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Abstract Background To evaluate association of 24 h–systolic blood pressure (SBP) variability and obstructive sleep apnea (OSA) as defined by the apnea-hypopnea index ≥5/h; and association of 24 h–SBP variability and prevalent cardiovascular disease (CVD) in OSA patients. Methods Participants underwent polysomongraphy to evaluate the presence of OSA, and 24 h–ambulatory blood pressure monitoring was applied to evaluate 24 h–SBP variability as indexed by weighted 24 h–standard deviation (SD) of SBP. Between-group differences were evaluated in participants with and without OSA. Participants with OSA were divided into high and low 24 h–SBP variability groups and between-group differences were evaluated. Results Mean age of 384 participants was 50 years old and 42.2% had OSA. Mean 24 h–systolic/diastolic BP were 130/78 mmHg, with mean weighted 24 h–SD of systolic/diastolic BP were 12.9/7.3 mmHg. Compared to those without OSA, OSA participants had higher clinic-, 24 h-, daytime- and nighttime-SBP, and weighted 24 h, daytime- and nighttime-SD of SBP. Age, prevalent CVD and OSA, usage of angiotensin converting enzyme inhibitor/angiotensin receptor blocker, calcium channel blocker and diuretic were significantly associated with 24 h–SBP variability. In OSA patients, compared to those with low variability, participants with high variability had higher weighted 24 h, daytime- and nighttime-SD of SBP. After adjusted for covariates including clinic-SBP and 24 h–SBP, per 1-SD increment weighted 24 h–SD of SBP was associated with 21% increased prevalent CVD. Conclusions Patients with newly-diagnosed OSA have higher 24 h–SBP variability compared to those without OSA; in OSA patients, increased 24 h–SBP variability is associated with increased prevalence of CVD.

The PSD-95/SAPAP/Shank complex functions as the major scaffold in orchestrating the formation and plasticity of the post-synaptic densities (PSDs). We previously demonstrated that the exquisitely specific SAPAP/Shank interaction is critical for Shank synaptic targeting and Shank-mediated synaptogenesis. Here, we show that the PSD-95/SAPAP interaction, SAPAP synaptic targeting, and SAPAP-mediated synaptogenesis require phosphorylation of the N-terminal repeat sequences of SAPAPs. The atomic structure of the PSD-95 guanylate kinase (GK) in complex with a phosphor-SAPAP repeat peptide, together with biochemical studies, reveals the molecular mechanism underlying the phosphorylation-dependent PSD-95/SAPAP interaction, and it also provides an explanation of a PSD-95 mutation found in patients with intellectual disabilities. Guided by the structural data, we developed potent non-phosphorylated GK inhibitory peptides capable of blocking the PSD-95/SAPAP interaction and interfering with PSD-95/SAPAP-mediated synaptic maturation and strength. These peptides are genetically encodable for investigating the functions of the PSD-95/SAPAP interaction in vivo.

SAR Ship Detection Dataset (SSDD) is the first open dataset that is widely used to research state-of-the-art technology of ship detection from Synthetic Aperture Radar (SAR) imagery based on deep learning (DL). According to our investigation, up to 46.59% of the total 161 public reports confidently select SSDD to study DL-based SAR ship detection. Undoubtedly, this situation reveals the popularity and great influence of SSDD in the SAR remote sensing community. Nevertheless, the coarse annotations and ambiguous standards of use of its initial version both hinder fair methodological comparisons and effective academic exchanges. Additionally, its single-function horizontal-vertical rectangle bounding box (BBox) labels can no longer satisfy the current research needs of the rotatable bounding box (RBox) task and the pixel-level polygon segmentation task. Therefore, to address the above two dilemmas, in this review, advocated by the publisher of SSDD, we will make an official release of SSDD based on its initial version. SSDD’s official release version will cover three types: (1) a bounding box SSDD (BBox-SSDD), (2) a rotatable bounding box SSDD (RBox-SSDD), and (3) a polygon segmentation SSDD (PSeg-SSDD). We relabel ships in SSDD more carefully and finely, and then explicitly formulate some strict using standards, e.g., (1) the training-test division determination, (2) the inshore-offshore protocol, (3) the ship-size reasonable definition, (4) the determination of the densely distributed small ship samples, and (5) the determination of the densely parallel berthing at ports ship samples. These using standards are all formulated objectively based on the using differences of existing 75 (161 × 46.59%) public reports. They will be beneficial for fair method comparison and effective academic exchanges in the future. Most notably, we conduct a comprehensive data analysis on BBox-SSDD, RBox-SSDD, and PSeg-SSDD. Our analysis results can provide some valuable suggestions for possible future scholars to further elaborately design DL-based SAR ship detectors with higher accuracy and stronger robustness when using SSDD.

