Epidemiological features and viral shedding in children with SARS-CoV-2 infection.

A pandemic of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection broke out all over the world; however, epidemiological data and viral shedding in pediatric patients are limited. We conducted a retrospective, multicenter study, and followed-up with all children from the families with SARS-CoV-2 infected members in Zhejiang Province, China. All infections were confirmed by testing the SARS-CoV-2 RNA with real-time reverse transcription PCR method, and epidemiological data between children and adults in the same families were compared. Effect of antiviral therapy was evaluated observationally and fecal-viral excretion times among groups with different antiviral regiments were compared with Kaplan-Meier plot. By 29 February 2020, 1298 cases from 883 families were confirmed with SARS-CoV-2 infection and 314 of which were families with children. Incidence of infection in child close contacts was significantly lower than that in adult contacts (13.2% vs 21.2%). The mean age of 43 pediatric cases was 8.2 years and mean incubation period was 9.1 days. Forty (93.0%) were family clustering. Thirty-three children had coronavirus disease 2019 (20 pneumonia) with mild symptoms and 10 were asymptomatic. Fecal SARS-CoV-2 RNA detection was positive in 91.4% (32/35) cases and some children had viral excretion time over 70 days. Viral clearance time was not different among the groups treated with different antiviral regiments. No subsequent infection was observed in family contacts of fecal-viral-excreting children. Children have lower susceptibility of SARS-CoV-2 infection, longer incubation, and fecal-viral excretion time. Positive results of fecal SARS-CoV-2 RNA detection were not used as indication for hospitalization or quarantine.

Correction to: Isoliquiritigenin Provides Protection and Attenuates Oxidative Stress-Induced Injuries via the Nrf2-ARE Signaling Pathway After Traumatic Brain Injury.

The original version of this article unfortunately contained a mistake. The Fluorescence Immunoassays text written in Materials and Methods section and Fig. 1i, j is incorrect. In Fig. 1j, the images corresponding to Sham and TBI + ILG are incorrect. In Fig. 1i the figure caption "TBI + EDA" are incorrect. The corrected text and Fig. 1i, j are given below.

Isoliquiritigenin Provides Protection and Attenuates Oxidative Stress-Induced Injuries via the Nrf2-ARE Signaling Pathway After Traumatic Brain Injury.

Traumatic brain injury (TBI) is a serious public health and medical problem worldwide. Oxidative stress plays a vital role in the pathogenesis of TBI. Nuclear factor erythroid 2-related factor 2 (Nrf2), an important factor in the cellular defense against oxidative stress, is activated following TBI. In this study, the protective effects of Isoliquiritigenin (ILG), a promising antioxidant stress drug, was evaluated as a protective agent against TBI. In a mouse model of controlled cortical impact Injury, we found that the ILG administration reduced the Garcia neuroscore, injury histopathology, brain water content, cerebral vascular permeability, the expression of cleaved caspase3, aquaporin-4, glial fibrillary acidic protein and the increased the expression of neurofilament light chain protein, indicating the protective effects against TBI in vivo. ILG treatment after TBI also restored the oxidative stress and promoted the Nrf2 protein transfer from the cytoplasm to the nucleus. We then used Nrf2-/- mice to test the protective effect of Nrf2 during ILG treatment of TBI. Our findings indicated that Nrf2-/- mice had greater brain injury and oxidative stress than wild-type (WT) mice and ILG was less effective at inhibiting oxidative stress and repairing the brain injury than in the WT mice. In vitro studies in SY5Y cells under oxygen glucose deprivation/re-oxygenation stimulation yielded results that were consistent with those obtained in vivo showing that ILG promotes Nrf2 protein transfer from the cytoplasm to the nucleus. Taken together, our findings demonstrate that Nrf2 is an important protective factor against TBI-induced injuries, which indicates that the protective effects of ILG are mediated by inhibiting oxidative stress after TBI via a mechanism that involves the promotion of Nrf2 protein transfer from the cytoplasm to the nucleus.

Differential response to copper stress in the reproductive resources and allocation of metallophyte Kummerowia stipulacea.

