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Abstract Background Retinopathy of Prematurity (ROP) is a proliferative retinal vascular disease occurring in the retina of premature infants and is the main cause of childhood blindness. Nowadays anti-VEGF and retinal photocoagulation are mainstream treatments for ROP, but they develop a variety of complications. Hydrogen (H2) is widely considered as a useful neuroprotective and antioxidative therapeutic method for hypoxic-ischemic disease without toxic effects. However, whether H2 provides physiological angiogenesis promotion, neovascularization suppression and glial protection in the progression of ROP is largely unknown.This study aims to investigate the effects of H2 on retinal angiogenesis, neovascularization and neuroglial dysfunction in the retinas of oxygen-induced retinopathy (OIR) mice. Methods In this study, mice that were seven days old and either wild-type (WT) or Nrf2-deficient (Nrf2−/−) were exposed to 75% oxygen for 5 days and then returned to normal air conditions. Different stages of hydrogen gas (H2) inhalation were administered. Vascular obliteration, neovascularization, and blood vessel leakage were analyzed and compared. To count the number of neovascularization endothelial nuclei, routine HE staining of retinal sections was conducted. Immunohistochemistry was performed using DyLight 594 labeled GSL I-isolectin B4 (IB4), as well as primary antibodies against proliferating cell nuclear antigen (PCNA), glial fibrillary acidic protein (GFAP), and Iba-1. Western blots were used to measure the expression of NF-E2-related factor 2 (Nrf2), vascular endothelial growth factor (VEGF), Notch1, Dll4, and HIF-1α. Additionally, the expression of target genes such as NQO1, HO-1, Notch1, Hey1, Hey2, and Dll4 was measured. Human umbilical vein endothelial cells (HUVECs) treated with H2 under hypoxia were used as an in vitro model. RT-PCR was used to evaluate the mRNA expression of Nrf2, Notch/Dll4, and the target genes. The expression of reactive oxygen species (ROS) was observed using immunofluorescence staining. Results Our results indicate that 3–4% H2 does not disturb retinal physiological angiogenesis, but ameliorates vaso-obliteration and neovascularization in OIR mice. Moreover, H2 prevents the decreased density and reverses the morphologic and functional changes in retinal astrocytes caused by oxygen-induced injury. In addition, H2 inhalation reduces microglial activation, especially in the area of neovascularization in OIR mice. H2 plays a protective role in vascular regeneration by promoting Nrf2 activation and suppressing the Dll4-induced Notch signaling pathway in vivo. Also, H2 promotes the proliferation of HUVECs under hypoxia by negatively regulating the Dll4/Notch pathway and reducing ROS levels through Nrf2 pathway aligning with our findings in vivo.Moreover, the retinal oxygen-sensing mechanisms (HIF-1α/VEGF) are also involved in hydrogen-mediated retinal revascularization and neovascularization suppression. Conclusions Collectively, our results indicate that H2 could be a promising therapeutic agent for POR treatment and that its beneficial effect in human ROP might involve the activation of the Nrf2-Notch axis as well as HIF-1α/VEGF pathways. Graphical Abstract

An improved Synthetic Aperture Radar (SAR) imaging algorithm is proposed to address the issues of low azimuth resolution and noise interference in the sparse sampling condition. Based on the existing L1/2 regularization theory and iterative threshold algorithm, the gradient operator is modified, which can improve the solution accuracy of the reconstructed image and reduce the load of calculation. Then, under full sampling and under-sampling conditions, the original and improved L1/2 iterative threshold algorithm are combined with the approximate observation model to image SAR echo signals and compare their imaging performance. The experimental findings demonstrate that the improved algorithm improves the azimuth resolution of SAR images and has higher convergence performance.

Azimuth multi-channel synthetic aperture radar (SAR) has always been an important technical means to achieve high-resolution wide-swath (HRWS) SAR imaging. However, in the space-borne azimuth multi-channel SAR system, random phase noise will be produced during the operation of each channel receiver. The phase noise of each channel is superimposed on the SAR echo signal of the corresponding channel, which will cause the phase imbalance between the channels and lead to the generation of false targets. In view of the above problems, this paper proposes a random phase noise compensation method for space-borne azimuth multi-channel SAR. This method performs feature decomposition by calculating the covariance matrix of the echo signal and converts the random phase noise estimation into the optimal solution of the cost function. Considering that the phase noise in the receiver has frequency-dependent and time-varying characteristics, this method calculates the phase noise estimation value corresponding to each range-frequency point in the range direction and obtains the phase noise estimation value by expectation in the azimuth direction. The proposed random phase noise compensation method can suppress false targets well and make the radar present a well-focused SAR image. Finally, the usefulness of the suggested method is verified by simulation experiments.

