Impaired gamma delta T cell-derived IL-17A and inflammasome activation during early respiratory syncytial virus infection in infants

© 2015 Australasian Society for Immunology Inc. Respiratory syncytial virus (RSV) infection remains a significant global health burden disproportionately affecting infants and leading to long-term lung disease. Interleukin (IL)-17A has been shown to be involved in regulating viral and allergic lung inflammatory responses, which has led to a more recent interest in its role in RSV infection. Using a neonatal mouse model of RSV, we demonstrate that neonates fail to develop IL-17A responses compared with adult mice; the main immediate IL-17A contributor in adults were γδ T cells. Antibody neutralization of IL-17A in adult mice caused increased lung inflammation and airway mucus from RSV, whereas exogenous IL-17A administration to RSV-infected neonates caused decreased inflammation but no change in airway mucus. We also observed a lack of pro-inflammatory cytokine production (IL-1β, IL-6) from infected neonates. Using human cord blood mononuclear cells (CBMCs) and adult peripheral blood mononuclear cells (PBMCs), we compared inflammasome activation by direct retinoic acid-inducible gene I agonism; CBMCs failed to induce pro-inflammatory cytokines or IL-17A+γδ T cells compared with PBMCs. Our results indicate that RSV disease severity is in part mediated by a lack of inflammasome activation and IL-17A production in neonates

GE11-antigen-loaded hepatitis B virus core antigen virus-like particles efficiently bind to TNBC tumor

PurposeThis study aimed to explore the possibility of utilizing hepatitis B core protein (HBc) virus-like particles (VLPs) encapsulate doxorubicin (Dox) to reduce the adverse effect caused by its off-target and toxic side effect.MethodsHere, a triple-negative breast cancer (TNBC) tumor-targeting GE11-HBc VLP was constructed through genetic engineering. The GE11 peptide, a 12-amino-acid peptide targeting epidermal growth factor receptor (EGFR), was inserted into the surface protein loops of VLPs. The Dox was loaded into HBc VLPs by a thermal-triggered encapsulation strategy. The in vitro release, cytotoxicity, and cellular uptake of TNBC tumor-targeting GE11-HBc VLPs was then evaluated.ResultsThese VLPs possessed excellent stability, DOX loading efficiency, and preferentially released drug payload at high GSH levels. The insertion of GE11 targeting peptide caused improved cellular uptake and enhanced cell viability inhibitory in EGFR high-expressed TNBC cells.ConclusionTogether, these results highlight DOX-loaded, EGFR-targeted VLPs as a potentially useful therapeutic choice for EGFR-overexpressing TNBC

Multi-functional hybrid protonated titanate nanobelts with tunable wettability

We present the preparation of millimetre-sized liquid marbles with strong mechanical strength and good deformability using self-assembled fluoroalkylsilane functionalized titanate nanobelt powder. The strength and deformability of the marbles are adjustable by changing the intrinsic wetting state of the titanate nanoparticles. The excellent chemical stability of surface layer on the liquid marbles consisting of the titanate nanobelts provides the possibility for qualitative and quantitative chemical sensing under a wide range of pH values.Environment and Water Industry Programme Office (EWI) under the National Research Foundation of Singapore[MEWR651/06/160]; National Nature Science Foundation of China[20773100, 51072170, 20620130427]; National Basic Research Program of China (973 Program)[2007CB935603]; Technical Program of Fujian Province, China[2007H0031

Asthma in Pregnancy: Pathophysiology, Diagnosis, Whole-Course Management, and Medication Safety

Asthma in pregnancy is a health issue of great concern. Physiological changes and drug compliance during pregnancy can affect asthma control in varying degrees, and the control level of asthma and the side effects of asthma medications are closely related to the adverse perinatal outcomes of mother and fetus. This article provides an update on the available literature regarding the alleviating or aggravating mechanism of asthma in pregnancy, diagnosis, disease assessment, and systematic management, to provide a new guidance for physician, obstetric joint doctor, and health care practitioner

MicroRNA-381 Negatively Regulates TLR4 Signaling in A549 Cells in Response to LPS Stimulation

It is widely reported that miR-381 is dysregulated in various tumors. However, the specific role of miR-381 in respiratory infections has not been reported. To probe this role, A549 cells were pretreated with 1 μg/mL LPS for 24 h. The level of miR-381 was detected using RT-qPCR. The expression of proinflammatory cytokines was determined using an ELISA kit and western blotting. Bioinformatics analysis was used to predict the target genes of miR-381, and a luciferase reporter assay was used to validate the expression of the target genes. miR-381 expression was increased in A549 cells treated with LPS, which is a ligand of TLRs. Further study revealed that the overexpression of miR-381 increased the activity of NF-κB signaling, thereby increasing the expression of IL-6, TNFα, and COX-2. Further study revealed that IκBα was a target gene of miR-381. The upregulation of miR-381 under LPS stimulation contributes to respiratory infections mainly by targeting IκBα

MicroRNA-381 Negatively Regulates TLR4 Signaling in A549 Cells in Response to LPS Stimulation

It is widely reported that miR-381 is dysregulated in various tumors. However, the specific role of miR-381 in respiratory infections has not been reported. To probe this role, A549 cells were pretreated with 1 g/mL LPS for 24 h. The level of miR-381 was detected using RT-qPCR. The expression of proinflammatory cytokines was determined using an ELISA kit and western blotting. Bioinformatics analysis was used to predict the target genes of miR-381, and a luciferase reporter assay was used to validate the expression of the target genes. miR-381 expression was increased in A549 cells treated with LPS, which is a ligand of TLRs. Further study revealed that the overexpression of miR-381 increased the activity of NF-B signaling, thereby increasing the expression of IL-6, TNF , and COX-2. Further study revealed that I B was a target gene of miR-381. The upregulation of miR-381 under LPS stimulation contributes to respiratory infections mainly by targeting I B

