Glutamyl-prolyl-tRNA synthetase (EPRS1) drives tubulointerstitial nephritis-induced fibrosis by enhancing T cell proliferation and activity.

Toxin- and drug-induced tubulointerstitial nephritis (TIN), characterized by interstitial infiltration of immune cells, frequently necessitates dialysis for patients due to irreversible fibrosis. However, agents modulating interstitial immune cells are lacking. Here, we addressed whether the housekeeping enzyme glutamyl-prolyl-transfer RNA synthetase 1 (EPRS1), responsible for attaching glutamic acid and proline to transfer RNA, modulates immune cell activity during TIN and whether its pharmacological inhibition abrogates fibrotic transformation. The immunological feature following TIN induction by means of an adenine-mixed diet was infiltration of EPRS1high T cells, particularly proliferating T and γδ T cells. The proliferation capacity of both CD4+ and CD8+ T cells, along with interleukin-17 production of γδ T cells, was higher in the kidneys of TIN-induced Eprs1+/+ mice than in the kidneys of TIN-induced Eprs1+/- mice. This discrepancy contributed to the fibrotic amelioration observed in kidneys of Eprs1+/- mice. TIN-induced fibrosis was also reduced in Rag1-/- mice adoptively transferred with Eprs1+/- T cells compared to the Rag1-/- mice transferred with Eprs1+/+ T cells. The use of an EPRS1-targeting small molecule inhibitor (bersiporocin) under clinical trials to evaluate its therapeutic potential against idiopathic pulmonary fibrosis alleviated immunofibrotic aggravation in TIN. EPRS1 expression was also observed in human kidney tissues and blood-derived T cells, and high expression was associated with worse patient outcomes. Thus, EPRS1 may emerge as a therapeutic target in toxin- and drug-induced TIN, modulating the proliferation and activity of infiltrated T cells.

Evaluating Implementation Costs of an Enhanced Recovery After Surgery (ERAS) Protocol in Colorectal Surgery: A Systematic Review.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols have been well documented in the current literature to improve healthcare outcomes by decreasing length of stay, resource utilization, and morbidity without increasing readmission rates or complications. This subsequently leads to a net decrease in hospital costs. However, the initial costs of implementing such a program have not been well described, which is crucial information for hospitals with less resources. The aim of this study was to provide a cohesive review of the current literature for the costs of implementing a colorectal surgery ERAS protocol. METHODS: A comprehensive review was conducted on five databases (Google Scholar, Web of Science, PROSPERO, PubMed, and Cochrane) with the assistance of a professional librarian. All relevant English articles published between 1995 and June 2021 were screened for eligibility prior to inclusion in the review. Cost data were converted to US dollars based on the exchange rate at the end time of the study period for standardization. RESULTS: Seven studies were included for review. The studies evaluated a range of 50-1295 patients through their respective ERAS programs, which were followed for 5 to 22 months. ERAS implementation costs ranged from $57 to $1536 per patient. Components for each ERAS program varied for each study, but ultimately, the greatest costs were attributed to personnel. CONCLUSIONS: Despite data heterogeneity and inconsistencies between cost breakdowns, a majority of the implementation cost was found to be secondary to personnel. This review demonstrates the need for a more standardized approach for reporting ERAS implementation costs through an open database as well as a potential streamlining of the ERAS protocol to facilitate implementation in institutions with less financial resources.

High Reliability of Ag Reflectors with AgCu Alloy for High Efficiency GaN-Based Light Emitting Diodes.

We propose an Ag reflector layer with an AgCu alloy layer as a thermally reliable reflector for high power flip-chip and vertical light emitting diodes (LEDs). By annealing the deposited Ag and Cu layers, intermixed grains and grain boundaries from the alloyed AgCu layer were formed on the LEDs, and CuO nano dots precipitated at the grain boundaries. A thick AgCu layer was deposited to cover the AgCu alloy layer. The precipitation of the CuO nano dots at the grain boundaries suppressed Ag agglomeration, leading to enhanced light reflectance after the annealing process. Consequently, the alloyed AgCu/Ag reflector produced by annealing at a high temperature of 500 °C demonstrated a higher reflectance of 78% and a lower contact resistance of 7.0 × 10-5 Ω · cm2.

