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We demonstrate a novel, to our knowledge, approach for phase-resolved coherent 3D surface imaging that utilizes synthetic wavelength phase-based ranging and line-scan off-axis holography. Our proof-of-concept system employs an akinetic tunable laser to perform fast wavelength switching and a galvanometer mirror for slow-axis mechanical scanning. Quantitative depth measurements of an anodized aluminum plate and 3D-printed depth calibration targets and a printed circuit board are demonstrated. Analyses of both shot-noise limited system performance and speckle noise are also presented. The proof-of-concept system achieves micron-scale depth precision with a FOV of 12.8 mm × 34 mm and a 50 ms image acquisition time.

We describe a fiber-based coherent receiver topology which utilizes intrinsic phase shifts from fiber couplers to enable instantaneous quadrature projection with shot-noise limited signal-to-noise ratio (SNR). Fused 3 × 3 fiber couplers generate three phase-shifted signals simultaneously that can be combined with quadrature projection methods to detect magnitude and phase unambiguously. We present a novel, to the best of our knowledge, differential detection topology which utilizes a combination of 3 × 3 and 2 × 2 couplers to enable quadrature projection with fully differential detection. We present a mathematical analysis of this 3 × 3 differential detection topology, extended methods for signal calibration, and SNR analysis. We characterize the SNR advantage of this approach and demonstrate a sample application illustrating simultaneous magnitude and phase imaging of a chrome-on-glass test chart.

Developmentally programmed polyploidy (whole-genome duplication) of cardiomyocytes is common across evolution. Functions of such polyploidy are essentially unknown. Here, in both Drosophila larvae and human organ donors, we reveal distinct polyploidy levels in cardiac organ chambers. In Drosophila, differential growth and cell cycle signal sensitivity leads the heart chamber to reach a higher ploidy/cell size relative to the aorta chamber. Cardiac ploidy-reduced animals exhibit reduced heart chamber size, stroke volume and cardiac output, and acceleration of circulating hemocytes. These Drosophila phenotypes mimic human cardiomyopathies. Our results identify productive and likely conserved roles for polyploidy in cardiac chambers and suggest that precise ploidy levels sculpt many developing tissues. These findings of productive cardiomyocyte polyploidy impact efforts to block developmental polyploidy to improve heart injury recovery., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2023. Published by The Company of Biologists Ltd.)

Wide field of view microscopy that can resolve 3D information at high speed and spatial resolution is highly desirable for studying the behaviour of freely moving model organisms. However, it is challenging to design an optical instrument that optimises all these properties simultaneously. Existing techniques typically require the acquisition of sequential image snapshots to observe large areas or measure 3D information, thus compromising on speed and throughput. Here, we present 3D-RAPID, a computational microscope based on a synchronized array of 54 cameras that can capture high-speed 3D topographic videos over an area of 135 cm2, achieving up to 230 frames per second at spatiotemporal throughputs exceeding 5 gigapixels per second. 3D-RAPID employs a 3D reconstruction algorithm that, for each synchronized snapshot, fuses all 54 images into a composite that includes a co-registered 3D height map. The self-supervised 3D reconstruction algorithm trains a neural network to map raw photometric images to 3D topography using stereo overlap redundancy and ray-propagation physics as the only supervision mechanism. The resulting reconstruction process is thus robust to generalization errors and scales to arbitrarily long videos from arbitrarily sized camera arrays. We demonstrate the broad applicability of 3D-RAPID with collections of several freely behaving organisms, including ants, fruit flies, and zebrafish larvae., Competing Interests: Competing interests RH and MH are cofounders of Ramona Optics, Inc., which is commercializing multi-camera array microscopes. MH, JP, TD, PR, VS, CBC, MZ, JPB, and GH are or were employed by Ramona Optics, Inc. during the course of this research. KCZ is a consultant for Ramona Optics, Inc. The remaining authors declare no competing interests.

We present a multi-modal fiber array snapshot technique (M-FAST) based on an array of 96 compact cameras placed behind a primary objective lens and a fiber bundle array. Our technique is capable of large-area, high-resolution, multi-channel video acquisition. The proposed design provides two key improvements to prior cascaded imaging system approaches: a novel optical arrangement that accommodates the use of planar camera arrays, and a new ability to acquire multi-modal image data acquisition. M-FAST is a multi-modal, scalable imaging system that can acquire snapshot dual-channel fluorescence images as well as differential phase contrast measurements over a large 6.59 mm × 9.74 mm field-of-view at 2.2- μ m center full-pitch resolution.

Noninvasive optical imaging through dynamic scattering media has numerous important biomedical applications but still remains a challenging task. While standard diffuse imaging methods measure optical absorption or fluorescent emission, it is also well-established that the temporal correlation of scattered coherent light diffuses through tissue much like optical intensity. Few works to date, however, have aimed to experimentally measure and process such temporal correlation data to demonstrate deep-tissue video reconstruction of decorrelation dynamics. In this work, a single-photon avalanche diode array camera is utilized to simultaneously monitor the temporal dynamics of speckle fluctuations at the single-photon level from 12 different phantom tissue surface locations delivered via a customized fiber bundle array. Then a deep neural network is applied to convert the acquired single-photon measurements into video of scattering dynamics beneath rapidly decorrelating tissue phantoms. The ability to reconstruct images of transient (0.1-0.4 s) dynamic events occurring up to 8 mm beneath a decorrelating tissue phantom with millimeter-scale resolution is demonstrated, and it is highlighted how the model can flexibly extend to monitor flow speed within buried phantom vessels., (© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Fast noninvasive probing of spatially varying decorrelating events, such as cerebral blood flow beneath the human skull, is an essential task in various scientific and clinical settings. One of the primary optical techniques used is diffuse correlation spectroscopy (DCS), whose classical implementation uses a single or few single-photon detectors, resulting in poor spatial localization accuracy and relatively low temporal resolution. Here, we propose a technique termed C lassifying R apid decorrelation E vents via P arallelized single photon d E tection (CREPE) , a new form of DCS that can probe and classify different decorrelating movements hidden underneath turbid volume with high sensitivity using parallelized speckle detection from a 32 × 32 pixel SPAD array. We evaluate our setup by classifying different spatiotemporal-decorrelating patterns hidden beneath a 5 mm tissue-like phantom made with rapidly decorrelating dynamic scattering media. Twelve multi-mode fibers are used to collect scattered light from different positions on the surface of the tissue phantom. To validate our setup, we generate perturbed decorrelation patterns by both a digital micromirror device (DMD) modulated at multi-kilo-hertz rates, as well as a vessel phantom containing flowing fluid. Along with a deep contrastive learning algorithm that outperforms classic unsupervised learning methods, we demonstrate our approach can accurately detect and classify different transient decorrelation events (happening in 0.1-0.4 s) underneath turbid scattering media, without any data labeling. This has the potential to be applied to non-invasively monitor deep tissue motion patterns, for example identifying normal or abnormal cerebral blood flow events, at multi-Hertz rates within a compact and static detection probe., Competing Interests: SX and RH have submitted a patent application related to this work, assigned to Duke University. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Liu, Yang, Jönsson, Qian, McKee, Kim, Konda, Zhou, Kreiß, Wang, Berrocal, Huettel and Horstmeyer.)

