ABSTRACT
Endothelial dysfunction is a crucial factor in promoting organ failure during septic shock. However, the underlying mechanisms are unknown. Here, we show that kidney injury after lipopolysaccharide (LPS) insult leads to strong endothelial transcriptional and epigenetic responses. Furthermore, SOCS3 loss leads to an aggravation of the responses, demonstrating a causal role for the STAT3-SOCS3 signaling axis in the acute endothelial response to LPS. Experiments in cultured endothelial cells demonstrate that IL-6 mediates this response. Furthermore, bioinformatics analysis of in vivo and in vitro transcriptomics and epigenetics suggests a role for STAT, AP1 and interferon regulatory family (IRF) transcription factors. Knockdown of STAT3 or the AP1 member JunB partially prevents the changes in gene expression, demonstrating a role for these transcription factors. In conclusion, endothelial cells respond with a coordinated response that depends on overactivated IL-6 signaling via STAT3, JunB and possibly other transcription factors. Our findings provide evidence for a critical role of IL-6 signaling in regulating shock-induced epigenetic changes and sustained endothelial activation, offering a new therapeutic target to limit vascular dysfunction.
Subject(s)
DNA Methylation , Endothelial Cells , DNA Methylation/genetics , Interleukin-6/genetics , Lipopolysaccharides , EndotheliumABSTRACT
PURPOSE: Pulmonary disease is the major cause of morbidity and mortality in osteogenesis imperfecta (OI). We investigated the contribution of intrinsic lung factors to impaired pulmonary function in children and young adults with OI types III, IV, VI. METHODS: Patients with type III (n=8), IV (n=21), VI (n=5), VII (n=2) or XIV (n=1) OI (mean age 23.6 years) prospectively underwent pulmonary function tests (PFTs) and thoracic CT and radiographs. RESULTS: PFT results were similar using arm span or ulnar length as height surrogates. PFTs were significantly lower in type III than type IV or VI OI. All patients with type III and half of type IV OI had lung restriction; 90% of patients with OI had reduced gas exchange. Patients with COL1A1 variants had significantly lower forced expiratory flow (FEF)25%-75% compared with those with COL1A2 variants. PFTs correlated negatively with Cobb angle or age. CT scans revealed small airways bronchial thickening (100%, 86%, 100%), atelectasis (88%, 43%, 40%), reticulations (50%, 29%, 20%), ground glass opacities (75%, 5%, 0%), pleural thickening (63%, 48%, 20%) or emphysema (13%, 19%, 20%) in type III, IV or VI OI, respectively. CONCLUSION: Both lung intrinsic and extrinsic skeletal abnormalities contribute to OI pulmonary dysfunction. Most young adult patients have restrictive disease and abnormal gas exchange; impairment is greater in type III than type IV OI. Decreased FEF25%-75% and thickening of small bronchi walls indicate a critical role for small airways. Lung parenchymal abnormalities (atelectasis, reticulations) and pleural thickening were also detected. Clinical interventions to mitigate these impairments are warranted. TRIAL REGISTRATION NUMBER: NCT03575221.
ABSTRACT
OBJECTIVE: To compare the plasma lipid profiles in women with normal pregnancies and those with mild or severe intrahepatic cholestasis of pregnancy (ICP). Our goal was to reveal lipidome-wide alterations in ICP and delve into the pathogenesis of ICP from a lipid metabolism perspective. DESIGN: Cross-sectional study, including women with normal pregnancies, women with mild ICP and women with severe ICP. SETTING: Gansu Provincial Hospital. POPULATION: Women with ICP were recruited from October 2019 to March 2020 in Gansu, China. METHODS: Untargeted lipidomics was used to analyse differentially expressed plasma lipids in controls, in women with mild ICP and in women with severe ICP (n = 30 per group). For lipidomics, liquid chromatography and Q-Exactive Plus Orbitrap mass spectrometry were performed. MAIN OUTCOME MEASURES: Differentially expressed lipids. RESULTS: Thirty-three lipids were differentially expressed in the severe and mild ICP groups, compared with the control group, and 20 of those were sphingolipids (ceramide, six species; sphingomyelin, 14 species). All differentially expressed sphingolipids in women with mild ICP were also differentially expressed in women with severe ICP; the fold change and significance of the differential expression were positively correlated with disease severity. CONCLUSIONS: We systematically characterized the lipidome-wide alterations in mild and severe ICP groups. The results indicated a link between ICP and disordered sphingolipid homeostasis. TWEETABLE ABSTRACT: Abnormal sphingolipid metabolism is involved in the pathogenesis of ICP.
