Augmented reality display with high eyebox uniformity over the full field of view based on a random mask grating.

Ensuring uniform illuminance in waveguide-based augmented reality (AR) display devices is crucial for providing an immersive and comfortable visual experience. However, there is a lack of a straightforward and efficient design method available to achieve illuminance uniformity over the full field of view. To address this issue, we propose a novel design that utilizes random mask gratings (RMGs) as the folding grating and the out-coupling grating. Unlike traditional approaches that modify the grating structure, we control the diffraction efficiency distribution by adjusting the filling factor of the mask while keeping the grating structure unchanged in one RMG. The grating structures are designed and optimized based on rigorous coupled wave analysis and particle swarm optimization. The feasibility of our method is verified by the simulation results in Lighttools. In the FOV range of 20°×15°, the eyebox uniformities of all fields are greater than 0.78, which can provide a good visual experience for users.

Hybrid waveguide based augmented reality display system with extra large field of view and 2D exit pupil expansion.

For a waveguide display device, the field of view (FOV) is a key parameter for evaluating its optical performance. To address this issue, we propose a hybrid waveguide system, which is composed of two projectors, two in-couplers, two half-mirror arrays and an out-coupler. We use two projectors to generate the left and right parts of the output image separately, which can increase the upper limit of the FOV significantly. Unlike conventional waveguide-based system, we use half-mirror arrays instead of folding gratings to realize 2D exit pupil expansion. By doing so, the total internal reflection condition can always be met during the pupil expansion process. To solve the difficulty in designing collimating optical system with large FOV, we propose a method of tilting the projection system. The hybrid waveguide system can realize a FOV of 88°(H) × 53°(V).

Effects of transcranial combined with peripheral repetitive magnetic stimulation on limb spasticity and resting-state brain activity in stroke patients.

Background and objective: Transcranial magnetic stimulation and peripheral repetitive magnetic stimulation (rPMS), as non-invasive neuromodulation techniques, can promote functional recovery in patients with post-stroke spasticity (PSS), but the effects of transcranial magnetic stimulation combined with peripheral magnetic stimulation on PSS remain largely unknown. Therefore, we examined the effects of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) combined with rPMS on PSS patients and its potential neural correlates to behavioral improvements. Methods: Forty-nine PSS patients were divided randomly into three groups: a combined group (n = 20), a LF-rTMS group (n = 15), and a control group (n = 14). The combined group received LF-rTMS and rPMS treatment, the rTMS group received LF-rTMS treatment, and the control group received only routine rehabilitation. All patients underwent Ashworth Spasm Scale (MAS), upper extremity Fugl-Meyer (FMA-UE), and modified Barthel Index (MBI) assessments before and after intervention. In addition, resting-state functional magnetic resonance imaging data were collected pre- and post-treatment to observe changes in the amplitude of low-frequency fluctuation (ALFF). Results: The MAS score was decreased, FMA-UE score and MBI scores were increased in the three groups after therapy than before therapy (all P < 0.05). In particular, the combined group showed significant effect on improved motor function and relieved spasticity in PSS (P < 0.01). Moreover, the combined treatment increased ALFF values mainly in the right supplementary motor area, right middle frontal gyrus, and right cerebellum, while reduced ALFF values mainly in the right post-central gyrus compared with pre-treatment. Compared with the LF-rTMS and control groups, the combined treatment increased ALFF values in the right cerebellum and reduced ALFF values mainly in the frontoparietal cortex. Improvements in the MAS score were positively correlated with the change in ALFF values in the right cerebellum (r = 0.698, P = 0.001) and the right supplementary motor area (r = 0.700, P = 0.001) after combined treatment. Conclusion: Transcranial combined with peripheral repetitive magnetic stimulation could improve spastic state and motor function in PSS patients, and this effect may be associated with altered cerebellar and frontoparietal cortical activity. Clinical trial registration: http://www.chictr.org.cn/index.aspx, identifier ChiCTR1800019452.

Wander and spread of a perfect Laguerre-Gauss beam under turbulent absorbent seawater.

