Publications by authors named "Wei Wen"

738 Publications

High-Temperature and Large-Polarization Ferroelectric with Second Harmonic Generation Response in a Novel Crown Ether Clathrate.

Chemistry 2021 Jul 28. Epub 2021 Jul 28.

JiangXi University of Science and Technology, Faculty of Materials Metallurgy and Chemistry, CHINA.

Molecular ferroelectrics of high-temperature reversible phase-transition are very rare and have attracted increasing attention in recent years. In this paper, we have successfully synthesized a novel high-temperature host-guest inclusion ferroelectric: [ (C 6 H 5 NF 3 ) (18-crown-6)][BF 4 ] (1) , which shows a pair of reversible peaks at 348 K (heating) and 331 K (cooling) with a heat hysteresis about 17 K by differential scanning calorimetry (DSC) measurements, indicating that 1 undergoes a reversible structural phase transition. The variable-temperature PXRD and temperature-dependent dielectric measurements further prove the phase-transition behavior of 1 . The second harmonic response demonstrates that 1 belongs to a non-centrosymmetric space group at room temperature and is a good nonlinear optical material. Meanwhile, 1 shows a wide optical band gap of about 4.43 eV in semiconducting property and is chiefly contributed by C, H and O atoms of the crystals. In particular, the ferroelectric measurements of 1 exhibit a typical polarization-electric hysteresis loop with large spontaneous polarization ( P s ) of about 4.06 μC/ cm 2 . This finding offers an alternative pathway for designing new ferroelectric-dielectric and nonlinear optical materials and related physical properties in organic- inorganic and other hybrid crystals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/chem.202101707DOI Listing
July 2021

Impact of supervised beego, a traditional Chinese water-only fasting, on thrombosis and haemostasis.

BMJ Nutr Prev Health 2021 5;4(1):4-17. Epub 2021 Jan 5.

Hematology Center of Cyrus Tang Medical Institute, Soochow University, Suzhou, China.

Beego is a traditional Chinese complete water-only fasting practice initially developed for spiritual purposes, later extending to physical fitness purposes. Beego notably includes a psychological induction component that includes meditation and abdominal breathing, light body exercise and ends with a specific gradual refeeding program before returning to a normal diet. Beego has regained its popularity in recent decades in China as a strategy for helping people in subhealthy conditions or with metabolic syndrome, but we are unaware of any studies examining the biological effects of this practice. To address this, we here performed a longitudinal study of beego comprising fasting (7 and 14 day cohorts) and a 7-day programmed refeeding phase. In addition to detecting improvements in cardiovascular physiology and selective reduction of blood pressure in hypertensive subjects, we observed that beego decreased blood triacylglycerol (TG) selectively in TG-high subjects and increased cholesterol in all subjects during fasting; however, the cholesterol levels were normalised after completion of the refeeding program. Strikingly, beego reduced platelet formation, activation, aggregation and degranulation, resulting in an alleviated thrombosis risk, yet maintained haemostasis by sustaining levels of coagulation factors and other haemostatic proteins. Mechanistically, we speculate that downregulation of G6B and MYL9 may influence the observed beego-mediated reduction in platelets. Fundamentally, our study supports that supervised beego reduces thrombosis risk without compromising haemostasis capacity. Moreover, our results support that beego under medical supervision can be implemented as non-invasive intervention for reducing thrombosis risk, and suggest several lines of intriguing inquiry for future studies about this fasting practice (http://www.chictr.org.cn/index.aspx, number, ChiCTR1900027451).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjnph-2020-000183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258074PMC
January 2021

Novel genetic variants associated with brain functional networks in 18,445 adults from the UK Biobank.

Sci Rep 2021 Jul 16;11(1):14633. Epub 2021 Jul 16.

Centre for Healthy Brain Aging, CHeBA, School of Psychiatry, University of New South Wales Medicine, Kensington, Sydney, NSW, 2052, Australia.

Here, we investigated the genetics of weighted functional brain network graph theory measures from 18,445 participants of the UK Biobank (44-80 years). The eighteen measures studied showed low heritability (mean h = 0.12) and were highly genetically correlated. One genome-wide significant locus was associated with strength of somatomotor and limbic networks. These intergenic variants were located near the PAX8 gene on chromosome 2. Gene-based analyses identified five significantly associated genes for five of the network measures, which have been implicated in sleep duration, neuronal differentiation/development, cancer, and susceptibility to neurodegenerative diseases. Further analysis found that somatomotor network strength was phenotypically associated with sleep duration and insomnia. Single nucleotide polymorphism (SNP) and gene level associations with functional network measures were identified, which may help uncover novel biological pathways relevant to human brain functional network integrity and related disorders that affect it.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-94182-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285376PMC
July 2021

Residue-specific binding mechanisms of PD-L1 to its monoclonal antibodies by computational alanine scanning.

Phys Chem Chem Phys 2021 Jul;23(29):15591-15600

Shanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, Shanghai Key Laboratory of Green Chemistry & Chemical Process, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China and NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai 200062, China. and Department of Chemistry, New York University, NY, NY 10003, USA and Collaborative Innovation Center of Extreme Optics, Shanxi University, Taiyuan, Shanxi 030006, China.

