-layered wave plate model to simulate the stress distribution in the window, which reveals different performances of the former and latter layers of the window under pressurization. Finally, we use a finite element model to simulate and understand some of the above experimental results. This proposed method is expected to provide new possibilities for monitoring the window stress and further ensure the safety of deep manned submersibles.

ROS-Autophagy pathway mediates monocytes-human umbilical vein endothelial cells adhesion induced by apelin-13.

Apelin is the endogenous ligand of APJ receptor. Both monocytes (MCs) and human umbilical vein endothelial cells (HUVECs) express apelin and APJ, which play important roles in the physiological processes of atherosclerosis. Our previous research indicated that apelin-13 promoted MCs-HUVECs adhesion. Here, we further explore the mechanism responsible for MCs-HUVECs adhesion induced by apelin-13. Apelin-13 promoted reactive oxygen species (ROS) generation and NOX4 expression in HUVECs. Apelin-13 inducedautophagy, increased proteins beclin1 and LC3-II/I expression and induced autophagy flux in HUVECs, which was blocked by NAC, catalase and DPI. Autophagy flux induced by apelin-13 was inhibited by NAC and catalase but not hydroxychloroquine (HCQ). NAC, catalase, and DPI prevented apelin-13 induced ICAM-1 expression in HUVECs. Rapamycin enhanced MCs-HUVECs adhesion that was reversed by NAC, catalase, and DPI. Down-regulation of beclin1 and LC3 by siRNA blocked MCs-HUVECs adhesion. Apelin-13 induced atherosclerotic plaque and increased NOX4, LC3-II/I expression in ApoE-/-(HFD) mouse model. Our results demonstrated that apelin-13 induced MCs-HUVECs adhesion via a ROS-autophagy pathway.

The endoplasmic reticulum stress-autophagy pathway is involved in apelin-13-induced cardiomyocyte hypertrophy in vitro.

Apelin is the endogenous ligand for the G protein-coupled receptor APJ, and plays important roles in the cardiovascular system. Our previous studies showed that apelin-13 promotes the hypertrophy of H9c2 rat cardiomyocytes through the PI3K-autophagy pathway. The aim of this study was to explore what roles ER stress and autophagy played in apelin-13-induced hypertrophy of cardiomyocytes in vitro. Treatment of H9c2 cells with apelin-13 (0.001-2 µmol/L) dose-dependently increased the production of ROS and the expression levels of NADPH oxidase 4 (NOX4). Knockdown of Nox4 with siRNAs effectively prevented the reduction of GSH/GSSG ratio in apelin-13-treated cells. Furthermore, apelin-13 treatment dose-dependently increased the expression of Bip and CHOP, two ER stress markers, in the cells. Knockdown of APJ or Nox4 with the corresponding siRNAs, or application of NADPH inhibitor DPI blocked apelin-13-induced increases in Bip and CHOP expression. Moreover, apelin-13 treatment increased the formation of autophagosome and ER fragments and the LC3 puncta in the ER of the cells. Knockdown of APJ, Nox4, Bip or CHOP with the corresponding siRNAs, or application of DPI or salubrinal attenuated apelin-13-induced overexpression of LC3-II/I and beclin 1. Finally, knockdown of Nox4, Bip or CHOP with the corresponding siRNAs, or application of salubrinal significantly suppressed apelin-13-induced increases in the cell diameter, volume and protein contents. Our results demonstrate that ER stress-autophagy is involved in apelin-13-induced H9c2 cell hypertrophy.

PAK1-cofilin phosphorylation mediates human lung adenocarcinoma cells migration induced by apelin-13.

Adipocytokines apelin peptide, the ligand of APJ (putative receptor related to the angiotensin receptor AT1), plays key roles in the pathogenesis and deterioration of cancer. In lung cancer, apelin elevating microvessel densities has been reported. Our previous research has characterized that apelin-13 promoted lung adenocarcinoma cell proliferation. However, the effect of apelin on metastasis in lung adenocarcinoma and the underlying mechanisms remain unclear. This study shows that apelin-13 induced human adenocarcinoma cell migration via the APJ receptor. Apelin-13 phosphorylated PAK1 and cofilin increase the migration of lung adenocarcinoma cells. Moreover, the results verify that over-expression of apelin and APJ contributed to reducing the effect of doxorubicin and razoxane on inhibiting lung adenocarcinoma cells metastasis. Hypoxia activated APJ expression and apelin release in lung adenocarcinoma cells. The results demonstrate a PAK1-cofilin phosphorylation mechanism to mediate lung adenocarcinoma cells migration promoted by apelin-13. This discovery further suggests that APJ and its downstream signalling is a potential target for anti-metastatic therapies in lung adenocarcinoma patients.

