Association Between Myocardial Oxygenation and Fibrosis in Duchenne Muscular Dystrophy: Analysis by Rest Oxygenation-Sensitive Magnetic Resonance Imaging.

BACKGROUND: Myocardial hypoxia has been demonstrated in many cardiomyopathies and is related to development of myocardial fibrosis. However, myocardial hypoxia and its association with myocardial fibrosis are understudied in Duchenne muscular dystrophy (DMD)-associated cardiomyopathy. PURPOSE: To evaluate myocardial hypoxia by oxygenation-sensitive (OS) cardiac magnetic resonance imaging, and further explore its association with fibrosis. STUDY TYPE: Prospective. SUBJECTS: Ninety-one DMD boys (8.78 ± 2.32) and 30 healthy boys (9.07 ± 2.30). FIELD STRENGTH/SEQUENCE: 3 T, Balanced steady-state free procession, Modified Look-Locker inversion recovery sequence and Single-shot phase-sensitive inversion recovery sequence. ASSESSMENT: Cardiac MRI data, including left ventricular functional, segmental native T1, and oxygenation signal-intensity (SI) according to AHA 17-segment model, were acquired. Patients were divided into LGE+ and LGE- groups. In patients with LGE, all segments were further classified as positive or negative segments by segmentally presence/absence of LGE. STATISTICAL TESTS: Variables were compared using Student's t, Wilcoxon, Kruskal-Wallis test and one-way analysis of variance. Bivariate Pearson or Spearman correlation were calculated to determine association between oxygenation SI and native T1. Variables with P < 0.10 in the univariable analysis were included in multivariable model. Receiver operating characteristic analysis was used to assess the performance of OS in diagnosing myocardial hypoxia. RESULTS: The myocardial oxygenation SI of DMD was significantly decreased in all segments compared with normal controls, and more obvious in the LGE+ segments (0.46 ± 0.03 vs. 0.52 ± 0.03). For patients with and without LGE, myocardial oxygenation SI were significantly negatively correlated with native T1 in all segments (r = -0.23 to -0.42). The inferolateral oxygenation SI was a significant independent associator of LGE presence (adjusted OR = 0.900). DATA CONCLUSION: Myocardial hypoxia evaluated by the OS-Cardiac-MRI indeed occurs in DMD and associate with myocardial fibrosis, which might be used as a biomarker in assessing myocardial damage in DMD. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

Left ventricular concentric hypertrophy with cardiac magnetic resonance imaging improves risk stratification in patients with Duchenne muscular dystrophy: a prospective cohort study.

BACKGROUND: The development of left ventricular (LV) remodeling has been associated with an increased cardiovascular risk and cardiogenic death, and different patterns of remodeling result in varying levels of prognosis. OBJECTIVE: To investigate the association between different patterns of LV remodeling and clinical outcomes in the preclinical stage of patients with Duchenne muscular dystrophy (DMD). MATERIALS AND METHODS: A total of 148 patients with DMD and 43 sex- and age-matched healthy participants were enrolled. We used the four-quadrant analysis method to investigate LV remodeling based on cardiac magnetic resonance (MR) imaging. Kaplan-Meier curves were generated to illustrate the event-free survival probability stratified by the LV remodeling pattern. Cox regression models were constructed and compared to evaluate the incremental predictive value of the LV remodeling pattern. RESULTS: During the median follow-up period of 2.2 years, all-cause death, cardiomyopathy, and ventricular arrhythmia occurred in 5, 35, and 7 patients, respectively. LV concentric hypertrophy (hazard ratio 2.91, 95% confidence interval 1.47-5.75, P=0.002) was an independent predictor of composite endpoint events. Compared to the model without LV concentric hypertrophy, the model with LV concentric hypertrophy had significant incremental predictive value (chi-square value 33.5 vs. 25.2, P=0.004). CONCLUSION: Age and late gadolinium enhancement positivity were positively correlated with clinical outcomes according to the prediction models. LV concentric hypertrophy was also an independent predictor for risk stratification and provided incremental value for predicting clinical outcomes in the preclinical stage of patients with DMD.