Canine susceptibility to human influenza viruses (A/pdm 09H1N1, A/H3N2 and B).

We investigated the infectivity and transmissibility of the human seasonal H3N2, pandemic (pdm) H1N1 (2009) and B influenza viruses in dogs. Dogs inoculated with human seasonal H3N2 and pdm H1N1 influenza viruses exhibited nasal shedding and were seroconverted against the viruses; this did not occur in the influenza B virus-inoculated dogs. Transmission of human H3N2 virus between dogs was demonstrated by observing nasal shedding and seroconversion in naïve dogs after contact with inoculated dogs. The seroprevalence study offered evidence of human H3N2 infection occurring in dogs since 2008. Furthermore, serological evidence of pdm H1N1 influenza virus infection alone and in combination with canine H3N2 virus was found in the serum samples collected from field dogs during 2010 and 2011. Our results suggest that dogs may be hosts for human seasonal H3N2 and pdm H1N1 influenza viruses.

Viral dominance of reassortants between canine influenza H3N2 and pandemic (2009) H1N1 viruses from a naturally co-infected dog.

BACKGROUND: Since avian-origin H3N2 canine influenza virus (CIV) was first identified in South Korea in 2008, the novel influenza virus has been reported in several countries in Asia. Reverse zoonotic transmission of pandemic H1N1 (2009) influenza virus (pH1N1) has been observed in a broad range of animal species. Viral dominance and characterization of the reassortants of both viruses was undertaken in the present study. FINDINGS: Here we describe the viral dominance of 23 CIV reassortants between pH1N1 and canine H3N2 influenza viruses from a naturally co-infected dog. These results indicate that the M gene of pandemic H1N1 and the HA gene of canine H3N2 are predominant in the reassortants. Furthermore, unlike the original canine H3N2 virus, some reassortants showed high pathogenicity in mice. CONCLUSIONS: This study suggests that continuous monitoring of influenza infection in companion animals may be necessary to investigate the potential of the emergence of novel influenza viruses.

Complete genome sequence of an avian-origin H3N2 canine influenza virus isolated from dogs in South Korea.

An avian-origin Korean H3N2 canine influenza virus (CIV) strain, designated A/canine/Korea/01/2007 (H3N2), was isolated from nasal swabs of pet dogs exhibiting severe respiratory syndrome in 2007. In the present study, we report the first complete genome sequence containing 3' and 5' noncoding regions (NCRs) of H3N2 CIV, which will provide important insights into the molecular basis of pathogenesis, transmission, and evolution of CIV.

Isotropic conductive paste for bioresorbable electronics.

Bioresorbable implantable medical devices can be employed in versatile clinical scenarios that burden patients with complications and surgical removal of conventional devices. However, a shortage of suitable electricalinterconnection materials limits the development of bioresorbable electronic systems. Therefore, this study highlights a highly conductive, naturally resorbable paste exhibiting enhanced electrical conductivity and mechanical stability that can solve the existing problems of bioresorbable interconnections. Multifaceted experiments on electrical and physical properties were used to optimize the composition of pastes containing beeswax, submicron tungstenparticles, and glycofurol. These pastes embody isotropic conductive paths for three-dimensional interconnects and function as antennas, sensors, and contact pads for bioresorbable electronic devices. The degradation behavior in aqueous solutions was used to assess its stability and ability to retain electrical conductance (∼7 â€‹kS/m) and structural form over the requisite dissolution period. In vitro and in vivo biocompatibility tests clarified the safety of the paste as an implantable material.

A novel reassortant canine H3N1 influenza virus between pandemic H1N1 and canine H3N2 influenza viruses in Korea.