Abundant seed production is a key life history trait for plant to maintain the stability of the whole population in adverse environments such as heavy metal contaminated mine area. In the current studies, we hypothesize that mine (metallicolous) populations of metallophytes have formed specialized reproductive strategies to adapt themselves to the heavy metal contaminated habitats, and differ from normal (non-metallicolous) populations in reproductive allocation. To test this hypothesis, the differences in reproductive resources and reproductive allocation between the copper mine and non-copper mine populations of pseudo-metallophyte Kummerowia stipulacea were comparatively examined under controlled Cu exposure experiments. Compared to non-copper mine population, copper mine population shows an increased seed output and larger reproductive effort under Cu stress. The increase of reproductive allocation in metallicolous population depends on not only seed size but also seed number per plant. The plants of metallicolous population increase allocation to the reproductive organs at the expense of a curtailment of allocation to vegetative traits, resulting in plants with shorter height and fewer branch numbers. There is little evidence displaying effect of root nodule on the reproductive resources and allocation. In addition, plants in metallicolous population reduce the transfer of Cu from roots to aboveground parts. These data suggest that plants of metallicolous population tend to invest more resources to reproductive output and increase their reproductive allocation in the adaptive evolution to Cu-enriched mine soils.

ERCC1 polymorphisms and risk of adult glioma in a Chinese population: a hospital-based case-control study.

To examine the associations of two polymorphisms in excision repair cross-complementing rodent repair deficiency complementation group 1 (ERCC1) gene, C8092A (rs3212986) and T19007C (rs11615), with the risk of adult glioma, we performed a hospital-based case-control study with 257 new cases of glioma and 278 controls in Wenzhou, China. Results showed that polymorphisms C8092A and T19007C in ERCC1 gene were not associated with the risk of glioma in a Chinese population. Further studies in Chinese populations with larger sample sizes are still warranted.

[Genetic structure and variation of Glyptothorax laosensis of the Lancang River based on cytochrome b].

The hillstream catfish, Glyptothorax laosensis, is endemic to basin of Lancang River (also known as Mekong River). Genetic variation was detected within and among 8 populations of G. laosensis in Lancang River based on mitochondrial cytochrome b sequences. A total 16 nucleotides sites were detected in 1 138 bp fragment, which defined 15 haplotypes from 129 sequences. The variation level was very low, with mean h=0.299 and π=0.00032, respectively, and no variation was detected in some populations. Hierarchical analysis of molecular variance (AMOVA) showed no significant genetic structuring among populations. The unimodel mismatch distribution of pairwise haplotype difference and the negatively selective neutrality test (Tajima's D=2.3696, P<0.02; Fu's Fs=20.975, P<0.05) suggested that a recent population expansion had occurred.

Exogenous platelet-derived growth factor improves neurovascular unit recovery after spinal cord injury.

The blood-spinal cord barrier plays a vital role in recovery after spinal cord injury. The neurovascular unit concept emphasizes the relationship between nerves and vessels in the brain, while the effect of the blood-spinal cord barrier on the neurovascular unit is rarely reported in spinal cord injury studies. Mouse models of spinal cord injury were established by heavy object impact and then immediately injected with platelet-derived growth factor (80 µg/kg) at the injury site. Our results showed that after platelet-derived growth factor administration, spinal cord injury, neuronal apoptosis, and blood-spinal cord barrier permeability were reduced, excessive astrocyte proliferation and the autophagy-related apoptosis signaling pathway were inhibited, collagen synthesis was increased, and mouse locomotor function was improved. In vitro, human umbilical vein endothelial cells were established by exposure to 200 µM H2O2. At 2 hours prior to injury, in vitro cell models were treated with 5 ng/mL platelet-derived growth factor. Our results showed that expression of blood-spinal cord barrier-related proteins, including Occludin, Claudin 5, and ß-catenin, was significantly decreased and autophagy was significantly reduced. Additionally, the protective effects of platelet-derived growth factor could be reversed by intraperitoneal injection of 80 mg/kg chloroquine, an autophagy inhibitor, for 3 successive days prior to spinal cord injury. Our findings suggest that platelet-derived growth factor can promote endothelial cell repair by regulating autophagy, improve the function of the blood-spinal cord barrier, and promote the recovery of locomotor function post-spinal cord injury. Approval for animal experiments was obtained from the Animal Ethics Committee, Wenzhou Medical University, China (approval No. wydw2018-0043) in July 2018.

