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Copper and copper alloy are commonly used to fabricate ship propellers and sealing valves that encounter harsh corrosion and wear. To improve their service life, Cu coating and Cu–AlN composite coatings with different volume content of AlN (10%, 20%, 30%) were prepared by cold spraying. The investigation focused on analyzing the coatings’ microstructure, microhardness, resistance to wear, and corrosion. Results show that the composite coatings with AlN have fewer pores and denser microstructure than the Cu coating. The coating demonstrates a relatively low deposition efficiency, resulting in the attainment of only 3.8 vol% of AlN when the feedstock AlN powder content was 30 vol%. The microhardness of Cu-3.8AlN coating is 159.7 HV, about 53.1% higher than that of Cu coating. The specific wear rate of Cu-3.8AlN coating is reduced by about 73.5% compared to that of Cu coating, measuring at 1.69 × 10−3 mm3/(N·m). Compared with other coatings, Cu-3.8AlN has the highest corrosion resistance (Ecorr = −0.199 V, Icorr = 1.2 μA/cm2, Rct = 3200 Ω·cm2). The Cu-3.8AlN coating exhibits superior wear and corrosion resistance among the four coatings, attributed to its highest level of densification and the presence of AlN particles.

Abstract Optimal integration of transcriptomics data and associated spatial information is essential towards fully exploiting spatial transcriptomics to dissect tissue heterogeneity and map out inter-cellular communications. We present SEDR, which uses a deep autoencoder coupled with a masked self-supervised learning mechanism to construct a low-dimensional latent representation of gene expression, which is then simultaneously embedded with the corresponding spatial information through a variational graph autoencoder. SEDR achieved higher clustering performance on manually annotated 10 × Visium datasets and better scalability on high-resolution spatial transcriptomics datasets than existing methods. Additionally, we show SEDR’s ability to impute and denoise gene expression (URL: https://github.com/JinmiaoChenLab/SEDR/ ).

Fibroblast heterogeneity remains undefined in eosinophilic esophagitis (EoE), an allergic inflammatory disorder complicated by fibrosis. We utilized publicly available single-cell RNA sequencing data (GSE201153) of EoE esophageal biopsies to identify fibroblast sub-populations, related transcriptomes, disease status-specific pathways and cell–cell interactions. IL13-treated fibroblast cultures were used to model active disease. At least 2 fibroblast populations were identified, F_A and F_B. Several genes including ACTA2 were more enriched in F_A. F_B percentage was greater than F_A and epithelial–mesenchymal transition upregulated in F_B vs. F_A in active and remission EoE. Epithelial–mesenchymal transition was also upregulated in F_B in active vs. remission EoE and TNF-α signaling via NFKB was downregulated in F_A. IL-13 treatment upregulated ECM-related genes more profoundly in ACTA2− fibroblasts than ACTA2+ myofibroblasts. After proliferating epithelial cells, F_B and F_A contributed most to cell–cell communication networks. ECM–Receptor interaction strength was stronger than secreted or cell–cell contact signaling in active vs. remission EoE and significant ligand–receptor pairs were driven mostly by F_B. This unbiased analysis identifies at least 2 fibroblast sub-populations in EoE in vivo, distinguished in part by ACTA2. Fibroblasts play a critical role in cell–cell interactions in EoE, most profoundly via ECM–receptor signaling via the F_B sub-group.

Ag-Sn-In-Ni-Te alloy ingots were produced through a heating–cooling combined mold continuous casting technique; they were then drawn into wires. However, during the drawing process, the alloy wires tended to harden, making further diameter reduction challenging. To overcome this, heat treatment was necessary to soften the previously drawn wires. The study investigated how variations in heat treatment temperature and holding time affected the microstructure, microhardness and corrosion resistance of the alloy wires. The results indicate that the alloy wires subjected to heat treatment at 700 °C for 2 h not only exhibited a uniform microstructure distribution, but also demonstrated low microhardness and excellent corrosion resistance.

A series of Ti41Zr25Be34-xNix (x = 4, 6, 8, 10 at.%) and Ti41Zr25Be34-xCux (x = 4, 6, 8 at.%) bulk metallic glasses were investigated to examine the influence of Ni and Cu content on the viscosity, thermoplastic formability, and nanoindentation of Ti-based bulk metallic glasses. The results demonstrate that Ti41Zr25Be30Ni4 and Ti41Zr25Be26Cu8 amorphous alloys have superior thermoplastic formability among the Ti41Zr25Be34-xNix and Ti41Zr25Be34-xCux amorphous alloys due to their low viscosity in the supercooled liquid region and wider supercooled liquid region. The hardness and modulus exhibit obvious variations with increasing Ni and Cu content in Ti-based bulk metallic glasses, which can be attributed to alterations in atomic density. Optimal amounts of Ni and Cu in Ti-based bulk metallic glasses enhance thermoplastic formability and mechanical properties. The influence of Ni and Cu content on the hardness of Ti-based bulk metallic glasses is discussed from the perspective of the mean atomic distance.