Ubiquitination on Lysine 247 of Newcastle Disease Virus Matrix Protein Enhances Viral Replication and Virulence by Driving Nuclear-Cytoplasmic Trafficking.

The Newcastle disease virus (NDV) matrix (M) protein is the pivotal element for viral assembly, budding, and proliferation. It traffics through the cellular nucleus but performs its primary function in the cytoplasm. To investigate the biological importance of M protein nuclear-cytoplasmic trafficking and the mechanism involved, the regulatory motif nuclear export signal (NES) and nuclear localization signal (NLS) were analyzed. Here, two types of combined NLSs and NESs were identified within the NDV-M protein. The Herts/33-type M protein was found to mediate efficient nuclear export and stable virus-like particle (VLP) release, while the LaSota-type M protein was retained mostly in the nuclei and showed retarded VLP production. Two critical residues, namely, 247 and 263, within the motif were identified and associated with nuclear export efficiency. We identified, for the first time, residue 247 as an important monoubiquitination site, of which its modification regulates the nuclear-cytoplasmic trafficking of NDV-M. Subsequently, mutant LaSota strains were rescued via reverse genetics, which contained either single or double amino acid substitutions that were similar to the M of Herts/33. The rescued LaSota (rLaSota) strains rLaSota-R247K, -S263R, and -double mutation (DM) showed about 2-fold higher hemagglutination (HA) titers and 10-fold higher 50% egg infective dose (EID50) titers than wild-type (wt) rLaSota. Furthermore, the mean death time (MDT) and intracerebral pathogenicity index (ICPI) values of those recombinant viruses were slightly higher than those of wt rLaSota probably due to their higher proliferation rates. Our findings contribute to a better understanding of the molecular mechanism of the replication and pathogenicity of NDV and even those of all other paramyxoviruses. This information is beneficial for the development of vaccines and therapies for paramyxoviruses. IMPORTANCE Newcastle disease virus (NDV) is a pathogen that is lethal to birds and causes heavy losses in the poultry industry worldwide. The World Organization for Animal Health (OIE) ranked Newcastle disease (ND) as the third most significant poultry disease and the eighth most important wildlife disease in the World Livestock Disease Atlas in 2011. The matrix (M) protein of NDV is very important for viral assembly and maturation. It is interesting that M proteins enter the cellular nucleus before performing their primary function in the cytoplasm. We found that NDV-M has a combined nuclear import and export signal. The ubiquitin modification of a lysine residue within this signal is critical for quick, efficient nuclear export and subsequent viral production. Our findings shed new light on viral replication and open up new possibilities for therapeutics against NDV and other paramyxoviruses; furthermore, we demonstrate a novel approach for improving paramyxovirus vaccines.

NDV-induced autophagy enhances inflammation through NLRP3/Caspase-1 inflammasomes and the p38/MAPK pathway.

Newcastle disease (ND), caused by the Newcastle disease virus (NDV), is a highly virulent infectious disease of poultry. Virulent NDV can cause severe autophagy and inflammation in host cells. While studies have shown a mutual regulatory relationship between autophagy and inflammation, this relationship in NDV infection remains unclear. This study confirmed that NDV infection could trigger autophagy in DF-1 cells to promote cytopathic and viral replication. NDV-induced autophagy was positively correlated with the mRNA levels of inflammatory cytokines such as IL-1ß, IL-8, IL-18, CCL-5, and TNF-α, suggesting that NDV-induced autophagy promotes the expression of inflammatory cytokines. Further investigation demonstrated that NLRP3 protein expression, Caspase-1 activity, and p38 phosphorylation level positively correlated with autophagy, suggesting that NDV-induced autophagy could promote the expression of inflammatory cytokines through NLRP3/Caspase-1 inflammasomes and p38/MAPK pathway. In addition, NDV infection also triggered mitochondrial damage and mitophagy in DF-1 cells, but did not result in a large leakage of reactive oxygen species (ROS) and mitochondrial DNA (mtDNA), indicating that mitochondrial damage and mitophagy do not contribute to the inflammation response during NDV infection.

