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Benzylamine coupling is a very important reaction for the synthesis of imine but still faces many challenges. Herein, we present a highly effective strategy towards the coupling reaction by using environmentally friendly catalysts. These catalysts are composed of Cu/Cu 2 O/Cu 3 N heterostructures supported by C 3 N 4 tubes and the composites were synthesized by one-step hydrothermal treatment followed by calcination. Cu 2 O, Cu 3 N, and C 3 N 4 all are responsive to visible light and the heterojunction formed can greatly enhance the charge separation. When used as photocatalysts for oxidative self-coupling of benzylamine at a low temperature of 323 K in air, Cu/Cu 2 O/Cu 3 N/C 3 N 4 was able to give conversion and selectivity values of up to 99% and 98%, respectively. The high efficiency of the catalysts is attributable to their ability to generate large quantities of free radicals (such as ·OH and ·O 2 - ) under visible-light irradiation., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Stress granules (SGs) are stress-induced membraneless condensates that store non-translating mRNA and stalled translation initiation complexes. Although metazoan SGs are dynamic compartments where proteins can rapidly exchange with their surroundings, yeast SGs seem largely static. To gain a better understanding of yeast SGs, we identified proteins that sediment after heat shock using mass spectrometry. Proteins that sediment upon heat shock are biased toward a subset of abundant proteins that are significantly enriched in intrinsically disordered regions (IDRs). Heat-induced SG localization of over 80 proteins were confirmed using microscopy, including 32 proteins not previously known to localize to SGs. We found that several IDRs were sufficient to mediate SG recruitment. Moreover, the dynamic exchange of IDRs can be observed using fluorescence recovery after photobleaching, whereas other components remain immobile. Lastly, we showed that the IDR of the Ubp3 deubiquitinase was critical for yeast SG formation. This work shows that IDRs can be sufficient for SG incorporation, can remain dynamic in vitrified SGs, and can play an important role in cellular compartmentalization upon stress.This article has an associated First Person interview with the first author of the paper., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

Inflammatory cytokines have been suggested to play important roles in radiation-induced lung injury (RILI). Identifying significantly changed circulating and tissue cytokines after thoracic irradiation will aid in deciphering the mechanism of RILI and identifying potential biomarkers to predict clinical outcome. Herein, the levels of 24 cytokines were measured in serial plasma samples and lung tissue samples collected from a pilot study where nonhuman primates (NHPs) received 11.5 Gy whole thoracic lung irradiation (WTLI) and were then treated with or without a medical countermeasure, AEOL 10150 [a superoxide dismutase (SOD) mimetic]. Seven plasma cytokines (i.e., IP-10, MCP-1, IL-12, IL-15, IL-16, IL-7 and IL-6) were found to be significantly changed at different time points due to WTLI. Plasma IP-10 and MDC were significantly changed between the vehicle group and the drug group. The levels of IP-10, MCP-1, MIP-1α, TARC, IL-17, TNF-β and IL-6 were significantly elevated in the lung tissue lysates of NHPs that received WTLI versus radiation-naïve NHPs. The terminal plasma concentrations of IP-10, MDC, TARC, IL-12, IL-15 and IL-6 were significantly correlated with their levels in the lung tissue. The levels of four cytokines (MCP-4, IL-17, TNF-β and IL-2) at early time points (≤8 weeks postirradiation) were significantly correlated with their terminal plasma levels, respectively. Statistical analysis indicated that circulating cytokines could be discriminatory predictors of AEOL 10150 treatment. Taken together, our data suggested that the cytokine profiles were significantly changed after WTLI as well as mitigator treatment, and that the plasma cytokine profiles could potentially be used to distinguish vehicle or mitigator treatment after WTLI in a NHP model., (©2020 by Radiation Research Society. All rights of reproduction in any form reserved.)

Increasing data indicate that insects serve as major reservoirs and vectors of viruses, which account for the continuously increasing ecological burden and infectious disease outbreaks. Uncovering the hidden diversity of viruses in insects will further the understanding of the ecological and evolutionary perspectives in the emergence of insect-associated virus diseases. In this study, we queried transcriptome sequencing (RNA-Seq) data from more than 600 species across 32 insect orders dwelling in different ecological habitats and recovered more than 1,213 RNA viruses that were recapitulated in 40 families, 2 unclassified genera, and many unspecified viral groups. These novel viruses included the well-known insect-associated viruses within Flaviviridae , Picornavirales , Bunyavirales , Mononegavirales , Nidovirales , Reoviridae , and Negevirus More appeared to form novel clusters within previously described taxa or could be resolved as paraphyletic, including the first astrovirus identified in insects, in which many were sufficiently divergent to warrant the establishment of new virus genera or families. Additionally, some viruses were closely related to the recognized plant-, fungus-, and vertebrate-specific species, implying the importance of relationships between insect behavior and virus spread. Comparative genome analyses also revealed high genomic variability with respect to the flexible gene pool and genome architecture of these newly described viruses, including the evidence for genome reshuffling first discovered in Dicistroviridae The data reflecting the genetically and ecologically diverse viral populations in insects greatly expand our understanding of RNA viruses in nature and highlight that the biodiversity of RNA viruses remains largely unexplored. IMPORTANCE Insects comprise the largest proportion of animals on earth and are frequently implicated in the transmission of vector-borne diseases. However, considerable attention has been paid to the phytophagous and hematophagous insects, with results that provide insufficient and biased information about the viruses in insects. Here, we have delivered compelling evidence for the exceptional abundance and genetic diversity of RNA viruses in a wide range of insects. Novel viruses were found to cover major categories of RNA viruses, and many formed novel clusters divergent from the previously described taxa, dramatically broadening the range of known RNA viruses in insects. These newly characterized RNA viruses exhibited high levels of genomic plasticity in genome size, open reading frame (ORF) number, intergenic structure, and gene rearrangement and segmentation. This work provides comprehensive insight into the origin, spread, and evolution of RNA viruses. Of course, a large-scale virome project involving more organisms would provide more-detailed information about the virus infections in insects., (Copyright © 2020 Wu et al.)

Cell surfaces are glycosylated in various ways with high heterogeneity, which usually leads to ambiguous conclusions about glycan-involved biological functions. Here, we describe a two-step chemoenzymatic approach for N-glycan-subtype-selective editing on the surface of living cells that consists of a first 'delete' step to remove heterogeneous N-glycoforms of a certain subclass and a second 'insert' step to assemble a well-defined N-glycan back onto the pretreated glyco-sites. Such glyco-edited cells, carrying more homogeneous oligosaccharide structures, could enable precise understanding of carbohydrate-mediated functions. In particular, N-glycan-subtype-selective remodeling and imaging with different monosaccharide motifs at the non-reducing end were successfully achieved. Using a combination of the expression system of the Lec4 CHO cell line and this two-step glycan-editing approach, opioid receptor delta 1 (OPRD1) was investigated to correlate its glycostructures with the biological functions of receptor dimerization, agonist-induced signaling and internalization.

Despite its isolation and extreme climate, Antarctica is home to diverse fauna and associated microorganisms. It has been proposed that the most iconic Antarctic animal, the penguin, experiences low pathogen pressure, accounting for their disease susceptibility in foreign environments. There is, however, a limited understanding of virome diversity in Antarctic species, the extent of in situ virus evolution, or how it relates to that in other geographic regions. To assess whether penguins have limited microbial diversity we determined the RNA viromes of three species of penguins and their ticks sampled on the Antarctic peninsula. Using total RNA sequencing we identified 107 viral species, comprising likely penguin associated viruses (n = 13), penguin diet and microbiome associated viruses (n = 82), and tick viruses (n = 8), two of which may have the potential to infect penguins. Notably, the level of virome diversity revealed in penguins is comparable to that seen in Australian waterbirds, including many of the same viral families. These data run counter to the idea that penguins are subject to lower pathogen pressure. The repeated detection of specific viruses in Antarctic penguins also suggests that rather than being simply spill-over hosts, these animals may act as key virus reservoirs.

