The landscape of angiogenesis and inflammatory factors in eyes with myopic choroidal neovascularization before and after anti-VEGF injection.

INTRODUCTION: To investigate the levels of angiogenesis and inflammatory cytokines in individuals with myopic choroidal neovascularization (mCNV) and the changes in these factors following intravitreal anti-VEGF injection. METHODS: Aqueous humor samples were gathered from eyes with mCNV, those with single macular bleeding (SMB) without mCNV in highly myopic eyes, and those with age-related cataracts. Using a multiplex bead immunoassay, we analyzed 28 angiogenesis and inflammatory factors in the aqueous humor. Furthermore, clinical data were documented for correlation analysis. RESULTS: In this study, the levels of vascular endothelial growth factor A (VEGF-A), interleukin 8 (IL-8), and fibroblast growth factors 1 (FGF-1) were significantly elevated in mCNV compared to SMB eyes (p < 0.05). Their odds ratios for mCNV occurrence were 1.05, 3.45, and 2.64, respectively. Hepatocyte growth factor (HGF) and VEGF-C were notably higher in mCNV than in cataract patients (p < 0.05), and VEGF-C correlated to the degree of myopic atrophic maculopathy (p = 0.024). Axial length exhibited a negative correlation with VEGF-A and positive correlations with VEGF-C, HGF, and MCP-1 (p < 0.01). Following anti-VEGF treatment, a reduction in VEGF-A, endothelin-1, and FGF-2 was noted in mCNV patients (p < 0.05), but MCP-1 levels increased. CONCLUSION: Our findings highlight the predominant role of angiogenesis and inflammation factors in mCNV pathogenesis. VEGF-C's correlation with axial length and atrophy suggests its involvement in the process of myopic atrophic maculopathy.

Effect of Sonic hedgehog gene-modified bone marrow mesenchymal stem cells on graft-induced retinal gliosis and retinal ganglion cells survival in diabetic mice.

AIM: To investigate the effects of Sonic hedgehog (Shh) gene-modified bone marrow mesenchymal stem cells (MSCs) on graft-induced retinal gliosis and retinal ganglion cells (RGCs) survival in diabetic mice. METHODS: Bone marrow-derived MSCs were genetically modified with the Shh gene to generate a stably transfected cell line of Shh-modified MSCs (MSC-Shh). Intravitreal injections of MSC-Shh and green fluorescent protein-modified MSCs (MSC-Gfp; control) were administered in diabetic mice. After 4wk, the effects of MSC-Shh on retinal gliosis were evaluated using fundus photography, and markers of gliosis were examined by immunofluorescence and Western blotting. The neurotrophic factors expression and RGCs survival in the host retina were evaluated using Western blotting and immunofluorescence. The mechanisms underlying the effects of MSC-Shh was investigated. RESULTS: A significant reduction of proliferative vitreoretinopathy (PVR) was observed after intravitreal injection of MSC-Shh compared to MSC-Gfp. Significant downregulation of glial fibrillary acidic protein (GFAP) was demonstrated in the host retina after MSC-Shh administration compared to MSC-Gfp. The extracellular signal-regulated kinase 1/2 (ERK1/2), protein kinase B (AKT) and phosphatidylin-ositol-3-kinase (PI3K) pathways were significantly downregulated after MSC-Shh administration compared to MSC-Gfp. Brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) levels were significantly increased in the host retina, and RGCs loss was significantly prevented after MSC-Shh administration. CONCLUSION: MSC-Shh administration reduces graft-induced reactive gliosis following intravitreal injection in diabetic mice. The ERK1/2, AKT and PI3K pathways are involved in this process. MSC-Shh also increases the levels of neurotrophic factors in the host retina and promoted RGCs survival in diabetic mice.

Clinical Outcomes After Cranioplasty With Titanium Mesh, Polyetheretherketone, or Composite Bone Cement: A Retrospective Study.