Clinical utilisation of multimodal quantitative magnetic resonance imaging in investigating muscular damage in Duchenne muscular dystrophy: a study on the association between gluteal muscle groups and motor function.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a neuromuscular disease characterised by progressive muscular weakness and atrophy. Currently, studies on DMD muscle function mostly focus on individual muscles; little is known regarding the effect of gluteal muscle group damage on motor function. OBJECTIVE: To explore potential imaging biomarkers of hip and pelvic muscle groups for measuring muscular fat replacement and inflammatory oedema in DMD with multimodal quantitative magnetic resonance imaging (MRI). MATERIALS AND METHODS: One hundred fifty-nine DMD boys and 32 healthy male controls were prospectively included. All subjects underwent MRI examination of the hip and pelvic muscles with T1 mapping, T2 mapping and Dixon sequences. Quantitatively measured parameters included longitudinal relaxation time (T1), transverse relaxation time (T2) and fat fraction. Investigations were all based on hip and pelvic muscle groups covering flexors, extensors, adductors and abductors. The North Star Ambulatory Assessment and stair climbing tests were used to measure motor function in DMD. RESULTS: T1 of the extensors (r = 0.720, P < 0.01), flexors (r = 0.558, P < 0.01) and abductors (r = 0.697, P < 0.001) were positively correlated with the North Star Ambulatory Assessment score. In contrast, T2 of the adductors (r = -0.711, P < 0.01) and fat fraction of the extensors (r = -0.753, P < 0.01) were negatively correlated with the North Star Ambulatory Assessment score. Among them, T1 of the abductors (b = 0.013, t = 2.052, P = 0.042), T2 of the adductors (b = -0.234, t = -2.554, P = 0.012) and fat fraction of the extensors (b = -0.637, t = - 4.096, P < 0.001) significantly affected the North Star Ambulatory Assessment score. Moreover, T1 of the abductors was highly predictive for identifying motor dysfunction in DMD, with an area under the curve of 0.925. CONCLUSION: Magnetic resonance biomarkers of hip and pelvic muscle groups (particularly T1 values of the abductor muscles) have the potential to be used as independent risk factors for motor dysfunction in DMD.

Longitudinal changes in magnetic resonance imaging biomarkers of the gluteal muscle groups and functional ability in Duchenne muscular dystrophy: a 12-month cohort study.

BACKGROUND: Quantitative magnetic resonance imaging (MRI) is considered an objective biomarker of Duchenne muscular dystrophy (DMD), but the longitudinal progression of MRI biomarkers in gluteal muscle groups and their predictive value for future motor function have not been described. OBJECTIVE: To explore MRI biomarkers of the gluteal muscle groups as predictors of motor function decline in DMD by characterizing the progression over 12 months. MATERIALS AND METHODS: A total of 112 participants with DMD were enrolled and underwent MRI examination of the gluteal muscles to determine fat fraction and longitudinal relaxation time (T1). Investigations were based on gluteal muscle groups including flexors, extensors, adductors, and abductors. The North Star Ambulatory Assessment and timed functional tests were performed. All participants returned for follow-up at an average of 12 months and were divided into two subgroups (functional stability/decline groups) based on changes in timed functional tests. Univariable and multivariable logistic regression methods were used to explore the risk factors associated with future motor function decline. RESULTS: For the functional decline group, all T1 values decreased, while fat fraction values increased significantly over 12 months (P<0.05). For the functional stability group, only the fat fraction of the flexors and abductors increased significantly over 12 months (P<0.05). The baseline T1 value was positively correlated with North Star Ambulatory Assessment and negatively correlated with timed functional tests at the 12-month follow-up (P<0.001), while the baseline fat fraction value was negatively correlated with North Star Ambulatory Assessment and positively correlated with timed functional tests at the 12-month follow-up (P<0.001). Multivariate regression showed that increased fat fraction of the abductors was associated with future motor function decline (model 1: odds ratio [OR]=1.104, 95% confidence interval [CI]: 1.026~1.187, P=0.008; model 2: OR=1.085, 95% CI: 1.013~1.161, P=0.019), with an area under the curve of 0.874. CONCLUSION: Fat fraction of the abductors is a powerful predictor of future motor functional decline in DMD patients at 12 months, underscoring the importance of focusing early on this parameter in patients with DMD.