Objective: To compare the median effective dose (ED 50 ) of intranasal dexmedetomidine for procedural sedation in uncooperative pediatric patients with acyanotic congenital heart disease before and after cardiac surgery., Methods: We prospectively recruited 47 children (22 in preoperative group and 25 in postoperative group) who needed sedation for transthoracic echocardiography (TTE). A modified up-and-down sequential study design was employed to determine dexmedetomidine dose for each patient with a starting dose of 2 μg/kg in both groups; dexmedetomidine doses for subsequent subjects were determined according to the responses from the previous subject using the up-and-down method at a 0.25 μg/kg interval. The ED 95 was determined using probit regression. The onset time, examination time, wake-up time and adverse effects were measured, and the safety was evaluated in terms of changes in vital signs every 5 min., Results: The ED 50 value of intranasal dexmedetomidine for sedation was 1.84 μg/kg (95% CI : 1.68-2.00 μg/kg) in children with congenital heart disease before cardiac surgery, and 3.38 μg/kg (95% CI : 3.21-3.54 μg/kg) after the surgery. No significant difference was found between the two groups in the demographic variables, onset time, examination time, wake-up time, or adverse effects., Conclusions: In children with acyanotic congenital heart disease, the ED 50 of intranasal dexmedetomidine for TTE sedation increases to 3.38 μg/ kg after cardiac surgery from the preoperative value of 1.84 μg/kg.

Utilizing Zn as a "fencing" agent has enabled the pyrolytic synthesis of atomically dispersed metal-nitrogen-carbon (AD-MNC) materials for broad electrocatalysis such as fuel cells, metal-air batteries, and water electrolyzers. Yet the Zn residue troubles the precise identification of the responsible sites in active service. Herein we developed a simple aerosil-assisted method for preparing AD-MNC materials to cautiously avoid the introduction of Zn. The combined analysis of extended X-ray absorption fine structure (EXAFS) and aberration-corrected high-resolution transition electron microscopy verified the atomic dispersion of Fe species in the as-made Fe-NC sample with a well-defined structure of Fe-N 4 . Besides, the EXAFS studies indicated the formation of oxygenated Fe-N 4 moieties (O-Fe-N 4 ) after the removal of aerosil nanoparticles. Therefore, the immobilization of Fe atoms in the carbon substrate was attributed to the heavily doping N and rich oxygen dangling species at the aerosil surface. Electrochemical measurements revealed that the as-made Fe-NC material furnished with O-Fe-N 4 moieties exhibited excellent oxygen reduction reaction (ORR) performance, characterized by individually indicating ∼22 mV higher half-wave potentials, with respect to commercial Pt/C catalyst. Density functional theory (DFT) computations suggested that the dangling oxygen ligand on the Fe-N 4 moiety could significantly boost the cleavage of OOH* and the reductive release of *OH intermediates, leading to the enhancement of overall ORR performance.

Visible thermal person re-identification (VT-ReID) is a challenging cross-modality pedestrian retrieval problem due to the large intra-class variations and modality discrepancy across different cameras. Existing VT-ReID methods mainly focus on learning cross-modality sharable feature representations by handling the modality-discrepancy in feature level. However, the modality difference in classifier level has received much less attention, resulting in limited discriminability. In this paper, we propose a novel modality-aware collaborative ensemble (MACE) learning method with middle-level sharable two-stream network (MSTN) for VT-ReID, which handles the modality-discrepancy in both feature level and classifier level. In feature level, MSTN achieves much better performance than existing methods by capturing sharable discriminative middlelevel features in convolutional layers. In classifier level, we introduce both modality-specific and modality-sharable identity classifiers for two modalities to handle the modality discrepancy. To utilize the complementary information among different classifiers, we propose an ensemble learning scheme to incorporate the modality sharable classifier and the modality specific classifiers. In addition, we introduce a collaborative learning strategy, which regularizes modality-specific identity predictions and the ensemble outputs. Extensive experiments on two cross-modality datasets demonstrate that the proposed method outperforms current state-of-the-art by a large margin, achieving rank- 1/mAP accuracy 51.64%/50.11% on the SYSU-MM01 dataset, and 72.37%/69.09% on the RegDB dataset.

Objectives: To compare the effects of intranasal dexmedetomidine (DEX) and DEX-ketamine (KET) on hemodynamics and sedation quality in children with congenital heart disease., Design: A randomized controlled, double-blind, prospective trial., Setting: A tertiary care teaching hospital., Participants: The study comprised 60 children undergoing transthoracic echocardiography (TTE)., Interventions: Patients were randomly allocated into the DEX group (group D [n = 30]) or the DEX-KET group (group D-K [n = 30]). Group D received 2 μg/kg of intranasal DEX; group D-K received 2 μg/kg of DEX and 1 mg/kg of KET intranasally., Measurements and Main Results: The primary outcome was the change in hemodynamics, measured using mean arterial pressure (MAP) and heart rate (HR). Secondary outcomes were onset time, wake-up time, and discharge time. No differences were found in mean arterial pressure or heart rate. The onset time was significantly shorter in group D-K than in group D (9.6 ± 2.9 minutes v 14.3 ± 3.4 minutes; p = 0.031). The wake-up time was longer in group D-K than in group D (52 ± 14.7 minutes v 39.6 ± 12.1 minutes; p = 0.017). The discharge time was longer in group D-K than in group D (61.33 ± 11.59 minutes v 48.17 ± 8.86 minutes; p < 0.001). No differences in hemodynamics were found between the 2 groups. Intranasal DEX was found to be as effective for TTE sedation as intranasal DEX-KET, with longer onset time and shorter recovery and discharge times., Conclusion: No differences in hemodynamics were found between the 2 groups. Intranasal DEX was found to be as effective for TTE sedation as is intranasal DEX-KET, with longer onset time and shorter recovery and discharge times., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Thyroid cancer is a common endocrine tumor, the incidence of which is increasing each year. Early diagnosis and treatment can effectively prevent thyroid cancer. This article uses Chinese's ultrasound reports to determine the value of early diagnosis., Methods: The clinical data center of the First Affiliated Hospital of Nanjing Medical University was screened for patients diagnosed with a thyroid nodule, who had undergone a thyroid function test, ultrasound records and pathological assessment. A total of 811 patients with a total of 1,290 pathologically confirmed nodules (506 benign and 784 malignant) were enrolled. Logistic regression was used to analyze the variables that significantly affected malignant nodules. The sensitivity and specificity of ultrasound thyroid imaging-reporting and data system (TI-RADS) classification results for benign and malignant tumors were calculated., Results: The age of the patients had a very significant difference in the classification of benign and malignant nodules (P<0.001), and the marital status was significantly different (P<0.05). Gender and medical insurance had no significant effect (P>0.05). Thyroglobulin (TG), free thyroxine (FT4), and free triiodothyronine (FT3) had significant effects (P=0.003) on the incidence of malignant nodules in patients, while thyroid-stimulating hormone (TSH) had no significant effect (P>0.05). Ultrasound analysis showed a Youden's index of 78.97%, a positive predictive value of 93.20%, and a negative predicted value of 84.10% at the most excellent classification effect. The sensitivity was 89.0%, the specificity was 89.9%; much greater than the classification model based on the thyroid function test (sensitivity =80.6%, specificity =55.8%)., Conclusions: The present study verifies the effectiveness of using TI-RADS classification for diagnosis of benign and malignant thyroid nodules, and explores the use of new analysis methods for clinical data. To reduce dependence on the doctors, ultrasound image data and clinical phenotypic data can be further used to assist clinical decision making., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/gs.2020.04.03). The authors have no conflicts of interest to declare., (2020 Gland Surgery. All rights reserved.)

