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1.
Mucosal Immunol ; 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013572

RESUMO

IL-10-expressing regulatory B cells (B10 cells) are dysfunctional in patients with many immune disorders. The underlying mechanism remains to be further elucidated. Glutamine is an essential nutrient for cell metabolism. This study aims to elucidate the role of glutaminolysis in maintaining the immune regulatory capacity in B10 cells. Peripheral blood samples were collected from 50 patients with allergic rhinitis and 50 healthy control subjects. B cells were isolated from blood samples by cell sorting with flow cytometry. The role of glutaminolysis in regulating B10 cell activities was assessed by immunological and biochemical approaches. The results showed that B cells from patients with allergic rhinitis expressed low levels of the transporter of glutamine and neutral amino acid. Glutaminolysis was required in the IL-10 expression in B cells. The glutamine catabolism was required in B10 cell generation. The mTOR activation mediated the glutaminolysis-associated B10 cell induction, and the suppression of the B cell glycogen synthase kinase-3 (GSK3) activation. GSK3 activation suppressed IL-10 expression in B cells. Inhibition of GSK3 enhanced IL-10 expression in B cells and alleviated experimental allergic rhinitis by generating immune competent type 1 regulatory T cells.

2.
J Am Soc Nephrol ; 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35017168

RESUMO

BACKGROUND: Untargeted plasma metabolomic profiling combined with machine learning (ML) may lead to discovery of metabolic profiles that inform our understanding of pediatric CKD causes. We sought to identify metabolomic signatures in pediatric CKD based on diagnosis: FSGS, obstructive uropathy (OU), aplasia/dysplasia/hypoplasia (A/D/H), and reflux nephropathy (RN). METHODS: Untargeted metabolomic quantification (GC-MS/LC-MS, Metabolon) was performed on plasma from 702 Chronic Kidney Disease in Children study participants (n: FSGS=63, OU=122, A/D/H=109, and RN=86). Lasso regression was used for feature selection, adjusting for clinical covariates. Four methods were then applied to stratify significance: logistic regression, support vector machine, random forest, and extreme gradient boosting. ML training was performed on 80% total cohort subsets and validated on 20% holdout subsets. Important features were selected based on being significant in at least two of the four modeling approaches. We additionally performed pathway enrichment analysis to identify metabolic subpathways associated with CKD cause. RESULTS: ML models were evaluated on holdout subsets with receiver-operator and precision-recall area-under-the-curve, F1 score, and Matthews correlation coefficient. ML models outperformed no-skill prediction. Metabolomic profiles were identified based on cause. FSGS was associated with the sphingomyelin-ceramide axis. FSGS was also associated with individual plasmalogen metabolites and the subpathway. OU was associated with gut microbiome-derived histidine metabolites. CONCLUSION: ML models identified metabolomic signatures based on CKD cause. Using ML techniques in conjunction with traditional biostatistics, we demonstrated that sphingomyelin-ceramide and plasmalogen dysmetabolism are associated with FSGS and that gut microbiome-derived histidine metabolites are associated with OU.

3.
Nanomedicine ; : 102522, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35032631

RESUMO

We developed surface-enhanced Raman scattering-lateral flow immunoassay (SERS-LFIA) biosensor strips based on SiO2@Au nanoparticles (NPs) for the specific and highly sensitive detection of ricin, staphylococcal enterotoxin B (SEB), and botulinum neurotoxin type A (BoNT/A). SiO2@Au NPs were used to prepare SERS tags with useful properties, such as light weight, uniform particle size, good dispersion, and high SERS performance. The detection limit of the SERS-LFIA strips developed herein for ricin, SEB, and BoNT/A was 0.1, 0.05, and 0.1 ng/mL. Their sensitivity was 100-fold higher than that of colloidal gold-LFIA strips, and the same batch of strips had good repeatability. Moreover, the test was completed within 15 min, indicating that the strips are suitable for the rapid and on-site detection of the said toxins. The SERS-LFIA strips based on SiO2@Au NPs developed herein for the detection of toxins is important to the prevention of bioterrorism attacks.