The wander and long-term spread of a beam caused by turbulence are two important factors affecting channel targeting and information receiving in optics communication systems. In this paper, the wander and long-term spread of a perfect Laguerre-Gauss (PLG)/circular perfect Laguerre-Gauss (CPLG) beam in turbulent absorbing seawater are studied. The analytical expression of the wander for a CPLG beam in the weak turbulent fluctuation region and the analytical expression of the long-term spread for a CPLG beam in a weak to strong turbulent fluctuation region are derived by using the Rytov approximation and the generalized Huygens-Fresnel integral, respectively. Through numerical analysis, we find that the optimal beam diameter and self-convergence effect of the PLG beam exist under given communication link conditions, the long-term spread of PLG beam is smaller than that of the LG beam, but the wander evolution trend of the PLG beam with increasing propagation distance is opposite to that of the LG beam. PLG and CPLG beams have stronger resistance disturbance of turbulence than that of Laguerre-Gauss and circular Laguerre-Gauss beams, respectively.

Effects of whole-body electromyostimulation training on upper limb muscles strength and body composition in moderately trained males: A randomized controlled study.

Resistance training has been known to have a positive effect on muscle performance in exercisers. Whole-body electromyostimulation (WB-EMS) is advertised as a smooth, time-efficient, and highly individualized resistance training technology. The purpose of this study is to evaluate the effects of WB-EMS training on maximum isometric elbow muscle strength and body composition in moderately trained males in comparison to traditional resistance training. The study was a randomized controlled single-blind trial. Twenty, moderately trained, male participants (25.15 ± 3.84, years) were randomly assigned to the following groups: a WB-EMS training group (n = 11) and a traditional resistance training group (the control group [CG]: n = 9). Both training intervention programs consisted of 18 training sessions for six consecutive weeks. All subjects performed dynamic movements with the WB-EMS or external weights (CG). The primary outcome variables included maximum isometric elbow flexor strength (MIEFS), maximum isometric elbow extensor strength (MIEES) and surface electromyography amplitude (sEMGRMS). Secondary outcomes involved lean body mass, body fat content, arm fat mass, and arm lean mass. ANOVAs, Friedman test and post hoc t-tests were used (P = 0.05) to analyze the variables development after the 6-week intervention between the groups. Significant time × group interactions for MIEFS (η2 = 0.296, P Bonferroni = 0.013) were observed, the increase in the WB-EMS group were significantly superior to the CG [23.49 ± 6.48% vs. 17.01 ± 4.36%; MD (95% CI) = 6.48 (1.16, 11.80); d = 1.173, P = 0.020]. There were no significant differences were observed between interventions regarding MIEES, sEMGRMS and body composition. These findings indicate that in moderately trained males the effects of WB-EMS were similar to a traditional resistance training, with the only exception of a significantly greater increase in elbow flexor strength. WB-EMS can be considered as an effective exercise addition for moderately trained males.

Long non-coding RNA SNHG22 facilitates hepatocellular carcinoma tumorigenesis and angiogenesis via DNA methylation of microRNA miR-16-5p.

Hepatocellular carcinoma (HCC) is considered as a common malignancy worldwide. Considerable evidence has illustrated that abnormally expressed long noncoding RNAs (lncRNAs) are in a close correlation with the initiation and progression of various tumors, including HCC. LncRNA small nucleolar RNA host gene 22 (SNHG22) has been reported to play important roles in tumor initiation, but its role and mechanism are little known in HCC. In our report, we discovered the high level of SNHG22 in HCC tissues and cells, and the high expression of SNHG22 was correlated with unfavorable clinical outcome in HCC patients. Functional assays implied that SNHG22 deficiency suppressed cell proliferation, migration, invasion, and angiogenesis in vitro. Additionally, it was also confirmed that silenced SNHG22 suppressed tumor growth and angiogenesis in vivo. Mechanistic exploration revealed that SNHG22 recruited DNMT1 to miR-16-5p DNA promoter through EZH2 and inhibited miR-16-5p transcription via DNA methylation. Finally, we verified that the suppression of miR-16-5p countervailed the suppressive effect of SNHG22 deficiency on HCC cell proliferation, migration, invasion, and angiogenesis. Conclusively, this study clarified the SNHG22/EZH2/DNMT1/miR-16-5p axis and revealed that SNHG22 could be an underlying biomarker for HCC.

An epigenomic landscape of cervical intraepithelial neoplasia and cervical cancer using single-base resolution methylome and hydroxymethylome.