Cranioplasty is a common neurosurgical procedure; however, the optimal material choice remains controversial. At the time of this writing, autologous bone, the preferred choice for primary cranioplasty, has a high incidence of complications such as infection and resorption, thus requiring frequent use of synthetic materials. Therefore, this study aimed to compare the clinical benefits of titanium mesh (Ti), polyetheretherketone (PEEK), and composite bone cement (CBC) in cranioplasty to provide a clear selection basis for clinicians and patients. This study retrospectively collected data from 207 patients who underwent cranioplasty with Ti (n=129), PEEK (n=54), and CBC (n=24) between January 2018 and December 2020 at Henan Provincial People's Hospital. Postoperative follow-up information after 6 months was used to compare the long-term effects of the 3 materials on the patients. There were no significant differences in the overall complication rate after cranioplasty among the 3 materials. However, subcutaneous effusion was more frequent with PEEK (24.07%) and CBC (20.83%) than with Ti (2.33%). Second, there were no significant differences in the increase in Glasgow Outcome Scale and Karnofsky Performance Status scores after cranioplasty among the 3 materials. Finally, we found that PEEK had the highest patient satisfaction and hospitalization cost, whereas the opposite was true for Ti. Although the surgical outcomes of the 3 implant materials were similar, an examination of clinical outcomes such as patient satisfaction showed significant differences, deepening people's perceptions of the 3 materials.

Tailored Apoptotic Vesicle Delivery Platform for Inflammatory Regulation and Tissue Repair to Ameliorate Ischemic Stroke.

Apoptotic vesicles (ApoVs) hold great promise for inflammatory regulation and tissue repair. However, little effort has been dedicated to developing ApoV-based drug delivery platforms, while the insufficient targeting capability of ApoVs also limits their clinical applications. This work presents a platform architecture that integrates apoptosis induction, drug loading, and functionalized proteome regulation, followed by targeting modification, enabling the creation of an apoptotic vesicle delivery system to treat ischemic stroke. Briefly, α-mangostin (α-M) was utilized to induce mesenchymal stem cell (MSC) apoptosis while being loaded onto MSC-derived ApoVs as an anti-oxidant and anti-inflammatory agent for cerebral ischemia/reperfusion injury. Matrix metalloproteinase activatable cell-penetrating peptide (MAP), a microenvironment-responsive targeting peptide, was modified on the surface of ApoVs to obtain the MAP-functionalized α-M-loaded ApoVs. Such engineered ApoVs targeted the injured ischemic brain after systemic injection and achieved an enhanced neuroprotective activity due to the synergistic effect of ApoVs and α-M. The internal protein payloads of ApoVs, upon α-M activation, were found engaged in regulating immunological response, angiogenesis, and cell proliferation, all of which contributed to the therapeutic effects of ApoVs. The findings provide a universal framework for creating ApoV-based therapeutic drug delivery systems for the amelioration of inflammatory diseases and demonstrate the potential of MSC-derived ApoVs to treat neural injury.

Maternal genetic polymorphisms in the major mitotic checkpoint genes MAD1L1 and MAD2L1 associated with the risk of survival in abnormal chromosomal fetuses.

Background: The genetic etiology of fetal chromosome abnormalities remains unknown, which brings about an enormous burden for patients, families, and society. The spindle assembly checkpoint (SAC) controls the normal procedure of chromosome disjunction and may take part in the process. Objective: The aim of this study was to explore the association between polymorphisms of MAD1L1 rs1801368 and MAD2L1 rs1283639804, involved in SAC and fetal chromosome abnormalities. Methods: The case-control study collected 563 cases and 813 health controls to test the genotypes of MAD1L1 rs1801368 and MAD2L1 rs1283639804 polymorphisms by polymerase chain reaction-restrictive fragment length polymorphism methods (PCR-RFLP). Results: MAD1L1 rs1801368 polymorphism was associated with fetal chromosome abnormalities alone or combined to lower homocysteine (HCY) levels (alone: dominant: OR: 1.75, 95%CI: 1.19-2.57, and p = 0.005; CT vs. CC: OR = 0.73, 95%CI: 0.57-0.94, and p = 0.016; lower HCY: C vs. T: OR = 0.74, 95%CI: 0.57-0.95, and p = 0.02; dominant: OR = 1.75, 95%CI: 0.79-1.92, and p = 0.005). No significant differences were found in other genetic models or subgroups (p > 0.05, respectively). MAD2L1 rs1283639804 polymorphism revealed a sole genotype in the studied population. HCY is significantly associated with fetal chromosome abnormalities in younger groups (OR: 1.78, 95%CI: 1.28-2.47, and p = 0.001). Conclusion: The results implied that the polymorphism of MAD1L1 rs1801368 may become the susceptibility factor to fetal chromosome abnormalities alone or combined to lower HCY levels but not to MAD2L1 rs1283639804 polymorphism. In addition, HCY significantly affects fetal chromosomal abnormalities in younger women.

