Search

ABSTRACT: The H9N2 subtype of the avian influenza virus (AIV) is widely prevalent in birds, threatening the poultry industry and providing genetic material for emerging human pathogens. The prevalence and genetic characteristics of H9N2 in Yunnan Province, China, are largely unknown. Samples were collected from live poultry markets (LPMs) and breeding farms in Yunnan Province. H9N2-positive samples were identified by polymerase chain reaction (PCR), with a high positivity rate of 42.86% in tissue samples. The positivity rate of swab samples in the LPMs in Kunming was 3.97% (17/564), but no AIV was detected in samples from poultry farms in Lijiang, Wenshan, and Yuxi. Evolutionary analysis and genotyping were performed for the 17 strains of isolated H9N2 virus. Phylogenetic analysis revealed that all H9N2 viral genes had 91.6%–100% nucleotide homology, belonged to the G57 genotype, and had high homology with H9N2 viruses isolated from Guangdong and Guangxi, suggesting that the H9N2 viruses in Yunnan Province may have been imported by chicks. Using a nucleotide divergence cutoff of 95%, we identified ten distinct H9N2 genotypes that continued to evolve. The surface genes of the H9N2 isolates displayed substantial genetic diversity, highlighting the genetic diversity and complexity of the H9N2-subtype AIVs in Yunnan. Molecular analysis demonstrated that all 17 strains of H9N2 isolates had mutations at H183N, Q226L, L31P, and I268V in hemagglutinin; S31N in matrix protein 2; and no replacements at positions 274 and 292 of the neuraminidase protein. Sixteen strains had the A558V mutation and one strain had the E627V mutation in polymerase basic protein 2. Analysis of these amino acid sites suggests that H9N2 influenza viruses in Yunnan continue to mutate and adapt to mammals and are sensitive to neuraminidase inhibitors but resistant to adamantanes. It is necessary to strengthen surveillance of AIV H9N2 subtypes in poultry and LPMs in Yunnan to further understand their genetic diversity.

Porcine epidemic diarrhea virus (PEDV) is a highly infectious pathogen that targets pig intestines to cause disease. It is globally widespread and causes huge economic losses to the pig industry. PEDV N protein is the protein that constitutes the core of PEDV virus particles, and most of it is expressed in the cytoplasm, and a small part can also be expressed in the nucleus. However, the role of related proteins in host nucleotide metabolic pathways in regulating PEDV replication have not been fully elucidated. In this study, PEDV-N-labeled antibodies were co-immunoprecipitated and combined with LC-MS to screen for host proteins that interact with N proteins. Bioinformatics analyses showed that the selected host proteins were mainly enriched in metabolic pathways. Moreover, co-immunoprecipitation and confocal microscopy confirmed that the second-largest subunit of RNA polymerase II (RPB2) and uridine phosphorylase 1 (UPP1) interacted with the N protein. RPB2 is the main subunit of RNA polymerase II and plays an important role in eukaryotic transcription. UPP1 is an enzyme that catalyzes reversible phosphorylation of uridine to uracil and ribo-1-phosphate to promote catabolism and bio anabolism. RPB2 overexpression significantly promoted viral replication, whereas UPP1 overexpression significantly inhibited viral replication. Studies on interactions between the PEDV N and host proteins are helpful in elucidating the pathogenesis and immune escape mechanism of PEDV.

Introduction:Bacillus licheniformis (B.licheniformis) was widely used in poultry feeds. However, it is still unclear about how B.licheniformis regulates the growth and development of Pekin ducks.Methods: The experiment was designed to clarify the effect and molecular mechanism of B. licheniformis on the lipid metabolism and developmental growth of Pekin ducks through multiomics analysis, including transcriptomic and metabolomic analyses.Results: The results showed that compared with the control group, the addition of 400 mg/kg B. licheniformis could significantly increase the body weight of Pekin ducks and the content of triglyceride (p < 0.05), at the same time, the addition of B. licheniformis could affect the lipid metabolism of liver in Pekin ducks, and the addition of 400 mg/kg B. licheniformis could significantly increase the content of lipoprotein lipase in liver of Pekin ducks. Transcriptomic analysis revealed that the addition of B. licheniformis primarily impacted fatty acid and glutathione, amino acid metabolism, fatty acid degradation, as well as biosynthesis and elongation of unsaturated fatty acids. Metabolomic analysis indicated that B. licheniformis primarily affected the regulation of glycerol phospholipids, fatty acids, and glycerol metabolites. Multiomics analysis demonstrated that the addition of B. licheniformis to the diet of Pekin ducks enhanced the regulation of enzymes involved in fat synthesis via the PPAR signaling pathway, actively participating in fat synthesis and fatty acid transport.Discussion: We found that B. licheniformis effectively influences fat content and lipid metabolism by modulating lipid metabolism-associated enzymes in the liver. Ultimately, this study contributes to our understanding of how B. licheniformis can improve the growth performance of Pekin ducks, particularly in terms of fat deposition, thereby providing a theoretical foundation for its practical application.Conclusion:B. licheniformis can increase the regulation of enzymes related to fat synthesis through PPAR signal pathway, and actively participate in liver fat synthesis and fatty acid transport, thus changing the lipid metabolism of Pekin ducks, mainly in the regulation of glycerol phospholipids, fatty acids and glycerol lipid metabolites.

IntroductionPorcine epidemic diarrhea (PED) is an acute, highly contagious, and high-mortality enterophilic infectious disease caused by the porcine epidemic diarrhea virus (PEDV). PEDV is globally endemic and causes substantial economic losses in the swine industry. The PEDV E protein is the smallest structural protein with high expression levels that interacts with the M protein and participates in virus assembly. However, how the host proteins interact with E proteins in PEDV replication remains unknown.MethodsWe identified host proteins that interact with the PEDV E protein using a combination of PEDV E protein-labeled antibody co-immunoprecipitation and tandem liquid-chromatography mass-spectroscopy (LC-MS/MS).ResultsBioinformatical analysis showed that in eukaryotes, ribosome biogenesis, RNA transport, and amino acid biosynthesis represent the three main pathways that are associated with the E protein. The interaction between the E protein and isocitrate dehydrogenase [NAD] β-subunit (NAD-IDH-β), DNA-directed RNA polymerase II subunit RPB9, and mRNA-associated protein MRNP 41 was validated using co-immunoprecipitation and confocal assays. NAD-IDH-β overexpression significantly inhibited viral replication.DiscussionThe antiviral effect of NAD-IDH-β suggesting that the E protein may regulate host metabolism by interacting with NAD-IDH-β, thereby reducing the available energy for viral replication. Elucidating the interaction between the PEDV E protein and host proteins may clarify its role in viral replication. These results provide a theoretical basis for the study of PEDV infection mechanism and antiviral targets.

Abstract Natural killer (NK) cells are promising alternatives for the production of “off-the-shelf” CAR products, posing a lower risk of cytokine release syndrome (CRS) than CAR-T cells. We synthesized four single VHH-directed anti-BCMA CARs, incorporating various intracellular regions (2B4 versus CD28) and hinge domains (CD28 versus IgG1) and ectopically producing IL-15. NK cells derived from peripheral blood (PB) were expanded ex vivo by K562-mbIL21 feeder cells. Stable CAR transduction was obtained through lentiviral transduction with the BaEV-Rless pseudotyped lentiviral vector. BCMA-CD28-IL15 CAR-NK cells with ectopic expression of IL-15 exhibited superior cytotoxicity were compared to BCMA-CD28 CAR-NK cells lacking IL-15 and BCMA-hIgG1-IL15 CAR-NK cells with an IgG1 hinge domain. We further assessed the cytotoxic capabilities of BCMA-2B4-IL15 CAR-NK cells with 2B4 intracellular domain. The BCMA-CD28-IL15 CAR-NK cells revealed stronger cytotoxicity and higher cytokine secretion against BCMA+ tumor cells than BCMA-2B4-IL15 CAR-NK cells in vitro. In the MM.1S-Luc mouse model, BCMA-CD28-IL15 CAR-NK inhibited the growth of tumor cells and prolonged mouse survival. These results show that the single VHH-directed BCMA CAR-NK cells exhibited remarkable specific killing ability, making them a potential candidate for immunotherapy in multiple myeloma treatment.