Subject(s)
Cholestasis, Intrahepatic , Pregnancy Complications , Case-Control Studies , Cross-Sectional Studies , Female , Humans , Lipidomics , Male , Pregnancy , SphingolipidsABSTRACT
Objective: To explore the outcomes after treatment of the complex bicondylar tibial plateau fracture through a midline longitudinal approach. Methods: A review of fifteen patients with an average age of (51.3±12.3) years old (range17-65yers;7 males, 8 females) surgically treated from October 2013 to Febuary 2018 were included. Sahatker â ¤ in 10, Sahatker â ¥ in 5; fractures of medial and lateral columns in 9, fractures of three columns in 6. All the patients were adopt a midline longitudinal approach combined with the posterior approach and bone grafting were conducted. Results: All cases were followed-up for (14.4±3.8) month, with an average of 12-24 month. All patients gained bone union during 12-16 weeks after operation, with an average of (15.2±1.3) weeks. There were significant differeces in both tibial plateau angle and posterior slope angle on radiography between preoperation and postoperation (P<0.05), there were no significant differeces in either tibial plateau angle or posterior slope angle on radiography between immediate postoperation and 12 months postoperation (P>0.05). At final follow-up,both the Lachman test and the Pivot-shift test were negative. All patients had complete knee extension, knee flexion angle 100°-135°, with an average of 117.7°±11.3°. The HSS (the Hospital for Special Surgery) score were 66-98, with an average of 85.1±9.3, six cases were excellent and seven cases were good, two cases was fair, the excellent and good rate was 86.7%. The Rasmussen radiological evaluationre were 9-18, with an average of 15.1±2.5, three cases were excellent and eleven cases were good, one cases was fair, the excellent and good rate was 93.3%. 1 patient had fat liquefactionof in antero incision, and got good outcomes after debridement dressing. Conclusion: The treatment of the complex bicondylar tibial plateau fracture through a midline longitudinal approach combined with the posterior approach can result in good exposure and satisfying knee function in short-term.
Subject(s)
Tibial Fractures , Adolescent , Adult , Aged , Bone Plates , Female , Fracture Fixation, Internal , Humans , Knee Joint , Male , Middle Aged , Tibia , Tibial Fractures/surgery , Treatment Outcome , Young AdultABSTRACT
Tubulointerstitial injury is found frequently in lupus nephritis. Immune complex deposits can occur in the tubular basement membranes (TBMs), although its significance in lupus nephritis patients remains unclear. This study assessed the clinical and prognostic features of lupus nephritis patients with TBM deposits in a large Chinese multicenter cohort. Complete data were collected from 195 patients with renal biopsy-proven lupus nephritis diagnosed in the Peking University First Hospital as the discovery cohort. A total of 102 lupus nephritis patients were enrolled from another four centers as the validation cohort. The status of TBM deposits was retrospectively assessed using electron microscopy, and the associations of the deposits with clinical data, pathological characteristics and renal outcomes were further analyzed. The percentage of positive TBM deposits was nearly 30% in the lupus nephritis patients. Using immuno-gold labeling, we found that 10/10 patients were positive for IgG, 7/10 were C3d positive, 6/10 were C1q positive, and 1/10 were C4d positive. Patients with TBM deposits presented with more active features, including a higher SLEDAI score (SLE Disease Activity Index) ( p < 0.001), higher serum creatinine level ( p = 0.001) and lower serum C3 level ( p < 0.001). These patients also presented with higher scores for most renal pathological indices, including the total activity indices score ( p < 0.001) and total chronicity indices score ( p = 0.001). TBM deposits affected renal outcomes in the univariate Cox hazards regression analysis (HR = 4.2, 95% CI = 1.3-14.3, p = 0.02). In conclusion, TBM deposits were common in lupus nephritis patients and correlated closely with the clinical disease activity and renal outcome.