Programmed cell death 1 receptor (PD-1) on the surface of T cells and its ligand 1 (PD-L1) are immune checkpoint proteins. Treating cancer patients with inhibitors blocking this checkpoint has significantly prolonged the survival rate of patients. In this study, we examined several monoclonal antibodies (mAbs) of PD-L1 and studied their detailed binding mechanism to PD-L1. An efficient computational alanine scanning method was used to perform quantitative analysis of hotspot residues that are important for PD-1/PD-L1 binding. A total of five PD-L1/mAb complexes were investigated and hotspots on both PD-L1 and mAbs were predicted. Our result shows that PD-L1M115 and PD-L1Y123 are two relatively important hotspots in all the five PD-L1/mAb binding complexes. It is also found that the important residues of mAbs binding to PD-L1M115 and PD-L1Y123 are similar to each other. The computational alanine scanning result is compared to the experimental measurements that are available for two of the mAbs (KN035 and atezolizumab). The calculated alanine scanning result is in good agreement with the experimental data with a correlation coefficient of 0.87 for PD-L1/KN035 and 0.6 for PD-L1/atezolizumab. Our computation found more hotspots on PD-L1 in the PD-L1/KN035 complex than those in the PD-L1/atezolizumab system, indicating stronger binding affinity in the former than the latter, which is in good agreement with the experimental finding. The present work provides important insights for the design of new mAbs targeting PD-L1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1cp01281aDOI Listing
July 2021

Predictive value of creatine kinase MB for contrast-induced acute kidney injury among myocardial infarction patients.

BMC Cardiovasc Disord 2021 Jul 13;21(1):337. Epub 2021 Jul 13.

Department of Cardiology, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.

Background: Predictive value of creatine kinase MB (CK-MB) for contrast-induced acute kidney injury (CI-AKI) among myocardial infarction (MI) patients has rarely been reported. We aim to evaluate the predictive value of CK-MB for CI-AKI among MI patients.

Methods: Totally, 1131 MI patients were included from the REduction of rIsk for Contrast-Induced Nephropathy (REICIN) study. The peak CK-MB before coronary angiography (CAG) was chosen. The study population was divided into two groups by log-transformed CK-MB cut-off point. The association between CK-MB and CI-AKI was tested by multivariable logistic regression. CK-MB was integrated with Age, creatinine and ejection fraction (ACEF) score and Mehran risk score (MRS) to evaluate the additive value of CK-MB. The integrated models were validated internally by the bootstrap method and externally by the PREdictive Value of COntrast voluMe to creatinine Clearance Ratio (PRECOMIN) study data set.

Results: Overall, 62(5.48%) patients developed CI-AKI, patients with CK-MB point > 4.7 displayed a higher incidence of CI-AKI than those without (11.9% vs. 4.0%, p < 0.001). CK-MB point > 4.7 was independently associated with CI-AKI (adjusted OR: 3.40, 95% CI: 1.93-5.98, p < 0.001). The additions of CK-MB to ACEF score, Mehran score A and Mehran score B resulted in increases in C-statistics, which ranged from 0.680 to 0.733 (p = 0.046), 0.694 to 0.727 (p = 0.091), 0.704 to 0.734 (p = 0.102), respectively. Internal validation also showed increases in C-statistics, and external validation performed well in discrimination and calibration.

Conclusions: Preprocedural peak CK-MB was a predictor of CI-AKI among MI patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12872-021-02155-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8276394PMC
July 2021

Difference in distribution functions: A new diffusion weighted imaging metric for estimating white matter integrity.

Neuroimage 2021 Jul 9;240:118381. Epub 2021 Jul 9.

Centre for Healthy Brain Aging (CHeBA), School of Psychiatry, UNSW Sydney, New South Wales 2052, Australia; Neuropsychiatric Institute (NPI), Euroa Centre, Prince of Wales Hospital, Randwick, New South Wales 2031, Australia.

Diffusion weighted imaging (DWI) is a widely recognized neuroimaging technique to evaluate the microstructure of brain white matter. The objective of this study is to establish an improved automated DWI marker for estimating white matter integrity and investigating ageing related cognitive decline. The concept of Wasserstein distance was introduced to help establish a new measure: difference in distribution functions (DDF), which captures the difference of reshaping one's mean diffusivity (MD) distribution to a reference MD distribution. This new DWI measure was developed using a population-based cohort (n=19,369) from the UK Biobank. Validation was conducted using the data drawn from two independent cohorts: the Sydney Memory and Ageing Study, a community-dwelling sample (n=402), and the Renji Cerebral Small Vessel Disease Cohort Study (RCCS), which consisted of cerebral small vessel disease (CSVD) patients (n=171) and cognitively normal controls (NC) (n=43). DDF was associated with age across all three samples and better explained the variance of changes than other established DWI measures, such as fractional anisotropy, mean diffusivity and peak width of skeletonized mean diffusivity (PSMD). Significant correlations between DDF and cognition were found in the UK Biobank cohort and the MAS cohort. Binary logistic analysis and receiver operator characteristic curve analysis of RCCS demonstrated that DDF had higher sensitivity in distinguishing CSVD patients from NC than the other DWI measures. To demonstrate the flexibility of DDF, we calculated regional DDF which also showed significant correlation with age and cognition. DDF can be used as a marker for monitoring the white matter microstructural changes and ageing related cognitive decline in the elderly.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroimage.2021.118381DOI Listing
July 2021

Deaminative -C-H alkylation by ruthenium(ii) catalysis.

Chem Sci 2021 Apr 9;12(23):8073-8078. Epub 2021 Apr 9.

Institut für Organische und Biomolekulare Chemie, Georg-August-Universität Göttingen Tammannstraße 2 37077 Goettingen Germany

Precise structural modifications of amino acids are of importance to tune biological properties or modify therapeutical capabilities relevant to drug discovery. Herein, we report a ruthenium-catalyzed -C-H deaminative alkylation with easily accessible amino acid-derived Katritzky pyridinium salts. Likewise, remote C-H benzylations were accomplished with high levels of chemoselectivity and remarkable functional group tolerance. The -C-H activation approach combined with our deaminative strategy represents a rare example of selectively converting C(sp)-N bonds into C(sp)-C(sp) bonds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1sc00986aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208126PMC
April 2021

Seneca Valley Virus 3C Protease Induces Pyroptosis by Directly Cleaving Porcine Gasdermin D.

J Immunol 2021 Jun 28. Epub 2021 Jun 28.

