Inhibition of miR-4640-5p alleviates pulmonary hypertension in chronic obstructive pulmonary disease patients by regulating nitric oxide synthase 1.

BACKGROUND: Pulmonary hypertension (PH) is a devastating disease characterized by vasoconstriction and vascular remodeling, leading to right ventricular failure and death. PH is a common complication of chronic obstructive pulmonary disease (COPD). Accumulating evidence demonstrate that microRNAs participate in the pathobiology of PH in COPD patients. In this study, we aimed to evaluate the expression and function of microRNA-4640-5p (miR-4640-5p) in PH. METHODS: The mRNA and protein levels were determined by quantitative polymerase chain reaction (qPCR) and western blot, separately. Functional assays and western blot were performed to determine the effects of miR-4640-5p and NOS1 on cell growth, migration. Besides, the dual-luciferase reporter assays were used to validate miR-4640-5p and NOS1 interactions. RESULTS: We found that miR-4640-5p expression was significantly higher in the lung tissues of COPD-PH patients than in the healthy controls while higher expression of miR-4640-5p was correlated with more severe COPD-PH. By using pulmonary artery smooth muscle cell (PASMC) in in vitro assays, we demonstrated that inhibition of miR-4640-5p suppressed cell proliferation and migration of PASMC via regulating mTOR/S6 signaling. Bioinformatics analysis and validation experiments revealed that nitric oxide synthase 1 (NOS1) was a direct downstream target of miR-4640-5p. Overexpression of NOS1 partially antagonized the effect of miR-4640-5p in regulating PASMC cell proliferation and migration. In addition, our findings suggested that miR-4640-5p/NOS1 axis regulated mitochondrial dynamics in PASMCs. Furthermore, in the hypoxia-induced PH rat model, inhibition of miR-4640-5p ameliorated PH with reduced right ventricular systolic pressure and Fulton index. CONCLUSIONS: miR-4640-5p regulates PH via targeting NOS1, which provides a potential diagnostic biomarker and therapeutic target for COPD-PH patients.

Spurious fringe processing for dielectric metasurface profile measurement using white-light scanning interferometry.

Dielectric metasurfaces, which are capable of manipulating incident light, have been a novel branch of flat optics. This modulation ability is realized by nanostructures with space-variant geometrical parameters such as height and diameter. Therefore, accurate profile measurement of metasurfaces is of great importance. White-light scanning interferometry is widely used for profile measurement. The step height is retrieved by locating the envelope's peak. However, spurious fringes attached to the desired fringes were observed at the measured area near the edge of nanostructures. Their amplitude distributions vary with the density of nanostructures as well as distance to the edge. Further, anomalous coherence signals with two fringe envelopes are produced, which result in inaccurate measurement results. We attributed this phenomenon to the complex light modulation by the nanostructures. When referring to the anomalous coherence signals for the top of the nanostructures, one envelope is produced by the top, and the other is produced by the bottom; however, it is difficult to distinguish these two, which is the same case for the bottom of the nanostructures. To automatically solve these obstacles, a signal processing method, which integrates the image segmentation technology to identify and divide the anomalous coherence signals, along with a Morlet wavelet transform to extract the fringe envelope, suitable for any measured area of the dielectric metasurface, is proposed. One metasurface belt consisting of seven kinds of nanopillars with varying arrayed densities that produce different coherence signals is measured. The diameter distribution ranges from 500 to 1250 nm with a constant height of 1850 nm. The local periods in the X and Y directions are 3020 and 1740 nm, respectively. Measurement results demonstrate the validity of the proposed method for spurious fringes processing.

Prediction of gold stage in patients hospitalized with COPD exacerbations using blood neutrophils and demographic parameters as risk factors.

BACKGROUND: Patients hospitalized with chronic obstructive pulmonary disease (COPD) exacerbations are unable to complete the pulmonary function test reliably due to their poor health conditions. Creating an easy-to-use instrument to identify the Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage will offer valuable information that assists clinicians to choose appropriate clinical care to decrease the mortality in these patients. The objective of this study was to develop a prediction model to identify the GOLD stage in the hospitalized exacerbation of chronic obstructive pulmonary disease (ECOPD) patients. METHODS: This prospective study involved 155 patients hospitalized for ECOPD. All participants completed lung function tests and the collection of blood neutrophils and demographic parameters. Receiver operating characteristic (ROC) curve was plotted based on the data of 155 patients, and was used to analyze the disease severity predictive capability of blood neutrophils and demographic parameters. A support vector regression (SVR) based GOLD stage prediction model was built using the training data set (75%), whose accuracy was then verified by the testing data set (25%). RESULTS: The percentage of blood neutrophils (denoted as NEU%) combined with the demographic parameters was associated with a higher risk to severe episode of ECOPD. The area under the ROC curve was 0.84. The SVR model managed to predict the GOLD stage with an accuracy of 90.24%. The root-mean-square error (RMSE) of the forced expiratory volume in one second as the percentage of the predicted value (denoted as FEV1%pred) was 8.84%. CONCLUSIONS: The NEU% and demographic parameters are associated with the pulmonary function of the hospitalized ECOPD patients. The established prediction model could assist clinicians in diagnosing GOLD stage and planning appropriate clinical care.