Subject(s)
Antigen-Antibody Complex/immunology , Glomerular Basement Membrane/immunology , Kidney Tubules/immunology , Lupus Nephritis/immunology , Adult , Antigen-Antibody Complex/ultrastructure , Biopsy , Chi-Square Distribution , China , Complement C1q/analysis , Complement C3d/analysis , Complement C4b/analysis , Female , Glomerular Basement Membrane/drug effects , Glomerular Basement Membrane/ultrastructure , Humans , Immunoglobulin G/analysis , Immunosuppressive Agents/therapeutic use , Kaplan-Meier Estimate , Kidney Tubules/drug effects , Kidney Tubules/ultrastructure , Lupus Nephritis/drug therapy , Lupus Nephritis/pathology , Male , Microscopy, Electron, Transmission , Middle Aged , Multivariate Analysis , Peptide Fragments/analysis , Prognosis , Proportional Hazards Models , Retrospective Studies , Severity of Illness Index , Young AdultABSTRACT
Objective: To investigate the relationship between UGT1A1*6, UGT1A1*28, UGT1A1*60 and UGT1A1*93 polymorphisms and irinotecan-induced severe adverse reactions(grade 3-4 delayed diarrhea and neutropenia) in Chinese cancer patients. Methods: A total of 141 cancer patients treated with irinotecan were enrolled in this study. Peripheral venous blood was collected and genomic DNA was extracted. The genetic polymorphisms of UGT1A1*6, UGT1A1*28, UGT1A1*60 and UGT1A1*93 were analyzed by PCR and direct sequencing. The adverse reactions during chemotherapy were observed and recorded. The incidence of severe adverse reactions was compared among patients with different genotypes. Results: Among 141 patients, the cases with UGT1A1*6 GG, GA and AA genotypes were 71, 54 and 16, while those with UGT1A1*28 TA6/6, TA6/7 and TA7/7 genotypes were 105, 33 and 3, respectively. The cases with UGT1A1*60 AA, AC and CC genotypes were 52, 80 and 9, while those with UGT1A1*93 GG, GA and AA genotypes were 105, 32 and 4, respectively. The patients with grade 3-4 delayed diarrhea and neutropenia were 23 and 56, respectively. Multivariate logistic regression analysis showed that UGT1A1*6 and UGT1A1*60 genetic polymorphisms were independent factors influencing the occurrence of grade 3-4 delayed diarrhea. The risk of grade 3-4 delayed diarrhea in homozygous AA carriers of UGT1A1*6 increased 3.79 times compared with that in wild-type GG carriers (95%CI: 1.35-10.67). Moreover, the risk of grade 3-4 delayed diarrhea in homozygous CC carriers of UGT1A1*60 was 20.42 times compared with that in wild-type AA carriers (95%CI: 3.52-118.33). In addition, UGT1A1*28 genetic polymorphism was an independent factor of the occurrence of grade 3-4 neutropenia. The patients with homozygous TA7/7 carriers of UGT1A1*28 had an 1.61 times higher risk of grade 3-4 neutropenia compared with those with wild-type TA6/6 carriers (95%CI: 1.44-12.65). There was no correlation between UGT1A1*93 genetic polymorphism and severe adverse reactions caused by irinotecan. Conclusion: The cancer patients who carried UGT1A1*6, UGT1A1*28 and UGT1A1*60 gene polymorphisms have high risk of severe adverse events caused by irinotecan-based chemotherapy.