State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China; and Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Center for Sustainable Pig Production, Wuhan, China

Seneca Valley virus (SVV), a newly emerging virus belonging to the family, has caused vesicular disease in the swine industry. However, the molecular mechanism of viral pathogenesis remains poorly understood. This study revealed that SVV infection could induce pyroptosis in SK6 cells in a caspase-dependent and -independent manner. SVV may inhibit caspase-1 activation at late infection because of 3C cleavage of NLRP3, which counteracted pyroptosis activation. Further study showed that 3C targeted porcine gasdermin D (pGSDMD) for cleavage through its protease activity. 3C cleaved porcine GSDMD (pGSDMD) at two sites, glutamine 193 (Q193) and glutamine 277 (Q277), and Q277 was close to the caspase-1-induced pGSDMD cleavage site. pGSDMD triggered cell death, which was similar to N-terminal fragment produced by caspase-1 cleavage of pGSDMD, and other fragments exhibited no significant inhibitory effects on cellular activity. Ectopic expression of pGSDMD converted 3C-induced apoptosis to pyroptosis in 293T cells. Interestingly, 3C did not cleave mouse GSDMD or human GSDMD. And, both pGSDMD and pGSDMD exhibited bactericidal activities in vivo. Nevertheless, pGSDMD cannot kill bacteria in vitro. Taken together, our results reveal a novel pyroptosis activation manner produced by viral protease cleavage of pGSDMD, which may provide an important insight into the pathogenesis of SVV and cancer therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4049/jimmunol.2001030DOI Listing
June 2021

Retinal Microvascular Changes in Uveal Melanoma Following Conbercept Injection after Plaque Radiotherapy as Detected By Optical Coherence Tomographic Angiography.

Retina 2021 Jun 18. Epub 2021 Jun 18.

Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Ophthalmology and Visual Science Key Lab, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Capital Medical University, Beijing, China.

Purpose: To investigate macular microvascular characteristics imaged by optical coherence tomography angiography (OCTA) in uveal melanoma (UM) patients following Conbercept injections after plaque radiotherapy.

Methods: Prospective comparative analysis comprising 15 UM patients with Conbercept injections and 30 patients without Conbercept injections after plaque radiotherapy by OCTA. The Conbercept group received intravitreal Conbercept injections at the time of plaque removal, 1 month, 3 months, 6 months , 9 months and 12 months after plaque removal (total, 6 injections). The control group had no intravitreal Conbercept injection.

Results: After initiation of Conbercept injections, superficial retinal vascular density (SVD) in whole image and parafovea region were significantly higher at 6 months, while there was no significant difference at 9 months and 12 months. in ANOVA analysis, SVD in whole image remained stable after Conbercept injections (P=0.069), while the SVD decreased significantly after plaque radiotherapy in control group (P=0.011). In multivariable linear regression, a higher SVD in whole image region at 6 months was significantly associated with intravitreal Conbercept injection (P=0.018), wider tumor base (P=0.026), and thinner tumor thickness (P=0.04).

Conclusions: OCTA can provide a quantitative evaluation of early retinal microvascular changes following radiotherapy. Intravitreal Conbercept treatment could partly relieve the retinal vascular damage in response to radiation therapy at early stage in patients with uveal melanoma, however may not be able to provide long-term positive functional outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/IAE.0000000000003236DOI Listing
June 2021

Simple MoS-Nanofiber Paper-Based Fluorescence Immunosensor for Point-of-Care Detection of Programmed Cell Death Protein 1.

Anal Chem 2021 06 14;93(25):8791-8798. Epub 2021 Jun 14.

Ministry of Education Key Laboratory for the Synthesis and Application of Organic Functional Molecules, Collaborative Innovation Center for Advanced Organic Chemical Materials Co-constructed by the Province and Ministry, College of Chemistry and Chemical Engineering, Hubei University, Wuhan 430062, P. R. China.

Programmed cell death protein 1 (PD-1) is one of the coinhibitory checkpoints upon T cell activation, the abnormal expression of which severely threatens host immune modulatation for chronic infection. Thus, fast and sensitive monitoring of PD-1 is of vital importance for early diagnosis and cancer treatment. The current detection methods largely based on enzyme-linked immunosorbent assay (ELISA) require time-consuming incubation and complicated washing steps. Herein, we designed a simple and portable nanofiber paper (NFP)-based fluorescence "off-on" immunosensor for PD-1 rapid determination. Molybdenum disulfide (MoS) nanosheets modified NFP (MoS-NFP) was employed for adsorbing and immobilizing CdSe/ZnS quantum dots-antibody (QDs-Ab) complex to construct a ready-to-use fluorescent immunosensor. The fluorescent signal of QDs-Ab was initially quenched by MoS under the Förster resonance energy transfer (FRET) effect. When the PD-1 target was specifically captured onto NFP by immunization, the QDs-Ab-PD-1 complex was promptly desorbed from the MoS-NFP surface, resulting in FRET impediment and fluorescence recovery. As an alternative quenching agent, graphene oxide (GO) served as a contrast to investigate NFP-based sensing performance. Owing to superior quenching and desorption efficiency, the MoS-NFP-based fluorescence immunosensor exhibited nearly 2-fold lower detection limit (85.5 pg/mL) than GO-NFP-based sensor (151 pg/mL) for PD-1 monitoring. Excellent selectivity and satisfactory recovery in PD-1 mouse cell culture supernatant samples were confirmed as well. In addition, the comparable detectability of the MoS-NFP-based immunosensor was accurately evaluated by a standard PD-1 mouse ELISA kit. This study displayed a simple, rapid, low-cost, and portable point-of-care PD-1 assay, indicating its broad application prospect toward clinical diagnoses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.analchem.1c00269DOI Listing
June 2021

Woman with seizures.

Eur J Intern Med 2021 07 11;89:106-107. Epub 2021 Jun 11.

Department of Emergency, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing 100730, P.R. China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejim.2021.05.014DOI Listing
July 2021

Brain Age Estimation From MRI Using Cascade Networks with Ranking Loss.