Abstract Background Wilms tumour (WT) is a mixed type of embryonal tumour that usually occurs in early childhood. However, our knowledge of the pathogenesis or progression mechanism of WT is inadequate, and there is a scarcity of beneficial therapeutic strategies. Methods High-throughput RNA sequencing was employed in this study to identify differentially expressed genes (DEGs) in clinical tumor samples and matching normal tissues. The STRING database was utilized to build a protein-protein interaction (PPI) network, and the Cytohubba method was used to identify the top 10 highly related HUB genes. Then, the key genes were further screened by univariate COX survival analysis. Subsequently, the XCELL algorithm was used to evaluate the tumour immune infiltration. RT-PCR, WB, and IF were used to verify the expression level of key genes in clinical tissues and tumour cell lines. Finally, the function of the key gene was further verified by loss-of-function experiments. Results We initially screened 1612 DEGs, of which 1030 were up-regulated and 582 were down-regulated. The GO and KEGG enrichment analysis suggested these genes were associated with ‘cell cycle’, ‘DNA replication’. Subsequently, we identified 10 key HUB genes, among them CCNB1 was strongly related to WT patients’ overall survival. Multiple survival analyses showed that CCNB1 was an independent indicator of WT prognosis. Thus, we constructed a nomogram of CCNB1 combined with other clinical indicators. Single gene GSEA and immune infiltration analysis revealed that CCNB1 was associated with the degree of infiltration or activation status of multiple immune cells. TIDE analysis indicated that this gene was correlated with multiple key immune checkpoint molecules and TIDE scores. Finally, we validated the differential expression level of CCNB1 in an external gene set, the pan-cancer, clinical samples, and cell lines. CCNB1 silencing significantly inhibited the proliferation, migration, and invasive capabilities of WIT-49 cells, also, promoted apoptosis, and in turn induced G2 phase cell cycle arrest in loss-of-function assays. Conclusion Our study suggests that CCNB1 is closely related to WT progression and prognosis, and serves as a potential target.

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

When entering a ferromagnet, a spin-singlet supercurrent decays rapidly, while a spin-triplet supercurrent can extend over much longer distances. Here, the authors observe long-range, spin triplet supercurrent in lateral Josephson junctions constructed using the van der Waals metallic ferromagnet Fe3GeTe2 as the weak link.

IntroductionNewcastle disease virus (NDV) is prevalent worldwide with an extensive host range. Among birds infected with velogenic NDV strains, chickens experience high pathogenicity and mortality, whereas ducks mostly experience mild symptoms or are asymptomatic. Ducks have a unique, innate immune system hypothesized to induce antiviral responses. Circular RNAs (circRNAs) are among the most abundant and conserved eukaryotic transcripts. These participate in innate immunity and host antiviral response progression.MethodsIn this study, circRNA expression profile differences post-NDV infection in duck embryo fibroblast (DEF) cells were analyzed using circRNA transcriptome sequencing. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to reveal significant enrichment of differentially expressed (DE) circRNAs. The circRNA-miRNA-mRNA interaction networks were used to predict the related functions of circRNAs. Moreover, circ-FBXW7 was selected to determine its effect on NDV infection in DEFs.ResultsNDV infection altered circRNA expression profiles in DEF cells, and 57 significantly differentially expressed circRNAs were identified post-NDV infection. DEF responded to NDV by forming circRNAs to regulate apoptosis-, cell growth-, and protein degradation-related pathways via GO and KEGG enrichment analyses. circRNA-miRNA-mRNA interaction networks demonstrated that DEF cells combat NDV infection by regulating cellular pathways or apoptosis through circRNA-targeted mRNAs and miRNAs. circ-FBXW7 overexpression and knockdown inhibited and promoted viral replication, respectively. DEF cells mainly regulated cell cycle alterations or altered cellular sensing to combat NDV infection.ConclusionThese results demonstrate that DEF cells exert antiviral responses by forming circRNAs, providing novel insights into waterfowl antiviral responses.

Abstract Background Traumatic aortic pseudoaneurysms (PSAs) classified as grade III aortic injuries are conventionally repaired as procedural emergencies, generally within 24 h of arrival. These patients typically require adequate resuscitation and treatment of multiple traumatic injuries, which complicate optimal management strategies of aortic PSAs. This study reviews the experience of an Asian single center to evaluate the efficacy and safety of delayed (> 24 h) endovascular repair for PSAs. Methods Twenty-seven patients with blunt aortic injury (BTAI) were brought to our institution between February 2014 and May 2020. Patients with other grades of aortic injuries (grade I, II, or IV) were excluded from the study, and the remaining patients with grade III aortic injuries were placed into the early ( 24 h) groups according to the timing of repair. Medical records and follow-up computed tomography (CT) scans were reviewed to document the outcomes of the procedures. Primary outcomes included mortality and complications. Results During this period, there were 14 patients (13 males and 1 females) with aortic PSAs, and each patient received thoracic endovascular aortic repair (TEVAR). Of these 14 patients, 1 underwent emergent TEVAR, and 13 underwent delayed repair (median 7 days, range, 3–14 days). Over a period of 8 years, the overall survival of our series was 100%. No paraplegia, stroke, ischemia of limb or other serious procedural complications were observed during the duration of follow-up. Conclusion The experience of our center indicates that delayed repair for selected PSAs could be permissible, which enables a repair in more controlled circumstances.

Abstract When high‐temperature superconducting (HTS) tapes in high voltage DC HTS devices are quenched, amounts of thermal bubbles are generated in liquid nitrogen (LN2) that will reduce the insulation strength greatly. Especially when resistive‐type superconducting fault current limiters meet a short‐circuit fault, the insulation strength of the LN2 decreased significantly due to the thermal bubbles and electrothermal pressure. Solid insulating barriers can improve the insulation strength of the LN2. The objective of this study is to obtain the effect of barrier thickness on the DC dielectric breakdown characteristics of LN2. Insulating barrier Polytetrafluoroethylene with three different thicknesses were tested. Three types of electrodes such as rod‐plane, needle‐plane, and plane‐plane were applied. The results showed that the barriers can increase the negative and positive breakdown voltage both with and without thermal bubbles in a slightly non‐uniform field (SNF) and non‐uniform field (NF). For the SNF, the DC breakdown voltage is higher when the barrier is thinner. The effect of the barrier thickness in the NF is lower than that in the SNF field. For the NF, the positive breakdown voltage is higher when the barrier is thicker.

Abstract The short‐circuit fault current of the urban rail transit systems is hard to interrupt due to the high amplitude and the high rising rate. The existing air DC circuit breakers applied in the rail transit DC traction system are difficult to interrupt the short‐circuit fault current quickly and reliably, and cannot meet the increasing demand of the system capacity. The objective of this paper is to design a novel DC combined apparatus including a DC fuse module and an artificial zero crossing module series‐connected to solve the problem of rapid isolation of short‐circuit fault current in DC traction systems. The DC fuse module consists of a DC fuse and a transfer switch with additional auxiliary coils. Experimental results show that the DC combined apparatus can interrupt the rated current, overload current, and short‐circuit current effectively within 6 ms. It can interrupt a 20 kA overload current within 5.12 ms, and the interrupting time of a prospective short‐circuit current of 100 kA is less than 5.08 ms. The designed DC combined apparatus has the full range of current interrupting capacity and has the advantages of low on‐state loss and low cost, which can significantly improve the reliability and stability of rail transit systems.