Intermolecular photocyclizations of N-(omega-hydroxyalkyl)tetrachlorophthalimide with alkenes leading to medium- and large-ring heterocycles--reaction modes and regio- and stereoselectivity of the 1,n-biradicals.

A new photocyclization strategy by using intermolecular tandem reactions between N-(omega-hydroxyalkyl)-4,5,6,7-tetrachlorophthalimides (1, 2, and 3) and a series of acyclic and cyclic alkenes is reported. Electron transfer of the triplet-excited phthalimide with the alkene and regioselective trapping of the alkene cation radical by the hydroxyl group at the phthalimide side chain gives a triplet 1,n-biradical, which after intersystem crossing (ISC) leads to regio- and diastereoselective synthesis of polycyclic heterocycles with an N,O-containing medium to large ring. Regio- and diastereoselectivity in the cyclizations are clarified by unambiguous steric structure assignments of the products by X-ray diffraction or extensive 2D NMR measurements. The diastereoselectivity is decided by the stereochemical course of the ISC process of the triplet 1,n-biradicals. These intermolecular photoreactions also furnish a new strategy to generate triplet 1,n-biradicals. Therefore, in photoreactions of 1 and 2 with phenylcyclohexene, the unprecedented stereoselective formation of products by intramolecular hydrogen-atom transfer in the 1,n-biradical intermediate was found (9 and 23). These facts provide direct verification to the reaction pathways of the 1,n-biradicals and give a new insight into the factors deciding reaction-pathway partitioning and stereoselectivity.

[Genetic diversity and differentiation between populations of Glyptothorax zanaensis in the middle and lower reaches of the Nujiang River].

The development of hydroelectricity in the Nujiang River would have adverse impacts on the populations of Glyptothorax zanaensis. In order to assess the genetic diversity and differentiation of this species, we sequenced the cytochrome b gene of the mitochondria in 102 individuals of the fish collected from 6 sampling sites (Gongshan, Gudeng and Lushui in the Nujiang Prefectural District and Daojie, Mengnuo and Mucheng in the Baoshan Municipal District). A total of 87 variation sites were detected in the fragment of 1 137 bp in length, with which the 102 samples were defined as 36 haplotypes. The haplotype diversity (h) and the nucleotide diversity (pi) of total samples were 0.851+/-0.028 and 0.01356+/-0.0008, respectively. Therefore, the genetic diversity of G. zanaensis was relatively low. However, the genetic diversity of the Nujiang population was significantly higher than that of the Baoshan population. The pairwise Fst value between the populations (0.475-0.846) was higher than that within the population (0.002-0.108), which implied that the Fst value was positively related to geographic distance. Analysis of molecular variance (AMOVA) showed that the genetic differentiation between the populations and within the populations were 53.65% and 46.35%, respectively. The fixation index (Fst value) was 0.5365, indicating that there existed significant differentiation between the Nujiang population and the Baoshan population. The phylogentic tree and networks of the haplotypes of G. zanaensis showed that there were two separate lineages: the Nujiang lineage and the Baoshan lineage. Each lineage represents at least one separated management unit, or belongs to an evolutionary significant unit. It was suggested that in the construction of hydroelectric projects the measures for protecting G. zanaensis should be adopted in fully considering the populations of G. zanaensis and the status quo of their population structure to avoid the occurrence of gene exchange among populations.

FRS: A simple knowledge graph embedding model for entity prediction.