4.
Drug Des Devel Ther ; 16: 155-164, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35046640

RESUMO

Background: Total knee arthroplasty (TKA) is a severe traumatic procedure, and femoral nerve block (FNB) combined with a sciatic nerve block (SNB) is widely used in TKA. However, injury of the sciatic nerve is clinically reported. Dexmedetomidine (DEX) could reduce stress and inflammation, as well as improve pain in TKA. This study aims to observe the analgesic impact of DEX combined with FNB in TKA. Methods: Eighty-eight patients undergoing TKA were included and randomly divided into two groups: DF group (FNB combined with DEX 0.6µg/kg before surgery, followed by DEX 0.2-0.4µg/kg/h until articular closure) and SF group (FNB combined with SNB). Each nerve was blocked with 0.375% ropivacaine 20mL, and all patients received general anesthesia routinely. The primary endpoint was the pain visual analog scale (VAS) score during activities at postoperative 24 hours. Results: There was no statistical difference in the pain VAS scores at any time point. The mean duration of analgesia for patients with rescue analgesic requests was comparable between the two groups: 25.4 ± 6.3 hours in the DF group vs 24.8 ± 6.4 hours in the SF group (two-sample t-test, p=0.738). The total dose of sufentanil was similar between groups (P=0.355). The maintenance dose of propofol and dose of rescue analgesics were comparable (all P>0.05). There were no statistical differences in the incidence of adverse events. However, the time to extubate in the DF group was significantly longer than those in the SF group (P<0.001). Conclusion: DEX combined with FNB could provide effective analgesia similar to SNB combined with FNB in TKA. Clinical Trial Registration: The trial was registered at the Chinese Clinical Trial Registry on November 17, 2019 (identifier: ChiCTR1900027552).

5.
Oral Dis ; 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35029006

RESUMO

BACKGROUND: Chronic periodontitis (CP) is a common disease of oral cavity, and approximately 35% of adults suffered from CP. Therefore, its underlying mechanism needs to be explored for new therapeutic approaches. Chemerin as a multifunctional adipokine, is found to be highly expressed in the gingival crevicular fluid (GCF), gingival tissues and the plasma of periodontitis patients. Thus, we aimed to uncover the underlying mechanism of chemerin in CP. METHODS: 36 CP patients and 25 healthy volunteers were enrolled. Periodontal ligament stem cells (PDLSCs) were isolated from CP patients and healthy ones respectively. Then normal PDLSCs or PDLSCs-differentiated osteoblasts were treated with different doses of recombinant human chemerin. RESULTS: Chemerin and inflammatory cytokines, including interleukin-1ß, interleukin-6 and tumor necrosis factor-α, were higher in the GCF and serum of CP patients than healthy ones. Moreover, chemerin was positively correlated with these three inflammatory cytokines respectively in CP patients. PDLSCs isolated from CP patients had higher expressions of chemerin and these cytokines than the ones isolated from normal individuals. Furthermore, chemerin dose-dependently increased inflammatory responses and inhibited osteogenic differentiation of PDLSCs. CONCLUSION: Chemerin accelerated inflammatory responses and suppressed osteogenic differentiation of PDLSCs, thus chemerin might sever as a therapeutic target of CP.

6.
Sens Actuators B Chem ; 351: 130897, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34658530

RESUMO

The rapid and accurate diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the early stage of virus infection can effectively prevent the spread of the virus and control the epidemic. Here, a colorimetric and fluorescent dual-functional lateral flow immunoassay (LFIA) biosensor was developed for the rapid and sensitive detection of spike 1 (S1) protein of SARS-CoV-2. A novel dual-functional immune label was fabricated by coating a single-layer shell formed by mixing 20 nm Au nanoparticles (Au NPs) and quantum dots (QDs) on SiO2 core to produce strong colorimetric and fluorescence signals and ensure good monodispersity and high stability. The colorimetric signal was used for visual detection and rapid screening of suspected SARS-CoV-2 infection on sites. The fluorescence signal was utilized for sensitive and quantitative detection of virus infection at the early stage. The detection limits of detecting S1 protein via colorimetric and fluorescence functions of the biosensor were 1 and 0.033 ng/mL, respectively. Furthermore, we evaluated the performance of the biosensor for analyzing real samples. The novel biosensor developed herein had good repeatability, specificity and accuracy, which showed great potential as a tool for rapidly detecting SARS-CoV-2.