During recent canine influenza surveillance in South Korea, a novel H3N1 canine influenza virus (CIV) that is a putative reassortant between pandemic H1N1 2009 and H3N2 CIVs was isolated. Genetic analysis of eight genes of the influenza virus revealed that the novel H3N1 isolate presented high similarities (99.1-99.9 %) to pandemic influenza H1N1, except for in the haemagglutinin (HA) gene. The HA gene nucleotide sequence of the novel CIV H3N1 was similar (99.6 %) to that of CIV H3N2 isolated in Korea and China. Dogs infected with the novel H3N1 CIV did not show any notable symptoms, in contrast to dogs infected with H3N2 CIV. Despite no visible clinical signs of disease, nasal shedding of virus was detected and the infected dogs presented mild histopathological changes.

Kidney VISTA prevents IFN-γ/IL-9 axis-mediated tubulointerstitial fibrosis after acute glomerular injury.

Severe glomerular injury ultimately leads to tubulointerstitial fibrosis that determines patient outcome, but the immunological molecules connecting these processes remain undetermined. The present study addressed whether V-domain Ig suppressor of T cell activation (VISTA), constitutively expressed in kidney macrophages, plays a protective role in tubulointerstitial fibrotic transformation after acute antibody-mediated glomerulonephritis. After acute glomerular injury using nephrotoxic serum, tubules in the VISTA-deficient (Vsir-/-) kidney suffered more damage than those in WT kidneys. When interstitial immune cells were examined, the contact frequency of macrophages with infiltrated T cells increased and the immunometabolic features of T cells changed to showing high oxidative phosphorylation and fatty acid metabolism and overproduction of IFN-γ. The Vsir-/- parenchymal tissue cells responded to this altered milieu of interstitial immune cells as more IL-9 was produced, which augmented tubulointerstitial fibrosis. Blocking antibodies against IFN-γ and IL-9 protected the above pathological process in VISTA-depleted conditions. In human samples with acute glomerular injury (e.g., antineutrophil cytoplasmic autoantibody vasculitis), high VISTA expression in tubulointerstitial immune cells was associated with low tubulointerstitial fibrosis and good prognosis. Therefore, VISTA is a sentinel protein expressed in kidney macrophages that prevents tubulointerstitial fibrosis via the IFN-γ/IL-9 axis after acute antibody-mediated glomerular injury.

Thickness-Dependence Electrical Characterization of the One-Dimensional van der Waals TaSe3 Crystal.

Needle-like single crystalline wires of TaSe3 were massively synthesized using the chemical vapor transport method. Since the wedged-shaped single TaSe3 molecular chains were stacked along the b-axis by weak van der Waals interactions, a few layers of TaSe3 flakes could be easily isolated using a typical mechanical exfoliation method. The exfoliated TaSe3 flakes had an anisotropic planar structure, and the number of layers could be controlled by a repeated peeling process until a monolayer of TaSe3 nanoribbon was obtained. Through atomic force and scanning Kelvin probe microscope analyses, it was found that the variation in the work function with the thickness of the TaSe3 flakes was due to the interlayer screening effect. We believe that our results will not only help to add a novel quasi-1D block for nanoelectronics devices based on 2D van der Waals heterostructures, but also provide crucial information for designing proper contacts in device architecture.

HA1-specific indirect ELISA for serological detection of canine influenza virus H3N2 infection in dogs.

An indirect ELISA using recombinant HA1 protein of canine influenza virus (CIV) as a coating antigen was developed and characterized for its application to serosurveillance in dogs. The CIV H3N2-specific indirect ELISA was developed using recombinant HA1 protein (baculovirus-expression system) as a coating antigen. A total of 65 CIV H3N2-positive or negative canine sera were tested by the indirect ELISA for receiver operating characteristic (ROC) analysis and results compared to those generated by the hemagglutination inhibition (HI) test. Canine sera collected 10 days following intranasal inoculation with canine H3N2, seasonal H3N2 (A/Brisbane/10/2007) or pandemic H1N1 influenza virus (A/California/04/2009) were used for the cross-reaction test. An adjusted optical density (OD) of 0.17 was determined to be the optimal cut-off value for seropositivity. The indirect ELISA showed 95.7% sensitivity and 94.7% specificity when compared to the HI test. A cross-reaction test was also performed using canine sera reactive with CIV H3N2, seasonal H3N2 (human) and pandemic H1N1 (human) influenza viruses. Based on the data generated in this study, the canine H3N2-associated ELISA using baculovirus expressed HA1 antigen will be useful for herd-based serological survey of the canine H3N2 virus infection in dogs.

