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1.
Sci Total Environ ; 806(Pt 2): 150634, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34597565

RESUMO

Numerous epidemiological studies have investigated the lipid interference effects of legacy PFASs, however, no studies on PFAS alternatives and blood lipids have been published. In this study, we explored the association between Cl-PFESAs, a typical PFASs alternative in China, and blood lipid profiles in 1336 Guangzhou community residents using linear and non-linear regression models. The results showed a deleterious effect of Cl-PFESAs and blood lipids: adjusted estimates (ß) for TC, TG, LDL-C and HDL-C per natural log unit increase of 6:2 Cl-PFESA were 0.029 (95% CI: 0.020, 0.038), 0.075 (95% CI: 0.049, 0.101), 0.035 (95% CI: 0.021, 0.049) and -0.071 (95% CI: -0.084, -0.058), respectively. The association between Cl-PFESAs and dyslipidemia was also positively significant (P < 0.05). Furthermore, a non-linear relationship was observed in Cl-PFESAs and serum lipid levels using a restricted cubic splines (RCS) model. In summary, our research suggested a negative impact of Cl-PFESAs on blood lipid patterns and a possible non-linear association.

2.
Nat Prod Bioprospect ; 11(6): 659-670, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34750765

RESUMO

Flavonoid glycoside scutellarin (SCU) has been widely applied in the treatment of cerebral ischemic diseases in China. In this article, we conducted research on the working mechanisms of SCU in hypoxia reoxygenation (HR) injury of isolated cerebral basilar artery (BA) and erebral ischemia reperfusion (CIR) injury in rat models. In isolated rat BA rings, HR causes endothelial dysfunction (ED) and acetylcholine (ACh) induces endothelium-dependent vasodilation. The myography result showed that SCU (100 µM) was able to significantly improve the endothelium-dependent vasodilation induced by Ach. However, SCU did not affect the ACh-induced relaxation in normal BA. Further studies suggested that SCU (10-1000 µM) dose-dependently induced relaxation in isolated BA rings which were significantly blocked by the cGMP dependent protein kinase (PKG) inhibitor Rp-8-Br-cGMPs (PKGI-rp, 4 µM). Pre-incubation with SCU (500 µM) reversed the impairment of endothelium-dependent vasodilation induced by HR, but the reversing effect was blocked if PKGI-rp (4 µM) was added. The brain slice staining test in rats' model of middle cerebral artery occlusion (MCAO) induced CIR proved that the administration of SCU (45, 90 mg/kg, iv) significantly reduced the area of cerebral infarction. The Western blot assay result showed that SCU (45 mg/kg, iv) increased brain PKG activity and PKG protein level after CIR surgery. In conclusion, our findings suggested that SCU possesses the ability of protecting brain cells against CIR injury through vascular endothelium protection and PKG signal.

3.
CNS Neurosci Ther ; 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34767694

RESUMO

AIMS: This study aimed to explore the pathomechanism of a mutation on the leucine-rich glioma inactivated 1 gene (LGI1) identified in a family having autosomal dominant lateral temporal lobe epilepsy (ADLTE), using a precise knock-in mouse model. METHODS AND RESULTS: A novel LGI1 mutation, c.152A>G; p. Asp51Gly, was identified by whole exome sequencing in a Chinese family with ADLTE. The pathomechanism of the mutation was explored by generating Lgi1D51G knock-in mice that precisely phenocopied the epileptic symptoms of human patients. The Lgi1D51G / D51G mice showed spontaneous recurrent generalized seizures and premature death. The Lgi1D51G /+ mice had partial epilepsy, with half of them displaying epileptiform discharges on electroencephalography. They also showed enhanced sensitivity to the convulsant agent pentylenetetrazole. Mechanistically, the secretion of Lgi1 was impaired in the brain of the D51G knock-in mice and the protein level was drastically reduced. Moreover, the antiepileptic drugs, carbamazepine, oxcarbazepine, and sodium valproate, could prolong the survival time of Lgi1D51G / D51G mice, and oxcarbazepine appeared to be the most effective. CONCLUSIONS: We identified a novel epilepsy-causing mutation of LGI1 in humans. The Lgi1D51G /+ mouse model, precisely phenocopying epileptic symptoms of human patients, could be a useful tool in future studies on the pathogenesis and potential therapies for epilepsy.

4.
Environ Int ; 158: 106913, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34624590

RESUMO

BACKGROUND: Epidemiological studies on the associations of legacy per- and polyfluoroalkyl substances (PFASs) and glucose homeostasis remain discordant. Understanding of PFAS alternatives is limited, and few studies have reported joint associations of PFASs and PFAS alternatives. OBJECTIVES: To investigate associations of novel PFAS alternatives (chlorinated perfluoroalkyl ether sulfonic acids, Cl-PFESAs and perfluorobutanoic acid, PFBA) and two legacy PFASs (Perfluorooctanoic acid, PFOA and perfluorooctane sulfonate, PFOS) with glucose-homeostasis markers and explore joint associations of 13 legacy and alternative PFASs with the selected outcomes. METHODS: We used cross-sectional data of 1,038 adults from the Isomers of C8 Health Project in China. Associations of PFASs and PFAS alternatives with glucose-homeostasis were explored in single-pollutant models using generalized linear models with natural cubic splines for PFASs. Bayesian Kernel Machine Regression (BKMR) models were applied to assess joint associations of exposures and outcomes. Sex-specific analyses were also conducted to evaluate effect modification. RESULTS: After adjusting for confounders, both legacy (PFOA, PFOS) and alternative (Cl-PFESAs and PFBA) PFASs were positively associated with glucose-homeostasis markers in single-pollutant models. For example, in the total study population, estimated changes with 95% confidence intervals (CI) of fasting glucose at the 95th percentile of 6:2Cl-PFESA and PFOS against the thresholds were 0.90 (95% CI: 0.59, 1.21) and 0.44 (95% CI: 0.26, 0.62). Positive joint associations were found in BKMR models with 6:2Cl-PFESA contributing most. Sex-specific associations existed in both single- and multi-pollutant models. CONCLUSIONS: Legacy and alternative PFASs were positively associated with glucose-homeostasis markers. 6:2Cl-PFESA was the primary contributor. Sex-specific associations were also identified. These results indicate that joint associations and effect modification should be considered in risk assessment. However, further studies are recommended to strengthen our findings and to elucidate the mechanisms of action of legacy and alternative PFASs.