Abstract Uveal melanoma (UM) is the most common primary intraocular malignant tumor in adults. More than half of UM cases develop distant metastasis to the liver, lung, bone, and other organs, which frequently results in patient death. However, the mechanisms underlying UM metastasis remain largely unknown. Here, we report that protein tyrosine kinase 2 (PTK2), a nonreceptor protein tyrosine kinase also known as focal adhesion kinase (FAK), was overexpressed in most examined UM specimens. Furthermore, we identified PTK2 expression as a novel independent risk factor that predicts poor prognosis of UM patients. Mechanistic studies revealed that PTK2 promotes the EMT phenotype, leading to metastasis of UM cells. We showed that PTK2, located on chromosome 8q, is a functional gene of chromosome 8q gain to UM metastasis, which may represent the molecular mechanism for the aberrant expression and activation of PTK2 in UM. Our data reveal a novel role and mechanism of PTK2 in the metastatic process of UM, suggesting PTK2 may be a potential prognostic biomarker for UM metastasis and a promising therapeutic target for UM treatment.

Background and Aims: Colon cancer can occur sporadically or in the setting of chronic inflammation, such as in patients with inflammatory bowel disease. We previously showed that A20, a critical negative regulator of tumor necrosis factor signal transduction, could regulate sporadic colon cancer development. In this report, we investigate whether A20 also acts as a tumor suppressor in a model of colitis-associated cancer. Methods: Colitis and colitis-associated tumors were induced in wild-type and A20 intestinal epithelial cell-specific knockout (A20dIEC) mice using dextran sodium sulfate and azoxymethane. Clinicopathologic markers of inflammation were assessed in conjunction with colonic tumor burden. Gene expression analyses and immunohistochemistry were performed on colonic tissue and intestinal enteroids. Nitric oxide (NO) production and activity were assessed in whole colonic lysates and mouse embryonic fibroblasts. Results: A20dIEC mice develop larger tumors after treatment with dextran sodium sulfate and azoxymethane than wild-type mice. In addition to elevated markers of inflammation, A20dIEC mice have significantly enhanced expression of inducible nitric oxide synthase (iNOS), a well-known driver of neoplasia. Enhanced iNOS expression is associated with the formation of reactive nitrogen species and DNA damage. Loss of A20 also enhances NO-dependent cell death directly. Conclusion: Mechanistically, we propose that A20 normally restricts tumor necrosis factor–induced nuclear factor kappa B–dependent production of iNOS in intestinal epithelial cells, thereby protecting against colitis-associated tumorigenesis. We also propose that A20 plays a direct role in regulating NO-dependent cell death.

Most polyp segmentation methods use convolutional neural networks (CNNs) as their backbone, leading to two key issues when exchanging information between the encoder and decoder: (1) taking into account the differences in contribution between different-level features, and (2) designing an effective mechanism for fusing these features. Unlike existing CNN-based methods, we adopt a transformer encoder, which learns more powerful and robust representations. In addition, considering the image acquisition influence and elusive properties of polyps, we introduce three standard modules, including a cascaded fusion module (CFM), a camouflage identification module (CIM), and a similarity aggregation module (SAM). Among these, the CFM is used to collect the semantic and location information of polyps from high-level features; the CIM is applied to capture polyp information disguised in low-level features, and the SAM extends the pixel features of the polyp area with high-level semantic position information to the entire polyp area, thereby effectively fusing cross-level features. The proposed model, named Polyp-PVT, effectively suppresses noises in the features and significantly improves their expressive capabilities. Extensive experiments on five widely adopted datasets show that the proposed model is more robust to various challenging situations (e.g., appearance changes, small objects, and rotation) than existing representative methods. The proposed model is available at https://github.com/DengPingFan/Polyp-PVT.

Abstract Previous video object segmentation approaches mainly focus on simplex solutions linking appearance and motion, limiting effective feature collaboration between these two cues. In this work, we study a novel and efficient full-duplex strategy network (FSNet) to address this issue, by considering a better mutual restraint scheme linking motion and appearance allowing exploitation of cross-modal features from the fusion and decoding stage. Specifically, we introduce a relational cross-attention module (RCAM) to achieve bidirectional message propagation across embedding sub-spaces. To improve the model’s robustness and update inconsistent features from the spatiotemporal embeddings, we adopt a bidirectional purification module after the RCAM. Extensive experiments on five popular benchmarks show that our FSNet is robust to various challenging scenarios (e.g., motion blur and occlusion), and compares well to leading methods both for video object segmentation and video salient object detection. The project is publicly available at https://github.com/GewelsJI/FSNet .

Ultrasonic pulse frequency tungsten inert gas welding technology was adopted to join Ti-22Al-25Nb alloy. There were some cracks in the Ti-22Al-25Nb alloy weld joint after post-weld heat treatment. The hardness and Young’s modulus of α2, O, and β/B2 phases in Ti-22Al-25Nb alloy were examined with an in situ nanoindentation technique. The phase transition stresses of three different phases in the weld joint of Ti-22Al-25Nb alloy were analyzed to explain why cracks occur in the weld joint of Ti-22Al-25Nb alloy during post-weld heat treatment. The results show that mean hardness is highest for the α2 phase, second-highest for the O phase, and lowest for the β/B2 phase; the mean Young’s modulus has the same trend in Ti-22Al-25Nb alloy. Phase transition stress results in cracks in the weld joint of Ti-22Al-25Nb alloy during post-weld heat treatment. By improving post-weld heat treatment, the ultimate strength of the Ti-22Al-25Nb alloy weld joints reaches 750 MPa, which is 72.5% that of the base material.