Subject(s)
Antineoplastic Agents, Phytogenic/adverse effects , Camptothecin/analogs & derivatives , Diarrhea/chemically induced , Glucuronosyltransferase/genetics , Neoplasms/drug therapy , Neutropenia/chemically induced , Polymorphism, Genetic , Adult , Camptothecin/adverse effects , China , Genotype , Humans , Irinotecan , Regression Analysis , Risk , Severity of Illness IndexABSTRACT
Complement activation has a deep pathogenic influence in immunoglobulin (Ig)A nephropathy (IgAN). C3a and C5a, small cleavage fragments generated by complement activation, are key mediators of inflammation. The fragments exert broad proinflammatory effects by binding to specific receptors (C3aR and C5aR, respectively). However, no studies thus far have investigated the effects of C3a, C5a and their receptors on IgAN. We observed that C3aR and C5aR antagonists repressed IgA-induced cell proliferation and interleukin (IL)-6 and monocyte chemotactic protein 1 (MCP-1) production in cultured human mesangial cells (HMCs). Furthermore, an IgAN mouse model induced by Sendai virus infection was employed to investigate the effects of C3aR and C5aR on IgAN in vivo for the first time. Wild-type (WT) and several knock-out mouse strains (C3aR-/- or C5aR-/- ) were immunized intranasally with increasing doses of inactivated virus for 14 weeks and were subjected to two intravenous viral challenges during the time-period indicated. In the Sendai virus-induced IgAN model, C3aR/C5aR-deficient mice had significantly reduced proteinuria, lower renal IgA and C3 deposition, less histological damage and reduced mesangial proliferation compared with WT mice. Both C3aR deficiency and C5aR deficiency, especially C3aR deficiency, inhibited renal tumour necrosis factor (TNF)-α, transforming growth factor (TGF)-ß, IL-1ß, IL-6 and MCP-1 expression significantly. However, C3aR/C5aR-deficient and WT mice with IgAN did not differ with respect to their blood urea nitrogen (BUN) and serum creatinine levels. Our findings provide further support for the idea that C3aR and C5aR are crucially important in IgAN, and suggest that pharmaceutically targeting C3aR/C5aR may hold promise for the treatment of IgAN.
Subject(s)
Glomerulonephritis, IGA/metabolism , Kidney/pathology , Receptor, Anaphylatoxin C5a/metabolism , Receptors, Complement/metabolism , Animals , Cell Proliferation , Cells, Cultured , Complement Activation , Complement C3a/metabolism , Complement C5a/metabolism , Cytokines/immunology , Disease Models, Animal , Female , Glomerulonephritis, IGA/pathology , Glomerulonephritis, IGA/virology , Humans , Mesangial Cells/cytology , Mesangial Cells/metabolism , Mice , Mice, Inbred BALB C , Mice, Knockout , RNA, Messenger/metabolism , Receptor, Anaphylatoxin C5a/genetics , Receptors, Complement/genetics , Sendai virus , Signal TransductionABSTRACT
To extrapolate the influence of plant cultivars varying in resistance levels to hosts on parasitoid life history traits, we estimated variation in parasitoid developmental and reproductive performances as a function of resistance in soybean cultivars, which were randomly chosen from a line of resistant genotypes. Our study showed that the parasitoid Meteorus pulchricornis varied widely in offspring survival and lifetime fecundity, but varied slightly in development time and adult body size, in response to the soybean cultivars that varied in resistance to the host Spodoptera litura. Furthermore, the variability in survival and lifetime fecundity was different between attacking the 2nd and the 4th instar host larvae, varying more in survival but less in lifetime fecundity when attacking the 4th than 2nd instar larvae. Our study provides further evidence supporting that plant resistance to herbivorous hosts have variable effects on different life history traits of higher trophic level parasitoids.