Optical coherence tomography (OCT) has seen widespread success as an in vivo clinical diagnostic 3D imaging modality, impacting areas including ophthalmology, cardiology, and gastroenterology. Despite its many advantages, such as high sensitivity, speed, and depth penetration, OCT suffers from several shortcomings that ultimately limit its utility as a 3D microscopy tool, such as its pervasive coherent speckle noise and poor lateral resolution required to maintain millimeter-scale imaging depths. Here, we present 3D optical coherence refraction tomography (OCRT), a computational extension of OCT which synthesizes an incoherent contrast mechanism by combining multiple OCT volumes, acquired across two rotation axes, to form a resolution-enhanced, speckle-reduced, refraction-corrected 3D reconstruction. Our label-free computational 3D microscope features a novel optical design incorporating a parabolic mirror to enable the capture of 5D plenoptic datasets, consisting of millimetric 3D fields of view over up to ±75° without moving the sample. We demonstrate that 3D OCRT reveals 3D features unobserved by conventional OCT in fruit fly, zebrafish, and mouse samples.

Frequency-modulated continuous wave (FMCW) light detection and ranging (LiDAR) is an emerging 3D ranging technology that offers high sensitivity and ranging precision. Due to the limited bandwidth of digitizers and the speed limitations of beam steering using mechanical scanners, meter-scale FMCW LiDAR systems typically suffer from a low 3D frame rate, which greatly restricts their applications in real-time imaging of dynamic scenes. In this work, we report a high-speed FMCW based 3D imaging system, combining a grating for beam steering with a compressed time-frequency analysis approach for depth retrieval. We thoroughly investigate the localization accuracy and precision of our system both theoretically and experimentally. Finally, we demonstrate 3D imaging results of multiple static and moving objects, including a flexing human hand. The demonstrated technique achieves submillimeter localization accuracy over a tens-of-centimeter imaging range with an overall depth voxel acquisition rate of 7.6 MHz, enabling densely sampled 3D imaging at video rate., (© 2022. The Author(s).)

This paper presents a microscopic imaging technique that uses variable-angle illumination to recover the complex polarimetric properties of a specimen at high resolution and over a large field-of-view. The approach extends Fourier ptychography, which is a synthetic aperture-based imaging approach to improve resolution with phaseless measurements, to additionally account for the vectorial nature of light. After images are acquired using a standard microscope outfitted with an LED illumination array and two polarizers, our vectorial Fourier ptychography (vFP) algorithm solves for the complex 2x2 Jones matrix of the anisotropic specimen of interest at each resolved spatial location. We introduce a new sequential Gauss-Newton-based solver that additionally jointly estimates and removes polarization-dependent imaging system aberrations. We demonstrate effective vFP performance by generating large-area (29 mm 2 ), high-resolution (1.24 μ m full-pitch) reconstructions of sample absorption, phase, orientation, diattenuation, and retardance for a variety of calibration samples and biological specimens., Competing Interests: RH: Ramona Optics Inc. (F,I,P,S), (© 2022 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

This work demonstrates a multi-lens microscopic imaging system that overlaps multiple independent fields of view on a single sensor for high-efficiency automated specimen analysis. Automatic detection, classification and counting of various morphological features of interest is now a crucial component of both biomedical research and disease diagnosis. While convolutional neural networks (CNNs) have dramatically improved the accuracy of counting cells and sub-cellular features from acquired digital image data, the overall throughput is still typically hindered by the limited space-bandwidth product (SBP) of conventional microscopes. Here, we show both in simulation and experiment that overlapped imaging and co-designed analysis software can achieve accurate detection of diagnostically-relevant features for several applications, including counting of white blood cells and the malaria parasite, leading to multi-fold increase in detection and processing throughput with minimal reduction in accuracy.

Purpose: To explore the effects of eicosapentaenoic acid (EPA) on biological activity and inflammatory factor expression of human gingival fibroblasts (HGFs)., Methods: The effects of EPA on the activity, morphology and cell cycle of HGFs were observed by living and dead cell staining, immunofluorescence staining and flow cytometry, respectively. HGFs were stimulated by lipopolysaccharides (LPS) of Porphyromonas gingivalis (P. gingivalis) or heat inactivated P. gingivalis, after which the effects of EPA on mRNA and protein expression of IL-6, IL-8 and IL-1β were observed by real-time PCR and ELISA, respectively. The gene and protein expression of heme oxygenase-1(HO-1) was also detected by real-time PCR and Western blotting, respectively. The data were analyzed with SPSS 22.0 software package., Results: 200 μmol/L EPA inhibited cell activity of HGFs; 100 μmol/L EPA did not affect cell activity and morphology of HGFs, and had no significant effect on cell cycle (P>0.05). EPA significantly downregulated gene expression of IL-6 and IL-1β, and protein expression of IL-6 stimulated by P. gingivalis LPS and heat-killed P.gingivalis(P<0.05), in a dose-dependent manner. EPA increased gene expression of HO-1 in a dose dependent manner(P<0.05), and upregulated HO-1 protein expression., Conclusions: EPA significantly inhibits the expression of inflammatory factors without affecting the biological activity of HGFs, which may be related to the induction of HO-1, suggesting the potential role of EPA in the prevention and treatment of periodontitis.