Abstract Risk of metastasis is increased by the presence of chromosome 3 monosomy in uveal melanoma (UM). This study aimed to identify more accurate biomarker for risk of metastasis in UM. A total of 80 patients with UM from TCGA were assigned to two groups based on the metastatic status, and bioinformatic analyses were performed to search for critical genes for risk of metastasis. SLC25A38, located on chromosome 3, was the dominant downregulated gene in metastatic UM patients. Low expression of SLC25A38 was an independent predictive and prognostic factor in UM. The predictive potential of SLC25A38 expression was superior to that of pervious reported biomarkers in both TCGA cohort and GSE22138 cohort. Subsequently, its role in promoting metastasis was explored in vitro and in vivo. Knock-out of SLC25A38 could enhance the migration ability of UM cells, and promote distant metastasis in mice models. Through the inhibition of CBP/HIF-mediated pathway followed by the suppression of pro-angiogenic factors, SLC25A38 was situated upstream of metastasis-related pathways, especially angiogenesis. Low expression of SLC25A38 promotes angiogenesis and metastasis, and identifies increased metastatic risk and worse survival in UM patients. This finding may further improve the accuracy of prognostic prediction for UM.

Copper-coated graphite and copper mixture powders were deposited on AZ31B magnesium alloy and 6061 T6 aluminum alloy substrates under different process parameters by a solid-state cold spray technique. The microstructure of the copper-coated graphite and copper composite coatings was visually examined using photographs taken with an optical microscope and a scanning electron microscope. The surface roughness of the coatings was investigated with a 3D profilometer. The thickness of the coatings was determined through the analysis of the microstructure images, while the adhesion of the coatings was characterized using the scratch test method. The results indicate that the surface roughness of the coatings sprayed on the two different substrates gradually decreases as gas temperature and gas pressure increase. Additionally, the thickness and adhesion of the coatings deposited on the two different substrates both increase with an increase in gas temperature and gas pressure. Comparing the surface roughness, thickness, and adhesion of the coatings deposited on the two different substrates, the surface roughness and adhesion of the coatings on the soft substrate are greater than those of the coatings on the hard substrate, while the thickness of the coatings is not obviously affected by the hardness of the substrate. Furthermore, it is noteworthy that the surface roughness, thickness, and adhesion of the copper-coated graphite and copper composite coatings sprayed on the two different substrates exhibit a distinct linear relationship with particle velocity.

Abstract Background Deep remission (DR) is a treatment target in IBD associated with reduced hospitalization and improved outcome. Randomized control trial (RCT) data demonstrates efficacy of anti-TNFα agents in achieving DR; however, real-world data (RWD) can provide information complementary to RCTs, specifically regarding treatment duration. In this systematic review with meta-analysis, we use real-world data (RWD) to determine rates of DR in IBD treated with anti-TNFα. Methods We completed a systematic search of MEDLINE and EMBASE on July 8, 2019 with review of major gastrointestinal conference abstracts from 2012 to 2019. Studies utilizing RWD (data not from phase I-III RCTs) of adult IBD patients treated with anti-TNFα agents were included. DR was defined by clinical and endoscopic remission at minimum. DR was assessed at 8 weeks, 6 months, 1 year, and 2 years. Risk of bias was assessed with the Newcastle Ottawa Scale. Results 29,033 publications were identified. Fifteen publications, nine manuscripts and six conference abstracts, were included encompassing 1212 patients (769 Crohn’s disease-CD, 443 ulcerative colitis-UC), and analyzed using Comprehensive Meta-Analysis. Rate of DR was 36.4% (95% CI 12.6–69.4%) at 8 weeks, 39.1% (95% CI 10.4–78%) at 6 months, 44.4% (95% CI 34.6–54.6%) at 1 year, and 36% (95% CI 18.7–58%) at 2 years. DR in CD at 1 year was 48.6% (95% CI 32.8–64.7%) and in UC was 43.6% (95% CI 32.8–55.1%). Conclusions The rate of DR was highest after 1 year of therapy, in nearly 45% of IBD patients treated with anti-TNFα. Similar rates were achieved between patients with UC and CD. The findings highlight the efficacy of anti-TNFα in real-world setting. Future studies using RWD can determine efficacy of newer IBD therapeutics in routine clinical practice.