Genetic characterization and evolutionary analysis of canine parvovirus in Tangshan, China.

Canine parvovirus (CPV) is a major enteric virus of carnivores worldwide that poses a considerable threat to dogs. In this study, we investigated the genetic variation of CPV in Tangshan, China, and the relationships between CPV disease and the vaccination status, age, and gender of dogs. Seventy-seven fecal samples from dogs in Tangshan that tested positive for CPV were obtained for analysis. Twenty-two full-length VP2 gene sequences were successfully amplified. The 22 strains included 17 CPV-2c variants, four new CPV-2a variants, and one new CPV-2b variant. Phylogenetic analysis showed that all of the CPV-2c strains clustered together and were closely related to CPV-2c strains from Asia but distantly related to CPV-2c strains from Europe. Further amino acid sequence analysis showed that, relative to CPV-2c strains from Europe, most of the CPV-2c stains in this study had A5G, F267Y, Y324I, and Q370R mutations. These findings provide a more comprehensive understanding of the variants of CPV circulating in China.

ß-Catenin-Specific Inhibitor, iCRT14, Promotes BoHV-1 Infection-Induced DNA Damage in Human A549 Lung Adenocarcinoma Cells by Enhancing Viral Protein Expression.

Oncolytic bovine herpesvirus type 1 (BoHV-1) infection induces DNA damage in human lung adenocarcinoma cell line A549. However, the underlying mechanisms are not fully understood. We found that BoHV-1 infection decreased the steady-state protein levels of p53-binding protein 1 (53BP1), which plays a central role in dictating DNA damage repair and maintaining genomic stability. Furthermore, BoHV-1 impaired the formation of 53BP1 foci, suggesting that BoHV-1 inhibits 53BP1-mediated DNA damage repair. Interestingly, BoHV-1 infection redistributed intracellular ß-catenin, and iCRT14 (5-[[2,5-Dimethyl-1-(3-pyridinyl)-1H-pyrrol-3-yl]methylene]-3-phenyl-2,4-thiazolidinedione), a ß-catenin-specific inhibitor, enhanced certain viral protein expression, such as the envelope glycoproteins gC and gD, and enhanced virus infection-induced DNA damage. Therefore, for the first time, we provide evidence showing that BoHV-1 infection disrupts 53BP1-mediated DNA damage repair and suggest ß-catenin as a potential host factor restricting both virus replication and DNA damage in A549 cells.

Isolation and phylogenetic analysis of strains of feline calicivirus in Beijing, China.

Feline calicivirus (FCV) is a contagious cat pathogen that causes oral ulceration and/or upper respiratory disease. In this study, we collected 61 samples from a pet hospital in Beijing and used PCR or RT-PCR to detect FCV and feline herpesvirus 1 (FHV-1). Approximately 44.3% (27/61) of the samples were FCV positive, and 23.0% (14/61) were coinfected with FCV and FHV-1. FCV was isolated from 15 samples. One isolate was from a cat with virulent systemic disease (VSD) signs, and 14 isolates were from cats with stomatitis or upper respiratory diseases. The range of genome sequence identity among these isolates was 76.1-100.0%. Four of the isolates were considered to be of the same strain, with sequence identity ranging from 99.5 to 99.7%, and two isolates, BJ-280 and BJ-288, had completely identical sequences. The genomic sequence identity ranged from 76.0 to 88.5% between the 15 isolates and several reference strains, including the F4 and F9 vaccine strains. These results demonstrate that many FCV strains are co-circulating in Beijing. Due to the diversity of FCV in Beijing, it is necessary to monitor the current prevalence of the virus. This study provides more information for the development of effective measures to control FCV.