Entity prediction is the task of predicting a missing entity that has a specific relation-ship with another given entity. Researchers usually use knowledge graphs embedding(KGE) methods to embed triples into continuous vectors for computation and perform the tasks of entity prediction. However, KGE models tend to use simple operations to refactor entities and relationships, resulting in insufficient interaction of components of knowledge graphs (KGs), thus limiting the performance of the entity prediction model. In this paper, we propose a new entity prediction model called FRS(Feature Refactoring Scoring) to alleviate the problem of insufficient interaction and solve information incom-pleteness problems in the KGs. Different from the traditional KGE methods of directly using simple operations, the FRS model innovatively provides the procedure of feature processing in the entity prediction tasks, realizing the alignment of entities and relationships in the same feature space and improving the performance of entity prediction model. Although FRS is a simple three-layer network, we find that our own model outperforms state-of-the-art KGC methods in FB15K and WN18. Through extensive experiments on FRS, we discover several insights. For example, the effect of embedding size and negative candidate sampling probability on experimental results is in reverse.

Edaravone attenuates traumatic brain injury through anti-inflammatory and anti-oxidative modulation.

Traumatic brain injury (TBI) is among the leading causes of irreversible neurological damage and death worldwide. The aim of the present study was to investigate whether edaravone (EDA) had a neuroprotective effect on TBI as well as to identify the potential mechanism. Results demonstrated that EDA suppressed inflammatory and oxidative responses in mice following TBI. This was evidenced by a reduction in glutathione peroxidase, interleukin 6, tumor necrosis factor-α and hydrogen peroxide levels, in addition to an increase in hemeoxygenase-1, quinone oxidoreductase 1 and superoxide dismutase levels, thereby mitigating neurofunctional deficits, cell apoptosis and structural damage. EDA prevented the transfer of NF-κB protein from the cytoplasm to the nucleus, whilst promoting the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) protein in mice following TBI. These results indicated that EDA exerted neuroprotective effects, including impeding neurofunctional deficits, cell apoptosis and structural damage, in mice with TBI, potentially via suppression of NF-κB-mediated inflammatory activation and promotion of the Nrf2 antioxidant pathway.

Corrigendum: Isoliquiritigenin Protects Against Pancreatic Injury and Intestinal Dysfunction After Severe Acute Pancreatitis via Nrf2 Signaling.

[This corrects the article DOI: 10.3389/fphar.2018.00936.].

Isoliquiritigenin Protects Against Pancreatic Injury and Intestinal Dysfunction After Severe Acute Pancreatitis via Nrf2 Signaling.

Severe acute pancreatitis (SAP) is a digestive system disease that is associated with a range of complications including intestinal dysfunction. In this study, we determined that the chalcone compound, isoliquiritigenin (ISL), reduces pancreatic and intestinal injury in a mouse model of SAP. These effects were achieved by suppressing oxidative stress and the inflammatory responses to SAP. This was evidenced by a reduction in histological score, and malondialdehyde (MDA), interleukin (IL)-6, tumor necrosis factor (TNF)-α and cleaved-caspase-3 (c-caspase-3) protein along with an increase in Nrf2, hemeoxygenase-1 (HO-1), quinone oxidoreductase 1 (NQO1), and superoxide dismutase (SOD). We then used Nrf2-/- mice to test the protective effect of Nrf2 during ISL treatment of SAP. Our results indicated that Nrf2-/- mice had greater pancreatic injury and intestinal dysfunction than wild-type mice. They also had reduced adherens junctions (P120-catenin) and tight junctions (occludin), and increased activated nuclear factor-κB (NF-κB) protein. In Nrf2-/- mice, ISL was less effective at these functions than in the WT mice. In conclusion, this study demonstrated that ISL exerts its protective effects against oxidative stress and inflammatory injury after SAP via regulation of the Nrf2/NF-κB pathway. It also showed that the efficacy of ISL in repairing the intestinal barrier damage caused by SAP is closely related to the Nrf2 protein. Our findings demonstrated that Nrf2 is an important protective factor against SAP-induced injuries in the pancreas and intestines.

Isoliquiritigenin protects against blood­brain barrier damage and inhibits the secretion of pro-inflammatory cytokines in mice after traumatic brain injury.