7.
Sci Total Environ ; 802: 149862, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34461473

RESUMO

Complete ammonia oxidizing (comammox) bacteria are frequently detected in wastewater biological nutrient removal (BNR) systems. This study identified "Candidatus Nitrospira nitrosa"-like comammox bacteria as the predominant ammonia oxidizers (97.5-99.4%) in a lab-scale BNR system with acetate and sludge fermentation liquid as external carbon sources. The total nitrogen and phosphorus removals of the system were 75.9% and 86.9% with minimal N2O emission (0.27%). Low ammonia concentration, mixotrophic growth potentials and metabolic interactions with diverse heterotrophs collectively contributed to the survival of comammox bacteria in the system. The recovered draft genomes of comammox bacteria indicated their potentials in using acetate and propionate but not butyrate. Acetate and propionate indeed stimulated the transcription of comammox amoA genes (up-regulated by 4.1 folds compared with no organic addition), which was positively correlated with the ammonia oxidation rate of the community (r = 0.75, p < 0.05). Comammox bacteria could provide vitamins/cofactors (e.g., cobalamin and biotin) to heterotrophs (e.g., Burkholderiaceae), and in return receive amino acids (e.g., phenylalanine and tyrosine) from heterotrophs, which they cannot synthesize. Compared with comammox bacteria, ammonia oxidizing bacteria (AOB) exhibited lower metabolic versatility, and lacked more pathways for the synthesis of amino acids and vitamin/cofactors, leading to their washout in the studied system. BNRs with comammox bacteria as the major nitrifiers hold great potentials in achieving superior performance at low aeration cost and low N2O emission and at full-scale plants.


Assuntos
Esgotos , Águas Residuárias , Amônia , Bactérias/genética , Carbono , Fermentação , Nitrificação , Nutrientes , Oxirredução , Filogenia
8.
Natl Sci Rev ; 8(11): nwab181, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34876999

RESUMO

A comprehensive review of weak decays of charmed hadrons (D 0/ +, [Formula: see text] and [Formula: see text]) based on analyses of the threshold data from e + e - annihilation in the BESIII experiment is presented. Current experimental challenges and successes in understanding decays of the charmed hadrons are discussed. Precise calibrations of quantum chromodynamics and tests of the standard model are provided by measurements of purely leptonic and semi-leptonic decays of charmed hadrons, and lepton universality is probed in purely leptonic decays of charmed mesons to three generations of leptons. Quantum correlations in threshold data samples provide access to strong phases in the neutral D meson decays and probe the decay dynamics of the charmed Λ c baryon. Charm physics studies with near-threshold production of charmed particle pairs are unique to BESIII, and provide many important opportunities and challenges.

9.
Polymers (Basel) ; 13(23)2021 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-34883684

RESUMO

Automatic fiber placement (AFP) is a type of labor-saving automatic technology for forming composite materials that are widely used in aviation and other fields. In this process, concave surface delamination is a common defect, as existing research on the conditions for this defect to occur is insufficient. To predict the occurrence of this defect, the concept of allowable interlaminar normal stress is proposed to define its occurrence conditions, and based on this concept, probe tests are carried out using the principle of time-temperature equivalence. Through the laying speed/allowable normal stress curve measured in the probe experiment, the physical meaning of allowable normal stress is discussed. At the same time, the measured curve is quantitatively analyzed, combined with viscoelastic theory and the molecular diffusion reptation model, and the dominating effect in the formation of a metal/prepreg layer and prepreg/prepreg layer is determined. Finally, the experimental data are used to guide the parameter selection in an automatic placement engineering case and prove its correctness.