Hydropericardium hepatitis syndrome (HHS) is primarily caused by fowl adenovirus serotype 4 (FAdV-4), causing high mortality in chickens. Although vaccination strategies against FAdV-4 have been adopted, HHS still occurs sporadically. Furthermore, no effective drugs are available for controlling FAdV-4 infection. However, type I and III interferon (IFN) are crucial therapeutic agents against viral infection. The following experiments were conducted to investigate the inhibitory effect of chicken IFN against FadV-4. We expressed recombinant chicken type I IFN-α (ChIFN-α) and type III IFN-λ (ChIFN-λ) in Escherichia coli and systemically investigated their antiviral activity against FAdV-4 infection in Leghorn male hepatocellular (LMH) cells. ChIFN-α and ChIFN-λ dose dependently inhibited FAdV-4 replication in LMH cells. Compared with ChIFN-λ, ChIFN-α more significantly inhibited viral genome transcription but less significantly suppressed FAdV-4 release. ChIFN-α- and ChIFN-λ-induced IFN-stimulated gene (ISG) expression, such as PKR, ZAP, IRF7, MX1, Viperin, IFIT5, OASL, and IFI6, in LMH cells; however, ChIFN-α induced a stronger expression level than ChIFN-λ. Thus, our data revealed that ChIFN-α and ChIFN-λ might trigger different ISG expression levels, inhibiting FAdV-4 replication via different steps of the FAdV-4 lifecycle, which furthers the potential applications of IFN antiviral drugs in chickens.

Abstract Newcastle disease (ND) is an acute, febrile, and highly contagious disease caused by the Newcastle disease virus (NDV), an important pathogen harmful to domestic poultry. Virulent NDV strain infection induces IL-1β expression and along with strong inflammatory response, ultimately results in death. Inhibition or overexpression of S1PR1, an important target for inflammatory disease treatment, regulates IL-1β expression, suggesting that S1PR1 may alter the degree of the inflammatory response induced by NDV infection by regulating pro-inflammatory cytokine expression. However, the molecular mechanism by which S1PR1 regulates IL-1β expression remains unclear. Here, we explore the expression and tissue distribution of S1PR1 after NDV infection and found that S1PR1 expression increased in the lungs, bursa of Fabricius, and DF-1. IL-1β expression induced by NDV was increased following treatment of cells with the S1PR1-specific agonist, SEW2871. In contrast, IL-1β expression induced by NDV was decreased after cells were treated with the S1PR1 inhibitor W146, suggesting that S1PR1 promotes NDV-induced IL-1β expression. Further investigation demonstrated that NDV induced IL-1β expression through p38, JNK/MAPK, and NLRP3/caspase-1 signaling molecules and S1PR1 affected the expression of IL-1β by activating the NLRP3/caspase-1 inflammasome but had no significant effect on p38 and JNK/MAPK. Our study shows that NDV infection promotes S1PR1 expression and induces IL-1β expression through p38, JNK/MAPK, and NLRP3/caspase-1 inflammasomes and that S1PR1 regulates IL-1β expression mainly through the NLRP3/caspase-1 inflammasome.

Abstract Superconducting fault current limiters (SFCLs) are important in improving the stability of electrical power systems. However, the existing resistive‐type DC SFCL has a long recovery time, which cannot meet the requirements of power system auto‐reclosure. Thus, it is necessary to investigate the methods of reducing recovery time of SFCLs. In the simulations on superconducting tapes, there is a lack of investigation about the effects of design factors of superconducting tapes and coils such as material, thickness, coil radius, coil winding method on recovery characteristics. The objective of this study is to obtain the effects of material and geometric properties of superconducting tapes and coils on recovery characteristics and obtain methods to reduce the recovery time. The recovery times under different conducting currents are also compared by simulations and experiments to verify simulation accuracy. The maximum error is below 40% and most of the cases have an error below 10%. Besides, by increasing tape thickness, the recovery time can be reduced by 22%. Tape materials and coil winding methods can be designed according to the auto‐reclosure and current‐limiting requirements of the power systems. The research provided directions for the design of superconducting tape and superconducting coil for resistive‐type DC SFCLs.

Antitumor activity of CD8+ T cells is potentially restrained by a variety of negative regulatory pathways that are triggered in the tumor microenvironment, yet, the exact mechanisms remain incompletely defined. Here, we report that intrinsic RIG-I in CD8+ T cells represents such a factor, as evidenced by observations that the tumor-restricting effect of endogenous or adoptively transferred CD8+ T cells was enhanced by intrinsic Rig-I deficiency or inhibition, with the increased accumulation, survival, and cytotoxicity of tumor-infiltrating CD8+ T cells. Mechanistically, T cell activation–induced RIG-I upregulation restrained STAT5 activation via competitive sequestering of HSP90. In accordance with this, the frequency of RIG-I+ tumor-infiltrating CD8+ T cells in human colon cancer positively correlated with attenuated survival and effector signatures of CD8+ T cells as well as poor prognosis. Collectively, these results implicate RIG-I as a potentially druggable factor for improving CD8+ T cell–based tumor immunotherapy.

IntroductionNewcastle disease virus (NDV) is an important avian pathogen prevalent worldwide; it has an extensive host range and seriously harms the poultry industry. Velogenic NDV strains exhibit high pathogenicity and mortality in chickens. Circular RNAs (circRNAs) are among the most abundant and conserved eukaryotic transcripts. They are part of the innate immunity and antiviral response. However, the relationship between circRNAs and NDV infection is unclear.MethodsIn this study, we used circRNA transcriptome sequencing to analyze the differences in circRNA expression profiles post velogenic NDV infection in chicken embryo fibroblasts (CEFs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to reveal significant enrichment of differentially expressed (DE) circRNAs. The circRNA- miRNA-mRNA interaction networks were further predicted. Moreover, circ-EZH2 was selected to determine its effect on NDV infection in CEFs.ResultsNDV infection altered circRNA expression profiles in CEFs, and 86 significantly DE circRNAs were identified. GO and KEGG enrichment analyses revealed significant enrichment of DE circRNAs for metabolism-related pathways, such as lysine degradation, glutaminergic synapse, and alanine, aspartic-acid, and glutamic-acid metabolism. The circRNA- miRNA-mRNA interaction networks further demonstrated that CEFs might combat NDV infection by regulating metabolism through circRNA-targeted mRNAs and miRNAs. Furthermore, we verified that circ-EZH2 overexpression and knockdown inhibited and promoted NDV replication, respectively, indicating that circRNAs are involved in NDV replication.ConclusionsThese results demonstrate that CEFs exert antiviral responses by forming circRNAs, offering new insights into the mechanisms underlying NDV-host interactions.

Fowl adenovirus-induced hepatitis–pericardial effusion syndrome outbreaks have been increasingly reported in China since 2015, resulting in substantial economic losses to the poultry industry. The genetic diversity of indigenous chicken results in different immune traits, affecting the evolution of these viruses. Although the molecular epidemiology of fowl adenovirus serotype 4 (FAdV-4) has been well studied in commercial broiler and layer chickens, the prevalence and genetic characteristics of FAdV-4 in indigenous chickens remain largely unknown. In this study, samples were collected from six indigenous chicken breeds in Yunnan province, China. FAdV-positive samples were identified in five of the six indigenous chicken populations via PCR and 10 isolates were obtained. All FAdVs belonged to serotype FAdV-4 and species FAdV-C. The hexon, fiber, and penton gene sequence comparison analysis demonstrated that the prevalence of FAdV-4 isolates in these chickens might have originated from other provinces that exported chicks and poultry products to Yunnan province. Moreover, several distinct amino acid mutations were firstly identified in the major structural proteins. Our findings highlighted the need to decrease inter-regional movements of live poultry to protect indigenous chicken genetic resources and that the immune traits of these indigenous chickens might result in new mutations of FAdV-4 strains.

Abstract Superconducting energy pipeline (SEP) is a new type of electrical energy transmission. It contains high‐temperature superconducting cables and liquefied natural gas pipelines and can simultaneously transmit electricity and liquefied natural gas (LNG). However, when the superconducting tapes in the superconducting cables in SEP quench and generate heat, bubbles will generate in the butt‐gaps of the insulation layer of superconducting cables, which can reduce the insulation strength of the cables significantly. In addition, the effects of bubbles in the butt‐gap of the insulation layer on the insulation properties of the superconducting cables are unknown. The objective here is to obtain the influences of bubbles in the insulation layer of superconducting cables in capacitive field, transitional field, and resistive field. Simulation results show that: Compared with the absence of bubbles, the big bubbles can increase the capacitive field strength of the PP film, the butt‐gap, and the kraft by 37.54%, 30.89%, and 18.5%, and increase the transition time from the capacitive field to the resistive field, but has almost no effect on the butt‐gap in the resistive field.