Subject(s)
Antibiosis , Glycine max/physiology , Host-Parasite Interactions , Hymenoptera/physiology , Spodoptera/physiology , Spodoptera/parasitology , Animals , Larva/growth & development , Larva/parasitology , Larva/physiology , Life History Traits , Spodoptera/growth & developmentABSTRACT
Hermansky-Pudlak syndrome (HPS) is a group of rare genetic disorders, with several subtypes leading to fatal adult-onset pulmonary fibrosis (PF) and no effective treatment. Circulating biomarkers detecting early PF have not been identified. We investigated whether endocannabinoids could serve as blood biomarkers of PF in HPS. We measured endocannabinoids in the serum of HPS, IPF, and healthy human subjects and in a mouse model of HPSPF. Pulmonary function tests (PFT) were correlated with endocannabinoid measurements. In a pale ear mouse model of bleomycin-induced HPSPF, serum endocannabinoid levels were measured with and without treatment with zevaquenabant (MRI-1867), a peripheral CB1R and iNOS antagonist. In three separate cohorts, circulating anandamide levels were increased in HPS-1 patients with or without PF, compared to healthy volunteers. This increase was not observed in IPF patients or in HPS-3 patients, who do not have PF. Circulating anandamide (AEA) levels were negatively correlated with PFT. Furthermore, a longitudinal study over the course of 5-14 years with HPS-1 patients indicated that circulating AEA levels begin to increase with the fibrotic lung process even at the subclinical stages of HPSPF. In pale ear mice with bleomycin-induced HpsPF, serum AEA levels were significantly increased in the earliest stages of PF and remained elevated at a later fibrotic stage. Zevaquenabant treatment reduced the increased AEA levels and attenuated progression in bleomycin-induced HpsPF. Circulating AEA may be a prognostic blood biomarker for PF in HPS-1 patients. Further studies are indicated to evaluate endocannabinoids as potential surrogate biomarkers in progressive fibrotic lung diseases.
ABSTRACT
The current study was to determine the predictors of survival in 491 Chinese patients with lupus nephritis (LN). All patients were evaluated and consecutively followed up from 2003 to 2010. The female: male ratio was 9.5:1, with a median age of 31.1 ± 12 years. Forty-nine (10.0%) patients were lost to follow-up and 47 (10.3%) patients died. The overall cumulative probability of survival at 5, 10, 15 and 20 years by Kaplan-Meier analysis was 88%, 77%, 53% and 45%, respectively. The log-rank test showed that the probability of survival was significantly decreased in the late-onset patients (≥50 years) (P = 0.036), patients with hypoproteinaemia (≤35 g/l) (P = 0.014), patients with increased creatinine (≥1.5 mg/dl) (P = 0.002) and patients with massive proteinuria (≥3.5 g/24 h) (P = 0.009). However, the probability of survival was significantly higher in patients treated with hydroxychloroquine (HCQ) (P = 0.003) than those not treated with it. Based on a multivariate model, increased creatinine (hazard ratio (HR) = 2.041; P = 0.017) and proteinuria ≥3.5 g/24hours (HR=1.716; P = 0.016) were independent risk factors. Glucocorticoid (HR = 0.457; P = 0.01) and HCQ (HR=0.197; P = 0.026) were independent protective factors. Our findings suggest that renal dysfunction and massive proteinuria are independent risk factors for mortality. HCQ could improve the survival of patients with LN.
Subject(s)
Lupus Nephritis/mortality , Adolescent , Adult , Age of Onset , Aged , Asian People , Child , China/epidemiology , Cohort Studies , Creatinine/blood , Female , Humans , Hydroxychloroquine/therapeutic use , Kaplan-Meier Estimate , Lupus Nephritis/drug therapy , Lupus Nephritis/physiopathology , Male , Middle Aged , Proportional Hazards Models , Proteinuria/physiopathology , Retrospective Studies , Risk Factors , Serum Albumin/metabolism , Young AdultABSTRACT
A proof of concept for using paper test as a suitable method in the production of monoclonal antibodies (MAbs) is reported. The paper test which detects antibodies against porcine circovirus type 2 (PCV2) using colloidal gold-labelled capsid protein as the antigen probe was applied exclusively in the screening of anti-PCV2 MAbs. It allowed the detection of 118 single cell clones within 30 min using naked eyes. MAbs with specific binding to authentic epitopes on the virus were selected using a blocking strategy in which the antibody was pre-incubated with PCV2 viral sample before applying to the test paper. Five hybridomas secreting MAbs against the capsid protein were obtained, with only three of them capable of binding to PCV2. The results were validated and confirmed using enzyme-linked immunosorbent assay and immunofluorescence assay. The paper test is simple, rapid, and independent on professional technicians and proves to be an excellent approach for the screening of MAbs against specific targets.