10.
Pediatr Rheumatol Online J ; 19(1): 167, 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34857002

RESUMO

BACKGROUND: The objective of this work was to describe magnetic resonance imaging (MRI) changes over time in inflammatory and structural lesions at the sacroiliac joint (SIJ) in children with spondyloarthritis (SpA) exposed and unexposed to tumor necrosis factor inhibitor (TNFi). METHODS: This was a retrospective, multicenter study of SpA patients with suspected or confirmed sacroiliitis who underwent at ≥2 pelvic MRI scans. Images were reviewed independently by 3 radiologists and scored for inflammatory and structural changes using the Spondyloarthritis Research Consortium of Canada (SPARCC) SIJ inflammation score (SIS) and structural score (SSS). Longitudinal, quantitative changes in patient MRI scans were measured using descriptive statistics and stratified by TNFi exposure. We used an average treatment effects (ATE) regression model to explore the average effect of TNFi exposure over time on inflammatory and structural lesions, adjusting for baseline lesion scores. RESULTS: Forty-six subjects were evaluated using the SIS (n = 45) and SSS (n = 18). Median age at baseline imaging was 13.6 years, 63% were male and 71% were white. Twenty-three subjects (50%) were TNFi exposed between MRI studies. The median change in SIS in TNFi exposed and unexposed subjects with a baseline SIS ≥0 was - 20.7 and - 14.3, respectively (p = 0.09). Eleven (85%) TNFi exposed and 8 (89%) unexposed subjects with a baseline SIS ≥0 met the SIS minimal clinically important difference (MCID; ≥2.5). Using the ATE model adjusted for baseline SIS, the average effect of TNFi on SIS in patients with a baseline SIS ≥2 was - 14.5 (p < 0.01). Unadjusted erosion change score was significantly worse in TNFi unexposed versus exposed subjects (p = 0.03) but in the ATE model the effect of TNFi was not significant. CONCLUSION: This study quantitatively describes how lesions in the SIJs on MRI change over time in patients exposed to TNFi versus unexposed. Follow-up imaging in TNFi exposed patients showed greater improvement than the unexposed group by most metrics, some of which reached statistical significance. Surprisingly, a majority of TNFi unexposed children with a baseline SIS≥2 met the SIS MCID. Additional studies assessing the short and long-term effects of TNFi on inflammatory and structural changes in juvenile SpA are needed.

11.
Brief Bioinform ; 2021 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-34891172

RESUMO

Identifying new indications for drugs plays an essential role at many phases of drug research and development. Computational methods are regarded as an effective way to associate drugs with new indications. However, most of them complete their tasks by constructing a variety of heterogeneous networks without considering the biological knowledge of drugs and diseases, which are believed to be useful for improving the accuracy of drug repositioning. To this end, a novel heterogeneous information network (HIN) based model, namely HINGRL, is proposed to precisely identify new indications for drugs based on graph representation learning techniques. More specifically, HINGRL first constructs a HIN by integrating drug-disease, drug-protein and protein-disease biological networks with the biological knowledge of drugs and diseases. Then, different representation strategies are applied to learn the features of nodes in the HIN from the topological and biological perspectives. Finally, HINGRL adopts a Random Forest classifier to predict unknown drug-disease associations based on the integrated features of drugs and diseases obtained in the previous step. Experimental results demonstrate that HINGRL achieves the best performance on two real datasets when compared with state-of-the-art models. Besides, our case studies indicate that the simultaneous consideration of network topology and biological knowledge of drugs and diseases allows HINGRL to precisely predict drug-disease associations from a more comprehensive perspective. The promising performance of HINGRL also reveals that the utilization of rich heterogeneous information provides an alternative view for HINGRL to identify novel drug-disease associations especially for new diseases.