Abstract Background Accumulating evidences indicate that the signal peptide-CUB-EGF-like domain-containing protein 3 (SCUBE3) plays a key role in the development and progression of many human cancers. However, the underlying mechanism and prognosis value of SCUBE3 in breast cancer are still unclear. Methods The clinical data of 137 patients with breast cancer who underwent surgical resection in Taizhou Hospital of Zhejiang Province were retrospectively analyzed. We first conducted a comprehensive study on the expression pattern of SCUBE3 using the Tumor Immune Estimation Resource (TIMER) and UALCAN databases. In addition, the expression of SCUBE3 in breast tumor tissues was confirmed by immunohistochemistry. The protein–protein interaction analysis and functional enrichment analysis of SCUBE3 were analyzed using the STRING and Enrichr databases. Moreover, tissue microarray (TMA) was used to analyze the relationship between SCUBE3 expression levels and clinical-pathological parameters, such as histological type, grade, the status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor (HER2). We further supplemented and identified the above results using the UALCAN and bc-GenExMiner v4.4 databases from TCGA data. The correlation between the expression of SCUBE3 and survival was calculated by multivariate Cox regression analysis to investigate whether SCUBE3 expression may be an independent prognostic factor of breast cancer. Results We found that the expression level of SCUBE3 was significantly upregulated in breast cancer tissue compared with adjacent normal tissues. The results showed that the distribution of breast cancer patients in the high expression group and the low expression group was significantly different in ER, PR, HER2, E-cadherin, and survival state (p 0.05). In addition, the high expression of SCUBE3 was associated with relatively poor prognosis of ER- (p = 0.012), PR- (p = 0.029), HER2 + (p = 0.007). The multivariate Cox regression analysis showed that the hazard ratio (HR) was 2.80 (95% CI 1.20–6.51, p = 0.0168) in individuals with high SCUBE3 expression, and HR was increased by 1.86 (95% CI 1.06–3.25, p = 0.0300) for per 1-point increase of SCUBE3 expression. Conclusions These findings demonstrate that the high expression of SCUBE3 indicates poor prognosis in breast cancer. SCUBE3 expression may serve as a potential diagnostic indicator of breast cancer.

Anti-TNF antibodies are effective for treating patients with inflammatory bowel disease (IBD), but many patients fail to respond to anti-TNF therapy, highlighting the importance of TNF-independent disease. We previously demonstrated that acute deletion of 2 IBD susceptibility genes, A20 (Tnfaip3) and Abin-1 (Tnip1), in intestinal epithelial cells (IECs) sensitized mice to both TNF-dependent and TNF-independent death. Here we show that TNF-independent IEC death after A20 and Abin-1 deletion was rescued by germ-free derivation or deletion of MyD88, while deletion of Trif provided only partial protection. Combined deletion of Ripk3 and Casp8, which inhibits both apoptotic and necroptotic death, completely protected against death after acute deletion of A20 and Abin-1 in IECs. A20- and Abin-1–deficient IECs were sensitized to TNF-independent, TNFR1-mediated death in response to lymphotoxin α (LTα) homotrimers. Blockade of LTα in vivo reduced weight loss and improved survival when combined with partial deletion of MyD88. Biopsies of inflamed colon mucosa from patients with IBD exhibited increased LTA and IL1B expression, including a subset of patients with active colitis on anti-TNF therapy. These data show that microbial signals, MyD88, and LTα all contribute to TNF-independent intestinal injury.

The most recent 3D object detectors for point clouds rely on the coarse voxel-based representation rather than the accurate point-based representation due to a higher box recall in the voxel-based Region Proposal Network (RPN). However, the detection accuracy is severely restricted by the information loss of pose details in the voxels. Different from considering the point cloud as voxel or point representation only, we propose a point-to-voxel feature learning approach to voxelize the point cloud with both the point-wise semantic and local spatial features, which maintains the voxel-wise features to build the high-recall voxel-based RPN and also provides the accurate point-wise features for refining the detection results. Another difficulty in object detection for point cloud is that the visible part varies a lot against the full view of object because of the perspective issues in data acquisition. To address this, we propose an attentive corner aggregation module to attentively aggregate the features of local point cloud surrounding a 3D proposal from the perspectives of eight corners in the proposal 3D bounding box. The experimental results on the competitive KITTI 3D object detection benchmark show that the proposed method achieves state-of-the-art performance.

The main challenge for scene parsing arises when complex scenes with highly diverse objects are encountered. The objects not only differ in scale and appearance but also in semantics. Previous works focus on encoding the multi-scale contextual information (via pooling or atrous convolutions) generally on top of compact high-level features (i.e., at a single stage). In this work, we argue that a rich set of cues exist at multiple stages of the network, encapsulating low, mid and high-level scene details. Therefore, an optimal scene parsing model must aggregate multi-scale context at all three levels of the feature hierarchy; a capability that lacks in state-of-the-art scene parsing models. To address this limitation, we introduce a novel architecture with three new blocks that systematically aggregate low, mid and high tier features. The heart of our approach is a high-level feature aggregation module that augments sparsely connected atrous convolution with dense local and layer-wise connections to avoid gridding artifacts. Besides, we employ a novel feature pyramid augmentation and semantic refinement unit to generate low- and mid-level features that are mixed with high-level features at the decoder. We extensively evaluate our proposed approach on the large-scale Cityscapes and ADE2K benchmarks. Our approach surpasses many latest models on both datasets, achieving mean intersection-over-union (mIoU) scores of 80.5% and 44.0% on Cityscapes and ADE20K, respectively.