Abstract Background Airway mucus hypersecretion is one of the important pathological features of chronic obstructive pulmonary disease (COPD). MUC5B is the main mucin expressed in the airways of COPD patients and has been indicated to play an important role in airway defense. However, the specific biological function of MUC5B in COPD and the possible mechanism are not clear. Methods We established a COPD model with 24-week-old MUC5B−/− mice exposed to cigarette smoke and tested our hypothesis through lung function tests, HE and PAS staining, immunohistochemistry (IHC), western blot, q-PCR and ELISA. Results Compared with MUC5B+/+ mice, MUC5B−/− mice had worse general condition and lung function, increased inflammatory infiltration, reduced goblet cell differentiation as indicated by decreased PAS staining (PAS grade: 1.8 ± 0.24 vs. 0.6 ± 0.16), reduced MUC5AC expression (ELISA: 0.30 ± 0.01 vs. 0.17 ± 0.01 mg/ml, q-PCR: 9.4 ± 1.7 vs. 4.1 ± 0.1 fold, IHC score: 3.1 ± 0.9 vs. 1.6 ± 0.7), increased macrophage secretion of inflammatory factors (TNF-α and IL-6) and expression of downstream pathway factors (ERK1/2 and NF-κB), decreased expression of SPDEF and STAT6, and increased expression of FOXA2. Conclusion The protective effect of MUC5B in the development of COPD was mediated by the promotion of goblet cell differentiation and the inhibition of inflammation. The role of MUC5B in regulating inflammation was related to macrophage function, and goblet cell differentiation was promoted by the induced expression of STAT6 and SPDEF. This study describes a mechanism of mucus hypersecretion and identifies MUC5B as a new target for the treatment of mucus hypersecretion.

Addressing the overheating fault detection and alarming of insulated busways in buildings, a system based on sensing volatile gases generated by the thermal degradation of the busduct insulation layer was proposed. By monitoring the concentration of volatile gases in the environment, the overheating fault of the busducts can be found early. The thermal degradation process of the busway insulating layer is analyzed, and the pyrolysis characteristic gas at low temperature is studied. The experimental platform has been built, by which the relation between the concentration of volatile gases and temperature of the insulated layer has been studied. By testing, the concentration of volatile organic compounds (VOCs) is proposed as the basis for judging the overheating fault in the alarming system. With the collected samples for training and testing, the AdaBoost classifier is used to identify the overheating fault. Finally, the design of the overheating fault alarming system is given.

Abstract Background Previous studies have revealed obesity, nutrition, lifestyle, genetic and epigenetic factors may be risk factors for the occurrence and development of non-alcoholic fatty liver disease (NAFLD). However, the effect of total polyunsaturated fatty acid (PUFA) consumption on the risk of NAFLD is uncertain. Therefore, this study aimed to determine whether the total PUFA intake is independently associated with the risk of NAFLD and explore the threshold of PUFA intake better illustrate the correlation between them in Chinese Han adults. Methods The present study was a retrospective case–control study. A total of 534 NAFLD patients and 534 controls matched by gender and age in the same center were included in this study. Using a semi-quantitative food frequency questionnaire in a health examination center in China to collect information about dietary intake and calculate nutrient consumption. A multivariate logistic regression model was used to estimate the association between total PUFA daily intake and its quartile and the incidence of NAFLD. Results Multivariate analyses suggested a significant association between total PUFA intake and the occurrence of NAFLD. A non-linear relationship between total PUFA consumption and NAFLD risk was detected after adjusting for potential confounding factors. There was a significant connection between PUFA and the risk of NAFLD (OR: 1.32, 95% CI: 1.23–1.41, P

Objectives To investigate the incidence, predisposing factors, diagnosis and management of subcapsular renal haematoma (SRH) after ureteroscopic lithotripsy (URSL).Design Retrospective observational study.Setting Shandong Provincial Hospital, a 4500-bed tertiary hospital in China.Participants The data from 1535 consecutive patients treated with URSL (including rigid URSL and flexible URSL) between January 2015 and October 2020 were retrospectively analysed.Main outcome measures SRH after URSL confirmed via CT. The characteristics, operative data and outcomes of these patients were documented and compared.Results Six patients were confirmed to have an SRH after URSL on CT. The total incidence of SRH after URSL was 0.39%. The incidences of SRH after rigid URSL and flexible URSL were 0.38% and 0.41%, respectively. Unendurable ipsilateral flank pain and a significant decrease in haemoglobin after surgery were the typical clinical manifestations of SRH after URSL. There were no significant differences in age, sex, history of diabetes mellitus, preoperative hypertension, body mass index, stone laterality or perfusion pressure (p>0.05). However, SRH was significantly associated with the stone size, stone location, degree of hydronephrosis and operative duration (p

Background: Yiyi Fuzi Baijiang powder (YFBP) is a traditional Chinese medicine used to treat colorectal cancer, although its bioactivity and mechanisms of action have not been studied in depth yet. The study intended to identify the potential targets and signaling pathways affected by YFBP during the treatment of colorectal cancer through pharmacological network analysis and to further analyze its chemical compositions and molecular mechanisms of action.Methods: The Traditional Chinese Medicine Systems Pharmacology (TCMSP), Traditional Chinese Medicine Integrated Database (TCMID), HitPredict (HIT), and Search Tool for Interactions of Chemicals (STITCH) databases were used to screen the bioactive components and promising targets of YFBP. Targets related to colorectal cancer were retrieved from the GeneCards and Gene Ontology databases. Cytoscape software was used to construct the “herb–active ingredient–target” network. The STRING database was used to construct and analyze protein–protein interactions (PPIs). Afterward, the R packages clusterProfiler and Cytoscape Hub plug-in were used to perform Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of target genes. The results of the network pharmacological analysis were also experimentally validated.Results: In total, 33 active components and 128 target genes were screened. Among them, 46 target genes were considered potential therapeutic targets that crossed the CRC target genes. The network pharmacology analysis showed that the active components of YFBP were correlated positively with CRC inflammatory target genes such as TLR4, TNF, and IL-6. The inflammation-related signaling pathways affected by the active components included the TNF-α, interleukin-17, and toll-like receptor signaling pathways. The active ingredients of YFBP, such as luteolin, β-sitosterol, myristic acid, and vanillin, may exert anti-tumor effects by downregulating SMOX expression via anti-inflammatory signaling and regulation of the TLR4/NF-κB signaling pathway.Conclusion: In the present study, the potential active components, potential targets, and key biological pathways involved in the YFBP treatment of CRC were determined, providing a theoretical foundation for further anti-tumor research.

BackgroundNeuroblastoma (NB) is the most frequent solid tumor in pediatrics, which accounts for roughly 15% of cancer-related mortality in children. NB exhibited genetic, morphologic, and clinical heterogeneity, which limited the efficacy of available therapeutic approaches. Recently, a new term ‘cuproptosis’ has been used to denote a unique biological process triggered by the action of copper. In this instance, selectively inducing copper death is likely to successfully overcome the limitations of conventional anticancer drugs. However, there is still a gap regarding the role of cuproptosis in cancer, especially in pediatric neuroblastoma.MethodsWe characterized the specific expression of cuproptosis-related genes (CRGs) in NB samples based on publicly available mRNA expression profile data. Consensus clustering and Lasso-Cox regression analysis were applied for CRGs in three independent cohorts. ESTIMATE and Xcell algorithm was utilized to visualize TME score and immune cell subpopulations’ relative abundances. Tumor Immune Dysfunction and Exclusion (TIDE) score was used to predict tumor response to immune checkpoint inhibitors. To decipher the underlying mechanism, GSVA was applied to explore enriched pathways associated with cuproptosis signature and Connectivity map (CMap) analysis for drug exploration. Finally, qPCR verified the expression levels of risk-genes in NB cell lines. In addition, PDHA1 was screened and further validated by immunofluorescence in human clinical samples and loss-of-function assays.ResultsWe initially classified NB patients according to CRGs and identified two cuproptosis-related subtypes that were associated with prognosis and immunophenotype. After this, a cuproptosis-related prognostic model was constructed and validated by LASSO regression in three independent cohorts. This model can accurately predict prognosis, immune infiltration, and immunotherapy responses. These genes also showed differential expression in various characteristic groups of all three datasets and NB cell lines. Loss-of-function experiments indicated that PDHA1 silencing significantly suppressed the proliferation, migration, and invasion, in turn, promoted cell cycle arrest at the S phase and apoptosis of NB cells.ConclusionsTaken together, this study may shed light on new research areas for NB patients from the cuproptosis perspective.