Comparison of Multiple Quantitative Evaluation Indices of Theoretical Knowledge and Clinical Practice Skills and Training of Medical Interns in Cardiovascular Imaging Using Blended Teaching and the Case Resource Network Platform (CRNP).

BACKGROUND This study aimed to compare multiple quantitative evaluation indices of levels of theoretical knowledge and clinical practice skills in training medical interns in cardiovascular imaging based on the use of the blended teaching (BT) online artificial intelligence (AI) case resource network platform (CRNP), including time and frequency indices and effectiveness of the CRNP. MATERIAL AND METHODS The study included 110 medical interns who were divided into the routine teaching (RT) group (n=55) and the blended teaching (BT) group (n=55). The two were assessed using the mini-clinical evaluation exercise (mini-CEX) that assessed clinical skills, attitudes, and behaviors and using an objective written questionnaire. The following four indices were compared between the RT and BT groups: the X-ray score (XS), the computed tomography angiography (CTA) score (CS), the cardiac magnetic resonance imaging (CMRI) score (MS), and the average score (AS). Seven assessment indicators included: the imaging description (ID), the qualitative diagnosis (QD), the differential diagnosis (DD), examination preparation (EP), interview skill (IS), position display (PD), and human care (HC). Indicators of CRNP use included: number of times (TN), average duration (AD), single maximum duration (SMD), and total duration (TD). RESULTS AS significantly correlated with AD (rAD=0.761) and TD (rTD=0.754), and showed moderate correlation with TN (rTN=0.595), but weak correlation with SMD (rSMD=0.404). CONCLUSIONS Levels of theoretical knowledge and clinical practice skills during medical intern training in cardiovascular imaging based on BT using the CRNP teaching technology improved theoretical knowledge and practical skills.

Artificial Intelligence and Myocardial Contrast Enhancement Pattern.

PURPOSE OF REVIEW: Machine learning (ML) and deep learning (DL) are two important categories of AI algorithms. Nowadays, AI technology has been gradually applied to cardiac magnetic resonance imaging (CMRI), covering the fields of myocardial contrast enhancement (MCE) pattern and automatic ventricular segmentation. This paper mainly discusses the relationship between machine learning and deep learning based on AI and pattern of MCE in CMRI. RECENT FINDINGS: It found that some histogram and GLCM parameters in ML algorithm had significant statistical differences in diagnosis of cardiomyopathy and differentiation of fibrosis and normal myocardial tissue. In the DL algorithm, there was no significant difference between CNN and observers in measuring myocardial fibrosis. The rapid development of texture parameter analysis methods would promote the medical imaging based on AI into a new era. Histogram and GLCM parameters are the research hotspot of unsupervised learning of MCE images. CNN has a great advantage in automatically identifying and quantifying myocardial fibrosis reflected by LGE images.

Detection and genetic characterization of porcine pegivirus from pigs in China.

Porcine pegiviruses (PPgV) have been first discovered in serum samples from domestic pigs in Germany in 2016 and then in the USA in 2018. To date, there is no documentation with respect to the presence of PPgVs in domestic pigs in China. Herein, we attempted to determine the presence and prevalence of PPgV in China and its genetic characterization. In this study, 469 sera were tested and 34 (7.25%) were positive for PPgV. An ascending trend of the positive rate for PPgV was observed from suckling piglets (1.61%) to nursing piglets (1.85%), finishing pigs (6.56%), and sows (11.34%). The complete genome sequence of a representative strain of PPgV, PPgV_GDCH2017, and the complete E2 gene of 17 PPgV isolates discovered in this study was determined. Sequence analysis indicated that PPgV_GDCH2017 was highly related to other PPgVs with nucleotide and amino acid identities ranging from 87.3 to 97.4% and 94.6-99.3%, respectively, in the complete coding region. Phylogenetic analyses demonstrated that the PPgV_GDCH2017 discovered in this study was closely related to the PPgVs from the USA and clustered in the same genus with pegiviruses from other hosts. The topology of the phylogenetic tree based on the complete E2 gene was consistent with that based on the complete genome of PPgV. Further studies on pathogenicity and pathogenesis of PPgVs are needed.