BACKGROUND: Cervical cancer (CC) is the second leading cause of cancer death among women worldwide. Epigenetic regulation of gene expression through DNA methylation and hydroxymethylation plays a pivotal role during tumorigenesis. In this study, to analyze the epigenomic landscape and identify potential biomarkers for CCs, we selected a series of samples from normal to cervical intra-epithelial neoplasia (CINs) to CCs and performed an integrative analysis of whole-genome bisulfite sequencing (WGBS-seq), oxidative WGBS, RNA-seq, and external histone modifications profiling data. RESULTS: In the development and progression of CC, there were genome-wide hypo-methylation and hypo-hydroxymethylation, accompanied by local hyper-methylation and hyper-hydroxymethylation. Hydroxymethylation prefers to distribute in the CpG islands and CpG shores, as displayed a trend of gradual decline from health to CIN2, while a trend of increase from CIN3 to CC. The differentially methylated and hydroxymethylated region-associated genes both enriched in Hippo and other cancer-related signaling pathways that drive cervical carcinogenesis. Furthermore, we identified eight novel differentially methylated/hydroxymethylated-associated genes (DES, MAL, MTIF2, PIP5K1A, RPS6KA6, ANGEL2, MPP, and PAPSS2) significantly correlated with the overall survival of CC. In addition, no any correlation was observed between methylation or hydroxymethylation levels and somatic copy number variations in CINs and CCs. CONCLUSION: Our current study systematically delineates the map of methylome and hydroxymethylome from CINs to CC, and some differentially methylated/hydroxymethylated-associated genes can be used as the potential epigenetic biomarkers in CC prognosis.

Combination of Structured Illumination Microscopy with Hyperspectral Imaging for Cell Analysis.

Existing structured illumination microscopy (SIM) allows super-resolution live-cell imaging in few color channels that provide merely morphological information but cannot acquire the sample spectrum that is strongly relevant to the underlying physicochemical property. We develop hyperspectral SIM which enables high-speed spectral super-resolution imaging in SIM for the first time. Through optically mapping the three-dimensional (x, y, and λ) datacube of the sample to the detector plane, hyperspectral SIM allows snapshot spectral imaging of the SIM raw image, detecting the sample spectrum while retaining the high-speed and super-resolution characteristics of SIM. We demonstrate hyperspectral SIM imaging and reconstruct a datacube containing 31 super-resolution images of different wavelengths from only 9 exposures, achieving a 15 nm spectral resolution. We show time-lapse hyperspectral SIM imaging that achieves an imaging speed of 2.7 s per datacube-31-fold faster than the existing wavelength scanning strategy. To demonstrate the great prospects for further combining hyperspectral SIM with various spectral analysis methods, we also perform spectral unmixing of the hyperspectral SIM result while imaging the spectrally overlapped sample.

Snapshot spectroscopic microscopy with double spherical slicer mirrors.

Snapshot hyperspectral microscopic imaging can obtain the morphological characteristics and chemical specificity of samples simultaneously and instantaneously. We demonstrate a double-slicer spectroscopic microscopy (DSSM) that uses two spherical slicer mirrors to magnify the target image and slice it. These slits are lined up and dispersed, then mapped onto an area-array detector. An anamorphosis unit optimizes the capacity of the limited pixels. With a single shot and image recombination, a data cube can be constructed for sample analysis, and a model of DSSM is simulated. The system covers the spectral range from 500 nm to 642.5 nm with 20 spectral channels. The spatial resolution is 417 nm, and the spectral resolution is 7.5 nm.

Simultaneous multicolour imaging using quantum dot structured illumination microscopy.

Multicolour structured illumination microscopy (SIM) is a powerful tool used for the investigation of the dynamic interaction between subcellular structures. Nevertheless, most of the multicolour SIM schemes are currently limited by conventional fluorescent dyes and wavelength-dependent optical systems, and can only sequentially record images of different colour channels instead of obtaining multicolour datasets simultaneously. To address these issues, we present a novel multicolour SIM scheme referred to as quantum dot structured illumination microscopy (QD-SIM). QD-SIM enables simultaneously excitation and collection of multicolour fluorescent signals. We also propose a theoretical analysis of the image formation in two-dimensional multicolour SIM to help combine the optically sectioned and super-resolution attributes of SIM. Based on this theory, QD-SIM enables optically sectioned, super-resolution, multicolour simultaneous imaging at a single plane.