Aptamer-Modified Erythrocyte Membrane-Coated pH-Sensitive Nanoparticles for c-Met-Targeted Therapy of Glioblastoma Multiforme.

Biomimetic drug delivery systems, especially red blood cell (RBC) membrane-based nanoparticle drug delivery systems (RNP), have been extensively utilized in tumor drug delivery because of their excellent biocompatibility and prolonged circulation. In this study, we developed an active targeting pH-sensitive RNP loaded with DOX by decorating an aptamer SL1 on RBC membranes (SL1-RNP-DOX) for c-Met-targeted therapy of glioblastoma multiforme (GBM). SL1 could specifically bind to c-Met, which is highly expressed in GBM U87MG cells and facilitate DOX delivery to GBM cells. In vitro studies demonstrated that U87MG cells had a higher uptake of SL1-RNP-DOX (3.25 folds) and a stronger pro-apoptosis effect than unmodified RNP-DOX. In vivo fluorescence imaging and tissue distribution further demonstrated the higher tumor distribution of SL1-RNP-DOX (2.17 folds) compared with RNP-DOX. As a result, SL1-RNP-DOX presented the best anti-GBM effect with a prolonged median survival time (23 days vs. 15.5 days) and the strongest tumor cell apoptosis in vivo among all groups. In conclusion, SL1-RNP-DOX exhibited a promising targeting delivery strategy for GBM therapy.

Reconstruction-Assisted Feature Encoding Network for Histologic Subtype Classification of Non-Small Cell Lung Cancer.

Accurate histological subtype classification between adenocarcinoma (ADC) and squamous cell carcinoma (SCC) using computed tomography (CT) images is of great importance to assist clinicians in determining treatment and therapy plans for non-small cell lung cancer (NSCLC) patients. Although current deep learning approaches have achieved promising progress in this field, they are often difficult to capture efficient tumor representations due to inadequate training data, and in consequence show limited performance. In this study, we propose a novel and effective reconstruction-assisted feature encoding network (RAFENet) for histological subtype classification by leveraging an auxiliary image reconstruction task to enable extra guidance and regularization for enhanced tumor feature representations. Different from existing reconstruction-assisted methods that directly use generalizable features obtained from shared encoder for primary task, a dedicated task-aware encoding module is utilized in RAFENet to perform refinement of generalizable features. Specifically, a cascade of cross-level non-local blocks are introduced to progressively refine generalizable features at different levels with the aid of lower-level task-specific information, which can successfully learn multi-level task-specific features tailored to histological subtype classification. Moreover, in addition to widely adopted pixel-wise reconstruction loss, we introduce a powerful semantic consistency loss function to explicitly supervise the training of RAFENet, which combines both feature consistency loss and prediction consistency loss to ensure semantic invariance during image reconstruction. Extensive experimental results show that RAFENet effectively addresses the difficult issues that cannot be resolved by existing reconstruction-based methods and consistently outperforms other state-of-the-art methods on both public and in-house NSCLC datasets. Supplementary material is available at https://github.com/lhch1994/Rafenet_sup_material.

Chaperonin-Containing TCP1 Subunit 5 Protects Against the Effect of Mer Receptor Tyrosine Kinase Knockdown in Retinal Pigment Epithelial Cells by Interacting With Filamentous Actin and Activating the LIM-Kinase 1/Cofilin Pathway.