Complete Genome Sequences of Noncoding Regions of Korean Equine H3N8 Influenza Virus.

We analyzed the complete genome sequence containing the 3' and 5' noncoding regions (NCRs) of the Korean H3N8 equine influenza virus (EIV), which will provide a better understanding of the pathogenesis, transmission, and evolution of EIV.

Complete Genome Sequences of H3N2 Canine Influenza Virus with the Matrix Gene from the Pandemic A/H1N1 Virus.

We analyzed the complete genome sequence containing the 3' and 5' noncoding regions (NCRs) of H3N2 canine influenza virus (CIV) with the matrix gene from the pandemic A/H1N1 virus, which will provide a better understanding of the pathogenesis, transmission, and evolution of variant CIV.

Complete Genome Sequence of a Canine-Origin H3N2 Feline Influenza Virus Isolated from Domestic Cats in South Korea.

A canine-origin Korean H3N2 feline influenza virus (FIV), A/feline/Korea/01/2010 (H3N2), was isolated in 2010 from a dead cat with severe respiratory disease. Here, we report the first complete genome sequence of this virus, containing 3' and 5' noncoding regions, which will help elucidate the molecular basis of the pathogenesis, transmission, and evolution of FIV.

Inter- and intraspecies transmission of canine influenza virus (H3N2) in dogs, cats, and ferrets.

BACKGROUND: The emergence of zoonotic viruses in domestic animals is a significant public health concern. Canine influenza virus (CIV) H3N2 is a virus that can infect companion animals and is, therefore, a potential public health concern. OBJECTIVE: This study investigated the inter- and intraspecies transmission of CIV among dogs, cats, and ferrets, under laboratory conditions, to determine whether transmission of the virus was possible between as well as within these domestic animal species. METHOD: The transmission routes for inter- and intraspecies transmission were airborne and direct contact, respectively. Transmission was conducted through intranasal infection of dogs followed by exposure to either cats or ferrets and by comingling infected and naïve animals of the same species. RESULTS: The interspecies transmission of CIV H3N2 via airborne was only observed from dogs to cats and not from dogs to ferrets. However, direct intranasal infection of either cats or ferrets with CIV could induce influenza-like clinical signs, viral shedding, and serological responses. Additionally, naïve cats and ferrets could be infected by CIV via direct contact with infected animals of the same species. CONCLUSION: Cats appear to be another susceptible host of CIV H3N2, whereas ferrets are not likely natural hosts. The molecular-based mechanism of interspecies and intraspecies transmission of CIV H3N2 should be further studied.

Prolonged shedding of the canine influenza H3N2 virus in nasal swabs of experimentally immunocompromised dogs.

PURPOSE: The avian origin canine influenza virus H3N2 has been recently isolated and found to be currently in dog population in South Korea and China. The purpose of this study was to clarify the relationship between immunosuppressive glucocorticoids used in veterinary clinical practice and viral shedding pattern of influenza in dogs. MATERIALS AND METHODS: Eight conventional beagle dogs were divided into control infection group and immunocompromised group. Dogs of both groups were infected with H3N2 canine influenza virus (2×10(6.0) EID50/0.1 mL). Dogs in immunocompromised group were given orally 3.0 mg/kg prednisolone for 7 days. Virus shedding was monitored using real-time polymerase chain reaction. After necropsy, histopathologic lesions were compared. RESULTS: We found that immunocompromised dogs exhibited more prolonged (8 days vs. 13 days) and higher magnitude viral shedding than control group (peak titer of viral shedding 4.6 vs. 5.5 EID50). CONCLUSION: Restricted use of immunosuppressive drugs in the clinical setting might help control the rapid spread of H3N2 through local dog populations.