Subject(s)
Circoviridae Infections , Circovirus , Swine Diseases , Animals , Antibodies, Monoclonal , Antibodies, Viral , Capsid Proteins , Circoviridae Infections/diagnosis , Circoviridae Infections/veterinary , Gold Colloid , Swine , Swine Diseases/diagnosisABSTRACT
Strigolactones are newly discovered plant hormones that perform various functions, from signaling in symbiotic interactions with arbuscular mycorrhizal fungi to controlling outgrowth of axillary buds. We examined the phylogenetic relationships of two carotenoid cleavage dioxygenase genes (CCD7 and CCD8) that are involved in consecutive upstream steps of the proposed strigolactone biosynthesis pathway. The CCD7 and CCD8 sequences from 11 model species, divided into two clades, correspond to sequences from monocotyledons and dicotyledons. However, the sequences from the primitive moss, Physcomitrella patens, appeared to be evolutionarily distinct from those of the angiosperms. CCD7 and CCD8 are much conserved, since no significant positive selection was detected among these plants. Ks values indicated that CCD7 and CCD8 diverged about 290 to 430 million years ago. As essential genes in the strigolactone pathway, the divergence timing of the conserved CCD7 and CCD8 genes reflects the approximate time of generation of strigolactone as a regulatory substance. This timing calculation also coincides with initiation of symbiosis between plants and microorganisms, inferred from the fossil record. Molecular evolution analyses of genes in metabolic pathways can provide insight concerning gene evolution.
Subject(s)
Carotenoids/metabolism , Dioxygenases/genetics , Evolution, Molecular , Genes, Plant/genetics , Lactones/metabolism , Plants/enzymology , Plants/genetics , Terpenes/metabolism , Base Sequence , Exons/genetics , Genetic Variation , Introns/genetics , Phylogeny , Plant Proteins/genetics , Plant Proteins/metabolism , Selection, Genetic , Sequence Analysis, DNA , Time FactorsABSTRACT
Prolactin receptor (PRLR) is a single transmembrane protein through which prolactin plays a wide variety of physiological roles in vertebrates. To understand its role in goose behavior, we cloned the gene of goose PRLR (gPRLR) in the Siji goose, a domestic goose with strong broodiness in China, and examined its expression level in different organs of adult geese. Our results showed that gPRLR cDNA contained 443 bp 5' untranslated region, 2,496 bp coding sequence that presumably comprises at least 14 exons, and 220 bp 3' untranslated region. The predicted goose PRLR contained 831 amino acids and exhibited identities of 87.7, 85.2, and 84.8% with chicken, pigeon, and turkey PRLR, respectively. It comprised a signal peptide of 24 amino acids at the N terminus, 2 ligand binding regions of the extracellular domain, each containing 2 pairs of cysteine residues and a pentapeptide of 5 amino acids known as WS motif (Tpr-Ser-any amino acid-Tpr-Ser), the 2 typical features highly conserved in the members of class 1 cytokine receptor superfamily. Phylogenetic analysis revealed that the goose PRLR is highly conserved during evolution. In addition, we discovered 2 other alternative splicing transcripts of gPRLR. One is generated by missing the last 95 bp of the first 330 bp of the 3,159 bp cDNA. The other is produced by an alternative transcription initiation, leading to creation of a novel first exon that is directly spliced to the third exon. Reverse transcription PCR analyses show that the gPRLR mRNA is widely expressed in the testis, seminal duct, ovary, oviduct, kidney, large intestine, and small intestine.