AbstractBackground:Tumor necrosis factor alpha-induced protein 3 (TNFAIP3) is a multifunctional ubiquitin binding and editing enzyme that regulates inflammation. Genetic studies have implicated polymorphisms within the TNFAIP3 locus to the development of numerous immune-related diseases. This study evaluated the frequencies of single-nucleotide polymorphism (SNPs) within the exonic regions of the TNFAIP3 gene and an associated point mutation from the Illumina array among a predominantly Hispanic cohort.Methods:Genomic DNA was obtained from 721 participants and sequencing of all TNFAIP3 exons and an intergenic point mutation (rs6920220) was performed. In-vitro functional assessment was performed by transfecting mutated TNFAIP3 constructs into TNFAIP3 knockout cells containing the NF-kB luciferase reporter and stimulating with TNFα. Comparative statistics were performed with Student’s t-test for continuous variables and chi-squared test for categorical variables.Results:Sequencing revealed two missense SNPs, rs146534657:A>G and rs2230926:T>G, both within exon 3 of TNFAIP3, which encodes the protein’s deubiquitinating enzymatic domain. Frequencies of all three point mutations differed significantly across racial groups (χ2-test, P = 0.014 to P < 0.001). Compared to Caucasians, rs146534657:A>G was overrepresented among Hispanics (odds ratio (OR) [95% CI] 4.05 [1.24−13.18]), and rs2230926:T>G was more prevalent among African-Americans (OR [95% CI] 3.65 [1.58−8.43]). In-vitro assays confirm rs146534657:A>G and rs2230926:T>G decrease the ability of TNFAIP3 to abrogate NF-κB activation by 2-fold (P < 0.01) and 1.7-fold (P < 0.01), respectively.Conclusions:This study reports the frequency of rs146534657:A>G among Hispanics and is the first to evaluate its potential physiologic impact, establishing a basis for future research as a potential biomarker among this population.

AIM: To observe the multimodal imaging characteristics of adult-onset foveomacular vitelliform dystrophy(AFVD). METHODS: Retrospective study. Six cases(11 eyes)of AFVD in Zhengzhou Second People Hospital from January 2015 to April 2018 were included. Amongst all of them, there were 2 men 3 eyes, 4 women 8 eyes, aged from 43-67 years(average 52.5±1.7 years). No abnormality was found in the anterior segment, intraocular pressure and electroretinogram(ERG). There was no family history. Best corrected visual acuity(BCVA)was from 0.08-0.8, EOG was normal in 9 eyes, slightly decreased in 2 eyes. Fundus color photography, optical coherence tomography angiography(OCTA), fundus fluorescein angiography(FFA)and indolecyanine green angiography(ICGA)of the patients were examined and analyzed. RESULTS: The fundi of all patients showed less than 1PD vitelliform lesions, showing hypofluorescence in FFA and ICGA. In the late phase of FFA,fluorescence accumulated in the lesion in some patients. In B-scan of OCTA, there was vitelliform substance which deposited between the photoreceptor and retinal pigment epithelium(RPE )layer. As the disease continues to progress, photoreceptor layer became thinner, RPE-Bruch layer became thinner or disappeared. In OCTA there was dark spot with strong reflection around it in choriocapillary layer. There was dark spot in En-face image. CONCLUSION: Multimodal imaging assist in diagnosing AFVD, reducing missed diagnosed and misdiagnosis, better understanding the pathogenesis, developing the treatment plan, judging prognosis.

Superconducting Bi _1.68 Pb _0.32 Sr _1.75 Ca _1.85 Cu _2.85 O _10+ _y (Bi-2223) powders were prepared by a conventional solid-state reaction using hand grinding and wet ball milling. The effects of the ball milling and sintering times on the phase evolution were examined by x-ray diffraction and magnetic susceptibility measurements. Single-phase Bi-2223 powders with a superconducting transition temperature of about 108 K were optimally prepared by wet ball milling for 20 h and sintering at 867 °C for 80 h. Finding these optimal preparation conditions were crucial for mass producing high-quality single-phase Bi-2223 precursor powders with a much lower cost of energy. Furthermore, we found that ball milling led to thinner grains than hand grinding.

Abstract Background To assess capillary dropout in the superficial retinal capillary plexus (SCP) by optical coherence tomography angiography (OCTA) in the early stage of diabetic retinopathy (DR). Methods This study was a cross-sectional observational study. Patients that underwent OCTA examinations in our hospital between November 2015 and May 2016 were included in the study. The subjects were divided into two groups: A) normal controls (41 eyes of 41 subjects) and B) the DR patients (49 eyes of 49 patients with mild non-proliferative DR (NPDR)). The retinal thickness and SCP vessel density were analyzed using built-in software in nine sections of the macular area; whole scan area; fovea; parafovea; and sub-sections of the parafovea, superior-hemi, inferior-hemi, temporal, superior, nasal, and inferior. The correlation between vessel density and retinal thickness was also analyzed. Results The SCP density was significantly lower (P 0.05). In the parafovea, superior-hemi, inferior-hemi, temporal, and nasal sectors of group B, the SCP density was negatively correlated with the corresponding retinal thickness (P