Prevalence and phylogenetic analysis of porcine diarrhea associated viruses in southern China from 2012 to 2018.

BACKGROUND: In China, large-scale outbreaks of severe diarrhea caused by viruses have occurred in pigs since late 2010. To investigate the prevalence and genetic evolution of diarrhea-associated viruses responsible for the outbreaks, a total of 2987 field diarrheal samples collected from 168 pig farms in five provinces in Southern China during 2012-2018 were tested. RESULTS: Porcine epidemic diarrhea virus (PEDV) was most frequently detected virus with prevalence rates between 50.21 and 62.10% in samples, and 96.43% (162/168) in premises, respectively. Porcine deltacoronavirus (PDCoV) was the second prevalent virus with prevalence rates ranging from 19.62 to 29.19% in samples, and 70.24% (118/168) in premises, respectively. Both transmissible gastroenteritis virus (TGEV) and porcine rotavirus (PoRV) were detected at low prevalence rates of < 3% in samples and 10.12% in premises. In this study, we identified a newly emerged swine acute diarrhea syndrome coronavirus (SADS-CoV) in diarrheal samples of piglets from Fujian province in Southern China, and the prevalence rate of SADS-CoV was 10.29% (7/68). Co-infections of these diarrhea-associated viruses were common. The most frequent co-infection was PEDV with PDCoV, with an average detection rate of 12.72% (380/2987, ranging from 8.26-17.33%). Phylogenetic analysis revealed that PEDVs circulating in Southern China during the last 7 years were clustered with the variant strains of PEDV in genotype IIa. The most frequent mutations were present in the collagenase equivalent (COE) and epitope regions of the spike gene of the PEDVs currently circulating in the field. Genetic relationships of PDCoVs were closely related with Chinese strains, other than those present in the USA, South Korea, Thailand and Lao's public. CONCLUSIONS: The findings of this study indicated that variant PEDV, PDCoV, and SADS-CoV were leading etiologic agents of porcine diarrhea, and either mono-infections or co-infections of pathogenic enteric CoVs were common in pigs in Southern China during 2012-2018. Thus, significant attention should be paid in order to effectively prevent and control porcine viral diarrhea.

Evaluation of Early Gadolinium Enhancement (EGE) and Cardiac Functional Parameters in Cine-Magnetic Resonance Imaging (MRI) on Artificial Intelligence in Patients with Acute Myocarditis: A Case-Controlled Observational Study.

BACKGROUND The diagnosis of myocarditis is challenging, and the treatment is generally delayed due to misdiagnosis or missed diagnosis. Endomyocardial biopsy (EMB) is not a specific or sensitive method. A case-controlled observational study was conducted to evaluate early gadolinium enhancement (EGE) and left ventricular functional parameters on Artificial Intelligence in cine-MRI in patients with acute myocarditis. MATERIAL AND METHODS We selected 21 patients with pathologically proven acute myocarditis. We analyzed the EGE findings (total/serial number and location of positive-segments using the 17-segment model according to the American Heart Association) and clinical characteristics (symptoms, arrhythmias in ECG, coronary angiography, and EMB). All patients were divided into positive EGE and negative EGE groups to analyze left ventricular functional parameters (LVEF, FS, LVEDD, LVEDV, LVESV, LVMM, LVSV, CO, and CI) on Artificial Intelligence. RESULTS We enrolled 21 patients (11 males) with a mean age of 32.6±9.8 years (range, 16 to 51 years). Abnormalities on EGE were found in 2/3 of patients, involving 41 segments among multiple locations on the myocardium. The differences in LVEF (40.2±10.2% vs. 51.3±3.6%), LVESV (69.0±16.1ml vs. 52.5±10.6ml) and LVSV (42.6±11.4 vs. 52.8±2.8 ml) on Artificial Intelligence was statistically significant between the positive EGE and negative EGE groups (p<0.05). CONCLUSIONS Our results suggest a significant role of EGE on the basis of Lake Louise criteria in evaluating patients with clinical suspicion of acute myocarditis. Parameters, including LVEF, LVESV, and LVSV, on Artificial Intelligence, may be useful independent predictors for capillary leakage and microcirculatory disturbance in myocarditis.