Traumatic brain injury (TBI) caused by an external mechanical force acting on the brain is a serious neurological condition. Inflammation plays an important role in prolonging secondary tissue injury after TBI, leading to neuronal cell death and dysfunction. Isoliquiritigenin (ILG) is a flavonoid monomer with anti-inflammatory characteristic. Thus, we had investigated the potential protective effects of ILG on TBI-induced injuries and identified the mechanisms underlying it. Here, we have demonstrated that ILG preserves blood brain barrier (BBB) integrity in vivo, suppresses the activation of microglia and inflammatory responses in mice after TBI, consequently leading to neurofunctional deficits, brain oedema, structural damage, and macrophage infiltration. In vitro, ILG exerts anti-inflammatory effect, and upregulates tight junction proteins 120­ß­catenin and occludin in SH­SY5Y cells under oxygen glucose deprivation/reoxygenation (OGD/D) condition. Additionally, we found that PI3K/AKT/GSK­3ß signalling pathway is involved in ILG treatment for TBI. To further confirm it, we had used SC79 (ethyl 2­amino­6­chloro­4­(1­cyano­2­ethoxy­2­oxoethyl)­4H­chromene­3­carboxylate), an Akt specific activator, to activate Akt, we found that SC79 partially reduces the protective effect of ILG for TBI. Overall, our current study reveals the neuroprotective role of ILG on TBI-induced BBB damage, downregulated tight junction proteins via PI3K/AKT/GSK­3ß signalling pathway. Furthermore, ILG suppresses the secretion of pro-inflammatory cytokines after TBI through inhibiting the PI3K/AKT/GSK­3ß/NF­κB signalling pathway. Our findings suggest that GSK­3ß is a key regulatory factor during TBI-induced secretion of inflammatory cytokines, neuronal apoptosis and destruction of BBB.

Expression of GLUT4 mRNA of peripheral tissues and insulin resistance in rats with severe traumatic brain injury.

OBJECTIVE: To evaluate the expression of glucose transporter-4 (GLUT4) mRNA in skeletal muscle and subcutaneous adipose tissues and investigate the mechanism of posttraumatic insulin resistance. METHODS: Sixteen adult male Wistar rats were randomly divided into 2 group (n equal to 8 in each group), i.e., severe traumatic brain injury (TBI) group due to falls from a height and normal control group. Blood glucose and serum insulin were measured at 0.5 h before trauma and 3 h, 24 h, 72 h, 7 d after trauma, respectively. And insulin sensitivity was calculated by insulin activity index (IAI) formula. Skeletal muscle and subcutaneous adipose tissue samples were collected at the same time when blood was sampled. The changes of expression of GLUT4 mRNA were observed using reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Accompanied by the decrease of insulin sensitivity, the expression of GLUT4 mRNA was significantly decreased in adipose tissues at 24 h and 72 h after trauma (P less than 0.01), however, such phenomena did not appear in skeletal muscle samples. CONCLUSIONS: To some extent, the development of posttraumatic insulin resistance is related to the abnormality of transcription activity of GLUT4 gene. Adipose tissues show some difference in the transcriptional level of GLUT4 gene after trauma as compared with skeletal muscle tissues.

Mitochondrial genome of the flat-lip gudgeon, Platysmacheilus exiguus (Teleostei, Cypriniformes).

The complete mitogenome of an endemic fish in China flat-lip gudgeon, Platysmacheilus exiguous, was determined using the polymerase chain reaction and directly sequenced with the primer walking method. The whole mitogenome was 16,604 bp in length, consisting of 13 protein-coding genes, 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes and 1 control region. It had the typical circular molecule structure of vertebrate's mitogenome. The whole base composition was estimated to be 30.77%A, 26.06%T, 26.64%C and 16.53%G with AT bias of 56.83%. The complete mitogenome of P. exiguus provides the fundamental data for conservation genetics study on this species.

Mitochondrial genome of silver gudgeon, Squalidus argentatus (Teleostei, Cypriniformes).

In this paper, we first determined the complete mitochondrial genome sequence of Squalidus argentatus, which was 16,607 bp in size and the whole base composition was estimated to be 30.48% A, 25.45% T, 27.36% C, 16.72% G with AT bias of 55.93%. The complete mitogenome comprised 13 protein-coding genes, 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes and 1 control region, with the gene order and content identical to other vertebrate mitogenomes. The complete mitogenome of S. argentatus provides the valuable information for population genetics and phylogeography studies on this species.

Analysis of posttraumatic stress disorder in children with road traffic injury in Wenzhou, China.