Objective: To observe the effect of electroacupuncture (EA) on the behavior, histomorphology and the expression of angiopoietin-1 (Angpt-1) in rats with spinal nerve injury, so as to explore its mechanism on neuropathic pain., Methods: Forty-five male SD rats were randomly divided into sham, model and EA groups ( n =15 rats in each group). Spinal nerve ligation (SNL) of the L5 lumbar vertebra was performed to establish a rat model of neuropathic pain. The rats in the EA group were given EA at "Zusanli" (ST36) and "Kunlun" (BL60) of the operation side with continuous wave at a frequency of 2 Hz and an intensity of 1.5 mA once a day, 30 minutes each time for 7 days. The sham group only exposed L5 spinal nerves without ligation. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were observed and recorded before modeling and on days 3,5,7,10,12 and 14 after modeling. L4-L6 segments of spinal cord were taken and the morphological changes of spinal dorsal horn were observed by HE staining. The changes of spinal dorsal horn nerve fiber structure were observed by silver plating staining. Angpt-1 expression was detected by Western blot and immunohistochemistry., Results: Compared with the sham group, the model group had significant reductions in MWT and TWL at each time point ( P <0.01); compared with the model group, the EA group had significant increases in MWT and TWL on days 10,12 and 14 after intervention ( P <0.05, P <0.01). HE staining showed that in the model group, the spinal dorsal horn showed degeneration and necrosis of neurons, nuclear fixation and shrinkage, and loose surrounding tissues. The degree of tissue damage of the EA group was milder than that of the model group. The silver staining results showed the model group had obvious neuronal fibrillary tangles, while there were fewer neuronal fibrillary tangles in the EA group. Compared with the sham group, the Angpt-1 expression in the model group was significantly decreased ( P <0.01), and compared with the model group, the EA group had a significant increase in the expression of Angpt-1 ( P <0.01)., Conclusion: EA can promote the recovery of nerve function in SNL rats by up-regulating Angpt-1 expression.

Anterior uveitis is the most common form of intraocular inflammation, and one of its main signs is the presence of white blood cells (WBCs) in the anterior chamber (AC). Clinically, the true composition of cells can currently only be obtained using AC paracentesis, an invasive procedure to obtain AC fluid requiring needle insertion into the AC. We previously developed a spectroscopic optical coherence tomography (SOCT) analysis method to differentiate between populations of RBCs and subtypes of WBCs, including granulocytes, lymphocytes and monocytes, both in vitro and in ACs of excised porcine eyes. We have shown that different types of WBCs have distinct characteristic size distributions, extracted from the backscattered reflectance spectrum of individual cells using Mie theory. Here, we further develop our method to estimate the composition of blood cell mixtures, both in vitro and in vivo . To do so, we estimate the size distribution of unknown cell mixtures by fitting the distribution observed using SOCT with a weighted combination of reference size distributions of each WBC type calculated using kernel density estimation. We validate the accuracy of our estimation in an in vitro study, by comparing our results for a given WBC sample mixture with the cellular concentrations measured by a hemocytometer and SOCT images before mixing. We also conducted a small in vivo quantitative cell mixture validation pilot study which demonstrates congruence between our method and AC paracentesis in two patients with uveitis. The SOCT based method appears promising to provide quantitative diagnostic information of cellular responses in the ACs of patients with uveitis., Competing Interests: RPM: Leica Microsystems (P). ANK: Leica Microsystems (P). JAI: Leica Microsystems (P, R), Carl Zeiss Meditec (P, R)., (© 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

Objective: To investigate the effect of electroacupuncture stimulation at "Zusanli"(ST36) and "Kunlun"(BL60) on the morphological changes of the spinal dorsal horn and the expression of p38 mitogen-activated protein kinase (p38MAPK) in the injured spinal cord of rats with neuropathic pain., Methods: Male Sprague-Dawley rats were randomly divided into sham model group, model group, electroacupuncture group, and medication group, with 10 rats in each group. Spinal nerve ligation of the L5 lumbar vertebra was performed to establish a rat model of neuropathic pain. The rats in the electroacupuncture group were given electroacupuncture at ST36 and BL60 of the operation side with dilatational wave at a frequency of 2 Hz/100 Hz and an intensity of 1.5 mA once a day, 30 minutes each time, and those in the medication group were given intraperitoneal injection of 100 mg/mL Gabapentin solution (100 mg/kg) once a day; the one-week intervention was started at one week after surgery. Mechanical withdraw threshold (MWT) and thermal withdrawal latency (TWL) were observed and recorded before modeling and on days 1,3,5,7,10,12 and 14 after modeling, and the motor function of the affected hindlimb was scored. Methenamine silver stain was used to observe the morphological changes of the spinal dorsal horn, and Western blot was used to measure the relative protein expression of p38MAPK and phospho-p38MAPK(p-p38MAPK) in L4-L6 spinal segments., Results: Compared with the sham model group, the model group had significant reductions in MWT and TWL at each time point ( P <0.001) and a significant increase in motor function score ( P <0.001); compared with the model group, the electroacupuncture group and the medication group had significant increases in MWT and TWL and a significant reduction in motor function score after treatment ( P <0.05). The model group had obvious neuronal fibrillary tangles, particle vacuolar degeneration, and vacuoles containing argyrophilic grains in the cytoplasm of neural cells under a light microscope, while there were fewer neuronal fibrillary tangles in the electroacupuncture group and reduced vacuolar degeneration in the medication group. Compared with the sham model group, the model group had significant increases in the protein expression of p-p38MAPK in the spinal dorsal horn ( P <0.001), and compared with the model group, the electroacupuncture group and the medication group had significant reductions in the protein expression of p-p38MAPK in the spinal dorsal horn( P <0.05)., Conclusion: Electroacupuncture stimulation at ST36 and BL60 can increase pain threshold, improve the motor function of the affected hindlimb, and improve the necrosis of neurofibrils in the spinal dorsal horn in rats with neuropathic pain, possibly by regulating the expression of p-p38MAPK in the spinal dorsal horn.