Simultaneous Temperature and Strain Measurements Using Polarization-Maintaining Few-Mode Bragg Gratings.

Simultaneous measurement of temperature and strain was demonstrated using a polarization-maintaining few-mode Bragg grating (PM-FMF-FBG) based on the wavelength and phase modulation of the even L P 11 mode. The wavelength shift sensitivity and the interrogated phase sensitivity of the temperature and strain were measured to be 10 pm·°C-1 and 0.73 pm·µÎµ-1 and -3.2 × 10-2 rad·°C-1 and 4 × 10-4 rad·µÎµ-1, respectively, with a discrimination efficiency of 98%. The polarization interference led to selective polarization excitation of the reflection spectra, and the calculated phase sensitivity agreed with the experimental results.

Broadband aberration-corrected snapshot spectrometer with a toroidal slicer mirror.

We demonstrate a broadband aberration-corrected snapshot spectrometer by developing a toroidal slicer mirror as the focusing mirror. A collimating slicer mirror and an integrated grating divide the entire wavelength range into several windows. The toroidal sub-mirrors of the focusing mirror compensate for the coma and correct the astigmatism at different windows to compress the spectral spots over the waveband. From 200 to 1000 nm, the RMS spot radii are less than 30 µm and the spectral resolution at 600 nm is 151.8 pm. The optics have a small volume of 11 cm×11 cm×1.5 cm by employing a folded structure.

Dysregulation of a long noncoding RNA reduces leptin leading to a leptin-responsive form of obesity.

Quantitative changes in leptin concentration lead to alterations in food intake and body weight, but the regulatory mechanisms that control leptin gene expression are poorly understood. Here we report that fat-specific and quantitative leptin expression is controlled by redundant cis elements and trans factors interacting with the proximal promoter together with a long noncoding RNA (lncOb). Diet-induced obese mice lacking lncOb show increased fat mass with reduced plasma leptin levels and lose weight after leptin treatment, whereas control mice do not. Consistent with this finding, large-scale genetic studies of humans reveal a significant association of single-nucleotide polymorphisms (SNPs) in the region of human lncOb with lower plasma leptin levels and obesity. These results show that reduced leptin gene expression can lead to a hypoleptinemic, leptin-responsive form of obesity and provide a framework for elucidating the pathogenic mechanism in the subset of obese patients with low endogenous leptin levels.

Comprehensive genomic variation profiling of cervical intraepithelial neoplasia and cervical cancer identifies potential targets for cervical cancer early warning.

BACKGROUND: To better understand the pathogenesis of cervical cancer (CC), we systematically analysed the genomic variation and human papillomavirus (HPV) integration profiles of cervical intraepithelial neoplasia (CIN) and CC. METHODS: We performed whole-genome sequencing or whole-exome sequencing of 102 tumour-normal pairs and human papillomavirus probe capture sequencing of 45 CCs, 44 CIN samples and 25 normal cervical samples, and constructed strict integrated workflow of genomic analysis. RESULTS: Mutational analysis identified eight significantly mutated genes in CC including four genes (FAT1, MLL3, MLL2 and FADD), which have not previously been reported in CC. Targetable alterations were identified in 55.9% of patients. In addition, HPV integration breakpoints occurred in 97.8% of the CC samples, 70.5% of the CIN samples and 42.8% of the normal cervical samples with HPV infection. Integrations of high-risk HPV strains in CCs, including HPV16, 18, 33 and 58, also occurred in the CIN samples. Moreover, gene mutations were detected in 52% of the CIN specimens, and 54.8% of these mutations occurred in genes that also mutated in CCs. CONCLUSION: Our results lay the foundation for a deep understanding of the molecular mechanisms and finding new diagnostic and therapeutic targets of CC.

Design of a high-performance in-coupling grating using differential evolution algorithm for waveguide display.

Illuminance nonuniformity caused by natural vignetting can seriously affect the display quality of large-field-of-view (FOV) waveguide displays. In this paper, an optimization method based on the differential evolution algorithm is proposed for in-coupling grating design to improve coupling efficiency and compensate for natural vignetting. The in-coupling grating parameters are optimized to achieve efficiency distributions in which efficiency increases continuously with incidence angle, realizing uniform illuminance over a large FOV of 45°. The angular uniformity reaches 0.89. Additionally, average diffraction efficiency reaches 89.13% for transverse-electric polarization at 532 nm and 76% in the wavelength region between 450 and 700 nm.