Diabetic retinopathy (DR) is one of the most common microvascular complications and its early detection is critical for the prevention of vision loss. Recent studies have indicated that microaneurysms (MAs) are the hallmark of DR. However, the detection of MAs relies on trained clinicians and relatively expensive software. Moreover, manual errors often lower the accuracy of this detection. Therefore, an automatic analysis technique is highly demanded in the detection of DR progression. In this paper, we present a novel and complete methodology involving two different ways from the view of MAs turnover and pathological risk factors to diagnose the progression of DR. Specifically, one approach follows the traditional image analysis-based roadmap to obtain MAs turnover. The other investigates seven pathological features, related with MAs turnover, to classify the unchanged, new, and resolved MAs by means of statistical analysis and pattern classification techniques. The evaluations on Grampian diabetes database show that the proposed image analysis method could achieve a sensitivity of 94% and a specificity of 93%, while the classification model could achieve 89% sensitivity and 88% specificity, respectively. We also analyzed the potential weight of pathological risk factors leading to the MAs turnover, which could provide an alternative guidance for the progression of DR than traditional detection methods. In conclusion, this study provides a novel and noninvasive detection technique for early diagnosis of diabetic retinopathy with a competitive accuracy.

Recently, L1-norm-based robust discriminant feature extraction technique has been attracted much attention in dimensionality reduction and pattern recognition. However, it does not relate to the scatter matrix which well characterizes the geometric structure of data. In this paper, we propose a robust formulation of graph embedding framework for dimensionality reduction. In this robust framework, we use L2-norm to measure the distance along space dimension and L1-norm to sum overall data points. The proposed robust graph embedding framework retains the traditional framework's desirable properties, such as rotational invariance and well geometric structure, and simultaneously suppresses outliers. Based on this framework, we develop a simple and robust feature extraction method, namely L2,1-norm-based discriminant locality preserving projections (L2,1-DLPP) and provide an effective iterative algorithm to solve L2,1-DLPP. Extensive experiments in artificial data and three popular face databases illustrate the effectiveness of our proposed method.

Abstract We used pulsed laser beam welding method to join Pd43Cu27Ni10P20 (at.%) bulk metallic glass and characterized the properties of the joint. Fusion zone and heat-affected zone in the weld joint can be maintained completely amorphous as confirmed by X-ray diffraction and differential scanning calorimetry. No visible defects were observed in the weld joint. Nanoindentation and bend tests were carried out to determine the mechanical properties of the weld joint. Fusion zone and heat-affected zone exhibit very similar elastic moduli and hardness when compared to the base material, and the weld joint shows high ductility in bending which is accomplished through the operation of multiple shear bands. Our results reveal that pulsed laser beam welding under appropriate processing parameters provides a practical viable method to join bulk metallic glasses.

AIM: To investigate the clinical efficacy of Ranibizumab combined with laser photocoagulation in the treatment of diabetic macular edema(DME). METHODS: The clinical data of 190 patients(190 eyes)with DME treated in our hospital from June 2014 to June 2016 were retrospectively analyzed; 90 patients(90 eyes)received intravitreal ranibizumab injections were included into control group, and 100 patients(100 eyes)received the combination of intravitreal ranibizumab injections and laser photocoagulation were included into observation group. The best corrected visual acuity(BCVA)between the two groups before and after operation was compared. The central macular thickness(CMT)and the leakage of macular edema of the two groups were measured by the optical coherence tomography(OCT)and fundus fluorescein angiography(FFA)respectively. The number of drug injection between the two groups was recorded. Then patients were followed up and the incidence of the complications was recorded. All the patients were followed up for 12mo. RESULTS: The average BCVA scores in the observation group after operation were significantly higher than those before operation. The preoperative average BCVA scores in the control group were lower than those at 1, 3, 6 and 12mo after operation. The difference between the two groups was statistically significant at 6 and 12mo after treatment(PP>0.05). CMT significantly decreased in both groups after treatment. CMT of the observation group was significantly thinner than that of the control group after 1, 3, 6 and 12mo treatments, the difference was statistically significant(PPPCONCLUSION: Compared with ranibizumab treatment alone, the combination of laser photocoagulation has better long-term vision improvement and better reduction of CMT. The combination treatment can also improve the condition of macular edema with less number of drug injection.

The accumulation of anthocyanins in leaves and stems of Mikania micrantha improves its adaptability to low-temperature environments during winter in areas where this species is invasive. The accumulation of anthocyanins in M. micrantha causes the plants to exhibit red coloration when encountering low-temperature environments during winter. Many studies have reported that the accumulation of anthocyanins near the plant surface filters light and improves photoprotection. However, the results of this study showed that the main role of anthocyanins accumulation in M. micrantha during winter was to increase both antioxidant capability and tolerance to low temperature. The results showed that the anthocyanin contents were significantly higher in red leaves and stems than in green leaves and stems, with more than 60-fold greater content in red leaves than in green leaves. In addition, the total antioxidant capability was significantly greater in red leaves and stems than in green leaves and stems. After 4°C treatment for 12 h, a large amount of reactive oxygen species accumulated in green leaves and stems, and the maximum photochemical efficiency decreased significantly. Compared with that of the green leaves, the net photosynthetic rate of red leaves was significantly higher. The biomass statistics revealed that the dry matter accumulation of M. micrantha plants with relatively large amounts of anthocyanins was significantly greater than that of plants with relatively low anthocyanin levels during the same period. Our results suggest that the accumulation of anthocyanins during winter is an adaptation strategy of M. micrantha to low winter temperatures.