Retinitis pigmentosa (RP), characterized by the gradual loss of rod and cone photoreceptors that eventually leads to blindness, is the most common inherited retinal disorder, affecting more than 2.5 million people worldwide. However, the underlying pathogenesis of RP remains unclear and there is no effective cure for RP. Mutations in the Mer receptor tyrosine kinase (MERTK) gene induce the phagocytic dysfunction of retinal pigment epithelium (RPE) cells, leading to RP. Studies have indicated that filamentous actin (F-actin)-which is regulated by chaperonin-containing TCP1 subunit 5 (CCT5)-plays a vital role in phagocytosis in RPE cells. However, whether CCT5/F-actin signaling is involved in MERTK-associated RP remains largely unknown. In the present study, we specifically knocked down MERTK and CCT5 through siRNA transfection and examined the expression of CCT5 and F-actin in human primary RPE (HsRPE) cells. We found that MERTK downregulation inhibited cell proliferation, migration, and phagocytic function; significantly decreased the expression of F-actin; and disrupted the regular arrangement of F-actin. Importantly, our findings firstly indicate that CCT5 interacts with F-actin and is inhibited by MERTK siRNA in HsRPE cells. Upregulating CCT5 using CCT5-specific lentiviral vectors (CCT5-Le) rescued the cell proliferation, migration, and phagocytic function of HsRPE cells under the MERTK knockdown condition by increasing the expression of F-actin and restoring its regular arrangement via the LIMK1/cofilin, but not the SSH1/cofilin, pathway. In conclusion, CCT5 protects against the effect of MERTK knockdown in HsRPE cells and demonstrates the potential for effective treatment of MERTK-associated RP.

AIR-Net: A novel multi-task learning method with auxiliary image reconstruction for predicting EGFR mutation status on CT images of NSCLC patients.

Automated and accurate EGFR mutation status prediction using computed tomography (CT) imagery is of great value for tailoring optimal treatments to non-small cell lung cancer (NSCLC) patients. However, existing deep learning based methods usually adopt a single task learning strategy to design and train EGFR mutation status prediction models with limited training data, which may be insufficient to learn distinguishable representations for promoting prediction performance. In this paper, a novel multi-task learning method named AIR-Net is proposed to precisely predict EGFR mutation status on CT images. First, an auxiliary image reconstruction task is effectively integrated with EGFR mutation status prediction, aiming at providing extra supervision at the training phase. Particularly, we adequately employ multi-level information in a shared encoder to generate more comprehensive representations of tumors. Second, a powerful feature consistency loss is further introduced to constrain semantic consistency of original and reconstructed images, which contributes to enhanced image reconstruction and offers more effective regularization to AIR-Net during training. Performance analysis of AIR-Net indicates that auxiliary image reconstruction plays an essential role in identifying EGFR mutation status. Furthermore, extensive experimental results demonstrate that our method achieves favorable performance against other competitive prediction methods. All the results executed in this study suggest that the effectiveness and superiority of AIR-Net in precisely predicting EGFR mutation status of NSCLC.

Post-traumatic brain injury glioma: Characteristics, report of 2 cases report and literature review.

BACKGROUND: Traumatic brain injury (TBI) as a pathogenetic factor in glioma remains controversial, and currently there is still no clear mechanism behind post-TBI glioma. Thus, we provide two case reports of post-TBI glioma contributing power to this research, and we provide a summary of the mechanisms of post-TBI glioma through literature review. METHODS: We report two cases of brain gliomas that developed in the scar of a previous brain trauma. Both patients were male and both had suffered prior traumatic brain injuries (time interval 10-20 years), and postoperative pathological findings reported glioblastoma and WHO grade III glioma, respectively. RESULTS: These two cases further support the association of between traumatic brain injury and gliomas development. CONCLUSION: Although the epidemiological investigation between TBI and glioma is still controversial, there are still some important aspects here that can determine the possibility between TBI and gliomagenesis. Besides, we found that the reparative response of neural stem cells and the dysregulation of inflammatory cells are timportant theories of the mechanism of post-TBI glioma.

Multimodal imaging and genetic analysis of adult-onset best vitelliform macular dystrophy in Chinese patients.

Compared to juvenile-onset best vitelliform macular dystrophy (BVMD), adult-onset BVMD is not well characterized and lacks strict diagnostic criteria. The present study aimed to evaluate the clinical and genetic characteristics of four advanced-age Chinese patients with adult-onset BVMD by combining multimodal imaging and genetic analysis. The four patients (all older than 50 years) were diagnosed with adult-onset BVMD at Zhongshan Ophthalmic Center (Guangzhou, China). Comprehensive ophthalmic examinations were performed, including analyses of best-corrected visual acuity, intraocular pressure, slit-lamp examination, fundus photography, optical coherence tomography, fundus fluorescein angiography and electrooculography. Genomic DNA was extracted from leukocytes isolated from peripheral blood obtained from these patients, their family members and 200 unrelated subjects from the same population. A total of 11 exons of the bestrophin-1 (BEST1) gene were amplified using PCR and sequenced. All of the four patients presented with lesions in the macular area. The patients were diagnosed with adult-onset BVMD based on multimodal imaging and genetic analysis. A total of four recurrent mutations, namely c.763C>T (p.Arg255Trp, p.R255W) in exon 7, c.584C>T (p.Ala195Val, p.A195V) in exon 5, c.910_912del GAT (p.304delAsp, p.D304del) in exon 8 and c.310G>C (p.Asp104His, p.D104H) in exon 4 of BEST1, were identified. Sorting intolerant from tolerant predicted that the amino acid substitutions p.R255W, p.A195V and p.D104H in the BEST1 protein were causing the damage. Combining multimodal imaging and genetic analysis was helpful in confirming the diagnosis of patients with adult-onset BVMD. These results maybe valuable for clinical and genetic counseling and for the development of therapeutic interventions for patients with BVMD.