IEEE Trans Med Imaging 2021 Jun 4;PP. Epub 2021 Jun 4.

Chronological age of healthy people is able to be predicted accurately using deep neural networks from neuroimaging data, and the predicted brain age could serve as a biomarker for detecting aging-related diseases. In this paper, a novel 3D convolutional network, called two-stage-age-network (TSAN), is proposed to estimate brain age from T1-weighted MRI data. Compared with existing methods, TSAN has the following improvements. First, TSAN uses a two-stage cascade network architecture, where the first-stage network estimates a rough brain age, then the second-stage network estimates the brain age more accurately from the discretized brain age by the first-stage network. Second, to our knowledge, TSAN is the first work to apply novel ranking losses in brain age estimation, together with the traditional mean square error (MSE) loss. Third, densely connected paths are used to combine feature maps with different scales. The experiments with 6586 MRIs showed that TSAN could provide accurate brain age estimation, yielding mean absolute error (MAE) of 2.428 and Pearson's correlation coefficient (PCC) of 0.985, between the estimated and chronological ages. Furthermore, using the brain age gap between brain age and chronological age as a biomarker, Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI) can be distinguished from healthy control (HC) subjects by support vector machine (SVM). Classification AUC in AD/HC and MCI/HC was 0.904 and 0.823, respectively. It showed that brain age gap is an effective biomarker associated with risk of dementia, and has potential for early-stage dementia risk screening. The codes and trained models have been released on GitHub.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TMI.2021.3085948DOI Listing
June 2021

Cholesterol-25-Hydroxylase Suppresses Seneca Valley Virus Infection via Producing 25-Hydroxycholesterol to Block Adsorption Procedure.

Virol Sin 2021 Jun 1. Epub 2021 Jun 1.

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, 430070, China.

Cholesterol-25-hydroxylase (CH25H) is a membrane protein associated with endoplasmic reticulum, and it is an interferon-stimulated factor regulated by interferon. CH25H catalyzes cholesterol to produce 25-hydroxycholesterol (25HC) by adding a second hydroxyl to the 25th carbon atom of cholesterol. Recent studies have shown that both CH25H and 25HC could inhibit the replication of many viruses. In this study, we found that ectopic expression of CH25H in HEK-293T and BHK-21 cell lines could inhibit the replication of Seneca Valley virus (SVV) and that there was no species difference. On the other hand, the knockdown of CH25H could enhance the replication of SVV in HEK-293T and BHK-21 cells, indicating the importance of CH25H. To some extent, the CH25H mutant without hydroxylase activity also lost its ability to inhibit SVV amplification. Further studies demonstrated that 25HC was involved in the entire life cycle of SVV, especially in repressing its adsorption process. This study reveals that CH25H exerts the advantage of innate immunity mainly by producing 25HC to block virion adsorption.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12250-021-00377-9DOI Listing
June 2021

The trans-ancestral genomic architecture of glycemic traits.

Nat Genet 2021 06 31;53(6):840-860. Epub 2021 May 31.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41588-021-00852-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610958PMC
June 2021

Artificial intelligence for the detection of age-related macular degeneration in color fundus photographs: A systematic review and meta-analysis.

EClinicalMedicine 2021 May 8;35:100875. Epub 2021 May 8.

Beijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Ophthalmology & Visual Sciences Key Lab, Medical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Hospital, Capital Medical University, 1 Dong Jiao Min Lane, Beijing 100730, China.

Background: Age-related macular degeneration (AMD) is one of the leading causes of vision loss in the elderly population. The application of artificial intelligence (AI) provides convenience for the diagnosis of AMD. This systematic review and meta-analysis aimed to quantify the performance of AI in detecting AMD in fundus photographs.

Methods: We searched PubMed, Embase, Web of Science and the Cochrane Library before December 31st, 2020 for studies reporting the application of AI in detecting AMD in color fundus photographs. Then, we pooled the data for analysis. PROSPERO registration number: CRD42020197532.

Findings: 19 studies were finally selected for systematic review and 13 of them were included in the quantitative synthesis. All studies adopted human graders as reference standard. The pooled area under the receiver operating characteristic curve (AUROC) was 0.983 (95% confidence interval (CI):0.979-0.987). The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were 0.88 (95% CI:0.88-0.88), 0.90 (95% CI:0.90-0.91), and 275.27 (95% CI:158.43-478.27), respectively. Threshold analysis was performed and a potential threshold effect was detected among the studies (Spearman correlation coefficient: -0.600,  = 0.030), which was the main cause for the heterogeneity. For studies applying convolutional neural networks in the Age-Related Eye Disease Study database, the pooled AUROC, sensitivity, specificity, and DOR were 0.983 (95% CI:0.978-0.988), 0.88 (95% CI:0.88-0.88), 0.91 (95% CI:0.91-0.91), and 273.14 (95% CI:130.79-570.43), respectively.

Interpretation: Our data indicated that AI was able to detect AMD in color fundus photographs. The application of AI-based automatic tools is beneficial for the diagnosis of AMD.

Funding: Capital Health Research and Development of Special (2020-1-2052).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eclinm.2021.100875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129891PMC
May 2021

LncRNA LOC146880 promotes esophageal squamous cell carcinoma progression via miR-328-5p/FSCN1/MAPK axis.

Aging (Albany NY) 2021 05 18;13(10):14198-14218. Epub 2021 May 18.

Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.

