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Solute carrier family 40 member 1 (SLC40A1) encodes ferroportin 1 (FPN1), the only known iron efflux transporter in mammalian cells, which is critical for maintaining systemic iron homeostasis and cellular iron balance. SLC40A1 plays a key role in regulating iron homeostasis and is involved in the pathogenesis of inflammatory, fibrotic, neurodegenerative diseases, and cancer, with dysfunction linked to mutations or epigenetic silencing. Its biological functions and regulatory mechanisms are complex and diverse. This article provides an overview of SLC40A1’s molecular and biological properties, elucidates its involvement in disease progression, and evaluates its clinical potential. The study seeks to enhance understanding of SLC40A1’s mechanisms, laying the groundwork for the development of targeted therapies.

Zika virus (ZIKV) infection during human pregnancy may lead to severe fetal pathology and debilitating impairments in offspring. However, the majority of infections are subclinical and not associated with evident birth defects. Potentially detrimental life-long health outcomes in asymptomatic offspring evoke high concerns. Thus, animal models addressing sequelae in offspring may provide valuable information. To induce subclinical infection, we inoculated selected porcine fetuses at the mid-stage of development. Inoculation resulted in trans-fetal virus spread and persistent infection in the placenta and fetal membranes for two months. Offspring did not show congenital Zika syndrome (e.g., microcephaly, brain calcifications, congenital clubfoot, arthrogryposis, seizures) or other visible birth defects. However, a month after birth, a portion of offspring exhibited excessive interferon alpha (IFN-α) levels in blood plasma in a regular environment. Most affected offspring also showed dramatic IFN-α shutdown during social stress providing the first evidence for the cumulative impact of prenatal ZIKV exposure and postnatal environmental insult. Other eleven cytokines tested before and after stress were not altered suggesting the specific IFN-α pathology. While brains from offspring did not have histopathology, lesions, and ZIKV, the whole genome expression analysis of the prefrontal cortex revealed profound sex-specific transcriptional changes that most probably was the result of subclinical in utero infection. RNA-seq analysis in the placenta persistently infected with ZIKV provided independent support for the sex-specific pattern of in utero-acquired transcriptional responses. Collectively, our results provide strong evidence that two hallmarks of fetal ZIKV infection, altered type I IFN response and molecular brain pathology can persist after birth in offspring in the absence of congenital Zika syndrome.

High throughput sequencing is currently revolutionizing the genomics field and providing new approaches to the detection and characterization of microorganisms. The objective of this study was to assess the detection of influenza D virus (IDV) in bovine respiratory tract samples using two sequencing platforms (MiSeq and Nanopore (GridION)), and species-specific qPCR. An IDV-specific qPCR was performed on 232 samples (116 nasal swabs and 116 tracheal washes) that had been previously subject to virome sequencing using MiSeq. Nanopore sequencing was performed on 19 samples positive for IDV by either MiSeq or qPCR. Nanopore sequence data was analyzed by two bioinformatics methods: What’s In My Pot (WIMP, on the EPI2ME platform), and an in-house developed analysis pipeline. The agreement of IDV detection between qPCR and MiSeq was 82.3%, between qPCR and Nanopore was 57.9% (in-house) and 84.2% (WIMP), and between MiSeq and Nanopore was 89.5% (in-house) and 73.7% (WIMP). IDV was detected by MiSeq in 14 of 17 IDV qPCR-positive samples with Cq (cycle quantification) values below 31, despite multiplexing 50 samples for sequencing. When qPCR was regarded as the gold standard, the sensitivity and specificity of MiSeq sequence detection were 28.3% and 98.9%, respectively. We conclude that both MiSeq and Nanopore sequencing are capable of detecting IDV in clinical specimens with a range of Cq values. Sensitivity may be further improved by optimizing sequence data analysis, improving virus enrichment, or reducing the degree of multiplexing.

Mucohaemorrhagic diarrhea caused by Brachyspira hyodysenteriae, swine dysentery, is a severe production limiting disease of swine. Recently, pigs in western Canada with clinical signs indistinguishable from swine dysentery were observed. Despite the presence of spirochetes on fecal smears, recognized Brachyspira spp. including B. hyodysenteriae could not be identified. A phylogenetically distinct Brachyspira, called \"B. hampsonii\" strain 30446, however was isolated. The purpose of this study was to experimentally reproduce mucohaemorrhagic colitis and characterize strain 30446 shedding following inoculation. Eighteen 13-week-old pigs were randomly assigned to inoculation (n = 12) or control (n = 6) groups in each of two trials. In trial 1, pigs were inoculated with a tissue homogenate collected from clinically affected field cases. In trial 2, pigs were inoculated with a pure broth culture of strain 30446. In both trials, mucohaemorrhagic diarrhea was significantly more common in inoculated pigs than controls, all of which remained healthy. In animals with mucohaemorrhagic diarrhea, significantly more spirochetes were observed on Gram stained fecal smears, and higher numbers of strain 30446 genome equivalents were detected by quantitative PCR (qPCR). Strain 30446 was cultured from colon and/or feces of all affected but no control animals at necropsy. \"Brachyspira hampsonii\" strain 30446 causes mucohaemorrhagic diarrhea in pigs following a 4-9 day incubation period. Fecal shedding was detectable by day 4 post inoculation, and rarely preceded the onset of mucoid or haemorrhagic diarrhea by more than 2 days. Culture and 30446-specific qPCR are reliable methods of detection of this organism in feces and tissues of diarrheic pigs. The emergence of a novel Brachyspira spp., such as \"B. hampsonii\", creates diagnostic challenges including higher risk of false negative diagnostic tests. We therefore recommend diagnostic laboratories routinely use Brachyspira culture, nox-based and species-specific PCR, and DNA sequencing to diagnose Brachyspira-associated colitis in pigs.