A20 is a ubiquitin-editing enzyme that is known to regulate inflammatory signaling and cell death. However, A20 mutations are also frequently found in multiple malignancies suggesting a potential role as a tumor suppressor as well. We recently described a novel role for A20 in regulating the wnt-beta-catenin signaling pathway and suppressing colonic tumor development in mice. The underlying mechanisms for this phenomenon are unclear. To study this, we first generated A20 knockout cell lines by genome-editing techniques. Using these cells, we show that loss of A20 causes dysregulation of wnt-dependent gene expression by RNAseq. Mechanistically, A20 interacts with a proximal signaling component of the wnt-signaling pathway, receptor interacting protein kinase 4 (RIPK4), and regulation of wnt-signaling by A20 occurs through RIPK4. Finally, similar to the mechanism by which A20 regulates other members of the receptor interacting protein kinase family, A20 modifies ubiquitin chains on RIPK4 suggesting a possible molecular mechanism for A20's control over the wnt-signaling pathway.

AIM:To investigate the therapeutic outcomes of idiopathic retinal vasculitis, aneurisms and neuroretinitis(IRVAN)syndrome by different treatments. METHODS:Seven patients(14 eyes)with IRVAN were enrolled in this study and divided into different stages. There were 4 eyes in stage Ⅱ and 10 eyes in stage Ⅲ. The visual acuity(VA)was ≥0.6 in 6 eyes, 0.3 in 4 eyes, and ≤0.1 in 4 eyes. Treatment involved retinal laser photocoagulation for peripheral retinal ischemia area in the 4 eyes in stage Ⅱ and panretinal laser photocoagulation(PRP)for the 10 eyes in stage Ⅲ. Two eyes in stage Ⅲ were also treated with intravitreal injection of ranibizumab and 4 eyes with vitrectomy before PRP. Visual acuity and fundus situations were measured after the treatments. The follow-up time was 6mo ～ 10a. RESULTS:After treatments, the final VA was improved in 6 eyes, remaining unchanged in 6 eyes, and decreased after improved in 2 eyes. It was as following:≥0.6 in 9 eyes, 0.3～0.6 in 4 eyes, and ≤0.1 in 1 eyes. Four eyes in stage Ⅱ maintained a good vision, but one of them had a new ischemia area. We treated it with PRP and there was no progression now. In stage Ⅲ, there were 2 eyes with unchanged VA, 2 eyes with improved VA, 2 eyes with improved VA after giving ranibizumab, 4 eyes with vitreous hemorrhage and with better VA after treatments, and in the 4 eyes, 2 eyes kept stable and another two had recurrent vitreous hemorrhage for several times and ended with poor vision. Fundus examination showed the closure of hemorrhage area and optic disc or retinal neovascularization shrinked.CONCLUSION:PRP is effective for eyes in stage Ⅱ. Eyes in stage Ⅲ could be treated with intravitreal injection of ranibizumab or vitrectomy in addition to PRP. Early PRP is effective to stop the progression.

One common hypothesis to explain the impacts of tandem duplications is that whole gene duplications commonly produce additive changes in gene expression due to copy number changes. Here, we use genome wide RNA-seq data from a population sample of Drosophila yakuba to test this 'gene dosage' hypothesis. We observe little evidence of expression changes in response to whole transcript duplication capturing 5' and 3' UTRs. Among whole gene duplications, we observe evidence that dosage sharing across copies is likely to be common. The lack of expression changes after whole gene duplication suggests that the majority of genes are subject to tight regulatory control and therefore not sensitive to changes in gene copy number. Rather, we observe changes in expression level due to both shuffling of regulatory elements and the creation of chimeric structures via tandem duplication. Additionally, we observe 30 de novo gene structures arising from tandem duplications, 23 of which form with expression in the testes. Thus, the value of tandem duplications is likely to be more intricate than simple changes in gene dosage. The common regulatory effects from chimeric gene formation after tandem duplication may explain their contribution to genome evolution.

Tandem duplications are an essential source of genetic novelty, and their variation in natural populations is expected to influence adaptive walks. Here, we describe evolutionary impacts of recently-derived, segregating tandem duplications in Drosophila yakuba and Drosophila simulans. We observe an excess of duplicated genes involved in defense against pathogens, insecticide resistance, chorion development, cuticular peptides, and lipases or endopeptidases associated with the accessory glands across both species. The observed agreement is greater than expectations on chance alone, suggesting large amounts of convergence across functional categories. We document evidence of widespread selection on the D. simulans X, suggesting adaptation through duplication is common on the X. Despite the evidence for positive selection, duplicates display an excess of low frequency variants consistent with largely detrimental impacts, limiting the variation that can effectively facilitate adaptation. Standing variation for tandem duplications spans less than 25% of the genome in D. yakuba and D. simulans, indicating that evolution will be strictly limited by mutation, even in organisms with large population sizes. Effective whole gene duplication rates are low at 1.17 × 10-9 per gene per generation in D. yakuba and 6.03 × 10-10 per gene per generation in D. simulans, suggesting long wait times for new mutations on the order of thousands of years for the establishment of sweeps. Hence, in cases where adaptation depends on individual tandem duplications, evolution will be severely limited by mutation. We observe low levels of parallel recruitment of the same duplicated gene in different species, suggesting that the span of standing variation will define evolutionary outcomes in spite of convergence across gene ontologies consistent with rapidly evolving phenotypes.