Unified equivalent circuit model for carbon nanotube-based nanocomposites.

Carbon nanotubes form a complex network in nanocomposites. In the network, the configuration of the nanotubes is various. A carbon nanotube may be curled or straight, and it may be parallel or crossed to another. As a result, carbon nanotube-based composites exhibit integrated characteristics of inductor, capacitor and resistor. In this work, it is hypothesised that carbon nanotube-based composites all adhere to a RLC interior circuit. To verify the hypothesis, three different composites, viz multi-walled carbon nanotube/polyvinylidene fluoride (MWCNT/PVDF), multi-walled carbon nanotube/epoxy (MWCNT/EP), multi-walled carbon nanotube/polydimethylsiloxane (MWCNT/PDMS) were fabricated and tested. The resistances and the dielectric loss tangent (tanδ) of the materials were measured in direct and alternating currents. The measurement shows that the value of tanδ is highly affected by the volume fraction of MWCNT in the composites. The experimental results prove that the proposed RLC equivalent circuit model can fully describe the electrical properties of the MWCNT network in nanocomposites. The RLC model provides a new route to detect the inductance and capacitance of carbon nanotubes. Moreover, the model also indicates that the carbon nanotube-based composite films may be used to develop wireless strain sensors.

Elevation of intracellular calcium and oxidative stress is involved in perfluorononanoic acid-induced neurotoxicity.

Perfluorononanoic acid (PFNA) is one of the major perfluorinated compounds found in both biological and abiotic samples and has recently been demonstrated to cause neurobehavioral defects in mammals. In this study, pheochromocytoma-12 (PC12) cells were exposed to various doses of PFNA to explore the cytotoxicity of PFNA to neurons and the possible mechanisms underlying these effects. The results showed that exposure to PFNA dose-dependently decreased the viability of PC12 cells and increased the release of lactate dehydrogenase into cell culture media. Exposure to PFNA increased the malondialdehyde content and decreased the total antioxidant capacity and glutathione peroxidase activity in PC12 cell culture supernatants. Exposure to PFNA increased the intracellular calcium level and upregulated the Ca2+/calmodulin-dependent protein kinase II (CaMKII) expression in PC12 cells. PFNA also decreased Bcl-2 expression and increased Bax expression in PC12 cells. These results suggested that exposure to PFNA elevated the intracellular calcium level and activated the CaMKII signaling pathway, which may aggravate oxidative stress in PC12 cells and lead to cell damage or cell apoptosis.

Phylogenetic, antigenic and biological characterization of pigeon paramyxovirus type 1 circulating in China.

BACKGROUND: For many years, ND has been one of the most important infectious pigeon diseases in China. In recent years, a high mortality has been observed in ND-infected pigeons in China. Mortality is from 40% to 80% or 100% in some cases. METHODS: The full-length genomes of four pigeon paramyxovirus type 1 (PPMV-1) strains, which were isolated from infected pigeons in China in 2012 and 2013, were sequenced and analyzed to determine the phylogenetic characteristics of PPMV-1 circulating in pigeons of China in recent years. Furthermore, cross hemagglutination inhibition and cross virus neutralization assays, as well as animal experiments were conducted to determine the antigenicity and pathogenicity of those viruses. Proteolytic cleavage sites (residues 112-117) of the F proteins were identified as the typical virulence motif, 112RRQKR↓F117 for all four PPMV-1 strains investigated. RESULTS: Phylogenetic analysis based on sequences of complete genomes and F gene revealed that the four PPMV-1 isolates and most of recent isolates in China were highly homologous to European isolates from 1998 to 2011. All those isolates were clustered in one clade of genotype VI NDV, termed as subgroup 4bii f. The R value was calculated based on cross hemagglutination inhibition and cross virus neutralization results, and confirmed antigenic difference of the PPMV-1 strains isolated in 2013 from the LaSota vaccine strain. Several mutations were identified in the surface glycoproteins F and HN, which probably gave rise to those antigenic differences. CONCLUSION: Our result suggested that the PPMV-1 strain prevailing in China in the last decade diverged from a common ancestor and was presumably transmitted from Europe. PPMV-1 isolates displayed obvious antigenic differences from vaccine strain LaSota. Even though PPMV-1 did not cause high mortality in experimental pigeons, the infected pigeons were exhibiting viral shedding for 3 weeks after infection, suggesting PPMV-1 is a potential threat to NDV control worldwide.