Apelin and APJ, a novel critical factor and therapeutic target for atherosclerosis.

Apelin is a bioactive peptide discovered recently that has been proved to be an endogenous ligand of the APJ receptor. Apelin and APJ are widely distributed in the central nervous system and peripheral tissues. Researches have confirmed that apelin/APJ involved in a wide range of physiological and pathological functions in the cardiovascular system. Investigations indicated that apelin is a novel critical factor in the development of atherosclerosis (AS). In this review, we discuss the roles of apelin in the vascular smooth muscle cell proliferation, monocytes-endothelial cell adhesion, and angiogenesis that potentially reveals a new cellular mechanism of AS. Considering these roles, apelin and APJ may be novel therapeutic targets of AS.

Diagnosis of prenatal 22q11.2 duplication syndrome: a two-case study.

The objective of the study was to perform the prenatal diagnosis of two foetuses with 22q11.2 duplication for 2.5 Mb after noninvasive prenatal testing (NIPT), and to explore the prenatal diagnosis and genetic characteristics of these foetuses. After amniocentesis, each foetus was diagnosed through karyotype analysis and single-nucleotide polymorphism array (SNP-array), and copy number variation using shotgun sequencing (CNV-seq) was carried out on each mother's peripheral blood for comparative analysis. Both pregnant woman 1 and pregnant woman 2 had foetal amniotic fluid chromosomal karyotypes of 46, XN. The SNP-array result for foetus 1 was arr[hg19] 22q11.21(18,648,856-21,800,471) x3; namely, 22q11.2 had a 3.1 Mb repeat, and the SNP-array result of foetus 2 was arr[hg19]22q11.2(18,648,855-21,464,764) x3; there was a 2.4 Mb repeat of 22q11.2. The CNV-Seq result of the peripheral blood of pregnant woman 1 was seq[hg19]22q11.2(18,953,139-21,449,967) x3; namely, in this mother's 22q11.2 region, there was ~2.5 Mb of duplicate fragment that was pathogenic to CNV. We confirmed that case 1 was inherited from the mother by CNV-seq. In both cases, however, there were key region deletions, including 41 OMIM genes such as CLTCL1, HIRA and TBX1. Both SNP-array and CNV-seq can effectively diagnose 22q11.2 duplication syndrome and clarify its fracture site and involved genes, which may facilitate understanding of the genotype and phenotype correlations.

Creep Monitoring of Submersible Observation Windows Using Mueller Matrix Imaging.

Safety of the observation window is one of the core concerns for manned submersibles. When subjected to underwater static pressure, extrusion and creep deformation always occur in the observation window, which can pose a threat to both safety and optical performance. To assess the deformation, real-time and non-contact monitoring methods are necessary. In this study, a conceptual setup based on the waveplate rotation and dual-DoFP (division of focal-plane polarimeter) polarization camera is built for the observation window's creep monitoring by measuring the Mueller matrix images of the samples under different pressures and durations. Then, a series of characteristic parameters, such as t1, R, r, R', are extracted from the Muller matrix images by Mueller matrix transformation (MMT), Mueller matrix polar decomposition (MMPD), correlation analysis and phase unwrapping method. The results demonstrate that these parameters can effectively describe the observation window's creep at different pressure levels which are simulated by finite element analysis. Additionally, more characterization parameters, such as ψ, A and D, are given from the Mueller matrix images and discussed to illustrate the method's potential for further applications and investigations. Ultimately, future devices based on this method could serve as a valuable tool for real-time and non-contact creep monitoring of the submersible observation windows.

An Oxidative Stress-Related Genes Signature for Predicting Survival in Bladder Cancer: Based on TCGA Database and Bioinformatics.

Background: Oxidative stress (OS) responses have been linked to oncogenesis and tumor progression and have recently been regarded as a potential strategy for tumor therapy. However, OS-related therapeutic targets have not been identified to date in the bladder cancer (BC). Methods: The mRNA expression and clinical data of BC were downloaded from the public database. Prognostic risk score signature was constructed using LASSO Cox regression analysis. External validation was performed in GSE15307 cohort. ESTIMATE, CIBERSORT, and ssGSEA algorithm were used to analyze immune cell infiltration and immune microenvironment. Next, functional enrichment analysis was performed to elucidate the mechanism underlying the signature. Additionally, we performed a nomogram to forecast the survival rate of individual BC patients. Results: An OS-related genes (OSRGs) signature was constructed. Overall survival was lower in the high-risk group than in the low-risk group, according to survival analyses. The area under the curve (AUC) of ROC curves further validated the prognostic signature's strong prediction performance in these two cohorts. The risk score was verified as an independent risk factor for BC by independent prognostic analysis. Moreover, as compared to TNM stage alone, a nomogram that integrated the risk score with TNM stage showed a much superior predictive value. Immune infiltration and tumor microenvironment studies indicated that immune cells and functions may play a significant role in carcinogenesis and development. The levels of expression of prognostic genes were shown to be substantially linked with drug sensitivity. Conclusion: We developed a novel OSRGs signature for predicting overall survival and impacting the immune status in patients with BC. New nomogram can help clinicians predict the survival rate of BC patients. These findings shed new light on the potential usage of OSRGs signature in BC patients.