Automated fast computational adaptive optics for optical coherence tomography based on a stochastic parallel gradient descent algorithm.

The transverse resolution of optical coherence tomography is decreased by aberrations introduced from optical components and the tested samples. In this paper, an automated fast computational aberration correction method based on a stochastic parallel gradient descent (SPGD) algorithm is proposed for aberration-corrected imaging without adopting extra adaptive optics hardware components. A virtual phase filter constructed through combination of Zernike polynomials is adopted to eliminate the wavefront aberration, and their coefficients are stochastically estimated in parallel through the optimization of the image metrics. The feasibility of the proposed method is validated by a simulated resolution target image, in which the introduced aberration wavefront is estimated accurately and with fast convergence. The computation time for the aberration correction of a 512 × 512 pixel image from 7 terms to 12 terms requires little change, from 2.13 s to 2.35 s. The proposed method is then applied for samples with different scattering properties including a particle-based phantom, ex-vivo rabbit adipose tissue, and in-vivo human retina photoreceptors, respectively. Results indicate that diffraction-limited optical performance is recovered, and the maximum intensity increased nearly 3-fold for out-of-focus plane in particle-based tissue phantom. The SPGD algorithm shows great potential for aberration correction and improved run-time performance compared to our previous Resilient backpropagation (Rprop) algorithm when correcting for complex wavefront distortions. The fast computational aberration correction suggests that after further optimization our method can be integrated for future applications in real-time clinical imaging.

Nonnull interferometric testing of spherical gratings under Littrow conditions with opposite diffraction orders.

Diffracted wavefront measurements are qualitative and comprehensive verifications for the spherical grating that was manufactured to specifications. Direct interferometric testing of the diffracted wavefront is convenient and implemented by tilting the spherical grating at a Littrow angle to obtain autoreflection and then results in a nonnull interferometric testing configuration. The diffracted wavefront of the spherical grating contains not only wavefront errors induced by the manufacturing imperfections but also inherent wavefront contributions from the autoreflection testing setup. The magnitudes of the latter are affected by both the spherical substrate and the groove pattern. Through the analysis of geometric aberrations of spherical gratings, the groove pattern contributions are demonstrated to be contrary for the opposite diffraction orders. A nonnull interferometric testing of spherical gratings is proposed without foreknowledge of the groove pattern, in which the wavefront errors contributed only by the manufacturing imperfections are derived from dual measurements under Littrow conditions with opposite diffraction orders. Simulations are implemented for varied line spacing (VLS) spherical gratings with an F-number slower than 1.5 and groove density varying from 150 to 300 lp/mm, and the residual error less than 0.004λ RMS is obtained. The residual misalignment error after conventionally removing defocus and tilt is further analyzed and discussed. A VLS grating in which the NA is 0.13 and groove density is 200 lp/mm is chosen as an experimental sample, and the diffracted wavefront error with 0.018λ RMS is obtained.

Subaperture stitching interferometry based on the combination of the phase correlation and iterative gradient methods.

Subaperture stitching interferometry (SAS) is an important method for map testing of large aperture optical components, in which a mechanical structure is often employed for the testing of each subaperture. By eliminating the phase deviation of the corresponding points in the overlapping regions of every adjacent subaperture, the whole aperture map can be obtained. Accurate subaperture positioning is an important guarantee for precise stitching. In this paper, a hybrid optimization algorithm is proposed to realize subpixel-level positioning accuracy in SAS based on the combination of the phase correlation and iterative gradient methods. The phase correlation method is adopted to calculate the pixel-level positioning deviation first, and the subpixel deviation is derived and then corrected by iterative optimization through the gradient method. The subpixel-level positioning accuracy of the proposed optimization algorithm is verified by simulations and a 76.2 mm off-axis parabolic mirror is chosen as an experimental testing sample. The surface map obtained from the proposed hybrid optimization method is consistent with the full aperture testing result, which also verifies that the proposed optimization algorithm is a powerful tool with subpixel-level positioning accuracy in SAS testing.

