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Human coronavirus NL63 (HCoV-NL63) is primarily associated with common cold in children, elderly and immunocompromised individuals. Outbreaks caused by HCoV-NL63 are rare. Here we report a cluster of HCoV-NL63 cases with severe lower respiratory tract infection that arose in Guangzhou, China, in 2018. Twenty-three hospitalized children were confirmed to be HCoV-NL63 positive, and most of whom were hospitalized with severe pneumonia or acute bronchitis. Whole genomes of HCoV-NL63 were obtained using next-generation sequencing. Phylogenetic and single amino acid polymorphism analyses showed that this outbreak was associated with two subgenotypes (C3 and B) of HCoV-NL63. Half of patients were identified to be related to a new subgenotype C3. One unique amino acid mutation at I507 L in spike protein receptor binding domain (RBD) was detected, which segregated this subgenotype C3 from other known subgenotypes. Pseudotyped virus bearing the I507 L mutation in RBD showed enhanced entry into host cells as compared to the prototype virus. This study proved that HCoV-NL63 was undergoing continuous mutation and has the potential to cause severe lower respiratory disease in humans.

Neuromyelitis optica spectrum disorder (NMOSD), a relapsing autoimmune disease of the central nervous system, mainly targets the optic nerve and spinal cord. To date, all attempts at the establishment of NMOSD animal models have been based on neuromyelitis optica immunoglobulin G antibody (NMO-IgG) and mimic the disease in part. To solve this problem, we developed a rodent model by opening the blood-brain barrier (BBB) with low frequency ultrasound, followed by injection of NMO-IgG from NMOSD patients and complement to mice suffering pre-existing neuroinflammation produced by experimental autoimmune encephalomyelitis (EAE). In this study, we showed that ultrasound with NMO-IgG and complement caused marked inflammation and demyelination of both spinal cords and optic nerves compared to blank control group, as well as glial fibrillary acidic protein (GFAP) and aquaporin-4 (AQP4) loss of spinal cords and optic nerves compared to EAE mice and EAE mice with only BBB opening. In addition, magnetic resonance imaging (MRI) revealed optic neuritis with spinal cord lesions. We further demonstrated eye segregation defects in the dorsal lateral geniculate nucleus (dLGN) of these NMOSD mice.

Haisheng Hu,1,* Chuanxu Cai,2,* Mingshan Xue,1 Jiaying Luo,1 Chenxi Liao,1 Huimin Huang,1,* Baoqing Sun1 1Department of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, National Clinical Research Center of Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510120, Guangdong, People’s Republic of China; 2Department of Laboratory Medicine, Shenzhen Institute of Respiratory Diseases, Shenzhen People’s Hospital, First Affiliated Hospital of Southern University of Science and Technology, Second Clinical Medical College of Jinan University, Shenzhen, Guangdong 518020, People’s Republic of China*These authors contributed equally to this workCorrespondence: Baoqing Sun First Affiliated Hospital of Guangzhou Medical University, 151 Yanjiangxi Road, Guangzhou 510120, Guangdong, People’s Republic of ChinaTel +86 20 8306 2865Fax +86 20 8306 2729Email sunbaoqing@vip.163.comObjective: The aim of this study was to analyse the level of serum matrix metalloproteinases (MMPs) in atopic and non-atopic COPD patients, providing guidance for clinical practice and theory for atopic COPD.Methods: Blood samples from 50 adult male patients with COPD, including 17 atopic and 33 non-atopic patients, were submitted for detection of MMP8, MMP9, surfactant associated protein D (SPD), noradrenaline (NE), leukotriene (LT) B4, recombinant proteoglycan (PRG4), Phadiatop sIgE, and tIgE levels. Patients’ Modified Medical Research Council Dyspnea Scale (mMRC), COPD Assessment Test (CAT), pulmonary function test results, FeNO, blood cell ratio and induced sputum were collected.Results: The level of serum tIgE in patients with atopic COPD [1876.00 kU/l (760.50, 5347.00)] was significantly higher than in patients with non-atopic COPD [377.00 kU/l (93.50, 581.50), P < 0.001]. The MMP8 levels in atopic COPD (1600 ± 1181 ng/mL) were significantly higher than in non-atopic COPD (973.3 ± 921.5 ng/mL, P = 0.0494), but there was no significant difference in MMP9, SPD, NE, LTB4, and PRG4 levels between the two groups. In atopic COPD patients, the rate of leukocyte (rs = 0.63, P < 0.001) and neutrophil (rs = 0.54, P < 0.05) were positively correlated with MMP8 levels, while lymphocyte rate was negatively correlated with MMP8 (rs = − 0.70, P < 0.001) and MMP9 levels (rs = − 0.54, P < 0.05). Optimal scale analysis showed that NE was most closely related to the basophil rate from induced sputum and FeNO levels (Cronbach’s alpha = 85.1%). Interestingly, all atopic COPD patients with mMRC ≥ 2, CAT ≥ 10, and CCQ ≥ 16 exhibited MMP8 levels > 1000 ng/mL.Conclusion: In general, tIgE and MMP8 levels were higher in atopic COPD patients than in non-atopic patients. NE levels were closely correlated with the basophil rate of induced sputum and FeNO levels, which may play an important role in the pathogenesis and development of atopic COPD.Keywords: chronic obstructive pulmonary disease, atopy, matrix metalloproteinases, immunoglobulin E, allergy

