Ultrasound Speckle Decorrelation Analysis-Based Velocimetry for 3D-Velocity-Components Measurement Using a 1D Transducer Array.

Ultrasound velocimetry has been widely used for blood flow imaging. However, the flow measurements are constrained to resolve the in-plane 2D flow components when using a 1D transducer array. In this work, an ultrasound speckle decorrelation analysis-based velocimetry (3C-vUS) is proposed for 3D velocity components measurement using a 1D transducer array. The 3C-vUS theory is first derived and validated with numerical simulations and phantom experiments. The in vivo testing results show that 3C-vUS can accurately measure the blood flow 3D-velocity-components of the human carotid artery at arbitrary probe-to-vessel angles throughout the cardiac cycle. With such capability, the 3C-vUS will alleviate the requirement of operators and promote disease screening for blood flow-related disorders.

Time-Lagged Functional Ultrasound for Multi-Parametric Cerebral Hemodynamic Imaging.

We introduce an ultrasound speckle decorrelation-based time-lagged functional ultrasound technique (tl-fUS) for the quantification of the relative changes in cerebral blood flow speed (rCBF [Formula: see text]), cerebral blood volume (rCBV) and cerebral blood flow (rCBF) during functional stimulations. Numerical simulations, phantom validations, and in vivo mouse brain experiments were performed to test the capability of tl-fUS to parse out and quantify the ratio change of these hemodynamic parameters. The blood volume change was found to be more prominent in arterioles compared to venules and the peak blood flow changes were around 2.5 times the peak blood volume change during brain activation, agreeing with previous observations in the literature. The tl-fUS shows the ability of distinguishing the relative changes of rCBFspeed, rCBV, and rCBF, which can inform specific physiological interpretations of the fUS measurements.

Exosomal miR-214-3p from senescent osteoblasts accelerates endothelial cell senescence.

BACKGROUND: Osteoporosis is a common systemic bone disease that leads to bone fragility and increases the risk of fracture. However, the pathogenesis of osteoporosis is considered to be highly complex. The exosomes can regulate the communication between cells. The specific mechanism of information transmission between osteoblasts and endothelial cells is worthy of further study. METHODS: Exosomes were isolated and verified from senescent osteoblasts. The source and properties of exosomes were determined by TEM, particle size analysis and western blot. We established the co-culture model of endothelial cells and senescent osteoblasts. We used qRT-PCR to identify differentially expressed miRNAs. The functional changes of vascular endothelial cells were verified by cell transfection. ß-Galactosidase cell senescence assay, Hoechst cell apoptosis assay, Ki67 cell proliferation assay and Transwell migration assay were used to verify cell senescence, apoptosis, proliferation, and migration. The potential target gene of miRNA was detected by bio-informatics pathway and double luciferase report. RESULTS: We discovered that senescent osteoblasts could promote the senescence and apoptosis of vascular endothelial cells and inhibit their proliferation and migration. miR-214-3p was upregulated in senescent osteoblast-derived exosomes. miR-214-3p could effectively promote senescence and apoptosis of endothelial cells and inhibit proliferation and migration ability. L1CAM is a miR-214-3p direct target gene determined by bio-informatics and double luciferase report. CONCLUSIONS: In conclusion, senescent osteoblast-derived exosomes can accelerate endothelial cell senescence through miR-214-3p/L1CAM pathway. Our experiments reveal the role of exosomes in the skeletal microenvironment.

Fully Automatic Dual-Probe Lung Ultrasound Scanning Robot for Screening Triage.

Two-dimensional lung ultrasound (LUS) has widely emerged as a rapid and noninvasive imaging tool for the detection and diagnosis of coronavirus disease 2019 (COVID-19). However, image differences will be magnified due to changes in ultrasound (US) imaging experience, such as US probe attitude control and force control, which will directly affect the diagnosis results. In addition, the risk of virus transmission between sonographer and patients is increased due to frequent physical contact. In this study, a fully automatic dual-probe US scanning robot for the acquisition of LUS images is proposed and developed. Furthermore, the trajectory was optimized based on the velocity look-ahead strategy, the stability of contact force of the system and the scanning efficiency were improved by 24.13% and 29.46%, respectively. Also, the control ability of the contact force of robotic automatic scanning was 34.14 times higher than that of traditional manual scanning, which significantly improves the smoothness of scanning. Importantly, there was no significant difference in image quality obtained by robotic automatic scanning and manual scanning. Furthermore, the scanning time for a single person is less than 4 min, which greatly improves the efficiency of screening triage of group COVID-19 diagnosis and suspected patients and reduces the risk of virus exposure and spread.