Subject(s)
Geese/genetics , Geese/metabolism , Receptors, Prolactin/metabolism , Amino Acid Sequence , Animals , Base Sequence , Cloning, Molecular , Gene Expression Regulation/physiology , Molecular Sequence Data , Phylogeny , Protein Isoforms , Receptors, Prolactin/genetics , Reverse Transcriptase Polymerase Chain Reaction/veterinary , Species SpecificityABSTRACT
This study aimed to evaluate the effects of dietary riboflavin deficiency (RD) on the lipid metabolism of duck breeders and duck embryos. A total of 40 female 40-wk-old white Pekin duck breeders were randomly divided into 2 groups, received either RD diet (1.48 mg riboflavin/kg) or control diet (16.48 mg riboflavin/kg, CON) for 14 wk. Each group consisted of 20 duck breeders (10 replicates per group, 2 birds per replicate), and all experiment birds were single-caged. At the end of the experiment, reproductive performance, hepatic riboflavin, hepatic flavin mononucleotide (FMN), hepatic flavin adenine dinucleotide (FAD), hepatic morphology, hepatic lipid contents, and hepatic protein expression of duck breeders and duck embryos were measured. The results showed that the RD had no effect on egg production and egg fertility but reduced egg hatchability, duck embryo weight, hepatic riboflavin, FMN, and FAD status compared to results obtained in the CON group (all P < 0.05). Livers from RD ducks presented enlarged lipid droplets, excessive accumulation of total lipids, triglycerides, and free fatty acids (all P < 0.05). In addition to excessive lipids accumulation, medium-chain specific acyl-CoA dehydrogenase expression was downregulated (P < 0.05), and short-chain specific acyl-CoA dehydrogenase expression was upregulated in maternal and embryonic livers (P < 0.05). RD did not affect maternal hepatic acyl-CoA dehydrogenase family member 9 (ACAD9) expression, but duck embryonic hepatic ACAD9 expression was reduced in the RD group (P < 0.05). Collectively, dietary RD conditioned lower egg hatchability and inhibited the development of duck embryos. Increased accumulation of lipids, both maternal and embryo, was impaired due to the reduced flavin protein expression, which caused inhibition of hepatic lipids utilization. These findings suggest that abnormal duck embryonic growth and low hatchability caused by RD might be associated with disorders of lipid metabolism in maternal as well as embryos.
Subject(s)
Ducks , Riboflavin Deficiency , Animals , Chickens , Diet/veterinary , Female , Lipid Metabolism , Riboflavin Deficiency/veterinaryABSTRACT
Hermansky-Pudlak syndrome (HPS) is a rare genetic disorder which, in its most common and severe form, HPS-1, leads to fatal adult-onset pulmonary fibrosis (PF) with no effective treatment. We evaluated the role of the endocannabinoid/CB1 R system and inducible nitric oxide synthase (iNOS) for dual-target therapeutic strategy using human bronchoalveolar lavage fluid (BALF), lung samples from patients with HPS and controls, HPS-PF patient-derived lung fibroblasts, and bleomycin-induced PF in pale ear mice (HPS1ep/ep ). We found overexpression of CB1 R and iNOS in fibrotic lungs of HPSPF patients and bleomycin-infused pale ear mice. The endocannabinoid anandamide was elevated in BALF and negatively correlated with pulmonary function parameters in HPSPF patients and pale ear mice with bleomycin-induced PF. Simultaneous targeting of CB1 R and iNOS by MRI-1867 yielded greater antifibrotic efficacy than inhibiting either target alone by attenuating critical pathologic pathways. Moreover, MRI-1867 treatment abrogated bleomycin-induced increases in lung levels of the profibrotic interleukin-11 via iNOS inhibition and reversed mitochondrial dysfunction via CB1 R inhibition. Dual inhibition of CB1 R and iNOS is an effective antifibrotic strategy for HPSPF.