12.
JAMA Netw Open ; 4(12): e2137250, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34928360

RESUMO

Importance: Despite concerns regarding the potential deleterious physical and mental health outcomes among family members of a child with a life-threatening condition (LTC), few studies have examined empirical measures of health outcomes among these family members. Objectives: To examine whether mothers, fathers, sisters, and brothers of children with 1 of 4 types of pediatric LTCs have higher rates of health care encounters, diagnoses, and prescriptions compared with families of children without these conditions. Design, Setting, and Participants: This retrospective cohort study included US families with commercial insurance coverage from a single carrier. Children who had 1 of 4 LTCs (substantial prematurity, critical congenital heart disease, cancer, or a condition resulting in severe neurologic impairment) were identified by a diagnosis in their insurance claim data between July 1, 2015, and June 30, 2016. Each case child and their family was matched with up to 4 control children and their families based on the age of the case and control children. Data were analyzed between August 2020 and March 2021. Exposures: Having a child or sibling with substantial prematurity, critical congenital heart disease, cancer, or a condition resulting in severe and progressive neurologic impairment. Main Outcomes: Rates of occurrence of health care encounters, physical and mental health diagnoses, and physical and mental health medication prescriptions, identified from insurance claims data, were compared between case and control families using a multivariable negative binomial regression model. The statistical analysis adjusted for observed differences between case and control families and accounted for clustering at the family level. Results: The study included 25 528 children (6909 case children [27.1%] and 18 619 control children [72.9%]; median age, 6.0 years [IQR, 1-13 years]; 13 294 [52.1%] male), 43 357 parents (11 586 case parents [26.7%] and 31 771 control parents [73.3%]; mean [SD] age, 40.4 [8.1] years; 22 318 [51.5%] female), and 25 706 siblings (7664 case siblings [29.8%] and 18 042 control siblings [70.2%]; mean [SD] age, 12.1 [6.5] years; 13 114 [51.0%] male). Overall, case mothers had higher rates of the composite outcome of health care encounters, diagnoses, and prescriptions compared with control mothers (incident rate ratio [IRR], 1.61; 95% CI, 1.54-1.68), as did case fathers compared with control fathers (IRR, 1.55; 95% CI, 1.46-1.64). Sisters of children with LTCs had higher rates of the composite outcome compared with sisters of children without LTCs (IRR, 1.68; 95% CI, 1.55-1.82), as did brothers of children with LTCs compared with brothers of children without LTCs (IRR, 1.70; 95% CI, 1.56-1.85). Conclusions and Relevance: In this cohort study, mothers, fathers, sisters, and brothers who had a child or sibling with 1 of 4 types of LTCs had higher rates of health care encounters, diagnoses, and medication prescriptions compared with families who did not have a child with that condition. The findings suggest that family members of children with LTCs may experience poorer mental and physical health outcomes. Interventions for parents and siblings of children with LTCs that aim to safeguard their mental and physical well-being appear to be warranted.


Assuntos
Doença Crônica/psicologia , Relações Pais-Filho , Pais/psicologia , Irmãos/psicologia , Adaptação Psicológica , Adulto , Cuidadores/psicologia , Criança , Doença Crônica/reabilitação , Estudos de Coortes , Feminino , Humanos , Masculino , Estudos Retrospectivos
13.
Front Pharmacol ; 12: 773235, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34925032

RESUMO

Abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs) is a critical pathological feature in the pathogenesis of pulmonary arterial hypertension (PAH), but the regulatory mechanisms remain largely unknown. Herein, we demonstrated that interferon regulatory factor 9 (IRF9) accelerated PASMCs proliferation by regulating Prohibitin 1 (PHB1) expression and the AKT-GSK3ß signaling pathway. Compared with control groups, the rats treated with chronic hypoxia (CH), monocrotaline (MCT) or sugen5416 combined with chronic hypoxia (SuHx), and mice challenged with CH had significantly thickened pulmonary arterioles and hyperproliferative PASMCs. More importantly, the protein level of IRF9 was found to be elevated in the thickened medial wall of the pulmonary arterioles in all of these PAH models. Notably, overexpression of IRF9 significantly promoted the proliferation of rat and human PASMCs, as evidenced by increased cell counts, EdU-positive cells and upregulated biomarkers of cell proliferation. In contrast, knockdown of IRF9 suppressed the proliferation of rat and human PASMCs. Mechanistically, IRF9 directly restrained PHB1 expression and interacted with AKT to inhibit the phosphorylation of AKT at thr308 site, which finally led to mitochondrial dysfunction and PASMC proliferation. Unsurprisingly, MK2206, a specific inhibitor of AKT, partially reversed the PASMC proliferation inhibited by IRF9 knockdown. Thus, our results suggested that elevation of IRF9 facilitates PASMC proliferation by regulating PHB1 expression and AKT signaling pathway to affect mitochondrial function during the development of PAH, which indicated that targeting IRF9 may serve as a novel strategy to delay the pathological progression of PAH.