We investigated the role of long non-coding RNA (lncRNA) LOC146880 in esophageal squamous cell carcinoma (ESCC). LOC146880 was significantly upregulated in ESCC tissues ( = 21) and cell lines compared to the corresponding controls. Higher LOC146880 expression correlated with poorer overall survival (OS) of ESCC patients. Moreover, CREB-binding protein (CBP) and H3K27 acetylation levels were significantly higher in the LOC146880 promoter in ESCC cell lines than in the controls. LOC146880 silencing inhibited proliferation, invasion, migration, and epithelial-mesenchymal transition of ESCC cells. LOC146880 silencing also induced G1-phase cell cycle arrest and apoptosis in ESCC cells. Bioinformatics analysis, dual luciferase reporter assays, and RNA immunoprecipitation assays showed that LOC146880 regulates FSCN1 expression in ESCC cells by sponging miR-328-5p. Moreover, FSCN1 expression correlated with activation of the MAPK signaling pathway in ESCC cells and tissues. xenograft tumor volume and liver metastasis were significantly reduced in nude mice injected with LOC146880-silenced ESCC cells as compared to those injected with control shRNA-transfected ESCC cells. These findings show that the LOC146880/miR-328-5p/FSCN1/MAPK axis regulates ESCC progression and . LOC146880 is thus a promising prognostic biomarker and potential therapeutic target in ESCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.203037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202886PMC
May 2021

The association between white matter hyperintensity volume and gait performance under single and dual task conditions in older people with dementia: A cross-sectional study.

Arch Gerontol Geriatr 2021 Jul-Aug;95:104427. Epub 2021 May 4.

Falls, Balance and Injury Research Centre, Neuroscience Research Australia, UNSW, Sydney, NSW, Australia; Prince of Wales Clinical School, Medicine, UNSW, Sydney, NSW, Australia. Electronic address:

Background: Understanding the relationship between white matter hyperintensities (WMHs) and gait may assist in understanding the central control of gait and determining treatment modalities. These relationships are yet to be realized in older people with dementia.

Objective: To examine the association between WMH volume and gait under single-task and dual task (DT) conditions in people with dementia.

Methods: Twenty-eight community-dwelling older people with dementia (median age=83 years; [IQR=77-86]; 36% female) had timed gait speed assessed at usual pace. Gait (speed, stride length, cadence) was assessed using the GAITRite® mat under three conditions (n = 18/28): a) single-task, b) functional DT: carrying a glass of water and c) cognitive DT: counting backwards from 30. WMH volumes were quantified using a fully automated segmentation toolbox.

Results: Total, temporal and parietal WMH volumes were negatively correlated with timed and functional DT gait speed, and with stride length under single-task, functional DT and cognitive DT conditions. Frontal WMH volumes were negatively correlated with timed gait speed and stride length under single-task and functional DT conditions. Participants with higher total WMH burden had significantly slower timed and functional DT gait speed and reduced stride length under single-task, functional DT and cognitive DT conditions compared to participants with lower WMH burden.

Conclusions: WMH volume was associated with slower gait speed and reduced stride length, but not cadence, under single-task and DT conditions in people with dementia. Further research is needed to confirm these findings and determine whether vascular risk management can improve gait in older people with dementia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.archger.2021.104427DOI Listing
June 2021

Iranian Brain Imaging Database: A Neuropsychiatric Database of Healthy Brain.

Basic Clin Neurosci 2021 Jan-Feb;12(1):115-132. Epub 2021 Jan 1.

Department of Medical Physics and Biomedical Engineering, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Introduction: The Iranian Brain Imaging Database (IBID) was initiated in 2017, with 5 major goals: provide researchers easy access to a neuroimaging database, provide normative quantitative measures of the brain for clinical research purposes, study the aging profile of the brain, examine the association of brain structure and function, and join the ENIGMA consortium. Many prestigious databases with similar goals are available. However, they were not done on an Iranian population, and the battery of their tests (e.g. cognitive tests) is selected based on their specific questions and needs.

Methods: The IBID will include 300 participants (50% female) in the age range of 20 to 70 years old, with an equal number of participants (#60) in each age decade. It comprises a battery of cognitive, lifestyle, medical, and mental health tests, in addition to several Magnetic Resonance Imaging (MRI) protocols. Each participant completes the assessments on two referral days.

Results: The study currently has a cross-sectional design, but longitudinal assessments are considered for the future phases of the study. Here, details of the methodology and the initial results of assessing the first 152 participants of the study are provided.

Conclusion: IBID is established to enable research into human brain function, to aid clinicians in disease diagnosis research, and also to unite the Iranian researchers with interests in the brain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.32598/bcn.12.1.1774.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114860PMC
January 2021

Myelinated Retinal Nerve Fiber Progression in a 10-Year Follow-Up. The Beijing Eye Study 2001/2011.

Am J Ophthalmol 2021 May 2;230:68-74. Epub 2021 May 2.

From the Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Sciences Key Laboratory, Beijing, China (Z.P., C.C.W., X.P., L.X., H.Y., Y.X.W., J.B.J.); Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University Heidelberg, Mannheim, Germany (J.B.J.); Institute of Clinical and Scientific Ophthalmology and Acupuncture Jonas & Panda, Heidelberg, Germany (J.B.J.); and Institute of Molecular and Clinical Ophthalmology Basel, Switzerland (J.B.J.).

Purpose: To assess the prevalence of myelinated retinal nerve fibers (MRNFs), the rate of their change in a 10-year follow-up, and associations with ocular and systematic parameters in a population-based cohort.

Design: Longitudinal population-based cohort study.

Methods: The Beijing Eye study including 4,439 participants aged 40+ years in 2001 and was repeated in 2011, with 2,695 individuals (66.4% of the surviving) being re-examined in 2011. All participants underwent detailed physical and ocular examinations. MRNFs were diagnosed on fundus photographs and their change was assessed using a flicker method of fundus photographs.