OBJECTIVE: Road traffic accidents are the leading health threat to children and cause significant long-term mental health problems. This study aimed to characterize posttraumatic stress disorder (PTSD) in children suffering from road traffic injuries (RTIs) in Wenzhou, China. METHODS: We conducted a retrospective study of 537 children (aged 1 to 13 years old) with RTIs. The epidemiological features, PTSD incidence, clinical manifestation, and risk factors were analyzed based on a customized PTSD risk factor questionnaire. The outcome factors were also evaluated by means of the logistic regression method. RESULTS: The PTSD incidence was 24.77% in children with RTIs. The incidence of PTSD was related to the personality, family environment, and family care of the children. It was found that early psychological intervention and reasonable family care from the family might promote physical and mental welfare as well as contribute to the development of more effective treatments to prevent PTSD. CONCLUSION: For susceptible children, in addition to dealing with the somatic injury, psychological intervention and family care should be carried out as early as possible.

bFGF Protects Against Blood-Brain Barrier Damage Through Junction Protein Regulation via PI3K-Akt-Rac1 Pathway Following Traumatic Brain Injury.

Many traumatic brain injury (TBI) survivors sustain neurological disability and cognitive impairments due to the lack of defined therapies to reduce TBI-induced blood-brain barrier (BBB) breakdown. Exogenous basic fibroblast growth factor (bFGF) has been shown to have neuroprotective function in brain injury. The present study therefore investigates the beneficial effects of bFGF on the BBB after TBI and the underlying mechanisms. In this study, we demonstrate that bFGF reduces neurofunctional deficits and preserves BBB integrity in a mouse model of TBI. bFGF suppresses RhoA and upregulates tight junction proteins, thereby mitigating BBB breakdown. In vitro, bFGF exerts a protective effect on BBB by upregulating tight junction proteins claudin-5, occludin, zonula occludens-1, p120-catenin, and ß-catenin under oxygen glucose deprivation/reoxygenation (OGD) in human brain microvascular endothelial cells (HBMECs). Both the in vivo and in vitro effects are related to the activation of the downstream signaling pathway, PI3K/Akt/Rac-1. Inhibition of the PI3K/Akt or Rac-1 by specific inhibitors LY294002 or si-Rac-1, respectively, partially reduces the protective effect of bFGF on BBB integrity. Overall, our results indicate that the protective role of bFGF on BBB involves the regulation of tight junction proteins and RhoA in the TBI model and OGD-induced HBMECs injury, and that activation of the PI3K/Akt /Rac-1 signaling pathway underlies these effects.

Regulation of Caveolin-1 and Junction Proteins by bFGF Contributes to the Integrity of Blood-Spinal Cord Barrier and Functional Recovery.

The blood-spinal cord barrier (BSCB) plays important roles in the recovery of spinal cord injury (SCI), and caveolin-1 is essential for the integrity and permeability of barriers. Basic fibroblast growth factor (bFGF) is an important neuroprotective protein and contributes to the survival of neuronal cells. This study was designed to investigate whether bFGF is beneficial for the maintenance of junction proteins and the integrity of the BSCB to identify the relations with caveolin-1 regulation. We examined the integrity of the BSCB with Evans blue dye and fluorescein isothiocyanate-dextran extravasation, measured the junction proteins and matrix metalloproteinases, and evaluated the locomotor function recovery. Our data indicated that bFGF treatment improved the recovery of BSCB and functional locomotion in contusive SCI model rats, reduced the expression and activation of matrix metalloproteinase-9, and increased the expressions of caveolin-1 and junction proteins, including occludin, claudin-5, p120-catenin, and ß-catenin. In the brain, in microvascular endothelial cells, bFGF treatment increased the levels of junction proteins, caveolin-1 small interfering RNA abolished the protective effect of bFGF under oxygen-glucose deprivation conditions, and the expression of fibroblast growth factor receptor 1 and co-localization with caveolin-1 decreased significantly, which could not be reversed by bFGF treatment. These findings provide a novel mechanism underlying the beneficial effects of bFGF on the BSCB and recovery of SCI, especially the regulation of caveolin-1.