Ectoparasites play an important role in virus transmission among vertebrates. Little, however, is known about the nature of those viruses that pass between invertebrates and vertebrates. In Australia, flies and fleas support the mechanical transmission of two viral biological controls against wild rabbits-rabbit hemorrhagic disease virus (RHDV) and myxoma virus. We compared virome compositions in rabbits and these ectoparasites, sequencing total RNA from multiple tissues and gut contents of wild rabbits, fleas collected from these rabbits, and flies trapped sympatrically. Meta-transcriptomic analyses identified 50 novel viruses from multiple RNA virus families. Rabbits and their ectoparasites were characterized by markedly different viromes, with virus abundance greatest in flies. Although viral contigs from six virus families/groups were found in both rabbits and ectoparasites, they clustered in distinct host-dependent lineages. A novel calicivirus and a picornavirus detected in rabbit cecal content were vertebrate specific; the newly detected calicivirus was distinct from known rabbit caliciviruses, while the picornavirus clustered with sapeloviruses. Several picobirnaviruses were also identified that fell in diverse phylogenetic positions, compatible with the idea that they are associated with bacteria. Further comparative analysis revealed that the remaining viruses found in rabbits, and all those from ectoparasites, were likely associated with invertebrates, plants, and coinfecting endosymbionts. While no full genomes of vertebrate-associated viruses were detected in ectoparasites, small numbers of reads from rabbit astrovirus, RHDV, and other lagoviruses were present in flies. This supports a role for flies in the mechanical transmission of RHDV, while their involvement in astrovirus transmission merits additional exploration. IMPORTANCE Ectoparasites play an important role in the transmission of many vertebrate-infecting viruses, including Zika and dengue viruses. Although it is becoming increasingly clear that invertebrate species harbor substantial virus diversity, it is unclear how many of the viruses carried by invertebrates have the potential to infect vertebrate species. We used the European rabbit ( Oryctolagus cuniculus ) as a model species to compare virome compositions in a vertebrate host and known associated ectoparasite mechanical vectors, in this case, fleas and blowflies. In particular, we aimed to infer the extent of viral transfer between these distinct types of host. Our analysis revealed that despite extensive viral diversity in both rabbits and associated ectoparasites, and the close interaction of these vertebrate and invertebrate species, biological viral transmission from ectoparasites to vertebrate species is rare. We did, however, find evidence to support the idea of a role of blowflies in transmitting viruses without active replication in the insect., (Copyright © 2020 Mahar et al.)

Background: Compared to radiation injury alone (RI), radiation injury combined wound (CI) further enhances acute radiation syndrome and subsequently mortality. We previously reported that therapy with Ghrelin, the 28-amino-acid-peptide secreted from the stomach, significantly increased 30-day survival and mitigated hematopoietic death by enhancing and sustaining granulocyte-colony stimulating factor (G-CSF) and keratinocyte chemoattractant (KC) in the blood and bone marrow; increasing circulating white blood cell depletion; inhibiting splenocytopenia; and accelerating skin-wound healing on day 30 after CI. Herein, we aimed to study the efficacy of Ghrelin on intestinal injury at early time points after CI., Methods: B6D2F1/J female mice were exposed to 60 Co-γ-photon radiation (9.5 Gy, 0.4 Gy/min, bilateral), followed by 15% total-body-surface-area skin wounds. Several endpoints were measured: at 4-5 h and on days 1, 3, 7, and 15., Results: Ghrelin therapy mitigated CI-induced increases in IL-1β, IL-6, IL-17A, IL-18, KC, and TNF-α in serum but sustained G-CSF, KC and MIP-1α increases in ileum. Histological analysis of ileum on day 15 showed that Ghrelin treatment mitigated ileum injury by increasing villus height, crypt depth and counts, as well as decreasing villus width and mucosal injury score. Ghrelin therapy increased AKT activation and ERK activation; suppressed JNK activation and caspase-3 activation in ileum; and reduced NF-κB, iNOS, BAX and Bcl-2 in ileum. This therapy recovered the tight junction protein and mitigated bacterial translocation and lipopolysaccharides levels. The results suggest that the capacity of Ghrelin therapy to reduce CI-induced ileum injury is mediated by a balanced NF-κB-AKT-MAPK network that leads to homeostasis of pro-inflammatory and anti-inflammatory cytokines., Conclusions: Our novel results are the first to suggest that Ghrelin therapy effectively decreases intestinal injury after CI., Competing Interests: Competing interestsThe authors declare that they have no conflict of interests., (© The Author(s) 2020.)

Mercury (Hg) and lead (Pb) accumulation since the Industrial Revolution has been generally observed to increase concurrently in lake sedimentary records around the world. Located downwind during the monsoon season from the rapidly developing South Asia, the Himalayas and the Tibetan Plateau are expected to receive direct anthropogenic Hg and Pb loadings, yet the source, pathway, and effects of such transport remain poorly known due to logistic challenges in accessing this region. When studying the sediment record from Lake Gokyo (4750 m above sea level (a.s.l.)) in the Himalayas, we find remarkably different Hg and Pb accumulation trends over the past 260 years. Although Hg accumulation has continued to increase since the Industrial Revolution, Pb accumulation peaked during that time and has been decreasing since then. Stable isotope analysis reveals that the decoupling trends between these two elements are due to different sources and pathways of Hg and Pb in the region. Both δ 202 Hg and Δ 199 Hg have been increasing since the Industrial Revolution, suggesting that anthropogenic Hg emissions from South Asia have been continuously increasing and that the Indian monsoon-driven wet deposition of atmospheric Hg is the dominant pathway for Hg accumulation in the sediments. In contrast, analysis of 206 Pb/ 207 Pb and 208 Pb/ 207 Pb ratios suggests that Pb accumulation in the sediments originates primarily from natural sources and that the decreasing trend of Pb accumulation is most likely due to a weakening input of atmospheric mineral dust by the westerlies. These decoupling trends highlight the ongoing issue of transboundary Hg transport to the Himalayas and the Tibetan Plateau that are source waters for major freshwater systems in Asia and calls for regional and international collaborations on Hg emission controls in South Asia.

Fasteners are critical and indispensable locking components in mechanical assembly. Submillimeter fasteners are massively and widely used in electronic devices. This study proposed an adjustable panoramic inspection system for M2 to M0.8 submillimeter fasteners. The system mainly consists of a panoramic imaging module, a back-light module, and an image grabbing and computing module. The panoramic imaging module would form four equal optical path lengths to keep the same imaging amplification between the different directions of the field of view. The back-light module was designed to provide uniform illumination and enhance the contrast of the pitch edge between the fasteners and the background. The image grabbing and computing module with a high-speed camera was designed to be adjustable for different sizes of submillimeter fasteners. The realized system can offer the function of four images in one shot to make a panoramic scene, independent illumination for recognizing, inspect screws from M0.8 to M2.0 screws, and short time consumption of image processing, such as 3.284 ms for M0.8 screws and 2.384 ms for M2.0 screws, to achieve examination of 6000 pieces in 1 min.

Mast cell-deficient mice are widely used to identify and quantify contributions of mast cells to diverse biological responses in vivo, including allergic inflammation. However, despite the fact that scores of genes have been identified as modifiers of allergic inflammation, most mast cell-deficient models have been available only on a single genetic background. We transferred the Kit W-sh allele onto the BALB/c background to generate BALB/c mast cell-deficient mice (BALB/c-Kit W-sh/W-sh ). BALB/c-Kit W-sh/W-sh mice have dramatically reduced mast cell numbers (0-2% of wild type) in all tissues examined, as well as subtle hematologic differences from the corresponding wild type mice, including splenomegaly with evidence of increased splenic hematopoiesis. We examined in BALB/c-Kit W-sh/W-sh mice models of allergic inflammation that are substantially diminished in C57BL/6-Kit W-sh/W-sh mast cell-deficient mice. In a model of acute allergic inflammation, i.e., IgE-dependent passive cutaneous anaphylaxis, both ear swelling and leukocyte infiltration were largely or entirely absent in BALB/c-Kit W-sh/W-sh mice. In contrast, in two different models of allergic airway inflammation, airway hyperresponsiveness, lung inflammation, and airway remodeling developed robustly in mast cell-deficient BALB/c-Kit W-sh/W-sh mice. These results support the conclusion that the importance of mast cell contributions in various models of allergic inflammation may be at least partially determined by genetic background.