Overexpression of the long noncoding RNA TRHDE-AS1 inhibits the progression of lung cancer via the miRNA-103/KLF4 axis.

AIM: The aim of this study was to explore the role and molecular basis of the long noncoding RNA (lncRNA) TRHDE-AS1 in lung cancer. METHODS: We used real-time polymerase chain reaction to analyze the messenger RNA expression levels of TRHDE-AS1, miR-103, and KLF4. The cell viability, proliferation, and invasion rates were assessed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Cell Counting Kit-8, and Transwell assays to elucidate the role of TRHDE-AS1. RESULTS: Our results demonstrated that the lncRNA TRHDE-AS1 is mainly located in the cytoplasm and that the cell proliferation and invasion were suppressed in the group of overexpressed TRHDE-AS1. We also showed that miR-103 could directly bind to TRHDE-AS1 and provided evidence of the oncogenic function of miR-103. Besides, we proved that miR-103 exerted its function by adjusting the expression level of the tumor-suppressor gene KLF4, and the expression level was negatively associated with miR-103. CONCLUSION: In summary, we determined that the effects of TRHDE-AS1 on proliferation, invasion, and cell death could be rescued by the overexpression of miR-103. Our experiments demonstrate that the TRHDE-AS1/miR-103/KLF4 axis may provide new evidence for understanding the molecular basis of lung cancer.

Construction method through multiple off-axis parabolic surfaces expansion and mixing to design an easy-aligned freeform spectrometer.

The classic Czerny-Turner spectrometer consists of a plane grating and two spherical mirrors. The optical path geometry adopted for incident and grating dispersed light is off-axis reflection, so the spherical collimating and focusing mirrors introduce coma and astigmatism. The conventional configuration is asymmetrical for coma automatic compensation, but suffers from astigmatism. We substitute the off-axis parabolic (OAP) surfaces for spherical surfaces of the collimating mirror and each sub-region of the focusing mirror, to achieve an aberration free configuration. The multiple OAP surfaces are then expanded and mixed, to construct a freeform surface integrating the collimating and focusing mirrors into a single element. Results show that a 0.1 nm spectral resolution is achieved over a bandwidth of 400 nm centered at 800 nm, in the designed spectrometer comprised of a plane grating and one freeform mirror. The construction method is advantageous to integrated optic design, and the resulting freeform mirror spectrometer is compact, and simplifies manufacture and alignment.

Wavefront propagation based on the ray transfer matrix and numerical orthogonal Zernike gradient polynomials.

The aberrated wavefront propagates along its normal. Both the magnitude and boundary change after the propagation. Wavefronts characterized by Zernike coefficients and a normalized pupil radius can also be represented by a bundle of feature rays normal to the local surface. A ray transfer matrix parameterized by the pupil radius and propagation distance is proposed to transfer these feature rays to obtain the slope and position data of the propagated feature rays. Numerical orthogonal Zernike gradient polynomials are derived to reconstruct the wavefront from the discrete data by using a numerical method. Two aberrated wavefronts are performed as examples to validate the accuracy and flexibility of the proposed numerical method.

Customized design and efficient fabrication of two freeform aluminum mirrors by single point diamond turning technique.

The precision single point diamond turning technique has been a promising technology for generating small and medium-sized freeform optical elements with high surface quality. In this paper, we present an extremely off-axis freeform optical system with a large 10.0 mm pupil diameter and a low 3.0 F-number over a wide 28° field of view. It is composed of two freeform aluminum mirrors, which are fabricated efficiently by the single point diamond turning machine. The manufacturing strategy and parameters are estimated rationally and comprehensively, based on the freeform surface characters. The freeform aluminum mirror surface can reach submicron surface accuracy and achieve nanometer surface roughness. The final assembled prototype of the off-axis two-mirror freeform display optical system has the advantages of compactness, a broad spectrum, and good display imaging performance.

Fluorescence assay for alkaline phosphatase based on ATP hydrolysis-triggered dissociation of cerium coordination polymer nanoparticles.