Background: The reported outcomes of pediatric dilated cardiomyopathy (DCM) have varied across studies. There are few outcome data concerning DCM in Chinese children. Therefore, we conducted a retrospective study to describe clinical features and determine risk factors for poor outcomes in children with DCM. Methods: We enrolled 121 children with DCM in our hospital from 2003 to 2021. General information and laboratory and echocardiographic data were collected and analyzed. Cox regression analysis was performed to determine risk factors for poor outcomes. Results: This study included 121 patients (69 males and 52 females). The median age at diagnosis was 10.8 years, and the follow-up time was 10.0 months. Eighty-two patients (67.8%) exhibited cardiac function classes III–IV at the time of diagnosis. Tachypnea was the most common symptom (78.5%). In echocardiography, the mean left ventricular end-diastolic dimension z score was 7.36 ± 2.73, and the left ventricular ejection fraction z score was −6.58 ± 2.17. The 1-, 2-, and 5-year survival rates were 51.2%, 43.8%, and 32.2%, respectively. Cox analysis revealed that cardiac function classes III–IV (hazard ratio [HR] = 1.801, 95% confidence interval [95% CI] = 1.030–3.149, p = 0.039) and calcium levels (HR = 0.219, 95% CI = 0.084–0.576, p = 0.002) were predictors of poor outcomes in children with DCM. Conclusions: Children with DCM are at high risk of death. Cardiac function class III–IV and calcium levels were related to the prognosis of pediatric DCM patients.

Highly pathogenic avian influenza (HPAI) H5N1 and low pathogenic avian influenza (LPAI) H7N9 viruses pose a severe threat to public health through zoonotic infection, causing severe respiratory disease in humans. While HPAI H5N1 human infections have typically been reported in Asian countries, avian H7N9 human infections have been reported mainly in China. However, Canada reported a case of fatal human infection by the HPAI H5N1 virus in 2014, and two cases of human illness associated with avian H7N9 virus infection in 2015. While the genomes of the causative viruses A/Alberta/01/2014 (H5N1) (AB14 (H5N1)) and A/British Columbia/1/2015 (H7N9) (BC15 (H7N9)) are reported, the isolates had not been evaluated for their pathogenicity in animal models. In this study, we characterized the pathogenicity of AB14 (H5N1) and BC15 (H7N9) and found that both strain isolates are highly lethal in mice. AB14 (H5N1) caused systemic viral infection and erratic proinflammatory cytokine gene expression in different organs. In contrast, BC15 (H7N9) replicated efficiently only in the respiratory tract, and was a potent inducer for proinflammatory cytokine genes in the lungs. Our study provides experimental evidence to complement the specific human case reports and animal models for evaluating vaccine and antiviral candidates against potential influenza pandemics.

Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) channel, which can result in chronic lung disease. The sequence of events leading to lung disease is not fully understood but recent data show that the critical pathogenic event is the loss of the ability to clear bacteria due to abnormal airway surface liquid secretion (ASL). However, whether the inhalation of bacteria triggers ASL secretion and whether this is abnormal in cystic fibrosis has never been tested. Here we show, using a novel synchrotron-based in vivo imaging technique, that wild-type pigs display both a basal and a Toll-like receptor-mediated ASL secretory response to the inhalation of cystic fibrosis relevant bacteria. Both mechanisms fail in CFTR −/− swine, suggesting that cystic fibrosis airways do not respond to inhaled pathogens, thus favoring infection and inflammation that may eventually lead to tissue remodeling and respiratory disease. Cystic fibrosis is caused by mutations in the CFTR chloride channel, leading to reduced airway surface liquid secretion. Here the authors show that exposure to bacteria triggers secretion in wild-type but not in pig models of cystic fibrosis, suggesting an impaired response to pathogens contributes to infection.