Objectives: To determine the 50% and 95% effective dose of intranasal dexmedetomidine sedation for transthoracic echocardiography in children with cyanotic and acyanotic congenital heart disease., Design: A prospective, nonrandomized study., Setting: A tertiary care teaching hospital., Participants: Patients younger than 18 months with known or suspected congenital heart disease scheduled for transthoracic echocardiography with sedation., Interventions: Patients were divided into a cyanotic group (blood oxygen saturation <85%) or an acyanotic group (blood oxygen saturation ≥85%). This study used Dixon's up-and-down method sequential allocation design. In both groups, the initial dose of intranasal dexmedetomidine was 2 μg/kg and the gradient of increase or decrease was 0.25 μg/kg., Measurements and Main Results: The 50% effective dose (95% confidence interval) of intranasal dexmedetomidine sedation for transthoracic echocardiography was 3.2 (2.78-3.55) μg/kg and 1.9 (1.69-2.06) μg/kg in the cyanotic and acyanotic groups, respectively. None of the patients experienced significant adverse events., Conclusion: The 50% (95% confidence intervals) effective doses of intranasal dexmedetomidine sedation for transthoracic echocardiography were 3.2 (2.78-3.55) μg/kg and 1.9 (1.69-2.06) μg/kg in children with cyanotic and acyanotic congenital heart disease, respectively., Competing Interests: Conflict of Interest The authors have nothing to disclose., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Mites are notorious for being vectors transmitting infectious pathogens and source of allergens causing allergic conditions in animals and humans. However, despite their huge impact on public health, the virome of mites remains unknown. Here we characterized the virus diversity and abundance of 14 species of medically important mites based on total RNA sequencing data sets generated in this study as well as those deposited in the Sequence Read Archive (SRA) database. A total of 47 genetically distinct viruses were identified and classified into 17 virus families or virus super-groups, and the viral sequences accounted for as much as 29.67% of total non-rRNA transcriptome in one mite library. The most commonly identified viruses are members of Picornavirales , among which we revealed more than one type of viruses that are evolutionarily related to dicistronic viruses but contain a single open reading frame, thus likely representing a recent example of host (i.e., mite)-related parallel evolution from dicistronic to monocistronic genomic form within the family Dicistroviridae To our best knowledge, this is the first time to perform comprehensive and systematic screening of RNA virome in medically important mites including house dust mites (HDM). Overall, the RNA virome identified here provides not only significant insights into the diversity and evolution of RNA viruses in mites, but also a solid knowledge base for studying their roles in human diseases. IMPORTANCE Mites are important group of arthropods that are associated with a variety of human diseases including scrub typhus and asthma. However, it remains unclear whether or not mites carry viruses that might play a role in human infections or allergic disease. In this study, we used a total transcriptomics approach to characterize and compare the complete RNA virome within mites that are relevant to human health and diseases. Specifically, our data revealed a large diversity, a high abundance, and a flexible genomic evolution for these viruses. Although most of the viruses identified here are unknown to associate with human infectious disease, the abundant presence of viral RNAs may play an immunomodulatory role in the development of allergic reactions such as asthma during environmental exposure to mite allergens, and therefore provide important insights into the mite-induced allergy and preparation of mite allergen vaccines., (Copyright © 2020 American Society for Microbiology.)

The diversity of pathogens associated with acute respiratory infection (ARI) makes diagnosis challenging. Traditional pathogen screening tests have a limited detection range and provide little additional information. We used total RNA sequencing ("meta-transcriptomics") to reveal the full spectrum of microbes associated with paediatric ARI. Throat swabs were collected from 48 paediatric ARI patients and 7 healthy controls. Samples were subjected to meta-transcriptomics to determine the presence and abundance of viral, bacterial, and eukaryotic pathogens, and to reveal mixed infections, pathogen genotypes/subtypes, evolutionary origins, epidemiological history, and antimicrobial resistance. We identified 11 RNA viruses, 4 DNA viruses, 4 species of bacteria, and 1 fungus. While most are known to cause ARIs, others, such as echovirus 6, are rarely associated with respiratory disease. Co-infection of viruses and bacteria and of multiple viruses were commonplace (9/48), with one patient harboring 5 different pathogens, and genome sequence data revealed large intra-species diversity. Expressed resistance against eight classes of antibiotic was detected, with those for MLS, Bla, Tet, Phe at relatively high abundance. In summary, we used a simple total RNA sequencing approach to reveal the complex polymicrobial infectome in ARI. This provided comprehensive and clinically informative information relevant to understanding respiratory disease.

Porcine reproductive and respiratory syndrome virus (PRRSV), an important pathogen that affects the pig industry, is a highly genetically diverse RNA virus. However, the phylogenetic and genomic recombination properties of this virus have not been completely elucidated. In this study, comparative analyses of all available genomic sequences of North American (NA)-type PRRSVs ( n  = 355, including 138 PRRSV genomes sequenced in this study) in China and the United States during 2014-2018 revealed a high frequency of interlineage recombination hot spots in nonstructural protein 9 (NSP9) and the GP2 to GP3 regions. Lineage 1 (L1) PRRSV was found to be susceptible to recombination among PRRSVs both in China and the United States. The recombinant major parent between the 1991-2013 data and the 2014-2018 data showed a trend from complex to simple. The major recombination pattern changed from an L8 to L1 backbone during 2014-2018 for Chinese PRRSVs, whereas L1 was always the major backbone for US PRRSVs. Intralineage recombination hot spots were not as concentrated as interlineage recombination hot spots. In the two main clades with differential diversity in L1, NADC30-like PRRSVs are undergoing a decrease in population genetic diversity, NADC34-like PRRSVs have been relatively stable in population genetic diversity for years. Systematic analyses of insertion and deletion (indel) polymorphisms of NSP2 divided PRRSVs into 25 patterns, which could generate novel references for the classification of PRRSVs. The results of this study contribute to a deeper understanding of the recombination of PRRSVs and indicate the need for coordinated epidemiological investigations among countries. IMPORTANCE Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant swine diseases. However, the phylogenetic and genomic recombination properties of the PRRS virus (PRRSV) have not been completely elucidated. In this study, we systematically compared differences in the lineage distribution, recombination, NSP2 polymorphisms, and evolutionary dynamics between North American (NA)-type PRRSVs in China and in the United States. Strikingly, we found high frequency of interlineage recombination hot spots in nonstructural protein 9 (NSP9) and in the GP2 to GP3 region. Also, intralineage recombination hot spots were scattered across the genome between Chinese and US strains. Furthermore, we proposed novel methods based on NSP2 indel patterns for the classification of PRRSVs. Evolutionary dynamics analysis revealed that NADC30-like PRRSVs are undergoing a decrease in population genetic diversity, suggesting that a dominant population may occur and cause an outbreak. Our findings offer important insights into the recombination of PRRSVs and suggest the need for coordinated international epidemiological investigations., (Copyright © 2020 American Society for Microbiology.)

From December 2019, an outbreak of unusual pneumonia was reported in Wuhan with many cases linked to Huanan Seafood Market that sells seafood as well as live exotic animals. We investigated two patients who developed acute respiratory syndromes after independent contact history with this market. The two patients shared common clinical features including fever, cough, and multiple ground-glass opacities in the bilateral lung field with patchy infiltration. Here, we highlight the use of a low-input metagenomic next-generation sequencing (mNGS) approach on RNA extracted from bronchoalveolar lavage fluid (BALF). It rapidly identified a novel coronavirus (named 2019-nCoV according to World Health Organization announcement) which was the sole pathogens in the sample with very high abundance level (1.5% and 0.62% of total RNA sequenced). The entire viral genome is 29,881 nt in length (GenBank MN988668 and MN988669, Sequence Read Archive database Bioproject accession PRJNA601736) and is classified into β-coronavirus genus. Phylogenetic analysis indicates that 2019-nCoV is close to coronaviruses (CoVs) circulating in Rhinolophus (Horseshoe bats), such as 98.7% nucleotide identity to partial RdRp gene of bat coronavirus strain BtCoV/4991 (GenBank KP876546, 370 nt sequence of RdRp and lack of other genome sequence) and 87.9% nucleotide identity to bat coronavirus strain bat-SL-CoVZC45 and bat-SL-CoVZXC21. Evolutionary analysis based on ORF1a/1b, S, and N genes also suggests 2019-nCoV is more likely a novel CoV independently introduced from animals to humans.

Effort expenditure not only discounts reward value prospectively but also accrues reward value retrospectively. To decompose the effort paradox in reward processing, the current event-related potential study investigated the neural dynamics underlying effects of effort expenditure on subsequent reward processing. Participants exerted one of two levels of effort to obtain an opportunity of winning a high or low amount of monetary reward, and we focused on electrophysiological activity during the anticipatory and consummatory phases of reward processing. During the anticipatory phase, the stimulus-preceding negativity was enhanced when potential high rewards were anticipated, but this reward effect disappeared following high-effort expenditure. During the consummatory phase, feedback-related ERPs were increased for high relative to low rewards, and this reward effect was enlarged following effort expenditure during the early stage (200-300 ms) as indexed by the reward positivity but not the late stage (400-600 ms) as indexed by the P3. Our findings provide a strong support for the psychological contrast theory and indicate that time matters in decomposing the effort paradox for reward processing such that effort expenditure reduces reward sensitivity during the anticipatory phase but enhances reward sensitivity during the consummatory phase., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

This publisher's note contains corrections to Opt. Lett.44, 2081 (2019)OPLEDP0146-959210.1364/OL.44.002081.