Ship detection from synthetic aperture radar (SAR) imagery is a fundamental and significant marine mission. It plays an important role in marine traffic control, marine fishery management, and marine rescue. Nevertheless, there are still some challenges hindering accuracy improvements of SAR ship detection, e.g., complex background interferences, multi-scale ship feature differences, and indistinctive small ship features. Therefore, to address these problems, a novel quad feature pyramid network (Quad-FPN) is proposed for SAR ship detection in this paper. Quad-FPN consists of four unique FPNs, i.e., a DEformable COnvolutional FPN (DE-CO-FPN), a Content-Aware Feature Reassembly FPN (CA-FR-FPN), a Path Aggregation Space Attention FPN (PA-SA-FPN), and a Balance Scale Global Attention FPN (BS-GA-FPN). To confirm the effectiveness of each FPN, extensive ablation studies are conducted. We conduct experiments on five open SAR ship detection datasets, i.e., SAR ship detection dataset (SSDD), Gaofen-SSDD, Sentinel-SSDD, SAR-Ship-Dataset, and high-resolution SAR images dataset (HRSID). Qualitative and quantitative experimental results jointly reveal Quad-FPN’s optimal SAR ship detection performance compared with the other 12 competitive state-of-the-art convolutional neural network (CNN)-based SAR ship detectors. To confirm the excellent migration application capability of Quad-FPN, the actual ship detection in another two large-scene Sentinel-1 SAR images is conducted. Their satisfactory detection results indicate the practical application value of Quad-FPN in marine surveillance.

Background/Aims: The aim of present study was to test the hypothesis that preconditioning with sodium hydrosulfide (NaHS) could enhance the capacity of migration, adhesion and proliferation of endothelial progenitor cells (EPCs) in vitro, and also could improve the efficacy of EPCs transplantation for re-endothelialization in nude mice with carotid artery injury. The paper further addressed the underlying mechanisms. Methods: EPCs were isolated from peripheral blood mononuclear cells of healthy male volunteers and the markers of EPCs were analyzed by flow cytometry. Thereafter, different concentrations of NaHS (25, 50, 100, 200 and 500 uM) were used for preconditioning EPCs. In vitro and in vivo migration, adhesion and proliferation as well as nitric oxide (NO) production of EPCs were evaluated. Carotid artery injury model was produced in nude mice and thereafter, NaHS-preconditioned EPCs were transplanted in order to evaluate their capacity of re-endothelialization. Results: Cellular immuno-staining showed that isolated cells expressed the key markers of EPCs. In vitro, EPCs proliferation rates and NO production were gradually increased in a NaHS-concentration dependent manner, while these benefits were blocked at a concentration of 500 uM NaHS. Similarly, the migration and adhesion rates of EPCs were also increased the most prominently at a concentration of 200 µM NaHS. In vivo, compared to the control group, treatment with NaHS-preconditioned EPCs significantly enhanced the capacity of re-endothelialization of EPCs. Fluorescent microscope revealed that there were more EPCs homing to the injury vessels in the NaHS-preconditioned EPCs group than the non-preconditioned group. With the administration of AMPK or eNOS inhibitors respectively, the above benefits of NaHS-preconditioning were abrogated. Conclusion: These results suggested that NaHS-preconditioning enhanced the biological function and re-endothelialization of EPCs through the AMPK/eNOS signaling pathway.

Abstract The novel anti-VEGF drug conbercept has been used in the treatment of several retinal neovascular diseases. Owning to the alteration of the structure, the newest drug is capable of combining more molecular targets and present higher affinity to the angiogenesis promoting factors. However, it is unknown whether it will cause any unwanted effects like other anti-VEGF agents. We studied the short-term safety of high concentration and high frequency intravitreal injection of conbercept in rabbits. Intraocular pressure, fundus-photography, ERGs were applied. Retinal morphology, the amount of apoptotic cells and protein levels of IL-6, IL-8 and TNF-α in the aqueous humor were determined. Retinal proteomics was detected using tandem mass tags (TMTs) quantitative mass spectrometry. The difference of IOP, ERGs, protein levels of inflammatory factors among rabbits received conbercept and PBS was not significant (P > 0.05). Fundus photographs and retinal morphology of animals in the conbercept-injected groups mimic those observed in the PBS-injected groups. No TUNEL-positive cell was seen in the retinal ganglion cell layer in the conbercept-injected groups. Proteomics did not show significant changes of inflammation or apoptosis associated proteins in the conbercept-injected eyes. We conclude that intravitreal injection of high concentration and high frequency conbercept is well tolerated at least in a short-term in rabbits.