Rapidly Measuring Scattered Polarization Parameters of the Individual Suspended Particle with Continuously Large Angular Range.

Suspended particles play a vital role in aquatic environments. We propose a method to rapidly measure the scattered polarization parameters of individual suspended particles with continuously large angular range (PCLAR), from 60° to 120° in one shot. A conceptual setup is built to measure PCLAR with 20 kHz; to verify the setup, 10 µm-diameter silica microspheres suspended in water, whose PCLAR are consistent with those simulated by Mie theory, are measured. PCLAR of 6 categories of particles are measured, which enables high-accuracy classification with the help of a convolutional neural network algorithm. PCLAR of different mixtures of Cyclotella stelligera and silica microspheres are measured to successfully identify particulate components. Furthermore, classification ability comparisons of different angular-selection strategies show that PCLAR enables the best classification beyond the single angle, discrete angles and small-ranged angles. Simulated PCLAR of particles with different size, refractive index, and structure show explicit discriminations between them. Inversely, the measured PCLAR are able to estimate the effective size and refractive index of individual Cyclotella cells. Results demonstrate the method's power, which intrinsically takes the advantage of the optical polarization and the angular coverage. Future prototypes based on this concept would be a promising biosensor for particles in environmental monitoring.

Identification and validation of a hypoxia-related prognostic signature in clear cell renal cell carcinoma patients.

ABSTRACT: Increasing evidence has shown that hypoxia is closely related to the development, progression, and prognosis of clear cell renal cell carcinoma (ccRCC). Nevertheless, reliable prognostic signatures based on hypoxia have not been well-established. This study aimed to establish a hypoxia-related prognostic signature and construct an optimized nomogram for patients with ccRCC.We accessed hallmark gene sets of hypoxia, including 200 genes, and an original RNA seq dataset of ccRCC cases with integrated clinical information obtained by mining the Cancer Genome Atlas database and the International Cancer Genome Consortium (ICGC) database. Univariate Cox regression analysis and multivariate Cox proportional hazards regression were performed to identify prognostic hub genes and further established prognostic model as well as visualized the nomogram. External validation of the optimized nomogram was performed in independent cohorts from the ICGC database.ANKZF1, ETS1, PLAUR, SERPINE1, FBP1, and PFKP were selected as prognostic hypoxia-related hub genes, and the prognostic model effectively distinguishes high-risk and low-risk patients with ccRCC. The results of receiver operating characteristic curve, risk plots, survival analysis, and independent analysis suggested that RiskScore was a useful tool and independent predictive factor. A novel prognosis nomogram optimized via RiskScore showed its promising performance in both the Cancer Genome Atlas-ccRCC cohort and an ICGC-ccRCC cohort.Our study reveals that the differential expressions of hypoxia-related genes are associated with the overall survival of patients with ccRCC. The prognostic model we established showed a good predictive and discerning ability in ccRCC patients. The novel nomogram optimized via RiskScore exhibited a promising predictive ability. It may be able to serve as a visualized tool for guiding clinical decisions and selecting effective individualized treatments.

Targeting drugs to APJ receptor: the prospect of treatment of hypertension and other cardiovascular diseases.

The APJ is a class A, rhodopsin-like G protein-coupled receptor (GPCR) with high sequence similarity to the angiotensin receptor AT1. APJ has been shown to be widely expressed in humans tissues, including the central nervous system, cardiovascular system, adipocytes and others. APJ plays an important role in the occurrence and development of cardiovascular and metabolic diseases including atherosclerosis (AS), coronary heart disease (CAD), heart failure(HF), pulmonary arterial hypertension (PAH), myocardial hypertrophy and atrial fibrillation, especially hypertension. Previous researchers found that apelin/APJ could induce vasodilation and then reduce blood pressure. Despite APJ is closely associated with many diseases, there are no drugs that can activate or inhibit APJ directly. In the current review, we have summarized recently reported peptides, small molecule agonists and antagonists targeting APJ. Given the role of apelin/APJ in hypertension and other cardiovascular diseases, we believe that the peptides and compounds based on APJ will be developed for treatment of these diseases.