Particulate matter with an aerodynamic diameter of less than 2.5 μm (PM 2.5 ) derived from automobile exhaust can lead to serious male spermatogenesis dysfunction, but its specific molecular mechanism is unclear. In this experiment, we focused on the blood-testis barriers (BTB) and explored the intracellular mechanisms underlying the fertility toxicity of PM 2.5 originating from automobile exhaust in the primary cultured Sertoli cells(SCs) of rats. After PM 2.5 exposure, excessive reactive oxygen species (ROS) and increased apoptosis of SCs were detected. The expression of the BTB related proteins including ZO-1, Occludin, N-cadherin and β-catenin were significantly decreased and the spatial arrangement of F-actin was completely disordered through Immunofluorescence and Western blots tests. The phosphorylation of Jun N-terminal kinase (JNK), extracellular signal regulatory kinase (ERK), p38 mitogen-activated protein kinase (MAPK) were upregulated and nuclear factor (erythroid-derived 2) -like 2-related factor (Nrf2) was downregulated respectively. However, combined utilization of vitamin C and E were observed to prevent the increase of ROS generation, reduce celluar apoptosis, increase the expression of BTB related proteins, reconstructed the spatial arrangement of F-actin as well as improved the Nrf2 expression and attenuated the phosphorylation of the MAPK kinases and cleaved caspase-3 levels. Furthermore, ERK inhibitor (SCH772984), JNK inhibitor (SP600125) and p38 MAPK inhibitor (SB203580) obviously up-regulated BTB-related proteins expression as well as activated Nrf2 expression at varying degrees, indicating that ROS-MAPKs-Nrf2 is involved in the signaling pathway that leads to PM 2.5 -induced spermatogenesis dysfunction. These findings indicate that PM 2.5 derived from automobile exhaust causes oxidative stress, which in turn causes cellular apoptosis of SCs and damage of the blood-testis barrier, resulting male spermatogenesis dysfunction, in which ROS-MAPK-Nrf-2 pathways may play a key role., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Peripheral blood inflammation factor neutrophil-lymphocyte ratio (NLR), platelet count (PLT) and nutritional factor serum albumin (ALB) have been proposed as prognostic markers of head and neck squamous carcinoma cancer (HNSCC) in recent years. In the current study, nomogram predict models based on pre-treatment hematological parameters and a modified risk-stratified score system have been built., Methods: A total of 197 patients with oropharyngeal, hypopharyngeal and laryngeal cancers receiving multimodality treatment between 2012 and 2014 were included. The pre-treatment ALB, neutrophil, lymphocyte and platelet count (PLT) were detected. Cancer-specific survival and locoregional recurrence (LRC) by 5 years' follow-up in the cases were obtained. To integrate clinical characteristics, we propose a modified risk-stratified score system. Kaplan-Meier method, proportional hazards COX model, logistic models were used to establish nomograms within external validation., Results: Five-year LRC was decreased (p=0.004) for 140 patients with pre-treatment NLR <2.77. Five-year LRC and 5-year cancer-specific survival were decreased (p=0.031, p=0.021) with pre-treatment PLT ≥248×10 9 /L. Comparison of univariate parametric models demonstrated that pre-treatment NLR evaluation and PLT>248×10 9 /L were better among tested models. On Bayesian information criteria (BIC) analysis, the optimal prognostic model was then used to develop nomograms predicting 3- and 5-year LRC. The external validation of this predictive model was confirmed in 57 patients from another hospital., Conclusion: Pre-treatment NLR elevation and PLT>248×10 9 /L are promising predictors of prognosis in patients with operable HNSCC. Nomograms based on the pre-treatment hematological markers and modified risk-stratified score system provide distinct risk stratifications. There results provided the feasibility of anti-inflammatory and antiplatelet treatments for HNSCC patients., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Ye et al.)

Papillomaviruses infect the skin and mucosal surfaces of diverse animal hosts with consequences ranging from asymptomatic colonization to highly malignant epithelial cancers. Increasing evidence suggests a role for papillomaviruses in the most common cutaneous malignancy of domestic cats, squamous cell carcinoma (SCC). Using total DNA sequencing we identified a novel feline papillomavirus in a nasal biopsy taken from a cat presenting with both nasal cavity lymphoma and recurrent squamous cell carcinoma affecting the nasal planum. We designate this novel virus as Felis catus papillomavirus 6 (FcaPV6). The complete FcaPV6 7453 bp genome was similar to those of other feline papillomaviruses and phylogenetic analysis revealed that it was most closely related to FcaPV3, although was distinct enough to represent a new viral type. Classification of FcaPV6 in a new genus alongside FcaPVs 3, 4 and 5 is supported. Archived excisional biopsy of the SCC, taken 20 months prior to presentation, was intensely positive on p16 immunostaining. FcaPV6, amplified using virus-specific, but not consensus, PCR, was the only papillomavirus detected in DNA extracted from the SCC. Conversely, renal lymphoma, sampled at necropsy two months after presentation, tested negative on FcaPV6-specific PCR. In sum, using metagenomics we demonstrate the presence of a novel feline papillomavirus in association with cutaneous squamous cell carcinoma., Competing Interests: The authors declare no conflict of interest.

Metagenomic sequencing has revolutionised our knowledge of virus diversity, with new virus sequences being reported faster than ever before. However, virus discovery from metagenomic sequencing usually depends on detectable homology: without a sufficiently close relative, so-called 'dark' virus sequences remain unrecognisable. An alternative approach is to use virus-identification methods that do not depend on detecting homology, such as virus recognition by host antiviral immunity. For example, virus-derived small RNAs have previously been used to propose 'dark' virus sequences associated with the Drosophilidae (Diptera). Here, we combine published Drosophila data with a comprehensive search of transcriptomic sequences and selected meta-transcriptomic datasets to identify a completely new lineage of segmented positive-sense single-stranded RNA viruses that we provisionally refer to as the Quenyaviruses . Each of the five segments contains a single open reading frame, with most encoding proteins showing no detectable similarity to characterised viruses, and one sharing a small number of residues with the RNA-dependent RNA polymerases of single- and double-stranded RNA viruses. Using these sequences, we identify close relatives in approximately 20 arthropods, including insects, crustaceans, spiders, and a myriapod. Using a more conserved sequence from the putative polymerase, we further identify relatives in meta-transcriptomic datasets from gut, gill, and lung tissues of vertebrates, reflecting infections of vertebrates or of their associated parasites. Our data illustrate the utility of small RNAs to detect viruses with limited sequence conservation, and provide robust evidence for a new deeply divergent and phylogenetically distinct RNA virus lineage., (© The Author(s) 2020. Published by Oxford University Press.)

Harvesting vibration energy to power wearable devices has become a hot research topic, while the output power and conversion efficiency of a vibration energy harvester with a single electromechanical conversion mechanism is low and the working frequency band and load range are narrow. In this paper, a new structure of piezoelectric electromagnetic coupling up-conversion multi-directional vibration energy harvester is proposed. Four piezoelectric electromagnetic coupling cantilever beams are installed on the axis of the base along the circumferential direction. Piezoelectric plates are set on the surface of each cantilever beam to harvest energy. The permanent magnet on the beam is placed on the free end of the cantilever beam as a mass block. Four coils for collecting energy are arranged on the base under the permanent magnets on the cantilever beams. A bearing is installed on the central shaft of the base and a rotating mass block is arranged on the outer ring of the bearing. Four permanent magnets are arranged on the rotating mass block and their positions correspond to the permanent magnets on the cantilever beams. The piezoelectric cantilever is induced to vibrate at its natural frequency by the interaction between the magnet on cantilever and the magnets on the rotating mass block. It can collect the nonlinear impact vibration energy of low-frequency motion to meet the energy harvesting of human motion.