Background: This study will be designed to appraise the effects of intraoperative pressure ulcer preventive nursing (IPUPN) on inflammatory markers (IMs) in patients with high-risk pressure ulcers (HRPU) based on high quality randomized controlled trials (RCTs)., Methods: In this study, we will perform a rigorous literature search from the following electronic databases: Cochrane Library, MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, and Chinese Biomedical Literature Database. All electronic databases will be retrieved from their initial time to March 1, 2020 without limitations of language and publication status. We will only consider high quality RCTs that explored the effects of IPUPN on IMs in patients with HRPU. Two investigators will identify relevant trials, extract data, and appraise risk of bias in each eligible trial. Data will be pooled by either a fixed-effects model or a random-effects model according to the results of heterogeneity identification. The primary outcomes include IMs, and incidence of new pressure ulcers. The secondary outcomes are time to ulcer development, quality of life, length of hospital stay, and adverse events. Statistical analysis will be undertaken using RevMan 5.3 software., Results: This study will summarize high quality clinical evidence of RCTs to evaluate the effects of IPUPN on IMs in patients with HRPU., Conclusion: The expected findings may provide helpful evidence to determine whether IPUPN is an effective intervention on IMs in patients with HRPU., Inplasy Registration Number: INPLASY202040029.

We present a tomographic imaging technique, termed Deep Prior Diffraction Tomography (DP-DT), to reconstruct the 3D refractive index (RI) of thick biological samples at high resolution from a sequence of low-resolution images collected under angularly varying illumination. DP-DT processes the multi-angle data using a phase retrieval algorithm that is extended by a deep image prior (DIP), which reparameterizes the 3D sample reconstruction with an untrained, deep generative 3D convolutional neural network (CNN). We show that DP-DT effectively addresses the missing cone problem, which otherwise degrades the resolution and quality of standard 3D reconstruction algorithms. As DP-DT does not require pre-captured data or pre-training, it is not biased towards any particular dataset. Hence, it is a general technique that can be applied to a wide variety of 3D samples, including scenarios in which large datasets for supervised training would be infeasible or expensive. We applied DP-DT to obtain 3D RI maps of bead phantoms and complex biological specimens, both in simulation and experiment, and show that DP-DT produces higher-quality results than standard regularization techniques. We further demonstrate the generality of DP-DT, using two different scattering models, the first Born and multi-slice models. Our results point to the potential benefits of DP-DT for other 3D imaging modalities, including X-ray computed tomography, magnetic resonance imaging, and electron microscopy.

In optical coherence tomography (OCT), the axial resolution is often superior to the lateral resolution, which is sacrificed for long imaging depths. To address this anisotropy, we previously developed optical coherence refraction tomography (OCRT), which uses images from multiple angles to computationally reconstruct an image with isotropic resolution, given by the OCT axial resolution. On the other hand, spectroscopic OCT (SOCT), an extension of OCT, trades axial resolution for spectral resolution and hence often has superior lateral resolution. Here, we present spectroscopic OCRT (SOCRT), which uses SOCT images from multiple angles to reconstruct a spectroscopic image with isotropic spatial resolution limited by the OCT lateral resolution. We experimentally show that SOCRT can estimate bead size based on Mie theory at simultaneously high spectral and isotropic spatial resolution. We also applied SOCRT to a biological sample, achieving axial resolution enhancement limited by the lateral resolution.

Traditional imaging systems exhibit a well-known trade-off between the resolution and the field of view of their captured images. Typical cameras and microscopes can either "zoom in" and image at high-resolution, or they can "zoom out" to see a larger area at lower resolution, but can rarely achieve both effects simultaneously. In this review, we present details about a relatively new procedure termed Fourier ptychography (FP), which addresses the above trade-off to produce gigapixel-scale images without requiring any moving parts. To accomplish this, FP captures multiple low-resolution, large field-of-view images and computationally combines them in the Fourier domain into a high-resolution, large field-of-view result. Here, we present details about the various implementations of FP and highlight its demonstrated advantages to date, such as aberration recovery, phase imaging, and 3D tomographic reconstruction, to name a few. After providing some basics about FP, we list important details for successful experimental implementation, discuss its relationship with other computational imaging techniques, and point to the latest advances in the field while highlighting persisting challenges.

Since its invention, the microscope has been optimized for interpretation by a human observer. With the recent development of deep learning algorithms for automated image analysis, there is now a clear need to re-design the microscope's hardware for specific interpretation tasks. To increase the speed and accuracy of automated image classification, this work presents a method to co-optimize how a sample is illuminated in a microscope, along with a pipeline to automatically classify the resulting image, using a deep neural network. By adding a "physical layer" to a deep classification network, we are able to jointly optimize for specific illumination patterns that highlight the most important sample features for the particular learning task at hand, which may not be obvious under standard illumination. We demonstrate how our learned sensing approach for illumination design can automatically identify malaria-infected cells with up to 5-10% greater accuracy than standard and alternative microscope lighting designs. We show that this joint hardware-software design procedure generalizes to offer accurate diagnoses for two different blood smear types, and experimentally show how our new procedure can translate across different experimental setups while maintaining high accuracy., Competing Interests: The authors declare that there are no conflicts of interest related to this article., (© 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

Optical coherence tomography (OCT) is a cross-sectional, micron-scale imaging modality with widespread clinical application. Typical OCT systems sacrifice lateral resolution to achieve long depths of focus for bulk tissue imaging, and hence tend to have better axial than lateral resolution. Such anisotropic resolution can obscure fine ultrastructural features. Furthermore, conventional OCT suffers from refraction-induced image distortions. Here, we introduce optical coherence refraction tomography (OCRT), which extends the superior axial resolution to the lateral dimension, synthesising undistorted cross-sectional image reconstructions from multiple conventional images acquired with angular diversity. In correcting refraction-induced distortions to register the OCT images, OCRT also achieves spatially resolved refractive index imaging. We demonstrate >3-fold improvement in lateral resolution as well as speckle reduction in imaging tissue ultrastructure, consistent with histology. With further optimisation in optical designs to incorporate angular diversity into clinical instruments, OCRT could be widely applied as an enhancement over conventional OCT.