14.
Ying Yong Sheng Tai Xue Bao ; 32(11): 4021-4028, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34898118

RESUMO

Planting grasses in orchards is important to maintain soil basic fertility, improve the soil ecological environment, and promote sustainable growth of fruit. However, the quantitative effects of grasses on nutrient content of orchard soil in China is unclear, as well as the mechanisms associated with higher fruit yield and quality in orchards. This meta-analysis included 62 literature published between 1990 and 2020 to quantify effects of soil depth, planting years of raw grasses, and raw grasses to the physical and chemical properties and fruit yield and quality of orchards, as well as to explore the impacts of grasses on the sustainable production of Chinese orchards. Between 1990 and 2020, compared with the non-grass orchards, the content of soil organic matter, alkali nitrogen and available phosphorus in orchard with grasses increased by 18%, 11%, and 27% respectively, and the soil bulk density was reduced by 20%. Orchard grass increased soil temperature by 23% when the temperature was below 10 ℃, and reduced soil temperature by about 8% when the temperature was above 10 ℃. Compared with annual grasses, perennial grasses (natural or artificial) significantly improved soil properties, fruit yield and quality. These findings indicated that long-term grass planting in orchards had far-reaching significance on sustainable production.


Assuntos
Malus , Solo , Frutas/química , Nitrogênio/análise , Fósforo
15.
Genet Med ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34906496

RESUMO

PURPOSE: BRG1/BRM-associated factor (BAF) complex is a chromatin remodeling complex that plays a critical role in gene regulation. Defects in the genes encoding BAF subunits lead to BAFopathies, a group of neurodevelopmental disorders with extensive locus and phenotypic heterogeneity. METHODS: We retrospectively analyzed data from 16,243 patients referred for clinical exome sequencing (ES) with a focus on the BAF complex. We applied a genotype-first approach, combining predicted genic constraints to propose candidate BAFopathy genes. RESULTS: We identified 127 patients carrying pathogenic variants, likely pathogenic variants, or de novo variants of unknown clinical significance in 11 known BAFopathy genes. Those include 34 patients molecularly diagnosed using ES reanalysis with new gene-disease evidence (n = 21) or variant reclassifications in known BAFopathy genes (n = 13). We also identified de novo or predicted loss-of-function variants in 4 candidate BAFopathy genes, including ACTL6A, BICRA (implicated in Coffin-Siris syndrome during this study), PBRM1, and SMARCC1. CONCLUSION: We report the mutational spectrum of BAFopathies in an ES cohort. A genotype-driven and pathway-based reanalysis of ES data identified new evidence for candidate genes involved in BAFopathies. Further mechanistic and phenotypic characterization of additional patients are warranted to confirm their roles in human disease and to delineate their associated phenotypic spectrums.