To overcome some major problems with traditional saliency evaluation metrics, full‐reference image quality assessment (IQA) metrics, which have similar but stricter objectives, are used. Inspired by the root mean absolute error, the authors propose a fitting‐based optimisation method for salient object detection algorithms. Their algorithm analyses the quantitative relationship between saliency and ground truth values, and uses the derived relationship to fit the saliency values to the original saliency maps. This ensures that the resulting images, which are composed of fitted values, are closer to the ground truth. The proposed algorithm first computes the statistics of the ground truth and saliency maps computed by each salient object detection algorithm. These statistics are used to compute the parameters of four fitting models, which generally agree with the characteristics of the statistical data. For a new saliency map, they use the fitting model with the computed parameters to obtain the fitted saliency values, which are confined to the range [0, 255]. Finally, they evaluate their saliency optimisation algorithm using traditional evaluation metrics, IQA metrics, and a content‐based image retrieval application. The results show that the proposed approach improves the quality of the optimised saliency maps.

Ischemic stroke, which accounts for 87% of all strokes, constitutes the leading cause of morbidity and mortality in China. Although the genetics and epigenetics of stroke have been extensively investigated, few studies have examined their relationships at different stages of stroke. This study assessed the characteristics of transcriptome changes at different stages of ischemic stroke using a mouse model of transient middle cerebral artery occlusion (tMCAO) and bioinformatics analyses. Cerebral cortex tissues from tMCAO mice at days 1, 3, 7, 14, and 28 were removed for RNA-Seq and small RNA-Seq library construction, sequencing, and bioinformatics analysis. We identified differentially expressed (DE) genes and miRNAs and revealed an association of the up-regulated or down-regulated DEmiRNAs with the correspondingly altered DEgene targets at each time point. In addition, different biological pathways were activated at different time points; thus, three groups of miRNAs were verified that may represent potential clinical biomarkers corresponding to days 1, 3, and 7 after ischemic stroke. Notably, this represents the first functional association of some of these miRNAs with stroke, e.g., miR-2137, miR-874-5p, and miR-5099. Together, our findings lay the foundation for the transition from a single-point, single-drug stroke treatment approach to multiple-time-point multi-drug combination therapies.

Objectives: This study was to evaluate platelet reactivity over time among patients with chronic kidney disease (CKD) receiving standard dose of clopidogrel after percutaneous coronary intervention (PCI). The effect of CYP2C19 loss-of-function genotypes on platelet reactivity was also determined. Methods: Patients with CKD (n = 138) on maintenance dose of clopidogrel after PCI were enrolled. Platelet reactivity was assessed by measuring P2Y12 reaction units (PRU) with VerifyNow P2Y12 assay, and platelet reactivity index (PRI) with flow cytometric using vasodilator-stimulated phosphoprotein (VASP) at baseline and 2 weeks later, respectively. The genotypes of CYP2C19 were also measured concurrently. Results: The proportion of patients with high platelet reactivity (HPR) ranged from 23.2% to 59.4%, and almost 1 in 5 patients had a dual conversion between HPR and non-HPR status. Patients carrying CYP2C19 loss-of-function genotypes showed a higher platelet reactivity than non-carriers, but with an undetermined HPR status between the first and second visits. The individual switch of HPR to non-HPR status existed in both loss-of-function genotype carriers and non-carriers. Conclusions: HPR conversions occur in a significant proportion of CKD patients with maintenance doses of clopidogrel treatment post-PCI, and this conversion was not confined to CYP2C19 loss-of-function genotype carriers. Risk stratification for treatment adjustment in personalized antiplatelet therapy should be investigated in future research.