There is potential clinical significance in identifying cellular responses in the anterior chamber (AC) of the eye, which can indicate hyphema (an accumulation of red blood cells [RBCs]) or aberrant intraocular inflammation (an accumulation of white blood cells [WBCs]). In this work, we developed a spectroscopic OCT analysis method to differentiate between populations of RBCs and subtypes of WBCs, including granulocytes, lymphocytes and monocytes, both in vitro and in ACs of porcine eyes. We developed an algorithm to track single cells within OCT data sets, and extracted the backscatter reflectance spectrum of each single cell from the detected interferograms using the short-time Fourier transform (STFT). A look-up table of Mie back-scattering spectra was generated and used to correlate the backscatter spectral features of single cells to their characteristic sizes. The extracted size distributions based on the best Mie spectra fit were significantly different between each cell type. We also studied theoretical backscattering models of single RBCs to further validate our experimental results. The described work is a promising step towards clinically differentiating and quantifying AC blood cell types., Competing Interests: ANK: Leica Microsystems (P). JAI: Leica Microsystems (P, R), Carl Zeiss Meditec (P, R).

More people die from melanoma after a stage I diagnosis than after a stage IV diagnosis, because the tools available to clinicians do not readily identify which early-stage cancers will be aggressive. Near-infrared pump-probe microscopy detects fundamental differences in melanin structure between benign human moles and melanoma and also correlates with metastatic potential. However, the biological mechanisms of these changes have been difficult to quantify, as many different mechanisms can contribute to the pump-probe signal. We use model systems (sepia, squid, and synthetic eumelanin), cellular uptake studies, and a range of pump and probe wavelengths to demonstrate that the clinically observed effects come from alterations of the aggregated mode from "thick oligomer stacks" to "thin oligomer stacks" (due to changes in monomer composition) and (predominantly) deaggregation of the assembled melanin structure. This provides the opportunity to use pump-probe microscopy for the detection and study of melanin-associated diseases.

Presently, data on the type 2 diabetes mellitus (T2DM) in Chinese Korean ethnicity are very scarce. This study aimed to explore the relationship between the transcription factor 7-like 2 (TCF7L2) and T2DM in Chinese Korean ethnicity population. This case-control study involved 43 T2DM Chinese Korean ethnicity patients (T2DM group) and 43 healthy Chinese Korean ethnicity normoglycemic subjects as controls (Control group). All included participants aged from 40 to 75 years old. Clinical and biological data were collected to determine the phenotypic traits. The restriction fragment length polymorphism-polymerase chain reaction was used to analyze the TCF7L2 by genotyping for rs7903146 (C/T). Spectrophotometer with Chronolab kits was used to conduct the biochemical analyses. TCF7L2 was associated with T2DM in the Chinese Korean ethnicity population (P < .01 for alleles, and P < .05 for genotypes). Significant differences were found 2 groups regarding the T allele (37.2% T2DM patients vs 15.1% healthy subjects, P < .01), and G allele (62.8% T2DM patients vs 84.9% healthy subjects, P < .01). The risk genotypes were GG (83.7% T2DM patients, vs 44.2% healthy control, P < .01), GT (4.7% T2DM patients, vs 20.9% healthy control, P = .04), and TT (11.6% T2DM patients, vs 34.9% healthy control, P = .01). The results of this study demonstrated that TCF7L2 is associated with T2DM in the Chinese Korean ethnicity population, which is an important risk factor for T2DM in this population.

Thermosensitive glucose-functionalized glycopolymers grafted gold nanoparticles (Glyco@GNPs) with good colloidal stability and thermosensitive in aqueous solution were fabricated by reversible addition-fragmentation chain transfer (RAFT) mediated one-pot synthesis. The formation of core-shell morphology with about a 60 nm gold core in diameter and a glycopolymer shell of about 80 nm in thickness was indicated by transmission electron microscopy (TEM). The recognition ability of the Glyco@GNPs toward lectin concannavalin A (Con A) was verified by ultraviolet-visible spectroscopy and dynamic light scattering (DLS). The good cytocompatibility of the glycopolymers and Glyco@GNPs was proven by MTT assay on L-929 cells. Glyco@GNPs could effectively inhibit hepatoma cells SMMC-7721 growth after recognizing Con A was also proved by MTT assay and flow cytometry assay., (Copyright © 2018 Elsevier B.V. All rights reserved.)

We investigate the electronic structures and electronic transport properties of zigzag phosphorene nanoribbons with oxygen-saturated edges (O-zPNRs) by using the spin-polarized density functional theory and the nonequilibrium Green's function method. The results show that the O-zPNR is an antiferromagnetic (AFM) or ferromagnetic (FM) semiconductor with spins localized at two ribbon edges anti-parallel or parallel with each other. The electronic transmission for the single AFM or FM O-zPNR is zero when a bias voltage is applied to the two electrodes made of the same type O-zPNR. Nonzero transmission arises for the AFM-AFM and FM-FM O-zPNR heterojunctions. The transmission spectrum and the electrical current are fully spin polarized for the FM-FM O-zPNR heterojunction. An in-plane transverse electrical field can effectively manipulate the electronic structure and spin-dependent electronic transport. It induces splitting of the spins of the two edges and makes the AFM O-zPNR become a half metal. Moreover, the transverse electrical field gives rise to the transmission spectrum and the spin polarized electrical current for the AFM-AFM O-zPNR heterojunction. The degree of spin polarization can be tuned by the strength of the transverse field.

We integrate spectroscopic optical coherence tomography (SOCT) with stimulated Raman scattering (SRS) to enable simultaneously multiplexed spatial and spectral imaging with sensitivity to many endogenous biochemical species that play an important role in biology and medicine. The combined approach, termed SRS-SOCT, overcomes the limitations of each individual method. Ultimately, SRS-SOCT has the potential to achieve fast, volumetric, and highly sensitive label-free molecular imaging. We demonstrate the approach by imaging excised human adipose tissue and detecting the lipids' Raman signatures in the high-wavenumber region.