BackgroundThe COVID-19 pandemic has killed over 6 million people worldwide. Despite the accumulation of knowledge about the causative pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the pathogenesis of this disease, cures remain to be discovered. We searched for certain peptides that might interfere with spike protein (S protein)-angiotensin-converting enzyme 2 (ACE2) interactions.MethodsPhage display (PhD)-12 peptide library was screened against recombinant spike trimer (S-trimer) or receptor-binding domain (S-RBD) proteins. The resulting enriched peptide sequences were obtained, and their potential binding sites on S-trimer and S-RBD 3D structure models were searched. Synthetic peptides corresponding to these and other reference sequences were tested for their efficacy in blocking the binding of S-trimer protein onto recombinant ACE2 proteins or ACE2-overexpressing cells.ResultsAfter three rounds of phage selections, two peptide sequences (C2, DHAQRYGAGHSG; C6, HWKAVNWLKPWT) were enriched by S-RBD, but only C2 was present in S-trimer selected phages. When the 3D structures of static monomeric S-RBD (6M17) and S-trimer (6ZGE, 6ZGG, 7CAI, and 7CAK, each with different status of S-RBDs in the three monomer S proteins) were scanned for potential binding sites of C2 and C6 peptides, C6 opt to bind the saddle of S-RBD in both 6M17 and erected S-RBD in S-trimers, but C2 failed to cluster there in the S-trimers. In the competitive S-trimer-ACE2-binding experiments, synthetic C2 and C6 peptides inhibited S-trimer binding onto 293T-ACE2hR cells at high concentrations (50 μM) but not at lower concentrations (10 μM and below), neither for the settings of S-trimer binding onto recombinant ACE2 proteins.ConclusionUsing PhD methodology, two peptides were generated bearing potentials to interfere with S protein-ACE2 interaction, which might be further exploited to produce peptidomimetics that block the attachment of SARS-CoV-2 virus onto host cells, hence diminishing the pathogenesis of COVID-19.

Wilms tumour (WT) is the most common kidney malignancy in children. Chemoresistance is the leading cause of tumour recurrence and poses a substantial therapeutic challenge. Increasing evidence has underscored the role of the tumour immune microenvironment (TIM) in cancers and the potential for immunotherapy to improve prognosis. There remain no reliable molecular markers for reflecting the immune landscape and predicting patient survival in WT. Here, we examine differences in gene expression by high-throughput RNA sequencing, focused on differentially expressed immune-related genes (IRGs) based on the ImmPort database. Via univariate Cox regression analysis and Lasso-penalized Cox regression analysis, IRGs were screened out to establish an immune signature. Kaplan-Meier curves, time-related ROC analysis, univariate and multivariate Cox regression studies, and nomograms were used to evaluate the accuracy and prognostic significance of this signature. Furthermore, we found that the immune signature could reflect the immune status and the immune cell infiltration character played in the tumour microenvironment (TME) and showed significant association with immune checkpoint molecules, suggesting that the poor outcome may be partially explained by its immunosuppressive TME. Remarkably, TIDE, a computational method to model tumour immune evasion mechanisms, showed that this signature holds great potential for predicting immunotherapy responses in the TARGET-wt cohort. To decipher the underlying mechanism, GSEA was applied to explore enriched pathways and biological processes associated with immunophenotyping and Connectivity map (CMap) along with DeSigN analysis for drug exploration. Finally, four candidate immune genes were selected, and their expression levels in WT cell lines were monitored via qRT-PCR. Meanwhile, we validated the function of a critical gene, NRP2. Taken together, we established a novel immune signature that may serve as an effective prognostic signature and predictive biomarker for immunotherapy response in WT patients. This study may give light on therapeutic strategies for WT patients from an immunological viewpoint.

Background Immune microenvironment is well recognized as a critical regulator across cancer types, despite its complex roles in different disease conditions. Intrahepatic cholangiocarcinoma (iCCA) is characterized by a tumor-reactive milieu, emphasizing a deep insight into its immunogenomic profile to provide prognostic and therapeutic implications.Methods We performed genomic, transcriptomic, and proteomic characterization of 255 paired iCCA and adjacent liver tissues. We validated our findings through H&E staining (n=177), multiplex immunostaining (n=188), single-cell RNA sequencing (scRNA-seq) (n=10), in vitro functional studies, and in vivo transposon-based mouse models.Results Integrated multimodule data identified three immune subgroups with distinct clinical, genetic, and molecular features, designated as IG1 (immune-suppressive, 25.1%), IG2 (immune-exclusion, 42.7%), and IG3 (immune-activated, 32.2%). IG1 was characterized by excessive infiltration of neutrophils and immature dendritic cells (DCs). The hallmark of IG2 was the relatively higher tumor-proliferative activity and tumor purity. IG3 exhibited an enrichment of adaptive immune cells, natural killer cells, and activated DCs. These immune subgroups were significantly associated with prognosis and validated in two independent cohorts. Tumors with KRAS mutations were enriched in IG1 and associated with myeloid inflammation-dominated immunosuppression. Although tumor mutation burden was relatively higher in IG2, loss of heterozygosity in human leucocyte antigen and defects in antigen presentation undermined the recognition of neoantigens, contributing to immune-exclusion behavior. Pathological analysis confirmed that tumor-infiltrating lymphocytes and tertiary lymphoid structures were both predominant in IG3. Hepatitis B virus (HBV)-related samples tended to be under-represented in IG1, and scRNA-seq analyses implied that HBV infection indeed alleviated myeloid inflammation and reinvigorated antitumor immunity.Conclusions Our study elucidates that the immunogenomic traits of iCCA are intrinsically heterogeneous among patients, posing great challenge and opportunity for the application of personalized immunotherapy.

Avian infectious bronchitis is a serious and highly contagious disease that is caused by the infectious bronchitis virus (IBV). From January 2021 to June 2022, 1008 chicken tissue samples were collected from various regions of southern China, and 15 strains of the IBV were isolated. Phylogenetic analysis revealed that the strains mainly comprised the QX type, belonging to the same genotype as the currently prevalent LX4 type, and identified four recombination events in the S1 gene, among which lineages GI-13 and GI-19 were most frequently involved in recombination. Further study of seven selected isolates revealed that they caused respiratory symptoms, including coughing, sneezing, nasal discharge, and tracheal sounds, accompanied by depression. Inoculation of chicken embryos with the seven isolates resulted in symptoms such as curling, weakness, and bleeding. Immunization of specific pathogen-free (SPF) chickens with inactivated isolates produced high antibody levels that neutralized the corresponding strains; however, antibodies produced by vaccine strains were not effective in neutralizing the isolates. No unambiguous association was found between IBV genotypes and serotypes. In summary, a new trend in IBV prevalence has emerged in southern China, and currently available vaccines do not provide protection against the prevalent IBV strains in this region, facilitating the continued spread of IBV.

In order to meet the demands of desirable efficiency, transformerless DC/DC equipment with great voltage step-down are inevitable needed. This research offers a unique type of high-frequency, high-voltage-gain DC/DC converter, which comprises a switched capacitor (SC) converter and a buck converter. Thanks to the transformation of a two-stage converter to a single-stage converter, it has a considerable ratio of step-down voltage transformation and a reasonable duty cycle. In addition, it can permit low voltage stress on the switches. The simple control method and easy driving circuit implementation makes it scalable for high-power-level devices. Low cost can be realized as fewer components are needed. Under all operational circumstances, total soft-charging and low equipment voltage stresses are accomplished. Compared to those classic high-voltage-gain converters, the proposed converter exhibits merits of higher efficiency, higher flexibility, lower ripples, and lower costs. A comprehensive analysis is carried out for the converter’s steady-state operations. With a 1 MHz switching frequency, a 900 W prototype of a 20-time converter is constructed, with a peak efficiency of 92.5%. Simulations and experiments verify the effectiveness of the theoretical investigation of the converter’s operation.