16.
Front Physiol ; 12: 704401, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34912233

RESUMO

Matrix metalloproteinase-12 (Mmp12) is upregulated by cigarette smoke (CS) and plays a critical role in extracellular matrix remodeling, a key mechanism involved in physiological repair processes, and in the pathogenesis of emphysema, asthma, and lung cancer. While cigarette smoking is associated with the development of chronic obstructive pulmonary diseases (COPD) and lung cancer, in utero exposures to CS and second-hand smoke (SHS) are associated with asthma development in the offspring. SHS is an indoor air pollutant that causes known adverse health effects; however, the mechanisms by which in utero SHS exposures predispose to adult lung diseases, including COPD, asthma, and lung cancer, are poorly understood. In this study, we tested the hypothesis that in utero SHS exposure aggravates adult-induced emphysema, asthma, and lung cancer. Methods: Pregnant BALB/c mice were exposed from gestational days 6-19 to either 3 or 10mg/m3 of SHS or filtered air. At 10, 11, 16, or 17weeks of age, female offspring were treated with either saline for controls, elastase to induce emphysema, house-dust mite (HDM) to initiate asthma, or urethane to promote lung cancer. At sacrifice, specific disease-related lung responses including lung function, inflammation, gene, and protein expression were assessed. Results: In the elastase-induced emphysema model, in utero SHS-exposed mice had significantly enlarged airspaces and up-regulated expression of Mmp12 (10.3-fold compared to air-elastase controls). In the HDM-induced asthma model, in utero exposures to SHS produced eosinophilic lung inflammation and potentiated Mmp12 gene expression (5.7-fold compared to air-HDM controls). In the lung cancer model, in utero exposures to SHS significantly increased the number of intrapulmonary metastases at 58weeks of age and up-regulated Mmp12 (9.3-fold compared to air-urethane controls). In all lung disease models, Mmp12 upregulation was supported at the protein level. Conclusion: Our findings revealed that in utero SHS exposures exacerbate lung responses to adult-induced emphysema, asthma, and lung cancer. Our data show that MMP12 is up-regulated at the gene and protein levels in three distinct adult lung disease models following in utero SHS exposures, suggesting that MMP12 is central to in utero SHS-aggravated lung responses.

17.
J Appl Microbiol ; 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34724303

RESUMO

AIMS: The Hawaiian Bobtail Squid (Euprymna scolopes) is a model organism for investigating host-symbiont relationships. The current scientific focus is on the microbiome within E. scolopes, while very little is known about the microbiome of the tanks housing E. scolopes. We examined the hypothesis that bacterial communities and geochemistry within the squid tank environment correlate with the production of viable paralarval squid. METHODS AND RESULTS: Total DNA was extracted from sediment and filtered water samples from 'productive' squid cohorts with high embryonic survival and paralarval hatching, 'unproductive' cohorts with low embryonic survival and paralarval hatching. As a control total DNA was extracted from environmental marine locations where E. scolopes is indigenous. Comparative analysis of the bacterial communities by the 16S rRNA gene was performed using next generation sequencing. Thirty-eight differentially abundant genera were identified in the adult tank waters. The majority of the sequences represented unclassified, candidate or novel genera. The characterized genera included Aquicella, Woeseia and Ferruginibacter, with Hyphomicrobium and Rhizohapis were found to be more abundant in productive adult tank water. In addition, nitrate and pH covaried with productive cohorts, explaining 67% of the bacterial populations. The lower abundance of nitrate-reducing bacteria in unproductive adult tank water could explain detected elevated nitrate levels. CONCLUSIONS: We conclude that microbiome composition and water geochemistry can negatively affect E. scolopes reproductive physiology in closed tank systems, ultimately impacting host-microbe research using these animals. SIGNIFICANCE AND IMPACT OF STUDY: These results identify the tight relationship between the microbiome and geochemistry to E. scolopes. From this study, it may be possible to design probiotic counter-measures to improve aquaculture conditions for E. scolopes.