Alkaline phosphatase (ALP) is a significant biomarker for diagnostics. Simple, selective and sensitive detection of ALP activity is thus of critical importance. In this study, an artful fluorescence assay for ALP is proposed based on adenosine triphosphate (ATP) hydrolysis-triggered disassociation and fluorescence quenching of cerium coordination polymer nanoparticles (CPNs). ATP, a recognized natural substrate of phosphatase, can serve as a superb "antenna" to sensitize the luminescence of Ce3+ with the aid of tris(hydroxymethyl) aminomethane (Tris), forming Ce3+-ATP-Tris CPNs. In the presence of ALP, ATP will be catalytically converted into adenosine and inorganic orthophosphate, however neither of them can sensitize Ce3+ in alkaline media. As a result, the obtained CPNs are disassociated, inducing the quenching of the fluorescence. On this basis, a straightforward fluorescence assay for ALP activity is rationally developed. The fluorescence quenching efficiency shows a linear relationship for ALP within the activity range from 0.1 to 10 mU mL-1 with a detection limit of 0.09 mU mL-1 under the optimal experimental conditions. Moreover, this facile yet effective fluorescence method featured simplicity, cost-effectiveness, high sensitivity and high selectivity and can be successfully utilized for the quantitative detection of ALP in human serum samples.

Mapping geometry in Fizeau transmission spheres with a small f-number.

The ideal mapping geometry in a Fizeau interferometer is to map equal height increments on a flat object and equal angle increments on a spherical surface to equal heights on the detector. So the initial intent of the optical design of Fizeau transmission spheres (TSs) is to provide R-θ mapping geometry for equal angle increments. The corresponding unequal heights mapping will introduce retrace error as coma when linear carrier fringes exist. On the contrary, equal heights mapping with R-sin θ mapping geometry will avoid linear carrier fringes induced coma error. These two different mapping geometries conflict especially for the TS with a small f-number. In this paper, we will first explore the design and the performance of the f/0.75 TS according to the two different mapping geometries, and then evaluate the mapping geometry for the commercial ZYGO f/0.75 TS, and give some engineering notes for the designers, the metrologists, and the fabricators in the optical laboratory.

Generalized shift-rotation absolute measurement method for high-numerical-aperture spherical surfaces with global optimized wavefront reconstruction algorithm.

In this paper, a generalized shift-rotation absolute measurement method is proposed to measure the absolute surface shape of high-numerical-aperture spherical surfaces. Based on the wavefront difference method, the high order misalignment aberrations can be removed from the measurements. Our generalized shift-rotation absolute measurement process only needs one rotational measurement position and one translational measurement position. A wavefront reconstruction method based on the self-adaptive differential evolution algorithm is proposed to calculate the Zernike polynomials coefficient ai of the absolute surface shape Wtest(x,y), the rotation angle Δθ, the translation δx along the x axis, and the translation δy along the y axis. The translation error and rotation error in other absolute measurement methods are avoided using our generalized shift-rotation absolute measurement method. Experimental absolute results of the test surface and reference surface are given and the difference of reference surface shapes between two testings in experiments is 0.12 nm root mean square.

Phase retrieval in moiré volume computed tomography based on spatial phase shifting by triple-crossed gratings.

Due to its advantages of nonintrusiveness, wide measurement range, and insensitivity to variation, Moiré deflectometry is a powerful tool for quantitative measurement of a flow field's physical parameters such as density and temperature. Moiré volume computed tomography (MVCT), combining the moiré deflectometry and volume optical computed tomography (VOCT), can realize real three-dimensional parameters reconstruction, in which the radial derivatives extraction of the projected phase is of great importance. In this paper, a spatial phase-shifting-interferometry-based MVCT system was proposed to extract the radial shearing phase distribution. The system is simple and compact, and consists of three crossed gratings and lenses, with no wave plates or polarizers introduced. Via using a 4-f system, the optical path was shortened, and four spatial phase-shifting grid moiré projections can be obtained simultaneously. Each grid interferogram was filtered and separated into two linear interferograms in two orthogonal directions. Moreover, a two-step spatial phase-shifting algorithm was applied to obtain the first-order derivative phase in two mutually perpendicular directions, respectively. Simulations were implemented to verify the feasibility and accuracy of the proposed phase retrieval method. The measured results for the radial first-order partial derivative of the phase projection of a propane flame in the experimental VOCT system are presented.

Coupling efficiency model for spectral beam combining of high-power fiber lasers calculated from spectrum.

We utilize the spectral broadening of Yb-doped fiber lasers in the spectral beam combining scheme to develop an analytical model of the coupling efficiency, which forms a critical factor in evaluating the practicality of the beam combination system. The simulation results predict a trend similar to the measured ones. Via increasing the number of simulating lasers, the model can be extended to calculate the combining efficiency of the resulting multiple-beam-combination system and estimate the optimal output power and combining efficiency. Moreover, the analytical model is suitable to investigate key parameters of Yb-doped lasers and filters, which is beneficial in enhancing the combining efficiency.