Abstract In this paper, we report a new type of MoS2-based grating sensor for in-plane biaxial strain gauges with a precision limit of ~ 1‰. The MoS2 grating is numerically simulated with different biaxial strains up to 5%. Our first-principles calculations reveal that the strain sensitivity of the MoS2 reflectance spectrum can be considered an additional strain sensor integrated with the grating structure, enabling the mapping of in-plane biaxial strains. Our experimental studies on a prototype MoS2-grating sensor further confirm that a strain component perpendicular to the grating period can cause intensity peak shifts in the grating’s first-order diffraction patterns. This work opens a new path towards the sensing of in-plane biaxial strain within a single-grating device. Our new approach is applicable for other materials that have predictable reflectance response under biaxial strains and the capacity to form a two-dimensional single-crystal layer.

Abstract Spintronics is the most promising technology to develop alternative multi-functional, high-speed, low-energy electronic devices. Due to their unusual physical characteristics, emerging two-dimensional (2D) materials provide a new platform for exploring novel spintronic devices. Recently, 2D spintronics has made great progress in both theoretical and experimental researches. Here, the progress of 2D spintronics has been reviewed. In the last, the current challenges and future opportunities have been pointed out in this field.

When the circuit breaker is switched on and off, the phenomenon of arc ablation will occur. Under the action of the electric arc, the surface of the contact is constantly damaged, resulting in deformation and material evaporation. With the increase in the electric arc temperature, the material loss on the contact surface of the circuit breaker increases. In this paper, according to the three major factors affecting the electrical life of the circuit breaker arc extinguishing chamber—the state of the arc contact, the nozzle, and the SF6 gas—the corresponding test detection methods and evaluation methods are proposed. With the continuous accumulation of the breaking current, the effective contact displacement between the arc contacts decreases and the average contact resistance increases. The effective contact displacement decreases exponentially with the increase in the cumulative breaking energy. The content of CF4 can be used not only to characterize the discharge ablation on the surface of the nozzle insulating material but also to characterize the discharge decomposition degree of SF6 in the system by adding carbonaceous compounds. Through the experiment, it is suggested that CF4 should reach 600 µl/l as the threshold for judging whether the arc extinguishing chamber needs maintenance. This method can be extended to the working condition evaluation of the arc extinguishing chamber of other types of the SF6 circuit breaker.

The power penetration line of high-speed railway adopts all-cable lines, and its failure will seriously affect the safety and reliability of railway transportation. The accurate location of the fault will greatly reduce the range of finding the cable fault point and the workload of cable fault repair, shorten the maintenance time, and improve the reliability of high-speed railway power supply. This paper introduces the current situation of power line fault location, analyzes various traveling wave location principles and the traveling wave transmission and attenuation characteristics of all-cable penetration lines, and analyzes the adaptability of the traditional traveling wave location technology in all-cable penetration line fault location. It is proposed that the distributed traveling wave location method can greatly reduce the transmission distance of fault traveling waves and can effectively reduce the influence of attenuation and distortion in the traveling wave transmission process. For different types of fault traveling waves, different fault transition resistances, and different positions of fault points, the method can achieve the accurate location. The practical application case shows that the technology has high location accuracy and meets the requirements of a precise location.

ObjectiveTo investigate the role of chemokines in Wilms tumours, especially their chemotaxis to immune cells and the role of DNA methylation in regulating the expression level of chemokines.MethodsRNAseqV2 gene expression and clinical data were downloaded from the TARGET database. DNA methylation data were downloaded from the GEO and cBioPortal database. The difference analysis and Kaplan-Meier(KM) analysis of chemokines were performed by edgeR package. Then predictive model based on chemokines was constructed by lasso regression and multivariate COX regression. ROC curve, DCA curve, Calibration curve, and Nomogram were used to evaluate the prognostic model. MCPcounter and Cibersort algorithm was used to calculate the infiltration of immune cells in Wilms tumour and para-tumour samples. Then the difference analysis of the immune cells was performed. The relationship between chemokines and immune cells were calculated by Pearson correlation. In addition, DNA methylation differences between Wilms tumour and para-tumour samples was performed. The correlation between DNA methylation and mRNA expression was calculated by Pearson correlation. Western blot(WB)and immunofluorescence were used to confirm the differential expression of CX3CL1 and T cells, and the correlation between them.ResultsA total of 16 chemokines were differentially expressed in tumour and para-tumour samples. A total of seven chemokines were associated with survival. CCL2 and CX3CL1 were positively correlated with prognosis, while high expression of CCL3, CCL8, CCL15, CCL18 and CXCL9 predicted poor prognosis. By lasso regression and multivariate COX regression, CCL3, CCL15, CXCL9 and CX3CL1 were finally included to construct a prediction model. The model shows good prediction ability. MCPcounter and Cibersort algorithm both showed that T cells were higher in para-tumour tissues than cancer tissues. Correlation analysis showed that CX3CL1 had a strong correlation with T cells. These were verified by Weston blot and immunofluorescence. DNA methylation analysis showed that various chemokines were different in para-tumours and tumours. CX3CL1 was hypermethylated in tumours, and the degree of methylation was negatively correlated with mRNA expression.Conclusion1. There is low T cell infiltration in nephroblastoma. 2. Chemokines such as CX3CL1 indicate a favourable prognosis and positively correlate with the number of T cells. 3. chemokines such as CX3CL1 are negatively regulated by DNA hypermethylation.

Circular RNA (circRNA), which is a newly discovered non-coding RNA, has been documented to play important roles in miRNA sponges, and the dysregulation of which is involved in cancer development. However, circRNA expression profiles and their role in initiation and progression of Wilms tumor (WT) remain largely unclear at present. Here, we used paired WT samples and high-throughput RNA sequencing to identify differentially expressed circRNAs (DE-circRs) and mRNAs (DE-mRs). A total of 314 DE-circRs and 1612 DE-mRs were identified. The expression of a subset of differentially expressed genes was validated by qRT–PCR. A complete circRNA-miRNA-mRNA network was then constructed based on the common miRNA targets of DE-circRs and DE-mRs identified by miRanda prediction tool. The Gene set enrichment analysis (GSEA) indicated that several signaling pathways involving targeted DE-mRs within the ceRNA network were associated with cell cycle and immune response, which implies their participation in WT development to some extent. Subsequently, these targeted DE-mRs were subjected to implement PPI analysis and to identify 10 hub genes. Four hub genes were closely related to the survival of WT patients. We then filtered prognosis-related hub genes by Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis to construct a prognosis-related risk score system based on a three-gene signature, which showed good discrimination and predictive ability for WT patient survival. Additionally, we analyzed the mutational landscape of these genes and the associations between their expression levels and those of immune checkpoint molecules and further demonstrated their potential impact on the efficacy of immunotherapy. qRT–PCR and western blotting (WB) analysis were used to validate key differentially expressed molecules at the RNA and protein levels, respectively. Besides these, we selected a key circRNA, circEYA1, for function validation. Overall, the current study presents the full-scale expression profiles of circRNAs and the circRNA-related ceRNA network in WT for the first time, deepening our understanding of the roles and downstream regulatory mechanisms of circRNAs in WT development and progression. We further constructed a useful immune-related prognostic signature, which could improve clinical outcome prediction and guide individualized treatment.