Subject(s)
Hermanski-Pudlak Syndrome/pathology , Nitric Oxide Synthase Type II/metabolism , Pulmonary Fibrosis/pathology , Receptor, Cannabinoid, CB1/metabolism , Adult , Animals , Antifibrotic Agents/pharmacology , Antifibrotic Agents/therapeutic use , Arachidonic Acids/metabolism , Bleomycin/adverse effects , Bronchoalveolar Lavage Fluid/chemistry , Disease Models, Animal , Endocannabinoids/metabolism , Female , Fibroblasts/cytology , Fibroblasts/drug effects , Fibroblasts/metabolism , Hermanski-Pudlak Syndrome/complications , Hermanski-Pudlak Syndrome/metabolism , Humans , Interleukin-11/metabolism , Lung/metabolism , Lung/pathology , Male , Mice, Inbred C57BL , Middle Aged , Nitric Oxide Synthase Type II/antagonists & inhibitors , Nitric Oxide Synthase Type II/genetics , Polyunsaturated Alkamides/metabolism , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/complications , Pulmonary Fibrosis/drug therapy , Receptor, Cannabinoid, CB1/antagonists & inhibitors , Receptor, Cannabinoid, CB1/genetics , Transforming Growth Factor beta1/metabolismABSTRACT
We demonstrate, both theoretically and experimentally, that cation vacancy can be the origin of ferromagnetism in intrinsic dilute magnetic semiconductors. The vacancies can be controlled to tune the ferromagnetism. Using Li-doped ZnO as an example, we found that while Li itself is nonmagnetic, it generates holes in ZnO, and its presence reduces the formation energy of Zn vacancy, and thereby stabilizes the zinc vacancy. Room temperature ferromagnetism with p type conduction was observed in pulsed laser deposited ZnO:Li films with certain doping concentration and oxygen partial pressure.
Subject(s)
Brain-Derived Neurotrophic Factor/blood , Brain-Derived Neurotrophic Factor/genetics , Gene Expression Regulation , Methionine/genetics , Polymorphism, Single Nucleotide/genetics , Stress Disorders, Post-Traumatic/blood , Stress Disorders, Post-Traumatic/genetics , Valine/genetics , Adolescent , Adult , Afghan Campaign 2001- , Animals , Disease Models, Animal , Female , Genotype , Humans , Iraq War, 2003-2011 , Male , Middle Aged , Military Personnel , Psychiatric Status Rating Scales , Rats , Reflex, Startle , Stress Disorders, Post-Traumatic/etiology , Young AdultABSTRACT
We report the growth of ultrathin single-crystal ZnO nanobelts by using a Ag-catalyzed vapor transport method. Extensive transmission electron microscopy and atomic force microscopy measurements reveal that the thickness of the ultrathin ZnO nanobelts is approximately 2 nm. Scanning electron microscopy and post-growth annealing studies suggest a '1D branching and 2D filling' growth process. Our results demonstrate the critical role of catalyst in the deterministic synthesis of nanomaterials with the desired morphology. In addition, these ultrafine nanobelts exhibit stable field emission with unprecedented high emission current density of 40.17 mA cm(-2). These bottom-up building blocks of ultrathin ZnO nanobelts may facilitate the construction of advanced electronic and photonic nanodevices.
ABSTRACT
Controlled synthesis of one-dimensional materials, such as nanowires and nanobelts, is of vital importance for achieving the desired properties and fabricating functional devices. We report a systematic investigation of the vapor transport growth of one-dimensional SnO(2) nanostructures, aiming to achieve precise morphology control. SnO(2) nanowires are obtained when SnO(2) mixed with graphite is used as the source material; adding TiO(2) into the source reliably leads to the formation of nanobelts. Ti-induced modification of crystal surface energy is proposed to be the origin of the morphology change. In addition, control of the lateral dimensions of both SnO(2) nanowires (from approximately 15 to approximately 115 nm in diameter) and nanobelts (from approximately 30 nm to approximately 2 microm in width) is achieved by adjusting the growth conditions. The physical properties of SnO(2) nanowires and nanobelts are further characterized and compared using room temperature photoluminescence, resonant Raman scattering, and field emission measurements.