Molecular Characterization of HBV DNA Integration in Patients with Hepatitis and Hepatocellular Carcinoma.

Infection by chronic hepatitis B virus (HBV) is one of the major causes of liver cirrhosis and primary hepatocellular carcinoma (HCC). Viral DNA integration into the host cell genome is a key mechanism of hepatocarcinogenesis. However, the molecular characterization and the potential clinical implications of HBV DNA integration into patients suffering from different hepatitis and HCC remain unclear. In this study, we analyzed HBV integrations in patients with hepatitis B and HCC using HBV probe-based capturing and next-generation sequencing. The results revealed that the sizes of the HBV integrations ranged from 28 bp to 3215 bp, including the full-length HBV DNA sequence. The integration breakpoints were preferentially distributed in the viral enhancer, X protein, and core protein regions of the HBV genome. The number of HBV integrations followed an increasing trend from hepatitis to HCC, which was positively correlated with the HBV virus load in patients with hepatitis. The number of HBV integrations in the HBeAg positive chronic hepatitis B group was significantly greater than that in the other hepatitis B groups (P < 0.05). However, the relative abundance of HBV integrations was significantly higher in HCC tissues than in the adjacent liver tissues. Interestingly, 61.6% (8/13) of HBV-human DNA integration fragments could be detected at the RNA level. Our results also showed that HBV integration-targeted genes (ITGs) were significantly enriched in many cancer-related pathways, such as MAPK, extracellular matrix (ECM)-receptor interaction, and the hedgehog signaling pathway. Individuals with HBV integrations exhibited shorter disease-free survival (DFS) and overall survival (OS) than those without HBV integrations in some ITGs including LINC00293 (long intergenic non-protein coding RNA 293; DFS P = 0.008, OS P = 0.009), FSHB (follicle stimulating hormone beta subunit; DFS P = 0.05, OS P = 0.186), and LPHN3 (latrophilin-3; DFS P = 0.493, OS P = 0.033). This study determined the underlying mechanism of HBV DNA integration in liver diseases and laid the foundation for future studies on the pathogenesis of liver cancer.

A noncanonical PPARγ/RXRα-binding sequence regulates leptin expression in response to changes in adipose tissue mass.

Leptin expression decreases after fat loss and is increased when obesity develops, and its proper quantitative regulation is essential for the homeostatic control of fat mass. We previously reported that a distant leptin enhancer 1 (LE1), 16 kb upstream from the transcription start site (TSS), confers fat-specific expression in a bacterial artificial chromosome transgenic (BACTG) reporter mouse. However, this and the other elements that we identified do not account for the quantitative changes in leptin expression that accompany alterations of adipose mass. In this report, we used an assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) to identify a 17-bp noncanonical peroxisome proliferator-activated receptor gamma (PPARγ)/retinoid X receptor alpha (RXRα)-binding site, leptin regulatory element 1 (LepRE1), within LE1, and show that it is necessary for the fat-regulated quantitative control of reporter (luciferase) expression. While BACTG reporter mice with mutations in this sequence still show fat-specific expression, luciferase is no longer decreased after food restriction and weight loss. Similarly, the increased expression of leptin reporter associated with obesity in ob/ob mice is impaired. A functionally analogous LepRE1 site is also found in a second, redundant DNA regulatory element 13 kb downstream of the TSS. These data uncouple the mechanisms conferring qualitative and quantitative expression of the leptin gene and further suggest that factor(s) that bind to LepRE1 quantitatively control leptin expression and might be components of a lipid-sensing system in adipocytes.

Compact high-resolution spectrometer using two plane gratings with triple dispersion.

We demonstrate a compact high-resolution spectrometer scheme using two plane gratings. In this approach, the rays are first diffracted by a fixed grating, then incident on a rotating grating at the Littrow diffraction angle, and are finally diffracted and reflected back to the fixed grating again. Thus, triple dispersion (TD) occurs during measurement, increasing the resolution. The formulae of this compact high-resolution spectrometer are rigorously derived. A design simulation with two gratings of 1050 lines/mm is performed and discussed. In addition, a prototype of this spectrometer has been built and tested. Its spectral resolution reaches a precision of 36 pm.