Jaundice is a detection index in many disease conditions commonly characterized by yellowish staining of the skin and mucous membranes. This work studies the postoperative care outcome in 1,246 patients (669 males and 577 females) with obstructive jaundice who underwent percutaneous transhepatic biliary drainage (PTBD). These patients were admitted to the interventional vascular surgery department of our hospital from February 2017 to February 2022. From the results, frequent wound re-dressing and maintenance of the drainage tube had significant positive influence on wound healing and patient recovery. The data also showed strict adherence by patients to the doctor’s recommendation advising them to visit the interventional specialist care clinic in time for wound dressing change and drainage tube maintenance. As a result, there was no significant difference in wound allergy, exudation, redness and loosening among patients. A cross-sectional analysis of the effect of age on recovery revealed variations in the healing pattern (wound loosening and the redness) between patients of different ages although the relationship is not very clear due to the limited sample size. Efficient drainage tube maintenance promoted recovery and prevented the occurrence of related complications such as PTBD tube blockage and biliary tract infection. The establishment of the interventional specialist care clinic used in this study additionally ensures patients’ safety, and the incidence of complications have been reduced drastically. These achievements are attributable to the implementation of regular dressing change, drainage tube maintenance and health education for patients with PTBD tube. These practices have also improved on the level of specialty in nursing practice, increased the professional value of nurses and better recognition by the society.

Abstract Newcastle disease virus (NDV) infection causes severe inflammation and is a highly contagious disease in poultry. Virulent NDV strains (GM) induce large quantities of interleukin-1β (IL-1β), which is the central mediator of the inflammatory reaction. Excessive expression of IL-1β exacerbates inflammatory damage. Therefore, exploring the mechanisms underlying NDV-induced IL-1β expression can aid in further understanding the pathogenesis of Newcastle disease. Here, we showed that anti-IL-1β neutralizing antibody treatment decreased body temperature and mortality following infection with virulent NDV. We further explored the primary molecules involved in NDV-induced IL-1β expression from the perspective of both the host and virus. This study showed that overexpression of NLRP3 resulted in increased IL-1β expression, whereas inhibition of NLRP3 or caspase-1 caused a significant reduction in IL-1β expression, indicating that the NLRP3/caspase-1 axis is involved in NDV-induced IL-1β expression. Moreover, ultraviolet-inactivated GM (chicken/Guangdong/GM/2014) NDV failed to induce the expression of IL-1β. We then collected virus from GM-infected cell culture supernatant using ultracentrifugation, extracted the viral RNA, and stimulated the cells further with GM RNA. The results revealed that RNA alone was capable of inducing IL-1β expression. Moreover, NLRP3/caspase-1 was involved in GM RNA-induced IL-1β expression. Thus, our study elucidated the critical role of IL-1β in the pathogenesis of Newcastle disease while also demonstrating that inhibition of IL-1β via anti-IL-1β neutralizing antibodies decreased the damage associated with NDV infection; furthermore, GM RNA induced IL-1β expression via NLRP3/caspase-1.

Electric fuses are protection devices with a long history. They are widely used in both high voltage and low voltage power systems. The pre-arc I-t (current versus time) characteristic is an important parameter of electric fuse. The traditional method of obtaining this parameter is designing the electrical fuse by experience, then conducting experiments to obtain the I-t characteristic. However, customers request specific of I-t characters first, and then the engineers have to design electric fuses based on the requirements, this is an inverse design problem of electric fuses. There is no research in this area yet. The objective of this paper is to propose a new method to solve the inverse design problem of electrical fuse with machine learning. The method contains two steps. First, finite element analysis is used to obtain training samples for machine learning. A total of 252 samples (pre-arc current-time result) are obtained by simulations. Second, an elastic network is used to solve the probabilistic inference model by utilizing 217 samples from the total of 252. The other 35 samples are used to evaluate inverse design problem solution results. The results show that this method can accurately predict the design parameters of the restricted zone of fuse element, including the thickness (T1) and radius (R1) of restricted zone. The average relative errors value of T1 and R1 are 15.7% and 3.4%, respectively. Increasing the penalty factor and elastic error decreases the relative error. By changing the penalty error to 0.8, the average relative errors value of T1 and R1 are reduced by 14.1% and 1.7%, respectively. By changing the elastic error to 0.8, the average relative errors value of T1 and R1 are reduced by 13.1% and 2.1%, respectively. The research results provide a new solution for the electrical fuse design problem.

Distribution transformer is the key equipment in the distribution power grid, and sampling inspection is the main method used to ensure quality control. Inspection comprises many testing processes. Due to various reasons, the testing results may occasionally have errors and be implausible. Only a few errors can be detected empirically by inspectors. To solve this problem, anomaly detection is proposed in this paper to determine implausible inspection reports and assist in re-inspecting. The well-known and representative anomaly detection algorithms, which are now used in many application domains are introduced. These algorithms include single Gaussian distribution and multivariate Gaussian distribution, local outlier factor, one-class SVM. Based on the distribution transformer inspection reports collected, anomaly samples are constructed manually. Train datasets and test datasets are then formulated. By comparing the testing results, the one-class SVM algorithm can detect anomaly samples in testing datasets correctly. Thus, it can be used to distinguish the abnormal samples (i.e., reports with measurement errors suspected) in the inspection reports of distribution transformer, which can help inspectors complete their inspecting work correctly and effectively.

Infectious bronchitis virus (IBV) and H9N2 avian influenza virus (AIV) are frequently identified in chickens with respiratory disease. However, the role and mechanism of IBV and H9N2 AIV co-infection remain largely unknown. Specific-pathogen-free (SPF) chickens were inoculated with IBV 2 days before H9N2 virus inoculation (IBV/H9N2); with IBV and H9N2 virus simultaneously (IBV+H9N2); with H9N2 virus 2 days before IBV inoculation (H9N2/IBV); or with either IBV or H9N2 virus alone. Severe respiratory signs, pathological damage, and higher morbidity and mortality were observed in the co-infection groups compared with the IBV and H9N2 groups. In general, a higher virus load and a more intense inflammatory response were observed in the three co-infection groups, especially in the IBV/H9N2 group. The same results were observed in the transcriptome analysis of the trachea of the SPF chickens. Therefore, IBV might play a major role in the development of respiratory disease in chickens, and secondary infection with H9N2 virus further enhances the pathogenicity by inducing a severe inflammatory response. These findings may provide a reference for the prevention and control of IBV and H9N2 AIV in the poultry industry and provide insight into the molecular mechanisms of IBV and H9N2 AIV co-infection in chickens.

In recent years, unmanned aerial vehicle (UAV) inspection has become one of the main means of daily operation and maintenance of overhead transmission lines. Since the key components of the UAV inspection system are composed of electronic components, it relies on data communication to realize data link transmission. In the actual operation process, the complex electromagnetic field environment has an obvious impact on its control and communication performance, especially when inspecting near the DC line. In this paper, combined with the research on the safety assurance technology of UAV inspection operations, the electromagnetic field simulation model of the UAV inspection operation on DC transmission lines is established. The electromagnetic field distribution around the wire is analyzed when the UAV is at different inspection distances, and the influence range and degree of the DC electromagnetic field on UAV inspection system are obtained. A true test platform for the inspection safety distance of the ±500 kV line UAV inspection was built, and the inspection safety distance test and research of the small rotary-wing UAV with a typical size, structure, and material was carried out. Through the test, when the current of the transmission line is 3 kA, the minimum safety distance of the UAV inspection operation of the ±500 kV DC transmission line straight tower is 3 m, and the distance is corrected in combination with the current. The research results of this paper can provide technical support for the inspection operation of small multi-rotor UAVs on ±500 kV transmission lines.

This paper presents an auxiliary passive circuit and control design for wireless power transfer (WPT) systems in DC microgrids to achieve optimal power transfer efficiency while maintain accurate output voltage regulation. An auxiliary inductance is added at the transmitter resonator to form a current sink to ensure zero voltage switching (ZVS) of the primary-side full-bridge inverter with even extremely light load conditions. Moreover, an adaptive proportional–integral (PI) controller is adopted to track the output voltage references by regulating the phase shift angle of the phase shift control for the full-bridge inverter. The coefficients of the adaptive PI controller are determined by the inductance of the auxiliary inductance. Both simulation and experimental results validated the effectiveness of the proposed circuit and control design in achieving optimal efficiency and output voltage regulation for WPT systems in DC microgrids with source and load variations.