Results: Out of 35 eyes (29 participants) with detected MRNFs at baseline (mean prevalence: 0.4% ± 0.26% per eye or 0.7% ± 0.41% per individual), 23 eyes from 20 individuals (17 [85%] participants with unilateral MRNFs) were re-examined in 2011. MRNF enlargement was detected in all 19 eyes (100%) with clear fundus photographs. The mean MRNF area increased from 4,233 ± 3,670 µm (range: 178-11,643 µm) at baseline to 5,243 ± 4,092 µm (range: 196-13,297 µm) at follow-up (P < .001), by 1,010 ± 1,026 µm (18-3,967 µm) or by 47% ± 74% (9%-315%). A larger MRNF increase was associated with an MRNF location distant from the optic disc as compared to a juxtapapillary location (P = .001, standardized regression coefficient beta: -0.53), smaller MRNF area at baseline (P = .006, beta: -0.34), and higher serum concentration of low-density lipoproteins (LDL) (P < .001, beta: 0.57).

Conclusions: MRNFs (mean prevalence per eye: 0.4%) showed, in association with higher LDL serum concentration and peripheral located MRNF, an enlargement during a 10-year follow-up, while in the same period no new MRNFs were detected in the total study cohort.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajo.2021.04.018DOI Listing
May 2021

Free-Standing N-Doped Porous Carbon Fiber Membrane Derived From Zn-MOF-74: Synthesis and Application as Anode for Sodium-Ion Battery With an Excellent Performance.

Front Chem 2021 16;9:647545. Epub 2021 Apr 16.

Collaborative Innovation Center for Advanced Organic Chemical Materials Co-constructed by the Province and Ministry, College of Chemistry and Chemical Engineering, Hubei University, Wuhan, China.

It is important to develop new energy storage and conversion technology to mitigate the energy crisis for the sustainable development of human society. In this study, free-standing porous nitrogen-doped carbon fiber (PN-CF) membranes were obtained from the pyrolysis of Zn-MOF-74/polyacrylonitrile (PAN) composite fibers, which were fabricated by an electrospinning technology. The resulting free-standing fibers can be cut into membrane disks and directly used as an anode electrode without the addition of any binder or additive. The PN-CFs showed great reversible capacities of 210 mAh g at a current density of 0.05 A g and excellent cyclic stability of 170.5 mAh g at a current density of 0.2 A g after 600 cycles in sodium ion batteries (SIBs). The improved electrochemical performance of PN-CFs can be attributed to the rich porous structure derived by the incorporation of Zn-MOF-74 and nitrogen doping to promote sodium ion transportation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fchem.2021.647545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086192PMC
April 2021

Orbitrap-MS-based untargeted metabolomics study on the therapeutic effect of colchicine on myocardial infarction.

Biomed Chromatogr 2021 Apr 27:e5148. Epub 2021 Apr 27.

Department of Cardiovascular Medicine, East Hospital, Tongji University School of Medicine, Shanghai, China.

Myocardial infarction (MI) is one of the most common causes of death worldwide. A metabolomic approach based on an ultra-high performance liquid chromatography-Orbitrap analytical method was established to analyze the metabolites and to investigate the therapeutic mechanism of colchicine. Forty-six biomarkers were significantly changed between the sham group and the MI group. Thirty-five metabolites were increased and 11 were decreased in MI rats, and colchicine reversed all of them. Pathway analysis showed that the TCA cycle, alanine, aspartate and glutamate metabolism, glycerophospholipid metabolism, aminoacyl-tRNA biosynthesis, glyoxylate and dicarboxylate metabolism and arginine biosynthesis were altered in the MI group. Ingenuity pathway function and network analysis showed that colchicine improved MI through regulation of cardiac β-adrenergic signaling and cardiac hypertrophy signaling. The present study provided a useful approach for exploring the mechanism of MI and evaluating the efficacy of colchicine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/bmc.5148DOI Listing
April 2021

Deep Learning-Based Estimation of Axial Length and Subfoveal Choroidal Thickness From Color Fundus Photographs.

Front Cell Dev Biol 2021 9;9:653692. Epub 2021 Apr 9.

Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Ophthalmology and Visual Sciences Key Laboratory, Medical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information Technology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China.

This study aimed to develop an automated computer-based algorithm to estimate axial length and subfoveal choroidal thickness (SFCT) based on color fundus photographs. In the population-based Beijing Eye Study 2011, we took fundus photographs and measured SFCT by optical coherence tomography (OCT) and axial length by optical low-coherence reflectometry. Using 6394 color fundus images taken from 3468 participants, we trained and evaluated a deep-learning-based algorithm for estimation of axial length and SFCT. The algorithm had a mean absolute error (MAE) for estimating axial length and SFCT of 0.56 mm [95% confidence interval (CI): 0.53,0.61] and 49.20 μm (95% CI: 45.83,52.54), respectively. Estimated values and measured data showed coefficients of determination of = 0.59 (95% CI: 0.50,0.65) for axial length and = 0.62 (95% CI: 0.57,0.67) for SFCT. Bland-Altman plots revealed a mean difference in axial length and SFCT of -0.16 mm (95% CI: -1.60,1.27 mm) and of -4.40 μm (95% CI, -131.8,122.9 μm), respectively. For the estimation of axial length, heat map analysis showed that signals predominantly from overall of the macular region, the foveal region, and the extrafoveal region were used in the eyes with an axial length of < 22 mm, 22-26 mm, and > 26 mm, respectively. For the estimation of SFCT, the convolutional neural network (CNN) used mostly the central part of the macular region, the fovea or perifovea, independently of the SFCT. Our study shows that deep-learning-based algorithms may be helpful in estimating axial length and SFCT based on conventional color fundus images. They may be a further step in the semiautomatic assessment of the eye.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.653692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063031PMC
April 2021

Malnutrition affects cholesterol paradox in coronary artery disease: a 41,229 Chinese cohort study.

Lipids Health Dis 2021 Apr 19;20(1):36. Epub 2021 Apr 19.

Department of Cardiology, Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.

Background: Several studies have found that a low baseline low -density lipoprotein cholesterol (LDL-C) concentration was associated with poor prognosis in patients with acute coronary syndrome (ACS), which is called the "cholesterol paradox". Low LDL-C concentration may reflect underlying malnutrition, which was strongly associated with increased mortality. The aim of this study was to investigate the cholesterol paradox in patients with CAD and the effects of malnutrition.