Danggui-Shaoyao-San (DSS) is a traditional Chinese medicine, which has long been used for pain treatment and has been demonstrated to possess anti-oxidative, cognitive enhancement, and anti-depressant effects. In the present study, the effects of aqueous extracts of DSS on spontaneous pain behaviors and long-term hyperalgesia were examined to investigate the anti-nociceptive effects and underlying mechanisms. Single pretreatment of DSS dose-dependently reduced spontaneous flinches/licking time in the second, rather than the first, phase after subcutaneous injection of 5 % formalin into one hindpaw, in doses of 2.4 and 9.6 g/kg. DSS also dose-dependently inhibited FOS and cyclooxygenase-2 (COX-2) expression in both superficial and deep layers within the spinal dorsal horn. Further, DSS reduced hypoalgesia in the injected paw from 1 to 3 days and produced anti-hyperalgesic actions in both the injected paw after 3 days and non-injected paw. These data suggest involvement of enhancement of descending pain inhibition by suppression of 5-HTT levels in the spinal dorsal horn and reduction of peripheral long-term inflammation, including paw edema and ulcers. These findings suggest that DSS may be a useful therapeutic agent for short- and long-term inflammation induced pain, through both anti-inflammatory and suppression of central sensitization mechanisms.

Tissue-engineered blood vessels (TEVs) are typically produced using the pulsatile, uniaxial circumferential stretch to mechanically condition and strengthen the arterial grafts. Despite improvements in the mechanical integrity of TEVs after uniaxial conditioning, these tissues fail to achieve critical properties of native arteries such as matrix content, collagen fiber orientation, and mechanical strength. As a result, uniaxially loaded TEVs can result in mechanical failure, thrombus, or stenosis on implantation. In planar tissue equivalents such as artificial skin, biaxial loading has been shown to improve matrix production and mechanical properties. To date however, multiaxial loading has not been examined as a means to improve mechanical and biochemical properties of TEVs during culture. Therefore, we developed a novel bioreactor that utilizes both circumferential and axial stretch that more closely simulates loading conditions in native arteries, and we examined the suture strength, matrix production, fiber orientation, and cell proliferation. After 3 months of biaxial loading, TEVs developed a formation of mature elastic fibers that consisted of elastin cores and microfibril sheaths. Furthermore, the distinctive features of collagen undulation and crimp in the biaxial TEVs were absent in both uniaxial and static TEVs. Relative to the uniaxially loaded TEVs, tissues that underwent biaxial loading remodeled and realigned collagen fibers toward a more physiologic, native-like organization. The biaxial TEVs also showed increased mechanical strength (suture retention load of 303 ± 14.53 g, with a wall thickness of 0.76 ± 0.028 mm) and increased compliance. The increase in compliance was due to combinatorial effects of mature elastic fibers, undulated collagen fibers, and collagen matrix orientation. In conclusion, biaxial stretching is a potential means to regenerate TEVs with improved matrix production, collagen organization, and mechanical properties.

We present a new OCT method for flow speed quantification and directional velocimetry: particle streak velocimetry-OCT (PSV-OCT). PSV-OCT generates two-dimensional, 2.5-vector component (vx ,|vy |,vz ) maps of microscale flow velocity fields. Knowledge of 2.5-vector components also enables the estimation of total flow speed. The enabling insight behind PSV-OCT is that tracer particles in sparsely-seeded fluid flow trace out streaks in (x,z,t)-space. The streak orientations in x-t and z-t yield vx and vz , respectively. The in-plane (x-z plane) residence time yields the out-of-plane speed |vy |. Vector component values are generated by fitting streaks to a model of image formation that incorporates equations of motion in 3D space. We demonstrate cross-sectional estimation of (vx ,|vy |,vz ) in two important animal models in ciliary biology: Xenopus embryos (tadpoles) and mouse trachea.

OCT is a popular cross-sectional microscale imaging modality in medicine and biology. While structural imaging using OCT is a mature technology in many respects, flow and motion estimation using OCT remains an intense area of research. In particular, there is keen interest in maximizing information extraction from the complex-valued OCT signal. Here, we introduce a Bayesian framework into the data workflow in OCT-based velocimetry. We demonstrate that using prior information in this Bayesian framework can significantly improve velocity estimate precision in a correlation-based, model-based framework for Doppler and transverse velocimetry. We show results in calibrated flow phantoms as well as in vivo in a Drosophila melanogaster (fruit fly) heart. Thus, our work improves upon the current approaches in terms of improved information extraction from the complex-valued OCT signal.

Epigallocatechin gallate (EGCG), one of the major catechins found in green tea, was suggested to play a role as a chemopreventive agent in various human cancer models. In this study, we reported that EGCG has a profound antitumor effect on human tongue carcinoma cells by directly regulating glycolysis. EGCG dose-dependently inhibited anchorage-independent growth and short-term EGCG exposure substantially decreased EGF-induced EGF receptor (EGFR), Akt and ERK1/2 activation, as well as the downregulation of hexokinase 2 (HK2). Furthermore, inhibition of EGCG‑mediated HK2 expression was involved in Akt, but not in ERK1/2 signaling pathway suppression. Overexpression of constitutively activated Akt1 rescued inhibition of EGCG‑induced glycolysis. Moreover, EGCG inhibited HK2 expression on mitochondrial outer membrane and induced apoptosis. In summary, the results suggested that EGCG or a related analogue, may have a role in the management of human tongue carcinoma.