Large radius of curvature measurement based on virtual quadratic Newton rings phase-shifting moiré-fringes measurement method in a nonnull interferometer.

We have proposed a virtual quadratic Newton rings phase-shifting moiré-fringes measurement method in a nonnull interferometer to measure the large radius of curvature for a spherical surface. In a quadratic polar coordinate system, linear carrier testing Newton rings interferogram and virtual Newton rings interferogram form the moiré fringes. It is possible to retrieve the wavefront difference data between the testing and standard spherical surface from the moiré fringes after low-pass filtering. Based on the wavefront difference data, we deduced a precise formula to calculate the radius of curvature in the quadratic polar coordinate system. We calculated the retrace error in the nonnull interferometer using the multi-configuration model of the nonnull interferometric system in ZEMAX. Our experimental results indicate that the measurement accuracy is better than 0.18% for a spherical mirror with a radius of curvature of 41,400 mm.

Carrier squeezing interferometry with π/4 phase shift: phase extraction in the presence of multi-beam interference.

Multi-beam interference exists in testing high-reflectivity surfaces with a Fizeau interferometer. In this paper, the multi-beam interference intensity was estimated as the sum of the first six order harmonics using the Fourier series expansion. Then, by adopting carrier squeezing interferometry with a π/4 phase shift, an algorithm was proposed to extract the phase from multi-beam interferograms. To ensure the separation of the lobes of phase-shift errors and the phase in the frequency domain, conditions of the necessary linear carrier in the proposed algorithm were derived. Simulation results indicated that the phase retrieving precision is better than PV 0.008λ and RMS 0.001λ, even when the reflection coefficient of the test surface is as high as 0.9 and the phase shift varies within π/4±π/20. Compared with the other algorithms, the proposed algorithm for multi-beam interference was validated by its good performance in the experiments, especially when the phase-shift error exists.

Modal wavefront estimation from its slopes by numerical orthogonal transformation method over general shaped aperture.

Wavefront estimation from the slope-based sensing metrologies zis important in modern optical testing. A numerical orthogonal transformation method is proposed for deriving the numerical orthogonal gradient polynomials as numerical orthogonal basis functions for directly fitting the measured slope data and then converting to the wavefront in a straightforward way in the modal approach. The presented method can be employed in the wavefront estimation from its slopes over the general shaped aperture. Moreover, the numerical orthogonal transformation method could be applied to the wavefront estimation from its slope measurements over the dynamic varying aperture. The performance of the numerical orthogonal transformation method is discussed, demonstrated and verified by the examples. They indicate that the presented method is valid, accurate and easily implemented for wavefront estimation from its slopes.

Alignment analyses of a galvanometer-based scanner in free-space Fourier domain optical coherence tomography.

Free-space Fourier domain optical coherence tomography is adopted for biomedical imaging with ultrahigh resolution, in which the setup consists of an interferometer and a spectrometer. Two-dimensional lateral sampling in the sample arm of the interferometer is achieved by using a galvanometer-based scanner. Optical path difference (OPD) drift in the full scan field of view is observed in the assembly process of the scanner. A galvo mirror mount offset with respect to the rotation axis is demonstrated as the derivation of this OPD drift by both geometric analyses and model building. Then, an iterative assembly process of the scanner is proposed with the OPD drift taken as the alignment criteria.

Applying slope constrained Qbfs aspheres for asphericity redistribution in the design of infrared transmission spheres.

An achromatic transmission sphere (TS) must be provided as an accessory for an infrared interferometer with a broadband wavelength channel. When designing an F/0.75 infrared TS using the one-asphere model of the two-lens-only package, the first surface was optimized as a strong asphere beyond our current testing ability, using either a slope-unconstrained Qbfs asphere equal to a conventional even asphere, or using a slope-constrained Qbfs asphere. We applied the asphere-splitting theory to redistribute the asphericity. Adopting only the slope-constrained Qbfs asphere, the strong asphere was successfully split into two weaker aspheres within our testing ability, getting a more manufacturable two-asphere TS solution. Besides, the TS solution with two weaker aspheres presented the same sensitivity to assembly errors compared to the solution with one strong asphere, as demonstrated by the analysis of the wavefront aberrations of the TS solutions. This phenomenon coincides well with the asphere-splitting theory, given that the total asphericity remains almost equivalent between the two solutions.