Learning rich features with hybrid loss for brain tumor segmentation.

BACKGROUND: Accurately segment the tumor region of MRI images is important for brain tumor diagnosis and radiotherapy planning. At present, manual segmentation is wildly adopted in clinical and there is a strong need for an automatic and objective system to alleviate the workload of radiologists. METHODS: We propose a parallel multi-scale feature fusing architecture to generate rich feature representation for accurate brain tumor segmentation. It comprises two parts: (1) Feature Extraction Network (FEN) for brain tumor feature extraction at different levels and (2) Multi-scale Feature Fusing Network (MSFFN) for merge all different scale features in a parallel manner. In addition, we use two hybrid loss functions to optimize the proposed network for the class imbalance issue. RESULTS: We validate our method on BRATS 2015, with 0.86, 0.73 and 0.61 in Dice for the three tumor regions (complete, core and enhancing), and the model parameter size is only 6.3 MB. Without any post-processing operations, our method still outperforms published state-of-the-arts methods on the segmentation results of complete tumor regions and obtains competitive performance in another two regions. CONCLUSIONS: The proposed parallel structure can effectively fuse multi-level features to generate rich feature representation for high-resolution results. Moreover, the hybrid loss functions can alleviate the class imbalance issue and guide the training process. The proposed method can be used in other medical segmentation tasks.

Retro-orbital injection of FITC-dextran combined with isolectin B4 in assessing the retinal neovascularization defect.

BACKGROUND: A reliable and effective method is required to deliver agent that can aid the in vivo imaging of retinal vessels. The aim of the present study was to evaluate retro-orbital (RO) injection of fluorescein-labeled isothiocyanate dextran (FITC-dextran) as a method of demonstrating retinal neovascularization (NV) and avascular areas in oxygen-induced retinopathy (OIR) mice. METHODS: Different concentrations of FITC-dextran were used to compare the efficacy of this agent in perfusing the retinal vessels. Hematoxylin-eosin (HE) staining was used to evaluate the safety of RO injection. The vitreous blood vessels and extent of NV were assessed in P17 OIR mice using FITC-dextran and compared with the corresponding measurements obtained following isolectin B4 staining or the combination of both methods. RESULTS: The fluorescence of small vessels and neovascular tufts could be observed clearly following RO injection of 0.05 ml of 25 mg/ml or 50 mg/ml FITC-dextran. No visible damage to tissues adjacent to the injection site was discovered. Vitreous blood flow was gradually reduced from P0 to P5 and eventually disappeared in P17 OIR mice, as demonstrated by FITC-dextran perfusion. The retinal NV areas assessed by isolectin B4 were larger than those assessed by FITC-dextran, but the retinal avascular areas were smaller. The combination of both methods could conduce to distinguish non-functional blood vessels. CONCLUSIONS: RO injection of FITC-dextran combined with isolectin B4 is an effective, optimal method for assessing the NV area and avascular area.

TXNIP positively regulates the autophagy and apoptosis in the rat müller cell of diabetic retinopathy.