Background: Although tumor invasion and metastasis are both classical hallmarks of cancer malignancy and the major causes of poor clinical outcomes among cancer patients, the underlying master regulators of invasion and metastasis remain largely unknown. In this study, we observed that an overexpression of microspherule protein 1 (MCRS1) promotes the invasion and metastasis of non-small cell lung cancer (NSCLC) cells. Furthermore, we sought to systematically investigate the pathophysiological functions and related mechanisms of MCRS1., Methods: Retrovirus-mediated RNA interference was employed to knockdown MCRS1 expression in NSCLC cell lines. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot respectively were used to measure levels of mRNA and protein. Further cell permeability assessment, invasion and proliferation assays were conducted to evaluate MCRS1 functions in vitro while nude mice experiments were performed to examine metastatic capability in vivo. Microarray analysis and microRNA (miRNA) sequencing were respectively carried out for mRNA and miRNA expression profiling, while chromatin immunoprecipitation (ChIP), luciferase reporter assay, and miRNA transfection were used to investigate the interaction between MCRS1 and miRNAs., Results: MCRS1 knockdown induced morphological alterations, increased monolayer integrity, decreased cellular invasion and metastasis, and attenuated stemness and drug resistance among tested NSCLC cells. The levels of MCRS1 expression were likewise correlated with tumor metastasis among NSCLC patients. We identified differentially expressed genes after MCRS1 silencing, which included cell junction molecules, such as ZO-1, Occludin, E-cadherin, and DSG2. However, these differentially expressed genes were not directly recognized by a transcriptional complex containing MCRS1. Furthermore, we found that MCRS1 binds to the miR-155 promoter and regulates its expression, as well as MCRS1 promotes epithelial-mesenchymal transition (EMT), invasion, and metastasis through the up-regulation of miR-155. Systematic investigations ultimately showed that MCRS1 was directly and negatively regulated by the binding of miR-129* to its 3'-UTR, with miR-129* overexpression suppressing the growth and invasion of NSCLC cells., Conclusions: MiR-129* down-regulation induced MCRS1 overexpression, which promotes EMT and invasion/metastasis of NSCLC cells through both the up-regulation of miR-155 and down-regulation of cell junction molecules. This miR-129*/MCRS1/miR-155 axis provides a new angle in understanding the basis for the invasion and metastasis of lung cancer.

Background: Neuraxial application of dexmedetomidine (DEX) as adjuvant analgesic has been invetigated in some randomized controlled trials (RCTs) but not been approved because of the inconsistency of efficacy and safety in these RCTs. We performed this meta-analysis to access the efficacy and safety of neuraxial DEX as local anaesthetic (LA) adjuvant., Methods: We searched PubMed, PsycINFO, Scopus, EMBASE, and CENTRAL databases from inception to June 2013 for RCTs that investigated the analgesia efficacy and safety for neuraxial application DEX as LA adjuvant. Effects were summarized using standardized mean differences (SMDs), weighed mean differences (WMDs) or odds ratio (OR) with suitable effect model. The primary outcomes were postoperative pain intensity and analgesic duration, bradycardia and hypotension., Results: Sixteen RCTs involving 1092 participants were included. Neuraxial DEX significantly decreased postoperative pain intensity (SMD, -1.29; 95% confidence interval (CI), -1.70 to -0.89; P<0.00001), prolonged analgesic duration (WMD, 6.93 hours; 95% CI, 5.23 to 8.62; P<0.00001) and increased the risk of bradycardia (OR, 2.68; 95% CI, 1.18 to 6.10; P = 0.02). No evidence showed that neuraxial DEX increased the risk of other adverse events, such as hypotension (OR, 1.54; 95% CI, 0.83 to 2.85; P = 0.17). Additionally, neuraxial DEX was associated with beneficial alterations in postoperative sedation scores and number of analgesic requirements, sensory and motor block characteristics, and intro-operative hemodynamics., Conclusion: Neuraxial DEX is a favorable LA adjuvant with better and longer analgesia. The greatest concern is bradycardia. Further large sample trials with strict design and focusing on long-term outcomes are needed.

The numbers and types of ionotropic glutamate receptors at most vertebrate central excitatory synapses are altered as a function of changes in input activity patterns that occur during postnatal development. Activity-dependent developmental alterations in glutamate receptors underlie lasting changes in synaptic efficacy (plasticity) and metaplasticity (the plasticity of synaptic plasticity), which are critical elements of normal brain maturation. Understanding the specific involvement of glutamate receptors in synaptic development and function is made multiplicatively complex by the existence of a large number of glutamate receptor subunits, numerous subunit-specific amino acid sequences that regulate receptor function, and subunit-specific synaptic insertion restrictions imposed by associated anchoring proteins. Many receptor properties are altered when subunits are switched, so it is unclear which individual receptor property or properties underlie changes in synaptic function and plasticity during postnatal development. As a result, a more detailed understanding of the factors that regulate synaptic and cognitive development will involve mutations in glutamate receptor subunits that separate individual receptor properties and permit synaptic insertion at both immature and mature synapses in genetically modified organisms. This position paper focuses on structural modifications in N-methyl-d-aspartate receptors (NMDARs) that occur during postnatal forebrain development and attempts to provide a method for pursuing a more complete understanding of the functional ramifications of developmental alterations in NMDAR subunit composition.

Titanium dioxide sols were synthesized by hydrothermal reactions with addition of poly (ethylene glycol) (Mw=20,000). Using techniques of X-ray diffraction, transmission electron microscopy, dynamic light scattering, and scanning electron microscopy, effect of PEG on the crystallographic properties, particle size, aggregating behavior, and the morphological properties of nanoparticles in the sols were studied. It was found that growth of anatase nanocrystallites was retarded by PEG. Average crystallite size of anatase nanocrystallites first decreased from 20.7 nm to 10.5 nm as the polymer concentration increased from 1 g/L to 3 g/L, and then changed little. Meanwhile, small amount of rutile phases like rutile nanowires, twin crystallites, and the "flowers" appeared continuously when the concentration increased from 3 g/L to 5 g/L. Mono-dispersion was obtained with relatively lower PEG concentration. The observed evolvement was discussed based on the interaction between the polymers and the nanocrystallites with assistance of FTIR. The coverage of polymer chains on surface of nanocrystallites leads to isolated reactors, which benefits the uniform coarsening rate of the nanocrystallites. The synthesized TiO(2) sols were utilized in dye sensitized solar cells. Performance parameters of the solar cells were discussed with assistance of dye desorption experiments. The improved dispersion in sols was found to benefit the photovoltaic performance of the cells., (Copyright © 2011. Published by Elsevier Inc.)