Person re-identification (Re-ID) aims at matching person images captured in non-overlapping camera views. To represent person appearance, low-level visual features are sensitive to environmental changes, while high-level semantic attributes, such as "short-hair" or "long-hair", are relatively stable. Hence, researches have started to design semantic attributes to reduce the visual ambiguity. However, to train a prediction model for semantic attributes, it requires plenty of annotations, which are hard to obtain in practical large-scale applications. To alleviate the reliance on annotation efforts, we propose to incrementally generate Deep Hidden Attribute (DHA) based on baseline deep network for newly uncovered annotations. In particular, we propose an auto-encoder model that can be plugged into any deep network to mine latent information in an unsupervised manner. To optimize the effectiveness of DHA, we reform the auto-encoder model with additional orthogonal generation module, along with identity-preserving and sparsity constraints. 1) Orthogonally generating: In order to make DHAs different from each other, Singular Vector Decomposition (SVD) is introduced to generate DHAs orthogonally. 2) Identity-preserving constraint: The generated DHAs should be distinct for telling different persons, so we associate DHAs with person identities. 3) Sparsity constraint: To enhance the discriminability of DHAs, we also introduce the sparsity constraint to restrict the number of effective DHAs for each person. Experiments conducted on public datasets have validated the effectiveness of the proposed network. On two large-scale datasets, i.e., Market-1501 and DukeMTMC-reID, the proposed method outperforms the state-of-the-art methods.

Treatment of chronic hepatitis B (CHB) typically requires life-long administration of drugs. Cohort and pre-clinical studies have established the link between a functional T-cell-mounted immunity and resolution of infection. TG1050 is an adenovirus 5-based vaccine that expresses HBV polymerase and domains of core and surface antigen and has shown immunogenicity and antiviral effects in mice. We performed a phase 1 clinical trial to assess safety and explore immunogenicity and early efficacy of TG1050 in CHB patients. This randomized, double blind, placebo-controlled study included two sequential phases: one single dose cohort (SD, n = 12) and one multiple (3) doses cohort (MD, n = 36). Patients, virally suppressed under nucleoside(d)tide analog NUC therapy, were randomized 1:1:1 across 3 dose levels (DL) and assigned to receive 10 9 , 10 10 , 10 11 virus particles (vp) of TG1050 and then randomized within each DL to placebo (3:1 and 9:3 vaccines/placebo in each DL, respectively, for the SD and MD cohorts). Cellular (ELISPOT) and antibody responses (anti-Adenovirus), as well as evolution of circulating HBsAg and HBcrAg, were monitored. All doses were well tolerated in both cohorts, without severe adverse event. TG1050 was capable to induce IFN-γ producing T-cells targeting 1 to 3 encoded antigens, in particular at the 10 10 vp dose. Overall, minor decreases of HBsAg were observed while a number of vaccinees reached unquantifiable HBcrAg by end of the study. In CHB patients under NUC, TG1050 exhibited a good safety profile and was capable to induce HBV-specific cellular immune response. These data support further clinical evaluation, especially in combination studies.

The advent of unbiased metagenomic virus discovery has revolutionized studies of virus biodiversity and evolution. Despite this, our knowledge of the virosphere, including in mammalian species, remains limited. We used unbiased metagenomic sequencing to identify RNA viruses in European field voles and rabbits. Accordingly, we identified a number of novel RNA viruses including astrovirus, rotavirus A, picorna-like virus and a morbilli-like paramyxovirus. In addition, we identified a sobemovirus and a novel luteovirus that likely originated from the rabbit diet. These newly discovered viruses were often divergent from those previously described. The novel astrovirus was most closely related to a virus sampled from the rodent-eating European roller bird ( Coracias garrulous ). PCR screening revealed that the novel morbilli-like paramyxovirus in the UK field vole had a prevalence of approximately 4%, and shared common ancestry with other rodent morbilli-like viruses sampled globally. Two novel rotavirus A sequences were detected in a UK field vole and a French rabbit, the latter with a prevalence of 5%. Finally, a highly divergent picorna-like virus found in the gut of the French rabbit virus was only ~35% similar to an arilivirus at the amino acid level, suggesting the presence of a novel viral genus within the Picornaviridae .

Background: There is no consensus on the optimal anesthesia method for intertrochanteric fracture surgeries in elderly patients. Our study aimed to compare the hemodynamics and perioperative outcomes of general anesthesia with endotracheal intubation, combined spinal-epidural anesthesia, and general anesthesia with laryngeal mask airway (LMA) and nerve block for intertrochanteric fracture surgeries in elderly patients., Methods: This is a retrospective study of 75 patients aged > 60 years scheduled for intertrochanteric fracture surgeries with general anesthesia with intubation (n = 25), combined spinal-epidural anesthesia (n = 25), and general anesthesia with LMA and nerve block (n = 25). The intraoperative hemodynamics were recorded, and the maximum variation rate was calculated. Postoperative analgesic effect was evaluated using the visual analog scale (VAS). Postoperative cognitive status was assessed using the Mini-Mental State Exam (MMSE)., Results: The maximum variation rate of intraoperative heart rate, systolic blood pressure, diastolic blood pressure differed significantly between the three groups (general anesthesia with intubation > combined spinal-epidural anesthesia > general anesthesia with LMA and nerve block). The VAS scores postoperative 2 h, 4 h, 6 h, and 8 h also differed significantly between the three groups (general anesthesia with intubation > combined spinal-epidural anesthesia > general anesthesia with LMA and nerve block). The VAS scores postoperative 24 h were significantly lower in the general anesthesia with LMA/nerve block group than the general anesthesia with intubation group and the combined spinal-epidural anesthesia group. The MMSE scores postoperative 15 min and 45 min differed significantly between the three groups (general anesthesia with intubation < combined spinal-epidural anesthesia < general anesthesia with LMA and nerve block). The MMSE scores postoperative 120 min in the general anesthesia with intubation group were the lowest among the three groups. There was no significant difference in the incidence of respiratory infection postoperative 24 h, 48 h, and 72 h between the three groups., Conclusion: Compared to general anesthesia with intubation and combined spinal-epidural anesthesia, general anesthesia with LMA and nerve block had better postoperative analgesic effect and less disturbances on intraoperative hemodynamics and postoperative cognition for elderly patients undergoing intertrochanteric fracture surgeries.

Background: Australian brushtail possums ( Trichosurus vulpecula ) are an introduced pest species in New Zealand, but native to Australia where they are protected for biodiversity conservation. Wobbly possum disease (WPD) is a fatal neurological disease of Australian brushtail possums described in New Zealand populations that has been associated with infection by the arterivirus ( Arteriviridae ) wobbly possum disease virus (WPDV-NZ). Clinically, WPD-infected possums present with chronic meningoencephalitis, choroiditis and multifocal neurological symptoms including ataxia, incoordination, and abnormal gait., Methods: We conducted a retrospective investigation to characterise WPD in native Australian brushtail possums, and used a bulk meta-transcriptomic approach (i.e. total RNA-sequencing) to investigate its potential viral aetiology. PCR assays were developed for case diagnosis and full genome recovery in the face of extensive genetic variation., Results: We identified genetically distinct lineages of arteriviruses from archival tissues of WPD-infected possums in Australia, termed wobbly possum disease virus AU1 and AU2. Phylogenetically, WPDV-AU1 and WPDV-AU2 shared only ~ 70% nucleotide similarity to each other and the WPDV-NZ strain, suggestive of a relatively ancient divergence. Notably, we also identified a novel and divergent hepacivirus ( Flaviviridae ) - the first in a marsupial - in both WPD-infected and uninfected possums, indicative of virus co-infection., Conclusions: We have identified marsupial-specific lineages of arteriviruses in mainland Australia that are genetically distinct from that in New Zealand, in some cases co-infecting animals with a novel hepacivirus. Our study provides new insight into the hidden genetic diversity of arteriviruses, the capacity for virus co-infection, and highlights the utility of meta-transcriptomics for disease investigation in a One Health context., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2019.)

DNA viruses comprise a wide array of genome structures and infect diverse host species. To date, most studies of DNA viruses have focused on those with the strongest disease associations. Accordingly, there has been a marked lack of sampling of DNA viruses from invertebrates. Bulk RNA sequencing has resulted in the discovery of a myriad of novel RNA viruses, and herein we used this methodology to identify actively transcribing DNA viruses in meta-transcriptomic libraries of diverse invertebrate species. Our analysis revealed high levels of phylogenetic diversity in DNA viruses, including 13 species from the Parvoviridae, Circoviridae , and Genomoviridae families of single-stranded DNA virus families, and six double-stranded DNA virus species from the Nudiviridae , Polyomaviridae , and Herpesviridae , for which few invertebrate viruses have been identified to date. By incorporating the sequence of a "blank" experimental control we also highlight the importance of reagent contamination in metagenomic studies. In sum, this work expands our knowledge of the diversity and evolution of DNA viruses and illustrates the utility of meta-transcriptomic data in identifying organisms with DNA genomes.