Method: A total of 41,229 CAD patients admitted to Guangdong Provincial People's Hospital in China were included in this study from January 2007 to December 2018 and divided into two groups (LDL-C < 1.8 mmol/L, n = 4863; LDL-C ≥ 1.8 mmol/L, n = 36,366). The Kaplan-Meier method and Cox regression analyses were used to assess the association between LDL-C levels and long-term all-cause mortality and the effect of malnutrition.

Result: In this real-world cohort (mean age 62.9 years; 74.9% male), there were 5257 cases of all-cause death during a median follow-up of 5.20 years [interquartile range (IQR): 3.05-7.78 years]. Kaplan-Meier analysis showed that low LDL-C levels were associated with a worse prognosis. After adjusting for baseline confounders (e.g., age, sex and comorbidities, etc.), multivariate Cox regression analysis revealed that a low LDL-C level (< 1.8 mmol/L) was not significantly associated with all-cause mortality (adjusted HR, 1.04; 95% CI, 0.96-1.24). After adjustment for nutritional status, the risk of all-cause mortality in patients with low LDL-C levels decreased (adjusted HR, 0.90; 95% CI, 0.83-0.98). In the final multivariate Cox model, a low LDL-C level was related to better prognosis (adjusted HR, 0.91; 95% CI, 0.84-0.99).

Conclusion: This study demonstrated that the cholesterol paradox existed in CAD patients but disappeared after accounting for the effects of malnutrition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12944-021-01460-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056540PMC
April 2021

Characteristics and potential sources of wintertime air pollution in Linfen, China.

Environ Monit Assess 2021 Apr 8;193(5):252. Epub 2021 Apr 8.

Beijing Polytechnic, Beijing, 100176, China.

Linfen in China's Shanxi Province suffers severe air pollution in winter. Understanding the characteristics of air pollution and providing scientific support to mitigate such pollution are urgent matters. This study investigated the variations of PM, PM, NO, SO, O, and CO in Linfen between December 1, 2019 and February 29, 2020. The mean concentrations of PM, PM, NO, SO, MDA8 (the maximum daily 8-h average) O, and CO were 106.2, 139.4, 47.2, 41.0, 57.0 μg m, and 1.8 mg m, respectively. Large amounts of pollutants emitted by coal burning, industry, vehicles, and residents contributed to air pollution. Unfavorable meteorological conditions, such as lower temperature, weaker wind, higher relative humidity, and reduced planetary boundary layer height, made the situation worse. Fireworks and firecrackers set off to celebrate traditional Chinese festivals caused the concentration of PM pollutants to spike, with the maximum daily mean concentration of PM reached 314 μg m and the peak hourly value reached 378.0 μg m. Suspensions of commercial and social activities due to COVID-19 reduced anthropogenic emissions, mainly from industry and transportation, which decreased the level of air pollutants other than O. Analyses involving backward trajectory cluster, the potential source contribution function, and concentration weighted trajectory demonstrated that PM pollution mainly came from local emissions in Shanxi Province and regional transport from Inner Mongolia, Shaanxi, Hebei, Henan, and Gansu provinces. Shanxi and its surrounding provinces should adopt measures such as tightening environmental management standards, promoting the use of renewable energy, and adjusting the transportation structure to reduce regional emissions. This study will help policy-makers draft plans and policies to reduce air pollution in Linfen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10661-021-09036-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8031341PMC
April 2021

Branching TiOnanowire arrays for enhanced ethanol sensing.

Nanotechnology 2021 Apr 27;32(29). Epub 2021 Apr 27.

State Key Laboratory of Silicon Materials and School of Materials Science and Engineering, Zhejiang University, Hangzhou 310027, People's Republic of China.

Nanostructure modulation is effective to achieve high performance TiO-based gas sensors. We herein report a wet-chemistry route to precipitate directly branched TiOnanowire arrays on alumina tubes for gas sensing applications. The optimized branched TiOnanowire array exhibits a response of 9.2 towards 100 ppm ethanol; whilst those of the pristine TiOnanowire array and the branched TiOnanowire powders randomly distributed are 5.1 and 3.1, respectively. The enhanced response is mainly contributed to the unique porous architecture and quasi-aligned nanostructure, which provide more active sites and also favor gas migration. Phase junctions between the backbone and the branch of the branched TiOnanowire arrays help the resistance modulation as a result of potential barriers. The facile precipitation of quasi-aligned arrays of branched TiOnanowires, which aregrown on ceramic tubes, thus provides a new economical synthetic route to TiO-based sensors with excellent properties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1088/1361-6528/abf5a0DOI Listing
April 2021

Combination of nitrous oxide and the modified inflation-deflation method for identifying the intersegmental plane in segmentectomy: A randomized controlled trial.

Thorac Cancer 2021 05 4;12(9):1398-1406. Epub 2021 Apr 4.

Department of Thoracic Surgery, Jiangsu Province Hospital, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: During thoracoscopic segmentectomy, accurately and rapidly identifying the intersegmental plane (ISP) is of great importance. This study aimed to investigate the effect and safety of a nitrous oxide (N O)/oxygen (O ) inspired mixture on the appearance time of the ISP (T ) via the modified inflation-deflation method.

Methods: A total of 65 participants who underwent segmentectomy were randomized into three groups: 75% N O (n = 24), 50% N O (n = 23) or 0% N O (n = 18). The 75% N O group received a gas mixture of N O/O (Fio = 0.25), the 50% N O group received N O/O (Fio = 0.5), and the 0% N O group received 100% oxygen during lung expansion. The appearance time of satisfactory and ideal planes was recorded. Furthermore, arterial blood gas at breathing room air, one-lung ventilation (OLV) before lung expansion, 5 and 15 min after lung expansion were also recorded.