Very few studies have examined the diagnostic sensitivity and specificity of currently available laboratory tests for detecting respiratory pathogens in cattle, and even fewer have examined test performance on samples from animals before the onset of clinical disease. In this study, Bayesian latent class modeling (BLCM) was used to assess diagnostic test performance in the absence of a gold standard on nasal swabs collected from 19 western Canadian feedlots. Viruses associated with bovine respiratory disease (BRD) were identified using qPCR from a commercial diagnostic laboratory from 760 nasal swabs collected from fall-placed calves (FPC) and yearlings (YRL) at and shortly after feedlot arrival. Using BLCM, the qPCR results were compared to previously reported matching nanopore metagenomic sequencing data for these same samples. Based on BLCM, test sensitivities and specificities were estimated for the detection of bovine coronavirus (BCoV), bovine herpesvirus type 1 (BoHV-1), bovine parainfluenza virus type 3 (BPIV-3), bovine respiratory syncytial virus (BRSV), and influenza D virus (IDV). Estimates informed by BLCM were not available for the detection of bovine viral diarrheal virus (BVDV) because qPCR did not detect this virus in any samples. Diagnostic sensitivity of qPCR was higher than metagenomic sequencing for detecting BCoV (qPCR 0.90, 95% CrI 0.81-0.99; sequencing 0.35, 95% CrI 0.25-0.46) and BoHV-1 (qPCR 0.39, 95% CrI 0.19-0.99; sequencing 0.04, 95% CrI 0.01-0.15). However, the estimated diagnostic sensitivity of metagenomic sequencing was higher than qPCR for identifying BRSV (qPCR 0.32, 95% CrI 0.22-0.43; sequencing 0.60, 95% CrI 0.44-0.77). No significant difference among sensitivities was noted for the detection of BPIV-3 (qPCR 0.42, 95% CrI 0.21-0.66; sequencing 0.52, 95% CrI 0.19-0.87) and IDV (qPCR 0.65, 95% CrI 0.53-0.79; sequencing 0.60, 95% CrI 0.48-0.73). Diagnostic specificity was comparable for most viruses, except for BCoV, where metagenomic sequencing (BCoV 0.91, 95% CrI 0.88-0.95) outperformed qPCR (BCoV 0.59, 95% CrI 0.51-0.68). The specificity and sensitivity for detection of BRD-associated bacteria from the same metagenomic data were also similar to those estimated for culture and qPCR results for the same samples. Estimated test sensitivities of both nanopore metagenomic sequencing and qPCR for the detection of BRD viruses of interest in nasal swab samples were moderate to very low for most viruses. While the tests varied in their ability to detect individual viruses, data from this study suggest nanopore metagenomic sequencing offers a potential alternative for diagnostic laboratories to identify three of six important BRD viruses as well as bacteria associated with BRD.

The combustion of biomass fuel boilers not only produces inorganic pollutants such as carbon oxides, nitrogen oxides, sulfur compounds, but also organic pollutants such as VOCs and PAHs, which directly affect the global biogeochemical cycle and atmospheric changes. Compared with foreign countries, there is relatively less research and related standards on the emission of organic pollutants from biomass fuel boilers in China. Therefore, it is necessary to study the emission characteristics of organic pollutants from biomass boilers, which can provide reference for the establishment of organic pollutant emission standards for biomass fuel boilers in China.The emission characteristics of volatile organic compounds(VOCs) and polycyclic aromatic hydrocarbons(PAHs) organic pollutants in the flue gas of three typical biomass-fired boilers in Chongqing were studied, and the emission concentrations of particulate matter, sulfur dioxides(SO2), and nitrogen oxides(NOX) were measured.The results show that the sulfur dioxide emissions from the three types of biomass-fired boilersrs are lower than the local standards in Chongqing, while nitrogen oxides and particulate matter have a phenomenon of exceeding the emission limits of the local standards in Chongqing. The main components of VOCs emitted from biomass powder and biomass particle combustion are OVOCs and aromatic hydrocarbons, while the main components of VOCs emitted from wood biomass combustion are alkynes. The gas-solid distribution pattern of PAHs during the combustion of three types of biomass is basically consistent. Low ring PAHs are mainly enriched in the gas phase, while medium and high ring PAHs are mainly enriched in particulate matter.

Porcine periweaning failure-to-thrive syndrome (PFTS) is characterized by anorexia and progressive debilitation of newly weaned pigs, of which some also demonstrate repetitive oral behaviour. Although no relevant porcine pathogens have been shown to be causally associated, inoculation of susceptible pigs using tissue homogenates is needed to rule out infectious etiologies. Eight snatched-farrowed porcine-colostrum-deprived (SF-pCD) pigs were inoculated with tissue homogenates made from PFTS-affected pigs orally, or combined orally, intraperitoneally (i.p.) and intramuscularly (i.m.) at day (D) 14 of age (INOC). On D21, i.p. and i.m. inoculation were repeated. Four sham-inoculated pigs served as control (CTRL). Three INOC pigs developed mixed bacterial septicemia between the first and second inoculation. All other pigs survived until termination on D49. Average daily gain (ADG) and the frequencies of diarrhea did not differ between INOC and CTRL pigs D14 and D29. Additionally, the progressive debilitation characteristic of PFTS was not observed in any pig, and repetitive oral behaviour was observed in both groups. In conclusion, PFTS was not experimentally reproduced by the current experimental approach providing evidence that PFTS may not have an infectious etiology.