Introduction: RSL3-induced ferroptosis is a cell death pathway dependent upon intracellular iron and is characterized by accumulation of lipid hydroperoxides. Glutaminolysis, a glutamine-fueled intracellular metabolic pathway, is an essential pathway of ferroptosis in cancer cells. Recent findings showed low-concentration paclitaxel (PTX) could inhibit cell death by upregulating p53 expression; downregulating glutaminolysis-related genes., Methods: The therapeutic effect of RSL3 plus low-concentration PTX combination therapy was investigated in HPSCC cells harboring mutant p53 ( mtp53 ). Relative cell viability, ferroptosis-specific lipid peroxidation and relevant protein expression were evaluated., Results: We demonstrated that neither PTX nor RSL3 in low concentration caused significant cell death; however, the combination therapy is shown to induce ferroptosis and significant cell death in mtp53 HPSCC. We discovered that low-concentration PTX enhanced the RSL3-induced ferroptosis by upregulating mtp53 expression. Furthermore, mtp53 -mediated transcriptional regulation of SLC7A11 could be the key determinant., Discussion: Although gain-of-function of p53 variants remains to be characterized, our findings provide new insight into the synergistical cell death by regulating ferroptosis and p53 ., Competing Interests: The authors declare that they have no competing interests in this work., (© 2019 Ye et al.)

Epinecidin-1 is an antimicrobial peptide derived from the orange-spotted grouper ( Epinephelus coioides ). The mature epinecidin-1 peptide is predicted to have an amphipathic α-helical structure and a non-helical hydrophilic domain at the C-terminal RRRH. The majority of work studying the potential pharmacological activities of epinecidin-1, utilize synthesized epinecidin-1 (Epi-1), which is made up of 21 amino acids, from the amino acid sequence of 22-42 residues of Epi-1-GFIFHIIKGLFHAGKMIHGLV. The synthetized Epi-1 peptide has been demonstrated to possess diverse pharmacological activities, including antimicrobial, immunomodulatory, anticancer, and wound healing properties. It has also been utilized in different clinical and agricultural fields, including topical applications in wound healing therapy as well as the enhancement of fish immunity in aquaculture. Hence, the present work aims to consolidate the current knowledge and findings on the characteristics and pharmacological properties of epinecidin-1 and its potential applications., (Copyright © 2019 Chee, Mang, Lau, Tan, He, Lee, Pusparajah, Chan, Lee and Goh.)

Mosquitoes harbor an extensive diversity of 'insect-specific' RNA viruses in addition to those important to human and animal health. However, because most studies of the mosquito virome have been conducted at lower latitudes, little is known about the diversity and evolutionary history of RNA viruses sampled from mosquitoes in northerly regions. Here, we compared the RNA virome of two common northern mosquito species, Culex pipiens and Culex torrentium , collected in south-central Sweden. Following bulk RNA-sequencing (meta-transcriptomics) of 12 libraries, comprising 120 specimens of Cx. pipiens and 150 specimens of Cx. torrentium , we identified 40 viruses (representing 14 virus families) of which 28 were novel based on phylogenetic analysis of the RNA-dependent RNA polymerase (RdRp) protein. Hence, we documented similar levels of virome diversity as in mosquitoes sampled from the more biodiverse lower latitudes. Many viruses were also related to those sampled on other continents, indicative of a widespread global movement and/or long host-virus co-evolution. Although the two mosquito species investigated have overlapping geographical distributions and share many viruses, several viruses were only found at a specific location at this scale of sampling, such that local habitat and geography may play an important role in shaping viral diversity in Culex mosquitoes., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Termitidae comprises ∼80% of all termite species [1] that play dominant decomposer roles in tropical ecosystems [2, 3]. Two major events during termite evolution were the loss of cellulolytic gut protozoans in the ancestor of Termitidae and the subsequent gain in the termitid subfamily Macrotermitinae of fungal symbionts cultivated externally in "combs" constructed within the nest [4, 5]. How these symbiotic transitions occurred remains unresolved. Phylogenetic analyses of mitochondrial data previously suggested that Macrotermitinae is the earliest branching termitid lineage, followed soon after by Sphaerotermitinae [6], which cultivates bacterial symbionts on combs inside its nests [7]. This has led to the hypothesis that comb building was an important evolutionary step in the loss of gut protozoa in ancestral termitids [8]. We sequenced genomes and transcriptomes of 55 termite species and reconstructed phylogenetic trees from up to 4,065 orthologous genes of 68 species. We found strong support for a novel sister-group relationship between the bacterial comb-building Sphaerotermitinae and fungus comb-building Macrotermitinae. This key finding indicates that comb building is a derived trait within Termitidae and that the creation of a comb-like "external rumen" involving bacteria or fungi may not have driven the loss of protozoa from ancestral termitids, as previously hypothesized. Instead, associations with gut prokaryotic symbionts, combined with dietary shifts from wood to other plant-based substrates, may have played a more important role in this symbiotic transition. Our phylogenetic tree provides a platform for future studies of comparative termite evolution and the evolution of symbiosis in this taxon., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Radionuclides from the Fukushima Daiichi Nuclear Power Plant were released directly into the ocean as a result of the Great East Japan Earthquake on March 11, 2011. This material became entrained in surface ocean currents and subsequently transported for great distances. In June 2011, a few months after the disaster, we began a surface ocean 129 I monitoring program, with samples from Scripps Pier, La Jolla, California, USA, with the expectation that surface currents originating off the east coast of Japan would eventually carry radionuclides to the La Jolla site. After 7 years of ocean transport, a distinct signal has not yet arrived at Scripps Pier. We have however, recorded an interesting systematic seasonal 129 I time series record that stems from surface circulation variations along the California coast. To provide a more comprehensive picture of the 129 I budget in coastal surface waters off the west coast of the U.S., we also include 129 I data from the Columbia River, and offshore sites along the coast of Washington State. Anthropogenic nuclides are carried by the Columbia River into the Pacific Ocean from the vicinity of the decommissioned Hanford nuclear facility. We find highly elevated 129 I/ 127 I values in the Columbia River, downstream from the Hanford site, but this anthropogenic 129 I becomes significantly diluted once it reaches the Pacific Ocean. Nonetheless, its imprint persists in surface seawater off the west coast of the U.S. that has significantly higher 129 I/ 127 I levels than other surface sites in the Pacific Ocean., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

We described a trifluoromethylation of alkenes using PhICF 3 Cl as bifunctional reagent. Chlorotrifluoromethylated products were obtained when nonconjugated alkenes were treated with PhICF 3 Cl in 1,4-dioxane at 60 °C, while vinyl C-H trifluoromethylated products were obtained by further elimination of hydrochloride in the case of those conjugated alkene substrates in DMF. Broad substrate scope, especially including complex alkenes bearing biological active motifs, suggests that this mild reaction is feasible for late-stage modification in drug discovery.

We isolated Tamdy virus (TAMV; strain XJ01/TAMV/China/2018) from Hyalomma asiaticum ticks infesting Bactrian camels in Xinjiang, China, in 2018. The genome of the strain showed high nucleotide similarity with previously described TAMV strains from Asia. Our study highlights the potential threat of TAMV to public health in China.