Colon carcinogenesis consists of a multistep process during which a series of genetic and epigenetic adaptations occur that lead to malignant transformation. Here, we have studied the role of A20 (also known as TNFAIP3), a ubiquitin-editing enzyme that restricts NFκB and cell death signaling, in intestinal homeostasis and tumorigenesis. We have found that A20 expression is consistently reduced in human colonic adenomas than in normal colonic tissues. To further investigate A20's potential roles in regulating colon carcinogenesis, we have generated mice lacking A20 specifically in intestinal epithelial cells and interbred these with mice harboring a mutation in the adenomatous polyposis coli gene (APC(min)). While A20(FL/FL) villin-Cre mice exhibit uninflamed intestines without polyps, A20(FL/FL) villin-Cre APC(min/+) mice contain far greater numbers and larger colonic polyps than control APC(min) mice. We find that A20 binds to the β-catenin destruction complex and restricts canonical wnt signaling by supporting ubiquitination and degradation of β-catenin in intestinal epithelial cells. Moreover, acute deletion of A20 from intestinal epithelial cells in vivo leads to enhanced expression of the β-catenin dependent genes cyclinD1 and c-myc, known promoters of colon cancer. Taken together, these findings demonstrate new roles for A20 in restricting β-catenin signaling and preventing colon tumorigenesis.

Cytoplasmic inclusion bodies formed in reovirus-infected cells are the sites of viral replication and assembly. Previous studies have suggested that the NS80 protein of aquareovirus may be involved in the formation of viral inclusion bodies. However, it remains unknown whether other viral proteins are involved in the process, and what regions of NS80 may act coordinately in mediating inclusion formation. Here, we observed that globular cytoplasmic inclusions were formed in virus-infected cells and viral proteins NS80 and NS38 colocalized in the inclusions. During transfection, singly expressed NS80 could form cytoplasmic inclusions and recruit NS38 and GFP-tagged VP4 to these structures. Further treatment of cells with nocodazole, a microtubule inhibitor, did not disrupt the inclusion, suggesting that inclusion formation does not rely on microtubule network. Besides, we identified that the region 530-742 of NS80 was likely the minimal region required for inclusion formation, and the C-tail, coiled-coil region as well as the conserved linker region were essential for inclusion phenotype. Moreover, with series deletions from the N-terminus, a stepwise conversion occurred from large condensed cytoplasmic to small nuclear inclusions, then to a diffused intracellular distribution. Notablely, we found that the nuclear inclusions, formed by NS80 truncations (471 to 513-742), colocalized with cellular protein β-catenin. These data indicated that NS80 could be a major mediator in recruiting NS38 and VP4 into inclusion structures, and the C-terminus of NS80 is responsible for inclusion formation.

The present study analyzed the consumption-based carbon emissions from fossil fuel consumption of Beijing in 2012. The multi-scale input–output analysis method was applied. It is capable of tracing the carbon emissions embodied in imports based on a global multi-regional input–output analysis using Eora data. The results show that the consumption-based carbon emission of Beijing has increased by 18% since 2007, which is 2.57 times higher than the production-based carbon emission in 2012. Only approximately 1/10 of the total carbon emissions embodied in Beijing’s local final demand originated from local direct carbon emissions. Meanwhile, more than 4/5 were from domestically imported products. The carbon emission nexus between Beijing and other Chinese regions has become closer since 2007, while the imbalance as the carbon emission transfer from Beijing to other regions has been mitigated. Instead, Beijing has imported more carbon emissions from foreign countries. Some carbon emission reduction strategies for Beijing concerning different goals are presented on the basis of detailed discussion.

For greenhouse gas (GHG) emissions by Beijing economy 2007, a concrete emission inventory covering carbon dioxide (CO2), methane (CH4), and nitrous oxide (N2O) is presented and associated with an input-output analysis to reveal the local GHG embodiment in final demand and trade without regard to imported emissions. The total direct GHG emissions amount to 1.06E + 08 t CO2-eq, of which energy-related CO2 emissions comprise 90.49%, non-energy-related CO2 emissions 6.35%, CH4 emissions 2.33%, and N2O emissions 0.83%, respectively. In terms of energy-related CO2 emissions, the largest source is coal with a percentage of 53.08%, followed by coke with 10.75% and kerosene with 8.44%. Sector 26 (Construction Industry) holds the top local emissions embodied in final demand of 1.86E + 07 t CO2-eq due to its considerable capital, followed by energy-intensive Sectors 27 (Transport and Storage) and 14 (Smelting and Pressing of Ferrous and Nonferrous Metals). The GHG emissions embodied in Beijing's exports are 4.90E + 07 t CO2-eq, accounting for 46.01% of the total emissions embodied in final demand. The sound scientific database totally based on local emissions is an important basis to make effective environment and energy policies for local decision makers.