18.
Artigo em Inglês | MEDLINE | ID: mdl-34725759

RESUMO

Nitrate (NO3-) loss and enrichment in water bodies caused by fertilization are a major environmental problem in agricultural areas. However, the quantitative contribution of different NO3- sources, especially chemical fertilizers (CF) and soil organic nitrogen (SON), to NO3- runoff loss remains unclear. In this study, a systematic investigation of NO3- runoff and its sources was conducted in a subtropical agricultural watershed located in Yujiang County, Jiangxi Province, China. A semi-monthly sampling was performed at the inlet and outlet from March 2018 to February 2019. Hydrochemical and dual NO3- isotope (15 N and 18O) approaches were combined to estimate the NO3- runoff loss and quantify the contribution of different sources with a Bayesian isotope mixing model. Source apportionment by Stable Isotope Analysis in R (SIAR) suggested that NO3- in runoff was mainly derived from nitrification of ammonium (NH4+) mineralized from SON (37-52%) and manure/sewage (M&S) (25-47%), while the contribution of CF was relatively small (14-25%). The contribution of various sources showed seasonal variations, with a greater contribution of CF in the wet growing season (March to August). Compared with the inlet which contributed 37-40% to runoff NO3-, SON contributed more at the outlet (49-52%). Denitrification in the runoff was small and appeared to be confined to the dry season (September to February), with an estimated NO3- loss of 2.73 kg N ha-1. The net NO3- runoff loss of the watershed was 34.5 kg N ha-1 yr-1, accounting for 15% of the annual fertilization rate (229 kg N ha-1 yr-1). Besides M&S (22%), fertilization and remineralization of SON (CF + SON) were the main sources for the NO3- runoff loss (78%), suggesting accelerated nitrification of NH4+ from CF (24%) and SON mineralization (54%). Our study indicates that NO3- runoff loss in subtropical agricultural watersheds is dominated by nonpoint source pollution from fertilization. SON played a more important role than CF. Besides, the contribution of sewage should not be neglected. Our data suggest that a combination of more rational fertilizer N application (CF), better management of SON, and better treatment of domestic sewage could alleviate NO3- pollution in subtropical China.

19.
J Pediatr ; 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34728234

RESUMO

OBJECTIVE: To compare key seizure and outcome characteristics between neonates with and without cardiopulmonary disease (CPD). STUDY DESIGN: The Neonatal Seizure Registry (NSR-1) is a multicenter, prospectively acquired cohort of neonates with clinical or EEG-confirmed seizures. CPD was defined as congenital heart disease, congenital diaphragmatic hernia, and exposure to extracorporeal membrane oxygenation. We assessed continuous electroencephalographic monitoring (cEEG) strategy, seizure characteristics, seizure management, and outcomes for neonates with and without CPD. RESULTS: We evaluated 83 neonates with CPD and 271 neonates without CPD. Neonates with CPD were more likely to have EEG-only seizures (40% vs. 21%, P <.001) and experience their first seizure later than those without CPD (174 vs. 21 hours of age, p<0.001), but they had similar seizure exposure (many-recurrent electrographic seizures 39% vs. 43%, p=0.27). Phenobarbital was the primary initial antiseizure medication (ASM) for both groups (90%), and both groups had similarly high rates of incomplete response to initial ASM administration (66% vs. 68%, p=0.75). Neonates with CPD were discharged from the hospital later (hazard ratio 0.34, 95%CI 0.25-0.45, p<0.001), although rates of in-hospital mortality were similar between the groups (hazard ratio 1.13, 95%CI 0.66-1.94, p=0.64). CONCLUSION: Neonates with and without CPD had a similarly high seizure exposure, but neonates with CPD were more likely to experience EEG-only seizures and had seizure onset later in the clinical course. Phenobarbital was the most common seizure treatment, but seizures were often refractory to initial ASM. These data support guidelines recommending cEEG in neonates with CPD and indicate a need for optimized therapeutic strategies.

20.
PhytoKeys ; 183: 9-19, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34720627

RESUMO

Haplodontiumaltunense X.R.Wang & S.Mamtimin, a new moss species of the family Bryaceae from Xinjiang Uygur Autonomous Region, China is described and illustrated. Genetic analysis based on ITS sequences shows that this species is a member of the Bryaceae and in the same clade as Anomobryum. Particularly distinctive features of the new species include: double peristome; the exostome has raised and membranous chomata with united lamellae between two teeth proximally; the endostome is poorly developed and all the endostomial material tightly adherent to the exostome.

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