AIMS: Diabetic retinopathy (DR) can cause vision loss in patients with diabetes. The present study evaluated the expression of thioredoxin interacting protein (TXNIP) and investigated the role of TXNIP in autophagy and apoptosis of DR. MAIN METHODS: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to measure the expression level of the targets. Clustered regularly interspaced short palindromic repeats/CRISPR-associated 9 (CRISPR/cas9) method was applied for knockout of TXNIP. TdT-mediated dUTP Nick-End Labeling (TUNEL) assay and flow cytometry were utilized to detect the apoptosis. Cell Counting Kit-8 (CCK-8) assay was used to evaluate the cell viability. EdU assay was carried out to measure the cell proliferation ability. Retinal immunohistochemistry, retinal frozen section immunofluorescence as well as the electroretinogram (ERG) recording were implemented to detect the function of the retina. KEY FINDINGS: TXNIP was up-regulated under hyperglycemic condition both in vivo and in vitro. Overexpression of TXNIP activated the autophagy and apoptosis in the rat müller cell. Knockout of TXNIP reduced the autophagy and apoptosis in the rat müller cell under high glucose condition. TXNIP positively regulates autophagy via inhibition of the PI3K/AKT/mTOR signaling pathway. Knockdown of TXNIP improved the visual response to light stimulus of DR. SIGNIFICANCE: Our study unraveled for the first time that TXNIP positively regulates the autophagy in rat müller cell under high glucose condition by inhibiting the PI3K/AKT/mTOR signaling pathway, providing a novel understanding in the pathogenesis of DR and suggesting a potential new therapeutic target of DR.

Engineered superparamagnetic iron oxide nanoparticles (SPIONs) for dual-modality imaging of intracranial glioblastoma via EGFRvIII targeting.

In this work, a peptide-modified, biodegradable, nontoxic, brain-tumor-targeting nanoprobe based on superparamagnetic iron oxide nanoparticles (SPIONs) (which have been commonly used as T 2-weighted magnetic resonance (MR) contrast agents) was successfully synthesized and applied for accurate molecular MR imaging and sensitive optical imaging. PEPHC1, a short peptide which can specifically bind to epidermal growth factor receptor variant III (EGFRvIII) that is overexpressed in glioblastoma, was conjugated with SPIONs to construct the nanoprobe. Both in vitro and in vivo MR and optical imaging demonstrated that the as-constructed nanoprobe was effective and sensitive for tumor targeting with desirable biosafety. Given its desirable properties such as a 100 nm diameter (capable of penetration of the blood-brain barrier) and bimodal imaging capability, this novel and versatile multimodal nanoprobe could bring a new perspective for elucidating intracranial glioblastoma preoperative diagnosis and the accuracy of tumor resection.

Size Dependency of Circulation and Biodistribution of Biomimetic Nanoparticles: Red Blood Cell Membrane-Coated Nanoparticles.

Recently, biomimetic nanoparticles, especially cell membrane-cloaked nanoparticles, have attracted increasing attention in biomedical applications, including antitumor therapy, detoxification, and immune modulation, by imitating the structure and the function of biological systems such as long circulation life in the blood. However, the circulation time of cell membrane-cloaked nanoparticles is far less than that of the original cells, greatly limiting their biomedical applications, while the underlying reasons are seldom demonstrated. In this study, the influence of particle size on the circulation and the biodistribution of red blood cell membrane-coated nanoparticles (RBC-NPs) as model biomimetic nanoparticles were investigated. Differently sized RBC-NPs (80, 120, 160, and 200 nm) were prepared by fusing RBC membranes on poly(lactic-co-glycolic acid) nanoparticles. It was shown that the particle size did not change the cellular uptake of these biomimetic nanoparticles by macrophage cells in vitro and their immunogenic responses in vivo. However, their circulation life in vivo decreased with the particle size, while their accumulation in the liver increased with the particle size, which might be related to their size-dependent filtration through hepatic sinusoids. These findings will provide experimental evidence for the design and the optimization of biomimetic nanoparticles.

A novel end-to-end brain tumor segmentation method using improved fully convolutional networks.

Accurate brain magnetic resonance imaging (MRI) tumor segmentation continues to be an active research topic in medical image analysis since it provides doctors with meaningful and reliable quantitative information in diagnosing and monitoring neurological diseases. Successful deep learning-based proposals have been designed, and most of them are built upon image patches. In this paper, a novel end-to-end brain tumor segmentation method is developed using an improved fully convolutional network by modifying the U-Net architecture. In our network, an innovative structure referred to as an up skip connection is first proposed between the encoding path and decoding path to enhance information flow. Moreover, an inception module is adopted in each block to help our network learn richer representations, and an efficient cascade training strategy is introduced to segment brain tumor subregions sequentially. In contrast to those patchwise methods, our model can automatically generate segmentation maps slice by slice. We have validated our proposal by using imaging data from the Multimodal Brain Tumor Image Segmentation Challenge (BRATS) 2015 and BRATS 2016. Experimental results compared with U-Net suggest that our method is 2.6%, 3.9%, and 5.2% higher (by using the BRATS 2015 training dataset) as well as 2.8%, 3.7%, and 8.1% (by using the BRATS 2017 training dataset) higher in terms of complete, core and enhancing tumor regions, respectively. Quantitative and visual evaluation of our method has revealed the effectiveness of the proposed improvements and indicated that our end-to-end segmentation method can achieve a performance that can compete with state-of-the-art brain tumor segmentation approaches.