Results: T was significantly shorter in the 75% N O group (320.2 ± 65.9 s) compared with that of the 50% N O group (552.4 ± 88.9 s, p < 0.001) and the 0% N O group (968.3 ± 85.5 s, p < 0.001), while the 50% N O group was shorter than that of the 0% N O group (p < 0.001). Arterial oxygenation was significantly improved in the 0% N O group only after lung expansion, before which there were no differences in mean PaO values among groups.

Conclusions: The use of N O in the inspired gas mixture during lung expansion is an applicable strategy to rapidly identify the ISP via the modified inflation-deflation method without any adverse effect on OLV related arterial oxygenation during segmentectomy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1759-7714.13919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088974PMC
May 2021

Wideband composite planar spiral antenna for generation of tunable angular momentum wave.

Opt Express 2021 Feb;29(3):3754-3763

In this paper, a composite planar spiral antenna consisting of an eight-arm equiangular spiral antenna and eight Archimedean spiral antennas has been designed to radiate electromagnetic wave carrying tunable angular momenta in a wide band. A tunable eight-way Wilkinson power divider network is used to offer three kinds of feeding modes for the equiangular spiral antenna, and thus the composite antenna can radiate the electromagnetic waves with angular momenta of the modes l=1, 2, and 3, respectively. The Archimedean spiral is introduced to improve the gain of the composite antenna in the case of the angular momentum of l=3. By analyzing axis ratio (AR) of the proposed antenna, the generated angular momentum of l=1 is spin angular momentum (SAM), and the angular momenta of both l=2 and 3 include SAM and orbital angular momentum (OAM). Simulated and measured results are given to demonstrate good performance including tunable modes, good purity and wide band.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1364/OE.414163DOI Listing
February 2021

1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans.

Transl Psychiatry 2021 03 22;11(1):182. Epub 2021 Mar 22.

Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41398-021-01213-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985307PMC
March 2021

The relationship between Subfoveal Choroidal Thickness and Hypertensive Retinopathy.

Sci Rep 2021 Mar 9;11(1):5460. Epub 2021 Mar 9.

Beijing Tongren Eye Center, Beijing Key Laboratory of Intraocular Tumor Diagnosis and Treatment, Beijing Tongren Hospital, Capital Medical University, 1 Dong Jiao Min Xiang, Dong Cheng District, Beijing, 100730, China.

The Beijing Eye Study 2011 is a population-based cross-sectional study in Northern China, which enrolled 3468 participants whose age were more than 50 years. A detailed ophthalmic examination was performed including spectral-domain optical coherence tomography with enhanced depth imaging for measurement of SFCT and fundus photography. Blood pressure, fundus photographs and choroidal OCT-images were available for 3237 (93.3%) subjects, with 1953 (56.3 ± 0.8%) of the study population fulfilled the diagnosis of hypertension and 1089 subjects having hypertensive retinopathy. For the hypertensive cases, the SFCT in patients with hypertensive retinopathy (286.48 ± 105.23 µm) was significantly thicker than subjects without hypertensive retinopathy (187.04 ± 78.80 µm, P < 0.001). SFCT was significantly associated with the stage of hypertensive retinopathy (P < 0.001), but not significantly associated with diastolic blood pressure (P = 0.94), history (P = 0.95) and years (P = 0.91) of hypertension. In conclusion, hypertension as systemic disease was not significantly affect the subfoveal choroidal thickness, but as ocular disease, hypertensive retinopathy was significantly related to changes of choroidal thickness. Lesions of choroid during chronic hypertension may play an important role in development of hypertensive retinopathy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-84947-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943765PMC
March 2021

Selective autophagy receptor SQSTM1/ p62 inhibits Seneca Valley virus replication by targeting viral VP1 and VP3.

Autophagy 2021 Mar 14:1-13. Epub 2021 Mar 14.

State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei, China.

Macroautophagy/autophagy plays a critical role in antiviral immunity through targeting viruses and initiating host immune responses. The receptor protein, SQSTM1/p62 (sequestosome 1), plays a vital role in selective autophagy. It serves as a receptor targeting ubiquitinated proteins or pathogens to phagophores for degradation. In this study, we explored the reciprocal regulation between selective autophagy receptor SQSTM1 and Seneca Valley virus (SVV). SVV infection induced autophagy. Autophagy promoted SVV infection in pig cells but played opposite functions in human cells. Overexpression of SQSTM1 decreased viral protein production and reduced viral titers. Further study showed that SQSTM1 interacted with SVV VP1 and VP3 independent of its UBA domain. SQSTM1 targeted SVV VP1 and VP3 to phagophores for degradation to inhibit viral replication. To counteract this, SVV evolved strategies to circumvent the host autophagic machinery to promote viral replication. SVV 3C targeted the receptor SQSTM1 for cleavage at glutamic acid 355, glutamine 392, and glutamine 395 and abolished its capacity to mediate selective autophagy. At the same time, the 3C-mediated SQSTM1 cleavage products lost the ability to inhibit viral propagation. Collectively, our results provide evidence for selective autophagy in host against viruses and reveal potential viral strategies to evade autophagic machinery for successful pathogenesis. Abbreviations: Baf.A1: bafilomycin A; Co-IP: co-immunoprecipitation; hpi: h post-infection; LIR: LC3-interacting region; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MOI: multiplicity of infection; PB1: N-terminal Phox/Bem1p; Rap.: rapamycin; Seneca Valley virus: SVV; SQSTM1/p62: sequestosome 1; SQSTM1-N355: residues 1 to 355 of SQSTM1; SQSTM1-C355: residues 355 to 478 of SQSTM1; SQSTM1-N392: residues 1 to 392 of SQSTM1; SQSTM1-C392: residues 392 to 478 of SQSTM1; SQSTM1-N388: residues 1 to 388 of SQSTM1; SQSTM1-N397: residues 1 to 397 of SQSTM1; UBA: ubiquitin association; Ubi: ubiquitin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15548627.2021.1897223DOI Listing
March 2021
-->