Compared to conventional radars, arc array synthetic aperture radar (SAR) enables wide-area observation under ideal conditions. However, helicopters carrying arc array SAR platforms are generally smaller in size and more sensitive to vibration, which has a greater impact on the imaging quality. In this paper, the vibration error of the arc array SAR platform is investigated, and a vibration error model of the arc array SAR platform is established. Based on the study of the vibration error model, a vibration phase estimation and compensation algorithm based on the delayed conjugate multiplication method is proposed. In the first step, distance pulse pressure processing is performed on the echo signal. In the second step, the pulse pressure signals and their delays in the same distance unit are subjected to conjugate multiplication, and the phase of the signal after conjugate multiplication is extracted. The extracted phase is then amplitude- and phase-compensated to estimate the vibration phase. In the third step, the vibration phase is compensated in the azimuthal direction of the distance pulse pressure signal, and the pairwise echo is eliminated, which completes the compensation of the airborne arc array SAR vibration platform.

Conventional squinted sliding spotlight synthetic aperture radar (SAR) imaging suffers from substantial swath width reduction and complex processing requirements due to the continuous variation in the squint angle and the large range cell migration (RCM) throughout the data acquisition interval. A novel two-dimensional (2D) beam scanning mode for high-resolution wide swath (HRWS) imaging is proposed. The key to the novel imaging mode lies in the synchronous scanning of azimuth and range beams, allowing for a broader and more flexible imaging swath with a high geometric resolution. Azimuth beam scanning from fore to aft was used to improve the azimuth resolution, while range beam scanning was adopted to illuminate the oblique wide swath to avoid the large RCM and the serious swath width reduction. Compared with the conventional sliding spotlight mode, both the swath width and swath length could be extended. According to the echo model of this imaging mode, an echo signal preprocessing approach is proposed. The key points of this approach are range data extension and azimuth data upsampling. A designed system example with a resolution of 0.5 m, swath width of 60 km, and azimuth coverage length of 134 km is presented. Furthermore, a simulation experiment on point targets was carried out. Both the presented system example and imaging results of point targets validated the proposed imaging mode.

Russian wildrye, Psathyrostachys junceus (Fisch.) Nevski, is widely distributed in the high latitude areas of Eurasia. It plays an important role in grassland ecosystem maintenance, as well as being a valuable palatable forage species for livestock and wildlife. Russian wildrye germplasm has rich phenotypic and genetic diversity and has potential for improvement through crossbreeding. In this study, fifteen Russian wildrye hybrid combinations were produced and one F1 population with 123 putative hybrids was obtained by crossing two individual plants with significant differences in nutritional characteristics and reproductive tiller number. Twelve phenotypic traits of the F1 population were measured for three consecutive years, and ten of the twelve traits were in line with the genetic characteristics of quantitative traits. Hybrid superiority was revealed among F1 hybrids in both nutritional and reproductive traits. One non-recurrent parent plant with the highest PCA-synthesis score was selected and used to make a backcross with the ‘BOZOISKY SELECT’ male parent, and 143 putative BC1 hybrids were obtained. Sixteen pairs of EST-SSR primers were randomly selected from polymorphic primers derived from different expressed tiller trait related genes. Three primer pairs that amplified both the paternal and maternal characteristic band were used to assess the purity of the F1 population, and three primer pairs (with one shared primer pair) were used to identify the BC1 population. The hybrid purity was 96.75% for the F1 population and 95.80% for the BC1 population, and the results were confirmed by self-fertility test through bagging isolation. The genetic similarity coefficients between the F1 progeny and the male parent ranged from 0.500 to 0.895, and those between the BC1 progeny and the male parent ranged from 0.667 to 0.939. A subset of individuals in the BC1 population had closer genetic distance to the recurrent parent, and genetic variation within the BC1 population decreased compared to the F1 population.

BackgroundMesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) have been increasingly proved as promising immunomodulators against some autoimmune disorders. However, the possible effect and the underlying mechanism of MSC-sEVs in autoimmune dry eye have been rarely studied.MethodsSmall extracellular vesicles from human umbilical cord mesenchymal stem cells (hUC-MSC-sEVs) were subconjunctivally injected to rabbit dry eye model, and their preventive or therapeutical effects were assessed by recording the clinical and histological scores. Quantitative real-time PCR (Q-PCR), western blot and flow cytometry were performed to evaluate the immunomodulatory effects of hUC-MSC-sEVs on macrophages and T regulatory cells (Tregs) both in vivo and in vitro, and the in vitro T cell proliferation was detected by Bromodeoxyuridine (BrdU) assay. In addition, high expression of miR-100-5p in hUC-MSC-sEVs was identified by Q-PCR, and the functional role of sEVs-miR-100-5p on macrophages was explored by a series of co-culture experiments using sEVs derived from hUC-MSCs transfected with miR-100-5p inhibitor.ResultsWe firstly demonstrated that hUC-MSC-sEVs had the preventive and therapeutical effects on rabbit autoimmune dacryoadenitis, an animal model of Sjögren’s syndrome (SS) dry eye. Further investigation revealed that hUC-MSC-sEVs administration effectively elicited macrophages into an anti-inflammatory M2 phenotype and elevated the proportion of Tregs both in vivo and in vitro, which contributed to reduced inflammation and improved tissue damage. Importantly, hUC-MSC-sEVs-educated macrophages with M2-like phenotype exhibited strong capacity to inhibit CD4+ T cell proliferation and promote Treg generation in vitro. Mechanistically, miR-100-5p was highly enriched in hUC-MSC-sEVs, and knockdown of miR-100-5p in hUC-MSC-sEVs partially blunted the promotion of hUC-MSC-sEVs on M2 macrophage polarization and even attenuated the effect of hUC-MSC-sEVs-educated macrophages on T cell suppression and Treg expansion.ConclusionOur data indicated that hUC-MSC-sEVs alleviated autoimmune dacryoadenitis by promoting M2 macrophage polarization and Treg generation possibly through shuttling miR-100-5p. This study sheds new light on the application of MSC-sEVs as a promising therapeutic method for SS dry eye.

Psathyrostachys juncea is a perennial forage grass which plays an important role in soil and water conservation and ecological maintenance in cold and dry areas of temperate regions. In P. juncea, a variety of biotic and abiotic stress related genes have been used in crop improvement, indicating its agronomic, economic, forage, and breeding value. To date, there have been few studies on the genetic structure of P. juncea. Here, the genetic diversity and population structure of P. juncea were analyzed by EST-SSR molecular markers to evaluate the genetic differentiation related to tillering traits in P. juncea germplasm resources. The results showed that 400 simple sequence repeat (SSR) loci were detected in 2,020 differentially expressed tillering related genes. A total of 344 scored bands were amplified using 103 primer pairs, out of which 308 (89.53%) were polymorphic. The Nei’s gene diversity of 480 individuals was between 0.092 and 0.449, and the genetic similarity coefficient was between 0.5008 and 0.9111, with an average of 0.6618. Analysis of molecular variance analysis showed that 93% of the variance was due to differences within the population, and the remaining 7% was due to differences among populations. Psathyrostachys juncea materials were clustered into five groups based on population genetic structure, principal coordinate analysis and unweighted pair-group method with arithmetic means (UPGMA) analysis. The results were similar between clustering methods, but a few individual plants were distributed differently by the three models. The clustering results, gene diversity and genetic similarity coefficients showed that the overall genetic relationship of P. juncea individuals was relatively close. A Mantel test, UPGMA and structural analysis also showed a significant correlation between genetic relationship and geographical distribution. These results provide references for future breeding programs, genetic improvement and core germplasm collection of P. juncea.

The block varying pulse repetition frequency (BV-PRF) scheme applied to spaceborne squint sliding-spotlight synthetic aperture radar (SAR) can resolve large-range cell migration (RCM) and reduce azimuth signal non-uniformity. However, in the BV-PRF scheme, different raw data blocks have different PRFs, and the raw data in each block are insufficiently sampled. To resolve the two problems, a novel azimuth full-aperture pre-processing method is proposed to handle the SAR raw data formed by the BV-PRF scheme. The key point of the approach is the resampling of block data with different PRFs and the continuous splicing of azimuth data. The method mainly consists of four parts: de-skewing, resampling, azimuth continuous combination, and Doppler history recovery. After de-skewing, the raw data with different PRFs can be resampled individually to obtain a uniform azimuth sampling interval, and an appropriate azimuth time shift is introduced to ensure the continuous combination of the azimuth signal. Consequently, the resulting raw data are sufficiently and uniformly sampled in azimuth, which could be well handled by classical SAR-focusing algorithms. Simulation results on point targets validate the proposed azimuth pre-processing approach. Furthermore, compared with methods to process SAR data with continuous PRF, the proposed method is more effective.