Erythroliposomes: Integrated Hybrid Nanovesicles Composed of Erythrocyte Membranes and Artificial Lipid Membranes for Pore-Forming Toxin Clearance.

Pore-forming toxins (PFTs) are the most common bacterial virulence proteins and play a significant role in the pathogenesis of bacterial infections; thus, PFTs are an attractive therapeutic target in bacterial infections. Inspired by the pore-forming process and mechanism of PFTs, we designed an integrated hybrid nanovesicle-the erythroliposome (called the RM-PL)-for PFT detoxification by fusing natural red blood cell (RBC) membranes with artificial lipid membranes. The lipid and RBC membranes were mutually beneficial when integrated into a hybrid nanovesicle structure. The RBC membrane endowed RM-PLs with the capacity for detoxification, while the PEGylated lipid membrane stabilized the RM-PLs and greatly improved the detoxification capacity of the RBC membrane. With α-hemolysin (Hlα) as a model PFT, we demonstrated that RM-PLs could not only significantly reduce the toxicity of Hlα to erythrocytes in vitro but also effectively sponge Hlα in vivo and rescue mice from Hlα-induced damage. Moreover, the high detoxification capacity of RM-PLs was shown to be partly related to the expression of the Hlα receptor protein, a disintegrin and metalloproteinase domain-containing protein 10 on the RBC membrane. Consequently, as a component integrating natural and artificial materials, the erythroliposome nanoplatform inspires potential strategies for antivirulence therapy.

Egr1 mediates retinal vascular dysfunction in diabetes mellitus via promoting p53 transcription.

OBJECTIVES: This study focused on investigating the expression and underlying molecular mechanism of early growth response 1 (Egr1) in diabetic retinopathy. METHODS: A microarray assay was applied to examine differentially expressed genes in the retina tissues of normal rats, as well as in those of streptozotocin-induced diabetic rats. Human retinal vascular endothelial cells (HRVECs) transfected with sh-NC, sh-Egr1 or sh-Egr1+ pVax1-p53 were cultured under high-glucose conditions and then used to explore the role of Egr1 in vitro. The effect of Egr1 on retinal vascular dysfunction caused by diabetes was examined by sh-Egr1 administration in vivo RESULTS: Early growth response 1 was found to be up-regulated in the retinas of diabetic rats compared to those of normal rats. Down-regulation of Egr1 in HRVECs under high-glucose conditions inhibited the apoptosis, migration and tube formation in vitro. Moreover, sh-Egr1 partially reduced the injurious effects of hyperglycaemia on retinal vascular function by decreasing apoptotic cells and microvascular formation in vivo. The reduction of Egr1 evidently down-regulated the p53 expression. Overexpression of p53 rescued the inhibition of sh-Egr1 in HRVECs under high-glucose concentration on apoptosis, migration and tube formation in vitro. CONCLUSION: Down-regulation of Egr1 partially reduced the injurious effects of hyperglycaemia on retinal vascular function via inhibiting p53 expression.

Different Culture or Different Mind? Perception and Acceptance of HPV Vaccine in China and in the U.S.

Unlike the United States, where human papillomavirus (HPV) vaccines have been available for decades, China recently approved its first HPV vaccines. Setting up a baseline comparison between these two countries, this study examines the influence of message framing, motivational orientation, cultural worldview, knowledge, and gender on young adults' intentions to get vaccinated. Compared to the U.S. participants, Chinese participants perceived HPV as a more severe risk and were more willing to get the vaccine. However, they were also more skeptical about vaccine safety. Inconsistencies with previous research emerged regarding the moderating effects of motivational orientation and cultural worldview. Findings from this study offer important implications for HPV vaccine promotion in China.