NEMO-Binding Domain Peptide Attenuates Lipopolysaccharide-Induced Acute Lung Injury by Inhibiting the NF-κB Signaling Pathway.

The aim of the present study is to investigate the protective effects and relevant mechanisms exerted by NEMO-binding domain peptide (NBD) against lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice. The ALI model was induced by intratracheally administered atomized LPS (5 mg/kg) to BABL/c mice. Half an hour before LPS administration, we treated the mice with increasing concentrations of intratracheally administered NBD or saline aerosol. Two hours after LPS administration, each group of mice was sacrificed. We observed that NBD pretreatment significantly attenuated LPS-induced lung histopathological injury in a dose-dependent manner. Western blotting established that NBD pretreatment obviously attenuated LPS-induced IκB-α and NF-κBp65 activation and NOX1, NOX2, and NOX4 overexpression. Furthermore, NBD pretreatment increased SOD and T-AOC activity and decreased MDA levels in lung tissue. In addition, NBD also inhibited TNF-α and IL-1ß secretion in BALF after LPS challenge. In conclusion, NBD protects against LPS-induced ALI in mice.

Damage evaluation based on a wave energy flow map using multiple PZT sensors.

A new wave energy flow (WEF) map concept was proposed in this work. Based on it, an improved technique incorporating the laser scanning method and Betti's reciprocal theorem was developed to evaluate the shape and size of damage as well as to realize visualization of wave propagation. In this technique, a simple signal processing algorithm was proposed to construct the WEF map when waves propagate through an inspection region, and multiple lead zirconate titanate (PZT) sensors were employed to improve inspection reliability. Various damages in aluminum and carbon fiber reinforced plastic laminated plates were experimentally and numerically evaluated to validate this technique. The results show that it can effectively evaluate the shape and size of damage from wave field variations around the damage in the WEF map.

Cardiac magnetic resonance-derived mitral annular plane systolic excursion: a robust indicator for risk stratification after myocardial infarction.

To explore the predictive value of mitral annular plane systolic excursion (MAPSE) derived by cardiac magnetic resonance (CMR) for major adverse cardiovascular events (MACE) in postmyocardial infarction (MI) patients. Patients with MI who underwent 3.0 T CMR (Chinese Clinical Trial Registry, ChiCTR2200055158) were recruited retrospectively. CMR parameters included MAPSE and LVEF. Patients were followed up for MACE for more than 6 months and were separated into a No-MACE group and a MACE group. A total of 165 post-MI patients were included, and 103 patients were finally analyzed (61 patients belonged to the No-MACE group, and 42 patients belonged to the MACE group). The LVEF and MAPSE of the patients belonging to the No-MACE group were considerably higher than those of the patients belonging to the MACE group. Both LVEF and MAPSE were effective indicators of the occurrence of MACE after MI. The risk of MACE decreased as LVEF and MAPSE increased. For the risk prediction of MACE after MI, compared with model I (chi-square value 4.0 vs. 31.4, P < 0.001) and model II (chi-square value 22.7 vs. 31.4, P = 0.003), model III had a significant incremental predictive value. Moreover, the cutoff value of MAPSE was 9.70 mm. CMR-derived MAPSE is an effective predictor of MACE occurrence in patients with MI, and MAPSE provided a significant incremental predictive value. Moreover, MAPSE could complement LVEF for superior risk stratification of MI patients.