MAC-ResNet: Knowledge Distillation Based Lightweight Multiscale-Attention-Crop-ResNet for Eyelid Tumors Detection and Classification

Eyelid tumors are tumors that occur in the eye and its appendages, affecting vision and appearance, causing blindness and disability, and some having a high lethality rate. Pathological images of eyelid tumors are characterized by large pixels, multiple scales, and similar features. Solving the problem of difficult and time-consuming fine-grained classification of pathological images is important to improve the efficiency and quality of pathological diagnosis. The morphology of Basal Cell Carcinoma (BCC), Meibomian Gland Carcinoma (MGC), and Cutaneous Melanoma (CM) in eyelid tumors are very similar, and it is easy to be misdiagnosed among each category. In addition, the diseased area, which is decisive for the diagnosis of the disease, usually occupies only a relatively minor portion of the entire pathology section, and screening the area of interest is a tedious and time-consuming task. In this paper, deep learning techniques to investigate the pathological images of eyelid tumors. Inspired by the knowledge distillation process, we propose the Multiscale-Attention-Crop-ResNet (MAC-ResNet) network model to achieve the automatic classification of three malignant tumors and the automatic localization of whole slide imaging (WSI) lesion regions using U-Net. The final accuracy rates of the three classification problems of eyelid tumors on MAC-ResNet were 96.8%, 94.6%, and 90.8%, respectively

Additions and corrections to Association of DNA Methylation and Mitochondrial DNA Copy Number with Human Semen Quality

Whether there is a relationship between quality, DNA methylation, and mitochondrial DNA (mtDNA) copy number in human-derived sperm specimens is unknown. A cohort (n = 118) of male partners of couples who were undergoing fertility assessment because of an idiopathic inability to conceive were recruited. Sperm motility parameters were determined by computer-aided sperm analysis (CASA), while sperm quality was assessed using World Health Organization criteria, mtDNA copy number was measured by real-time PCR, and DNA methylation patterns were analyzed employing high-melting resolution PCR and bisulfite sequencing PCR. The mtDNA copy number negatively correlated with semen parameters, including sperm motility, concentration, morphology, progression, and motion characteristics (r for ?0.19 to ?0.54; P < 0.05 for all). As a surrogate marker for global DNA methylation, LINE-1 negatively correlated with sperm motility (r = ?0.25; P = 0.009). Meanwhile, after adjustment for age, length of abstinence, smoking, and alcohol intake, there was a suggested association for increased LINE-1 methylation and mtDNA copy number tertiles versus sperm motility (odd ratios were 1.0, 2.6, and 4.7, and 1.0, 2.5, and 4.9, respectively). Altered mtDNA copy number and DNA methylation may serve as genetic and epigenetic markers to assess human sperm quality together with CASA parameters

Association of DNA Methylation and Mitochondrial DNA Copy Number with Human Semen Quality

Whether there is a relationship between quality, DNA methylation, and mitochondrial DNA (mtDNA) copy number in human-derived sperm specimens is unknown. A cohort (n = 118) of male partners of couples who were undergoing fertility assessment because of an idiopathic inability to conceive were recruited. Sperm motility parameters were determined by computer-aided sperm analysis (CASA), while sperm quality was assessed using World Health Organization criteria, mtDNA copy number was measured by real-time PCR, and DNA methylation patterns were analyzed employing high-melting resolution PCR and bisulfite sequencing PCR. The mtDNA copy number negatively correlated with semen parameters, including sperm motility, concentration, morphology, progression, and motion characteristics (r for ?0.19 to ?0.54; P < 0.05 for all). As a surrogate marker for global DNA methylation, LINE-1 negatively correlated with sperm motility (r = ?0.25; P = 0.009). Meanwhile, after adjustment for age, length of abstinence, smoking, and alcohol intake, there was a suggested association for increased LINE-1 methylation and mtDNA copy number tertiles versus sperm motility (odd ratios were 1.0, 2.6, and 4.7, and 1.0, 2.5, and 4.9, respectively). Altered mtDNA copy number and DNA methylation may serve as genetic and epigenetic markers to assess human sperm quality together with CASA parameters

Multifunctional superhydrophobic composite materials with remarkable mechanochemical robustness, stain repellency, oil-water separation and sound-absorption properties

Superhydrophobic materials have attracted immense commercial and academic interests in recent years. However, the poor mechanical durability has restricted their practical applications where high durability is required. Here, a facile one-pot synthesis method was reported to fabricate multifunctional superhydrophobic composite materials with remarkable mechanochemical robustness, stain repellency, oil-water separation and sound-absorption. Their mechanical and chemical durability could be greatly improved by chemically adhering epoxy resin microspheres (ERMs) on 3-D porous skeleton structures of latex sponge. The materials could retain superhydrophobicity after going through sandpaper abrasion, ultrasonication, multiple knife scratch, tape peeling and finger wiping, and exposure to UV irradiation and high temperature. The materials are able to maintain the repellency against strong acid and alkali droplets. The combined excellent mechanical properties, liquid repellency & selectivity, and other functional properties displayed by this type of material have made it a strong candidate for a range of industrial applications.Accepted versio