Previous studies have reported that short-term vagus nerve stimulation (VNS) improves cardiac function in rats with chronic heart failure (CHF). The molecular mechanisms are unclear. The potential effect of microRNA (miR)-205 in apoptosis of short-term VNS was examined. A total of 3 weeks after inducing CHF, the rats were divided into three groups: Sham stimulation in sham operated rats, sham stimulation in CHF rats (CHF-SS), and treated with VNS in CHF rats (CHF-VNS). The right vagus nerve of the neck was stimulated for 72 h in CHF rats with rectangular pulses of 40 msec duration at 1 Hz and 5 V. miR-205 was focused on, which exhibited differential expression in the miRNA microarray analysis of CHF rats, and the effects of VNS on apoptosis were examined. It was verified that the expression level of miR-205 in the CHF-SS group was increased, and the expression was reduced in the CHF-VNS group. Furthermore, mimics or inhibitor of miR-205 was transfected into H9c2 to investigate its function on apoptosis. Baculoviral IAP repeat-containing protein 2 (Birc2) was confirmed a target of miR-205 through a dual luciferase reporter assay and western blotting. It was demonstrated that downregulated miR-205 decreased apoptosis in H9c2 cells. The apoptosis-associated proteins were further detected in H9c2 cells and rat tissue. The mRNA and protein expression levels of caspase-3 and Bcl-2-associated X protein were decreased in the CHF-VNS group, the expression of Birc2 and B-cell lymphoma 2 were increased. The results were consistent with the in vitro study in the miR-205 inhibitor group. The present study demonstrated that short-term VNS decreased apoptosis by downregulating miR-205 in rats with CHF. Therefore, the results of the present study provide basic evidence for short-term VNS in the clinical treatment of CHF.

Background The participation of long noncoding RNAs (lncRNAs) in myocardial infarction has recently been noted. However, their underlying roles in the border zone of myocardial infarction remain unclear. This study uses microarrays to determine the profiles of lncRNAs and mRNAs in the border zone. Methods Bioinformatics methods were employed to uncover their underlying roles. Highly dysregulated lncRNAs was further validated via PCR. Results Four hundred seven lncRNAs and 752 mRNAs were upregulated, while 132 lncRNAs and 547 mRNAs were downregulated in the border zone of myocardial infarction. A circos graph was constructed to visualize the chromosomal distribution and classification of the dysregulated lncRNAs and mRNAs. The upregulated mRNAs in the border zone were most highly enriched in cytokine activity, binding, cytokine receptor binding and related processes, as ascertained through Go analysis. Pathway analysis of the upregulated mRNAs showed the most significant changes were in the TNF signaling pathway, cytokine–cytokine receptor interaction and chemokine signaling pathway and similar pathways and interactions. An lncRNA–mRNA co-expression network was established to probe into the underlying functions of the 10 most highly dysregulated lncRNAs based on their co-expressed mRNAs. In the co-expression network, we found 16 genes directly involved in myocardial infarction, including Alox5ap, Itgb2 and B4galt1. The lncRNAs AY212271, EF424788 and MRAK088538, among others, might be associated with myocardial infarction. BC166504 is probably a key lncRNA in the border zone of myocardial infarction. Conclusions The results may have revealed some aberrantly expressed lncRNAs and mRNAs that contribute to the underlying pathophysiological mechanisms of myocardial infarction.

Although optic neuritis and myelitis are the core clinical characteristics of neuromyelitis optica spectrum disorders (NMOSD), appropriate animal models of NMOSD with myelitis and optic neuritis are lacking. we developed a mouse model of NMOSD by intravenously injecting 100 µg neuromyelitis optica immunoglobulin G antibody (NMO-IgG) and complement into experimental allergic encephalomyelitis (EAE) mice after reversible blood-brain barrier (BBB) opening by microbubble-enhanced low-frequency ultrasound (MELFUS). Animals were assessed by histopathology. We found noticeable inflammation and demyelination concomitant with the loss of aquaporin-4 (AQP4) and glial fibrillary acidic protein (GFAP) expression in the spinal cord, brain and optic nerve, as well as human IgG and C9neo deposition. Thus, with the help of MELFUS, we established an NMOSD mouse model with the core lesions of NMOSD by applying a considerably lower dose of human NMO-IgG, which may help identify the pathogenesis and facilitate the development of other neuroimmune disease models in the future.