Summary: Kibra is a synaptic scaffold protein regulating learning and memory. Alterations of Kibra-encoding gene WWC1 cause various neuronal disorders, including Alzheimer’s disease and Tourette syndrome. However, the molecular mechanism underlying Kibra’s function in neurons is poorly understood. Here we discover that Kibra, via its N-terminal WW12 tandem domains, binds to a postsynaptic density enriched protein, Dendrin, with a nanomolar dissociation constant. On the basis of the structure of Kibra WW12 in complex with Dendrin PY motifs, we developed a potent peptide inhibitor capable of specifically blocking the binding between Kibra and Dendrin in neurons. Systematic administration of the inhibitory peptide attenuated excitatory synaptic transmission, completely blocked long-term potentiation induction, and impaired spatial learning and memory. A Kibra mutation found in Tourette syndrome patients causes defects in binding to Dendrin. Thus, Kibra can modulate spatial learning and memory via binding to Dendrin. : Ji et al. report that the memory-related molecule Kibra, via its WW tandem domains, specifically binds to the synaptic protein Dendrin with a low-nanomolar dissociation constant to modulate spatial learning and memory. Keywords: Kibra, Dendrin, WW domains, tandem repeats, scaffold protein, synaptic complex, synaptic transmission, learning and memory, psychiatric disorder, Tourette syndrome

Ship detection in synthetic aperture radar (SAR) images is becoming a research hotspot. In recent years, as the rise of artificial intelligence, deep learning has almost dominated SAR ship detection community for its higher accuracy, faster speed, less human intervention, etc. However, today, there is still a lack of a reliable deep learning SAR ship detection dataset that can meet the practical migration application of ship detection in large-scene space-borne SAR images. Thus, to solve this problem, this paper releases a Large-Scale SAR Ship Detection Dataset-v1.0 (LS-SSDD-v1.0) from Sentinel-1, for small ship detection under large-scale backgrounds. LS-SSDD-v1.0 contains 15 large-scale SAR images whose ground truths are correctly labeled by SAR experts by drawing support from the Automatic Identification System (AIS) and Google Earth. To facilitate network training, the large-scale images are directly cut into 9000 sub-images without bells and whistles, providing convenience for subsequent detection result presentation in large-scale SAR images. Notably, LS-SSDD-v1.0 has five advantages: (1) large-scale backgrounds, (2) small ship detection, (3) abundant pure backgrounds, (4) fully automatic detection flow, and (5) numerous and standardized research baselines. Last but not least, combined with the advantage of abundant pure backgrounds, we also propose a Pure Background Hybrid Training mechanism (PBHT-mechanism) to suppress false alarms of land in large-scale SAR images. Experimental results of ablation study can verify the effectiveness of the PBHT-mechanism. LS-SSDD-v1.0 can inspire related scholars to make extensive research into SAR ship detection methods with engineering application value, which is conducive to the progress of SAR intelligent interpretation technology.

BackgroundA large proportion of genetic risk remains unexplained for structural heart disease involving the interventricular septum (IVS) including hypertrophic cardiomyopathy and ventricular septal defects. This study sought to develop a reproducible proxy of IVS structure from standard medical imaging, discover novel genetic determinants of IVS structure, and relate these loci to diseases of the IVS, hypertrophic cardiomyopathy, and ventricular septal defect.MethodsWe estimated the cross-sectional area of the IVS from the 4-chamber view of cardiac magnetic resonance imaging in 32 219 individuals from the UK Biobank which was used as the basis of genome wide association studies and Mendelian randomization.ResultsMeasures of IVS cross-sectional area at diastole were a strong proxy for the 3-dimensional volume of the IVS (Pearson r=0.814, P=0.004), and correlated with anthropometric measures, blood pressure, and diagnostic codes related to cardiovascular physiology. Seven loci with clear genomic consequence and relevance to cardiovascular biology were uncovered by genome wide association studies, most notably a single nucleotide polymorphism in an intron of CDKN1A (rs2376620; β, 7.7 mm2 [95% CI, 5.8-11.0]; P=6.0×10-10), and a common inversion incorporating KANSL1 predicted to disrupt local chromatin structure (β, 8.4 mm2 [95% CI, 6.3-10.9]; P=4.2×10-14). Mendelian randomization suggested that inheritance of larger IVS cross-sectional area at diastole was strongly associated with hypertrophic cardiomyopathy risk (pIVW=4.6×10-10) while inheritance of smaller IVS cross-sectional area at diastole was associated with risk for ventricular septal defect (pIVW=0.007).ConclusionsAutomated estimates of cross-sectional area of the IVS supports discovery of novel loci related to cardiac development and Mendelian disease. Inheritance of genetic liability for either small or large IVS, appears to confer risk for ventricular septal defect or hypertrophic cardiomyopathy, respectively. These data suggest that a proportion of risk for structural and congenital heart disease can be localized to the common genetic determinants of size and shape of cardiovascular anatomy.