Yungang Grottoes were built in the mid-5th century A. D., and named as a UNESCO World Heritage site in 2001. Most of the grottoes were built on the feldspathic quartz sandstones. They were seriously damaged due to the environmental impact. The main form of the weathering is the powdered weathering. The weathering conditions are generally characterized by electrical sounding, penetration resistance, molecular spectroscopy, etc. However, although these methods can give good results about the weathering conditions for a specified sample or site, they are not suitable for providing a global profile of the weathering conditions. The present paper provides a method for effectively and roundly assessing the overall powdered weathering conditions of the Yungang Grottoes based on hyperspectral imaging. Powdered weathering could change the structure and granularity of the sandstone, and thus change the spectral reflectance of the sandstone surface. Based on the hyperspectral data collected from 400 nm to 1 000 nm and normalized by log residuals method, the powdered weathering conditions of the sandstones were classified into strong weathering and weak weathering. The weathering profile was also mapped in the Envi platform. The mapping images were verified using the measured hyperspectal data of the columns in front of the 9th and 10th grottoes as the examples. The mapping images were substantially fitted to the real observations, showing that hyperspectral imaging can be used to estimate the overall powdered weathering of the sandstones.

Background: Oesophageal squamous cell carcinoma (OSCC) is one of the leading causes of cancer-related death worldwide. However, the mechanism by which the OSCC develops remains largely unknown. Ion channels are important for cancer development. Whether the transient receptor potential canonical (TRPC), known as the non-selective cation channels, plays a role in OSCC development is unknown., Methods: The expression of TRPC6, a member of TRPC subfamily, was examined in samples from patients with OSCC by immunostaining and in situ hybridisation. The effects of TRPC6 channels on OSCC cell cycle progression, cell growth and in vivo tumour formation were investigated. The functional TRPC6 channels were found in OSCC cells by electrophysiology and Ca(2+) imaging analysis., Results: The expression of TRPC6 at protein and mRNA levels was markedly increased in human OSCC specimens than that in normal human oesophageal tissues. Blockade of TRPC6 channels in human OSCC cells inhibited elevation of intracellular Ca(2+) concentration ([Ca(2+)](i)) and activation of Cdc2 kinase. Meanwhile, the OSCC cell cycle was arrested at G2 phase and the cell growth was suppressed. Furthermore, inhibition of TRPC6 channels suppressed in nude mice the tumour formation generated by injection of the OSCC cells., Conclusion: TRPC6 channels play a critical role in the development of OSCC. The [Ca(2+)](i) elevation regulated by TRPC6 channels is essential for G2 phase progression and OSCC development. These channels might be a novel target for therapeutic intervention of OSCC.

Hyperaccumulator biomass harvested after heavy-metal phytoremediation must be considered as hazardous waste that should be contained or treated appropriately before disposal or reuse. As a potential method to detoxify the biomass and to convert this material to a suitable fertilizer or mulch, leaching of heavy metals from Sedum plumbizincicola biomass was studied by using ammonia-ammonium chloride solution as a leaching agent. The research was carried out in two phases: (i) a leaching study to determine the heavy metal:zinc extraction efficiency of this leaching agent and (ii) a thermodynamic analysis to identify the likely reactions and stable Zn(II) species formed in the leaching systems. Experimentally, a Taguchi orthogonal experiment with four variable parameter elements: leaching temperature, nNH4Cl:nNH3 ratio, leaching time and solid-liquid ratio, each at three levels, was used to optimize the experimental parameters by the analysis of variances. Application of the Taguchi technique significantly reduced the time and cost required for the experimental investigation. The findings indicate that leaching temperature had the most dominant effect on metal extraction performance, followed by nNH4Cl:nNH3 ratio, solid-liquid ratio and leaching time. Accordingly, the optimum leaching conditions were determined as temperature: 60 degrees C, nNH4Cl:nNH3 = 0.6, leaching time: 2 h and solid/liquid ratio: 5:1. The total zinc removal after leaching under the optimum conditions reached 97.95%. The thermodynamic study indicated that the dominant species produced by the leaching process should be the soluble species Zn(NH3)4(2+).

Ovarian cancer (OC) is the leading cause of death from gynecological malignancy. However, the mechanism by which OC develops remains largely unknown. Increases in cytosolic free Ca(2+) ([Ca(2+)](i)) can result in different physiological changes including cell growth, differentiation and death. The transient receptor potential (TRP) C channels are nonselective cation channels with permeability to Ca(2+). Here we report that TRPC3 channels promote human OC growth. The TRPC3 protein levels in human OC specimens were greatly increased than those in normal ovarian specimens. Downregulating TRPC3 expression in SKOV3 cells, a human OC cell line, led to reduction of proliferation, suppression in epidermal growth factor-induced Ca(2+) influx, dephosphorylation of Cdc2 and CaMKIIalpha and prolonged progression through M phase of these cells. Further, decreased the expression of TRPC3 suppressed the tumor formation generated by injecting SKOV3 cells in nude mice. Together, our results suggest that increased activity of TRPC3 channels is necessary for the development of OCs.

Aim: To study the correlation between 5-HT-induced pain response and the contribution by individual 5-HTR subtypes including 5-HT1R, 5-HT2R and 5-HT3R at the level of peripheral primary afferent., Methods: The experiments were done on acutely isolated trigeminal ganglion (TG) neurons using whole-cell patch clamp technique and the nociceptive effect was observed on behavior experiments by intraplantar injection of test drugs., Results: The majority of cells examined responded to 5-HT in a manner of concentration dependence (10(-6) - 10(-3) mol/) (61.4%, 54/88) and with a fast activating and rapid desensitizing inward current (I(5-HT)), which was thought to be mediated by the activation of 5-HT3R, since it could be blocked by 5-HT3R antagonist ICS 205930 and mimicked by 5-HT3R agonist 2-methyl-5-HT. It was found that I(5-HT) was potentiated by 5-HT2R agonist alpha-methyl-5-HT markedly, while 5-HT1R agonist R-(+)-UH 301 did not. In behavioral experiment performed on conscious rats, intraplantar injection of 5-HT(10(-5), 10(-4) and 10(-3) mol/L) induced an increment of cumulative lifting time first 20 min in a manner of concentration dependence. By dissociating 5-HTR subtypes using their corresponding antagonists (ICS and CYP) the potency order of hindpaw lifting time was identified as follows: 5-HT > 5-HT + ICS > 5-HT + CYP., Conclusion: The results suggest that in 5-HT-induced nociceptive response at the primary sensory level 5-HT3R may play a role of initiation, but 5-HT2R mediates maintaining and modulatory effect in the processes of nociceptive information convey.