Exosomal miR-767 from senescent endothelial-derived accelerating skin fibroblasts aging via inhibiting TAB1.

Skin aging is a complicated physiological process, and microRNA-mediated regulation has been shown to contribute to this process. Exosomes mediate intercellular communication through miRNAs, mRNAs and proteins, and participate in many physiological and pathological processes. Vascular endothelial cell-derived exosomes have been confirmed to be involved in the development of many diseases, however, their effects on skin aging have not been reported. In this study, senescent endothelial cells could regulate skin fibroblast functions and promote cell senescence through exosomal pathway. miR-767 was highly expressed in senescent vascular endothelial cells and their exosomes, and miR-767 is also upregulated in skin fibroblasts after treatment with exosomes derived from senescent vascular endothelial cells. In addition, transfection with miR-767 mimic promoted senescence of skin fibroblasts, while transfection with miR-767 inhibitor reversed the effect of D-galactose. Double luciferase analysis confirmed that TAB1 was a direct target gene of miR-767. Furthermore, miR-767 expression was increased and TAB1 expression was decreased in D-galactose induced aging mice. In mice that overexpressed miR-767, HE staining showed thinning of dermis and senescence appearance. In conclusion, senescent vascular endothelial cell-derived exosome mediated miR-767 regulates skin fibroblasts through the exosome pathway. Our study reveals the role of vascular endothelial cell-derived exosomes in aging in the skin microenvironment and contributes to the discovery of new targets for delaying senescence.

A Method for Improving the Prediction of Outpatient Visits for Hospital Management: Bayesian Autoregressive Analysis.

The number of outpatient visits is generally influenced by various factors that are difficult to quantify and obtain, resulting in some irregular fluctuations. The traditional statistical methodology seldom considers these uncertainties. Accordingly, this paper presents a Bayesian autoregressive (AR) analysis to propose a forecasting framework to cope with the strict requirements. The AR model was conducted to identify the linear and autocorrelation relationships of historical series, and Bayesian inference was used to correct and optimize the AR model parameters. Posterior distribution of parameters was stably and reliably obtained by Gibbs sampling on the condition of the convergent Markov chain. Meanwhile, the lag orders of the AR model were adjusted based on the series characteristics. To increase the variability and generality of the dataset, the developed Bayesian AR model was evaluated at seven hospitals in China. The results demonstrated that the Bayesian AR model had varying degrees of decline in the MAPE value in the seven sets of experimental data. The reductions ranged from 0.1431% to 0.0342%, indicating effective optimization of the Bayesian inference in the AR model parameters and reflecting the useful correction of the lag order adjustment strategy. The proposed Bayesian AR framework showed high accuracy index and stable prediction accuracy, thereby outperforming the traditional AR model.

Endothelial Cell-Derived Extracellular Vesicles Target TLR4 via miRNA-326-3p to Regulate Skin Fibroblasts Senescence.

Backgrounds: Skin aging could be regulated by the aberrant expression of microRNAs. In this manuscript, we explain that endothelial cell-derived extracellular vesicles could act as supporters to deliver exogenous miR-326-3p to accelerate skin fibroblasts senescence. Methods: ß-galactosidase senescence staining assay, Hoechst 33258 apoptosis staining assay, and Ki67 staining assay were used to evaluate the biological function of mouse skin fibroblasts. Real-time PCR was applied to assay miRNAs and mRNAs expressions. Western blot was used to detect TLR4 protein expression. The target gene of miRNA were identified using a double luciferase reporter assay. miR-326-3p mimic/inhibitor and siRNA-TLR4 can demonstrate a nonnegligible link between miR-326-3p-TLR4 and skin aging. Results: In coculture experiment, senescence endothelial cells could promote the skin fibroblasts senescence and apoptosis via extracellular vesicles pathway. In contrast, miR-326-3p mimics accelerated senescence and apoptosis of skin fibroblasts, while miR-326-3p inhibitor could dramatically delay skin fibroblasts senescence and apoptosis. TLR4 was proved to be a miR-326-3p directly target gene via double luciferase assay. After skin fibroblasts transfected with siRNA-TLR4, cellular senescence and apoptosis were significantly increased. Furthermore, the skin tissues of aging mice were shown with overexpression of miR-326-3p and decrease of TLR4 gene and protein expression levels. Conclusions: Endothelial cell-derived extracellular vesicles delivery of miR-326-3p was found to have a function in skin fibroblasts via target TLR4. Therefore, endothelial cell-derived extracellular vesicles in antiaging therapies might be a new treatment way for delaying skin aging.