To avoid two apertures adopted in air-borne continuous-wave (CW) synthetic aperture radar (SAR) systems, the novel air-borne linear frequency modulation range interrupted continuous wave (LFMRICW) SAR imaging mode is presented here. Different from the conventional air-borne CW imaging mode, it only requires one antenna to transmit radar pulses and receive its echoes. The system design of this mode is given in detail, and its imaging processor based on a linear prediction model (LPM) is proposed according to echo characteristics. Simulation results on distributed targets validate the presented new air-borne imaging scheme and its corresponding imaging processor.

A synthetic aperture radar (SAR) system can be seriously contaminated by radio frequency systems because of working in the same microwave frequency bands, which would degrade the SAR image quality and affect the accuracy of image interpretation. In this paper, a novel radio frequency interference (RFI) suppression approach including RFI identification, band-stop filtering and a removed spectrum iterative adaptive approach (RSIAA) is proposed. First, the smoothing process is added before RFI signal detection to improve the RFI detection capacity. Afterwards, the band-stop filtering with a broaden factor is proposed to mitigate the residual RFI, and it ensures the accuracy of the following removed spectrum recovery by the RSIAA. Finally, the removed spectrum components are estimated from available adjacent spectrum data by the RSIAA in turn to obtain the desired range spectra. Compared with the conventional range frequency filtering method for RFI suppression, the capacity of the weak RFI signal detection is improved, and the increased sidelobes due to the discontinuous spectra are well suppressed. Simulation experiments on both simulated SAR raw data, Gaofen-3 and Sentinel-1 SAR raw data validate the proposed RFI suppression approach.

In a multichannel geosynchronous spaceborne–airborne bistatic synthetic aperture radar (GEO-SA-BiSAR) system, the airborne receiver can obtain high-resolution microwave images with good signal-to-noise ratios (SNRs) by passively receiving echoes from the desired area. Since the Doppler modulation and range history of a moving target are obviously different from a stationary target, a signal geometry model for moving targets in multichannel GEO-SA-BiSAR is established in this paper. According to simulation results, the along track velocity introduces target defocusing in azimuth, and the slant range velocity mainly causes multiple false targets. To resolve these problems, a modified multichannel reconstruction method in azimuth channel GEO-SA-BiSAR is proposed according to the azimuth multichannel impulse response of the imaged moving target. Before azimuth multichannel raw data combination, both spatial-variant range cell migration correction (RCMC) and azimuth nonlinear chirp scaling (ANLCS) should be performed to reduce the influence of the range offset and lower the Doppler bandwidth of the whole raw data, respectively. Afterward, a novel azimuth multichannel reconstruction algorithm is carried out via the modified reconstruction matrix based on the estimated target velocity. The target slant range velocity estimation is implemented by introducing the signal intensity ratio (SIR). Compared with the conventional method for the stationary target to handle the raw data of the moving target, the false targets could be obviously suppressed by using the proposed approach. Imaging results on both simulated point and distributed scene targets validate the proposed multichannel reconstruction approach.

Human migration, influenced by social conflict and natural disasters as well as global climate change, has become recognized as a major "planetary force." It has also brought to the forefront, new specialties of integrative biology-such as high-altitude medicine-and the impact of hitherto understudied environmental factors on human pathophysiology in these new geographical settings. For people migrating to or living in high-altitude regions, environmental hypoxia is a primary challenge. Decreased partial pressure of oxygen in environmental air, caused by lower barometric pressure, puts living organisms in a hypoxic state. When there is a serious inability to adapt, death may ensue. Research efforts over the past few years have applied mass spectrometry-based proteomics analyses to uncover the mechanisms of hypoxia-related high-altitude pathophysiology. The differential proteomic profiles in plasma and tissues under high-altitude hypoxia conditions, as compared with sea level controls, and the multitudinous hypoxia-specific proteins identified elucidate mechanisms underlying high-altitude hypoxia acclimatization and diseases, and provide a foundation for development of new therapeutic, prophylactic, and diagnostic approaches. In this expert review and innovation analysis, we highlight the current proteomics findings on high-altitude hypoxia, and suggest paths forward toward effective interventions to address this key challenge in high-altitude medicine. [ABSTRACT FROM AUTHOR]