Mobile Edge Computing (MEC) is vital to support the numerous, future applications that are envisioned in the 5G and beyond mobile networks. Since computation capabilities are available at the edge of the network, applications that need ultra low-latency, high bandwidth and reliability can be deployed more easily. This opens up the possibility of developing smart resource allocation approaches that can exploit the MEC infrastructure in an optimized way and, at the same time, fulfill the requirements of applications. However, up to date, the progress of research in this area is limited by the unavailability of publicly available true MEC topologies that could be used to run extensive experiments and to compare the performance on different solutions concerning planning, scheduling, routing etc. For this reason, we decided to infer and make publicly available several synthetic MEC topologies and scenarios.Specifically, based on the experience we have gathered with our experiments Xiang et al. [1], we provide data related to 3 randomly generated topologies, with increasing network size (from 25 to 100 nodes). Moreover, we propose a MEC topology generated from OpenCellID [2] real data and concerning the Base Stations’ location of 234 LTE cells owned by a mobile operator (Vodafone) in the center of Milan. We also provide realistic reference parameters (link bandwidth, computation and storage capacity, offered traffic), derived from real services provided by MEC in the deployment of 5G networks.

BackgroundMicroRNAs (miRs) have been shown to be closely associated with the occurrence and development of tumors and to have potential as diagnostic and therapeutic targets. The detection of miRs by noninvasive imaging technology is crucial for deeply understanding their biological functions. Our aim was to develop a novel miR-21-responsive gene reporter system for magnetic resonance imaging (MRI) visualization of the miR-21 dynamics in neuroblastoma.MethodsThe reporter gene ferritin heavy chain (FTH1) was modified by the addition of 3 copies of the sequence completely complementary to miR-21 (3xC_miR-21) to its 3’-untranslated region (3’ UTR) and transduced into SK-N-SH cells to obtain SK-N-SH/FTH1-3xC_miR-21 cells. Then, the antagomiR-21 was delivered into cells by graphene oxide functionalized with polyethylene glycol and dendrimer. Before and after antagomiR-21 delivery, FTH1 expression, MRI contrast and intracellular iron uptake were assayed in vitro and in vivo.ResultsIn the SK-N-SH/FTH1-3xC_miR-21 cells, FTH1 expression was in an “off” state due to the combination of intratumoral miR-21 with the 3’ UTR of the reporter gene. AntagomiR-21 delivered into the cells bound to miR-21 and thereby released it from the 3’ UTR of the reporter gene, thus “switching on” FTH1 expression in a dose-dependent manner. This phenomenon resulted in intracellular iron accumulation and allowed MRI detection in vitro and in vivo.ConclusionMRI based on the miR-21-responsive gene reporter may be a potential method for visualization of the endogenous miR-21 activity in neuroblastoma and its response to gene therapy.

Background: Neuron apoptosis, regulated by endoplasmic reticulum (ER) stress in the hippocampus, is an essential factor influencing the cognitive impairment induced by hypobaric hypoxia. Hypoxia mainly changes the activating transcription factor (ATF6) pathway of ER stress. However, the role of ATF6 in neuron survival, apoptosis, and upstream regulation is still controversial.Methods: We established a hypobaric hypoxia-induced C57BL/6 murine model and cell lines exposed to 1% hypoxia, including PC12 and HT22. First, we tested the expressions of interleukin 6 (IL-6), IL-1β, and IL-10 in C57BL/6 mice’s hippocampus under hypoxia using enzyme-linked immunosorbent assay (ELISA). We determined the signal transducer and activator of transcription 3 (STAT3) phosphorylation at tyrosine (Tyr)705 by western blot and the expression of ATF6, 78-kDa glucose-regulated protein (GRP78), and C/-EBP homologous protein (CHOP) related to ER stress by immunofluorescence (IF), western blot, and qRT-PCR; they were then verified on the cell model. Additionally, IL-6 (40 ng/mL) and STAT3 siRNA were used to treat the PC12 cells for 48 and 4 h to activate or silence STAT3, respectively. Subsequently, the cells of siRNA group were exposed to 1% hypoxia for 48 h. Furthermore, the ATF6 and CHOP expressions were detected with western blot and qRT-PCR. Finally, we examined the binding of STAT3 to the ATF6 promoter by chromatin immunoprecipitation (ChIP)-seq.Results: The results showed that IL-6 increased, IL-10 decreased in the hypoxia group, and IL-1β showed no difference between the hypoxia and the normoxia groups. Neuron apoptosis was significantly elevated by exposure to hypoxia for 48h in PC12 cells. The hypobaric hypoxia-induced ER stress proteins, ATF6, GRP78, and CHOP, and the p-STAT3 (Tyr705) expressions increased both in in vivo and in vitro. Besides, STAT3 silencing significantly promoted the ATF6 expression and inhibited CHOP, while STAT3 activation downregulated the expression of ATF6 and upregulated CHOP in PC12 cells. The ChIP-seq assay demonstrated that p-STAT3 (Tyr705) protein could bind to the ATF6 promoter region in HT22 cells.Conclusion: Phosphorylation of STAT3 at the Tyr705 site contributes to hypoxia-induced neuron apoptosis by downregulating ATF6, which might explain the inflammatory reaction and apoptosis of the hippocampal neurons induced by ER stress.

Renal fibrosis is a common pathological feature of various kidney diseases, leading to irreversible renal failure and end-stage renal disease. However, there are still no effective treatments to reverse renal fibrosis. This study aimed to explore the potential mechanism of a targeted drug for fibrosis. Here, unilateral ureteral obstruction (UUO)-treated mice and a TGF-β1-treated human renal tubular epithelial cell line (HK-2 cells) were used as models of renal fibrosis. Based on the changes of mRNA in UUO kidneys detected by transcriptome sequencing, MK-2206, an Akt inhibitor, was predicted as a potential drug to alleviate renal fibrosis through bioinformatics. We dissolved UUO mice with MK-2206 by gastric gavage and cultured TGF-β-induced HK-2 cells with MK-2206. Histopathological examinations were performed after MK-2206 intervention, and the degree of renal fibrosis, as well as the expression of Akt/mTOR pathway-related proteins, were evaluated by immunohistochemical staining, immunofluorescence staining, and Western blot. The results showed that MK-2206 significantly improved the pathological structure of the kidney. Furthermore, MK-2206 intervention effectively inhibited UUO- and TGF-β1-induced epithelial-mesenchymal transition, fibroblast activation, and extracellular matrix deposition. Mechanistically, MK-2206 treatment attenuated the activation of the Akt/mTOR signaling pathway. Taken together, our study revealed for the first time that MK-2206 is a promising drug for the improvement of renal fibrosis.

An Internet of Vehicles (IoV) allows forming a self-organized network and broadcasting messages for the vehicles on roads. However, as the data are transmitted in an insecure network, it is essential to use an authentication mechanism to protect the privacy of vehicle users. Recently, Ying et al. proposed an authentication protocol for IoV and claimed that the protocol could resist various attacks. Unfortunately, we discovered that their protocol suffered from an offline identity guessing attack, location spoofing attack, and replay attack, and consumed a considerable amount of time for authentication. To resolve these shortcomings, we propose an improved protocol. In addition, we provide a formal proof to the proposed protocol to demonstrate that our protocol is indeed secure. Compared with previous methods, the proposed protocol performs better in terms of security and performance.

Paralytic shellfish poisoning (PSP) toxin is widely contained in seafood and its product. It brings great harm to human health when people eat it. During the past two decades, shellfish toxin quantitative analysis methods develop fast, such as mouse bioassay (MBA), chemical analysis method, immunoassay and cell-based assay (CBA). However, there are some disadvantages in these analytical methods such as time consuming, high cost. Therefore, a more suitable method is in demand. In this study, a novel method using high-frequency surface acoustic wave resonator (SAWR)-based sensor combined with living cells was developed for shellfish toxin continuous monitoring. The mouse tongue isolated taste bud (MTITB) cells cell lines were used as the sensing elements to establish the sensor device for PSP toxin carbamoyl toxin (CT) quantitative monitoring. The sensor device is in serial with SAWR. SAWR output frequency was recorded for detecting characterization. HEK293 cell lines were cultured on electrode and utilized as negative control. The results showed that MTITB cell-based sensor had selective responses to CT. This method is promising in PSP toxins rapid quantitative determination.