A Cephalopod-Inspired Soft-Robotic Siphon for Thrust Vectoring and Flow Rate Regulation.

Cephalopods could simultaneously achieve both accurate positioning and agile bodily maneuvers by coordinating the mantle and the funnel, which is ideal for underwater robotic applications toward a compact propulsor with combined thrust vectoring and regulation. For a wide range of underwater applications from videography to manipulation, this novel approach would offer a compact and integrated alternative to the state-of-the-art with multiple vectoring thrusters. This article presents a biomimetic soft-robotic siphon (BSRS) as the propulsor unit, consisting of a novel central flow-regulative duct (CFRD) encircled by three circumferential siphon actuation muscles (SAMs). Hydraulic pressurization of the SAMs could enable both thrust vectoring by deflecting the BSRS and flow regulation by proportionally alternating the orifice of the CFRD. The design, modeling, and fabrication of the BSRS are presented in detail. Experiments using a prototype BSRS were conducted for validating the performances of deflection deformation and flow regulation, showing bending range of over 180° and flow-restricting capability of up to 100%. A burst effect was achieved with the ability of exceeding the constant flow rate by up to 50%, enabling tremendous thrust increase in very short time. This work proves the feasibility of combining omnidirectional deflection with flow regulation within a soft-robotic mechanism, paving the way to compact water-jetting propulsion for underwater robots.

Exosome-derived microRNAs contribute to prostate cancer chemoresistance.

Certain microRNAs (miRNAs) play a key role in cancer cell chemoresistance. However, the pleiotropic functions of exosome-derived miRNAs on developing chemoresistance remain unknown. In the present study, we aimed to construct potential networks of miRNAs, which derived from the exosome of chemoresistant prostate cancer (PCa) cells, with their known target genes using miRNA expression profiling and bioinformatic tools. Global miRNA expression profiles were measured by microarray. Twelve miRNAs were initially selected and validated by qRT-PCR. Known targets of deregulated miRNAs were utilized using DIANA-TarBase database v6.0. The incorporation of deregulated miRNAs and target genes into KEGG pathways were utilized using DIANA-mirPath software. To construct potential miRNA regulatory networks, the overlapping parts of miRNAs and their targer genes from the selected KEGG pathway 'PCa progression (hsa05215)' were visualized by Cytoscape software. We identified 29 deregulated miRNAs, including 19 upregulated and 10 downregulated, in exosome samples derived from two kinds of paclitaxel resistance PCa cells (PC3-TXR and DU145-TXR) compared with their parental cells (PC3 and DU145). The enrichment results of deregulated miRNAs and known target genes showed that a few pathways were correlated with several critical cell signaling pathways. We found that hub hsa-miR3176, -141-3p, -5004-5p, -16-5p, -3915, -488­3p, -23c, -3673 and -3654 were potential targets to hub gene androgen receptor (AR) and phosphatase and tensin homolog (PTEN). Hub gene T-cell factors/lymphoid enhancer-binding factors 4 (TCF4) target genes were mainly regulated by hub hsa-miR-32-5, -141-3p, -606, -381 and -429. These results may provide a linkage between PCa chemoresistance and exosome regulatory networks and thus lead us to propose that AR, PTEN and TCF4 genes may be the important genes which are regulated by exosome miRNAs in chemoresistance cancer cells.

Polysaccharide Extracted from Laminaria japonica Delays Intrinsic Skin Aging in Mice.

This study aimed to determine the effect of topically applied Laminaria polysaccharide (LP) on skin aging. We applied ointment containing LP (10, 25, and 50 µg/g) or vitamin E (10 µg/g) to the dorsal skin of aging mice for 12 months and young control mice for 4 weeks. Electron microscopy analysis of skin samples revealed that LP increased dermal thickness and skin collagen content. Tissue inhibitor of metalloprotease- (TIMP-) 1 expression was upregulated while that of matrix metalloproteinase- (MMP-) 1 was downregulated in skin tissue of LP-treated as compared to untreated aging mice. Additionally, phosphorylation of c-Jun N-terminal kinase (JNK) and p38 was higher in aging skin than in young skin, while LP treatment suppressed phospho-JNK expression. LP application also enhanced the expression of antioxidative enzymes in skin tissue, causing a decrease in malondialdehyde levels and increases in superoxide dismutase, catalase, and glutathione peroxidase levels relative to those in untreated aging mice. These results indicate that LP inhibits MMP-1 expression by preventing oxidative stress and JNK phosphorylation, thereby delaying skin collagen breakdown during aging.