Background and Purpose— Intracerebral hemorrhage (ICH) is a neurologically destructive stroke, for which no valid treatment is available. This preclinical study examined the therapeutic effect of PD-L1 (programmed death ligand 1), a B7 family member and a ligand for both PD-1 (programmed death 1) and B7-1 (CD80), in a murine ICH model. Methods— ICH was induced by injecting autologous blood into 252 male C57BL/6 and Rag1 −/− mice. One hour later, ICH mice were randomly assigned to receive an intraperitoneal injection of vehicle, PD-L1, or anti–PD-L1 antibody. Neurological function was assessed along with brain edema, brain infiltration of immune cells, blood–brain barrier integrity, neuron death, and mTOR (mammalian target of rapamycin) pathway products. Results— PD-L1 significantly attenuated neurological deficits, reduced brain edema, and decreased hemorrhage volume in ICH mice. PD-L1 specifically downsized the number of brain-infiltrating CD4 + T cells and the percentages of Th1 and Th17 cells but increased the percentages of Th2 and regulatory T cells. In the PD-L1–treated group, we observed an amelioration of the inflammatory milieu, decreased cell death, and enhanced blood–brain barrier integrity. PD-L1 also inhibited the mTOR pathway. The administration of anti–PD-L1 antibody produced the opposite effects to those of PD-L1 in ICH mice. Conclusions— PD-L1 provided protection from the damaging consequences of ICH.

Few studies addressed trans-regional differences in allergen sensitization between areas within a similar latitudinal range but with distinct geomorphological features. We investigated specific IgE (sIgE) positivity to common allergens in populations from two southern China provinces. Using a uniformed protocol, serum samples were collected from 2778 subjects with suspected atopy in coastal Guangdong and inland Yunnan. The overall prevalence of sIgE positivity were 57.8% (95% CI: 56.0%, 59.6%) from Guangdong vs 60.9% (95% CI: 59.1%, 62.7%) from Yunnan. House dust mite (d1) was the most common allergen in both regions. Among d1-sensitized subjects, only 35.7% (208/583) in Guangdong and 22.9% (147/642) in Yunnan tested positive for d1 alone. Among those poly-sensitized d1-positive subjects, cockroach was the most common co-sensitizing aeroallergen. 41.9% of the d1-sensitized Guangdong subjects showed high-class sIgE reactivity (≥class 4), in contrast to a very low percentage of such reactivity in Yunnan. However, 36.3% of d1-sensitized subjects in Yunnan were concomitantly positive for tree pollen mix. Surprisingly, Yunnan subjects showed high prevalence of sIgE positivity for crabs and shrimps, either by overall or by age-group analysis, compared with their Guangdong counterparts (both P

There is so far a paucity of data about allergen component-resolved diagnosis, and the prevalence of grass pollen allergen components in China, in contrast to those from western countries. Even in this country, allergies to grass pollen allergen components in the vast south are inadequately described. This study aimed to determine the major sensitizing grass pollens in Guangzhou, the largest city in Guangdong province of southern China. Included in this study were 258 patients having allergic rhinitis with or without asthma and 88 healthy controls. ImmunoCap100 was used to examine the serum samples for sIgE to Bermuda, Timothy, and Humulus scandens. Subjects who tested positive were further examined for sIgE to Bermuda antigen Cyn d 1, Timothy antigens Phl p 1/4/5/6/7/11/12, and CCD. The relationship of grass pollen allergy to specific antigen sensitization was assessed. As a result, 22.5% of patients with allergic rhinitis and/or asthma were positive for Bermuda-sIgE, 13.6% for Timothy-sIgE, and 7.0% for Humulus scandens-sIgE. These patients were more likely to be sensitized compared with controls (P

A highly selective palladium bis(acetoacetonate)/copper(I) chloride [Pd(acac)2/CuCl] catalytic system for the preparation of dibenzopyranones has been developed. Tandem decarboxylative coupling and lactonization can be realized in one pot using commercially available starting materials. The reaction proceeded well for a range of different substrates.

Although the number of studies on allergic diseases in the general population of southern China is increasing, only a few have addressed food allergy (FA) in children in this region. The present study aimed to investigate the prevalence, clinical manifestations, spectrum of allergens, and related risk factors of FA in preschool children in Guangdong Province, southern China.A random cluster-sampling method was used to select 24 kindergartens from 12 cities in Guangdong Province. The parents or guardians of the children were requested to complete a questionnaire on general information and data regarding FA diagnosis and symptoms in the children and their first-degree relatives. Thereafter, the Chi-square test, multivariate regression analysis, and Spearman's rank-order correlation coefficient analysis were performed to identify statistically significant differences.Analysis of 2540 valid questionnaires revealed an FA prevalence rate of 4%. Adverse food reactions were due to the consumption of shrimp (4.4%), crab (3.2%), mango (2.3%), cow's milk and dairy products (1.9%), and eggs (1.4%). Logistic regression analysis indicated that a history of FA and a history of allergic rhinitis in the first-degree relatives were the major factors leading to FA in children.The incidence of FA in children in Guangdong Province is higher than that commonly believed. An individual's genetic background is an important risk factor for FA. Hence, mitigation of the impact of lifestyle and environmental factors should be carefully considered to reduce the incidence of childhood FA.

A highly selective palladium bis(acetoacetonate)/copper(I) chloride [Pd(acac)2/CuCl] catalytic system for the preparation of dibenzopyranones has been developed. Tandem decarboxylative coupling and lactonization can be realized in one pot using commercially available starting materials. The reaction proceeded well for a range of different substrates.