Background: Published Canadian epidemiologic data on hepatitis B virus (HBV) infection include single-centre studies or are focused on Indigenous populations. We performed a study to characterize the demographic and clinical features, liver disease status and treatment of people with chronic hepatitis B in Canada., Methods: In this descriptive, opportunistic, cross-sectional study, available data for people known to be monoinfected with HBV were collected by the Canadian HBV Network from existing clinical databases, with support from the National Microbiology Laboratory, Public Health Agency of Canada. Data were collected in all provinces with the exception of New Brunswick and Newfoundland and Labrador. We analyzed the data using parametric and nonparametric statistical methods, with a significance level of p < 0.05., Results: In the 9380 unique patient records reviewed, the median age was 48 years, and 5193 patients (55.4%) were male. Ethnicity information was available for 7858 patients, of whom 5803 (73.8%) were Asian, 916 (11.6%) were black and 914 (11.6%) were white. Most of those tested (5556/6796 [81.8%]) were negative for HBV e-antigen, and most of those with fibrosis data (3481/4260 [81.7%]) had minimal liver fibrosis, with more advanced fibrosis noted in older people (> 40 yr). Of the 980 patients with genotype data, 521 (53.2%) had genotype B or C infection. Most of the 9241 patients with known confirmed treatment status received tenofovir disoproxil fumarate (1655 [17.9%]), lamivudine (1434 [15.5%]) or entecavir (548 [5.9%])., Interpretation: Based on available data, Canadian patients with chronic hepatitis B are predominantly Asian and negative for HBV e-antigen, and have genotype B or C infection. Interprovincial variations were noted in antiviral treatment regimen. This multicentre nationwide study provides data regarding patients with chronic hepatitis B and may inform future studies on the epidemiologic features of HBV infection in Canada., Competing Interests: Competing interests: Carla Coffin reports investigator-initiated research grants/research materials from GlaxoSmithKline, Gilead Sciences, Arbutus Biopharma and Bristol-Myers Squibb, and educational grants from Merck, Gilead Sciences and Janssen Pharmaceutica. She is on the advisory board for Merck, Gilead Sciences and GlaxoSmithKline, and the Trial Guidance and Publication Committee for Spring Bank Pharmaceuticals, and has participated as a local site principal investigator in clinical trials for Gilead Sciences, Spring Bank Pharmaceuticals, Transgene and Janssen Pharmaceutica. Alnoor Ramji reports clinical investigator grants from Allergan, Arbutus Biopharma, Gilead Sciences, Janssen Pharmaceutica, Intercept Pharmaceuticals, Norvartis, Merck, Spring Bank Pharmaceuticals and Assembly Biosciences; personal fees from AbbVie, Gilead Sciences, Intercept Pharmaceuticals, Lupin and Merck; and grants from AbbVie, Celgene Corporation, Gilead Sciences, Janssen Pharmaceutica, Intercept Pharmaceuticals and Merck. Karen Doucette reports a grant from Gilead Sciences. Keith Tsoi reports personal fees from Gilead Sciences, Merck, AbbVie and Intercept Pharmaceuticals, and nonfinancial support from Gilead Sciences. Brian Conway reports grants and honoraria from AbbVie, Gilead Sciences, Indivior, Merck and Viiv Healthcare. He has acted as a consultant for these companies. Lisa Barrett reports grants from AbbVie and personal fees from AbbVie, Bristol-Myers Squibb, Gilead Sciences and ViiV Healthcare. Stephen Congly reports grants from Allergan, Gilead Sciences, Genfit, Boehringer Ingelheim and Bristol-Myers Squibb, and personal fees from Allergan. Edward Tam reports grants from AbbVie, Gilead Sciences, Merck, Intercept Pharmaceuticals and Janssen Pharmaceutica, and personal fees from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Merck, Intercept Pharmaceuticals and Janssen Pharmaceutica. David Wong reports other funding from AbbVie, Merck and Gilead Sciences. Alex Wong reports grants and personal fees from Gilead Sciences. Harry Janssen reports grants from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceutica, MedImmune, Merck and Roche, and personal fees from AbbVie, Benitec Biopharma, Bristol-Myers Squibb, Gilead Sciences, Janssen Pharmaceutica, MedImmune, Roche, Arbutus Biopharma and Vir Biotechnology. Scott Fung reports speaking and teaching fees from Gilead Sciences and Bristol-Myers Squibb, and consulting fees from Gilead Sciences. No other competing interests were reported., (Copyright 2019, Joule Inc. or its licensors.)

Models of host-microbe dynamics typically assume a single-host population infected by a single pathogen. In reality, many hosts form multi-species aggregations and may be infected with an assemblage of pathogens. We used a meta-transcriptomic approach to characterize the viromes of nine avian species in the Anseriformes (ducks) and Charadriiformes (shorebirds). This revealed the presence of 27 viral species, of which 24 were novel, including double-stranded RNA viruses (Picobirnaviridae and Reoviridae), single-stranded RNA viruses (Astroviridae, Caliciviridae, Picornaviridae), a retro-transcribing DNA virus (Hepadnaviridae), and a single-stranded DNA virus (Parvoviridae). These viruses comprise multi-host generalist viruses and those that are host-specific, indicative of both virome connectivity (host sharing) and heterogeneity (host specificity). Virome connectivity was apparent in two well described multi-host virus species -avian coronavirus and influenza A virus- and a novel Rotavirus species that were shared among some Anseriform species, while virome heterogeneity was reflected in the absence of viruses shared between Anseriformes and Charadriiformes, as well as differences in viral abundance and alpha diversity among species. Overall, we demonstrate complex virome structures across host species that co-exist in multi-species aggregations.

While CTA is an established clinical gold standard for imaging large cerebral arteries and veins, an important challenge that currently remains for CTA is its limited performance in imaging small perforating arteries with diameters below 0.5 mm. The purpose of this work was to theoretically and experimentally study the potential benefits of using photon counting detector (PCD)-based CT (PCCT) to improve the performance of CTA in imaging these small arteries. In particular, the study focused on an important component of the CTA image package known as the maximum intensity projection (MIP) image. To help understand how the physical properties of a detector quantitatively influence the MIP image quality, a theoretical model on the statistical properties of MIP images was developed. After validating this model, it was used to explore the individual and joint contribution of the following detector properties to the MIP signal-to-noise ratio (SNR): inter-slice noise covariance, spatial resolution along the z direction, and native pixel pitch along z. The model demonstrated that superior slice sensitivity, reduced inter-slice noise correlation, and smaller native pixel pitch along z provided by PCDs lead to improved vessel SNR in MIP images. Finally, experiments were performed by scanning an anthropomorphic cerebral angiographic phantom using a benchtop PCCT system and a commercial MDCT system. The experimental MIP results consistently demonstrated that compared with MDCT, PCCT provides superior vessel conspicuity and reduced artifactual stenosis.

Phase separation drives numerous cellular processes, ranging from the formation of membrane-less organelles to the cooperative assembly of signaling proteins. Features such as multivalency and intrinsic disorder that enable condensate formation are found not only in cytosolic and nuclear proteins, but also in membrane-associated proteins. The ABC transporter Rv1747, which is important for Mycobacterium tuberculosis ( Mtb ) growth in infected hosts, has a cytoplasmic regulatory module consisting of 2 phosphothreonine-binding Forkhead-associated domains joined by an intrinsically disordered linker with multiple phospho-acceptor threonines. Here we demonstrate that the regulatory modules of Rv1747 and its homolog in Mycobacterium smegmatis form liquid-like condensates as a function of concentration and phosphorylation. The serine/threonine kinases and sole phosphatase of Mtb tune phosphorylation-enhanced phase separation and differentially colocalize with the resulting condensates. The Rv1747 regulatory module also phase-separates on supported lipid bilayers and forms dynamic foci when expressed heterologously in live yeast and M. smegmatis cells. Consistent with these observations, single-molecule localization microscopy reveals that the endogenous Mtb transporter forms higher-order clusters within the Mycobacterium membrane. Collectively, these data suggest a key role for phase separation in the function of these mycobacterial ABC transporters and their regulation via intracellular signaling., Competing Interests: The authors declare no conflict of interest.

Background: The intranasal route of dexmedetomidine (DEX) administration is becoming increasingly popular for providing adequate sedation during short examinations in infants and children. However, data on the 90% effective dose (ED90) of intranasal DEX are rare in children under 3 years old., Methods: This is a double-blind trial using a biased coin design up-and-down sequential method (BCD-UDM). Fifty-three children aged under 3 years old requiring DEX for EEG were included in our study. The first patient received 2.5 μg kg -1 DEX, and the dose of DEX administered to the subsequent patient was determined by the response of the previous patient. The patient responses were recorded and analysed to calculate the ED90 by isotonic regression. The 95% confidence interval (CI) was estimated using a bootstrapping method., Results: Fifty-three patients were included in our study, of which 45 patients were successfully sedated, and the 8 instances of failed sedation were rescued using sevoflurane inhalation, allowing the completion of the procedure. The 90% effective dose of DEX was calculated to be 3.28 µg kg -1 , and the 95% CI was 2.74 ~ 3.39 µg kg -1 . No significant adverse events occurred in any of the patients., Conclusion: The 90% effective dose of intranasal DEX sedation for EEG was 3.28 μg kg -1 in children under 3 years old., (© 2019 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)