5.
Chemosphere ; 278: 130486, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34126693

RESUMO

Per- and polyfluoroalkyl substances (PFAS) exposure has been linked to diabetes, but evidence on the association of isomers of PFAS with type 2 diabetes (T2D) remains scant. This population based cross-sectional study aimed to investigate associations between serum PFAS isomers, glucose-homeostasis markers and T2D, adjusted for multiple potential confounders. We used data from "Isomers of C8 Health Project in China" from July 2015 to October 2016. A total of 10 PFAS including isomers of PFOS and PFOA were measured in serum of 1045 Chinese adults. Fasting blood glucose, fasting insulin, homeostasis model of insulin (HOMA-IR) and beta cell function (HOMA-ß) were considered as markers of glucose-homeostasis. We found significant positive associations between serum PFAS isomers and glucose-homeostasis markers, namely, fasting blood glucose, fasting insulin and HOMA-IR. Per log-unit increase in branched (br)-PFOS concentration was associated with increased fasting blood glucose (ß = 0.25, 95% CI: 0.18, 0.33), fasting insulin (ß = 2.19, 95% CI: 1.44, 2.93) and HOMA-IR (ß = 0.69, 95% CI: 0.50, 0.89). As compared to br-PFOS, linear (n)-PFOS and -PFOA showed lesser significant associations with glucose-homeostasis makers. Further, exposure to all PFAS including isomeric PFOS, PFOA and PFHxS increased the risk of T2D with br-PFOS exhibiting the highest risk (OR = 5.41, 95% CI: 3.68-7.96). The associations were stronger among women than men. In conclusion, chronic exposure to PFAS isomers was associated with impaired glucose-homeostasis and may increase the prevalence of T2D in Chinese adults. Given the ubiquity of PFAS in the environment and the public health burden of T2D, future studies are warranted to corroborate the findings.


Assuntos
Ácidos Alcanossulfônicos , Diabetes Mellitus Tipo 2 , Poluentes Ambientais , Fluorcarbonetos , Adulto , Caprilatos , China , Estudos Transversais , Diabetes Mellitus Tipo 2/induzido quimicamente , Feminino , Glucose , Homeostase , Humanos , Masculino
6.
PLoS Genet ; 17(6): e1009608, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34161333

RESUMO

The X-linked GRIA3 gene encodes the GLUA3 subunit of AMPA-type glutamate receptors. Pathogenic variants in this gene were previously reported in neurodevelopmental diseases, mostly in male patients but rarely in females. Here we report a de novo pathogenic missense variant in GRIA3 (c.1979G>C; p. R660T) identified in a 1-year-old female patient with severe epilepsy and global developmental delay. When exogenously expressed in human embryonic kidney (HEK) cells, GLUA3_R660T showed slower desensitization and deactivation kinetics compared to wildtype (wt) GLUA3 receptors. Substantial non-desensitized currents were observed with the mutant but not for wt GLUA3 with prolonged exposure to glutamate. When co-expressed with GLUA2, the decay kinetics were similarly slowed in GLUA2/A3_R660T with non-desensitized steady state currents. In cultured cerebellar granule neurons, miniature excitatory postsynaptic currents (mEPSCs) were significantly slower in R660T transfected cells than those expressing wt GLUA3. When overexpressed in hippocampal CA1 neurons by in utero electroporation, the evoked EPSCs and mEPSCs were slower in neurons expressing R660T mutant compared to those expressing wt GLUA3. Therefore our study provides functional evidence that a gain of function (GoF) variant in GRIA3 may cause epileptic encephalopathy and global developmental delay in a female subject by enhancing synaptic transmission.


Assuntos
Proteínas do Ovo/genética , Mutação com Ganho de Função , Proteínas de Membrana/genética , Neurônios/metabolismo , Receptores de AMPA/genética , Espasmos Infantis/genética , Sequência de Aminoácidos , Animais , Cerebelo/metabolismo , Cerebelo/patologia , Pré-Escolar , Proteínas do Ovo/metabolismo , Feminino , Expressão Gênica , Células HEK293 , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Modelos Moleculares , Neurônios/patologia , Cultura Primária de Células , Conformação Proteica , Receptores de AMPA/metabolismo , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Espasmos Infantis/metabolismo , Espasmos Infantis/patologia
7.
Appl Biochem Biotechnol ; 193(10): 3029-3044, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33970424

RESUMO

Xylanase plays a vital role in the efficient utilization of xylan, which accounts for up to 30% of plant dry matter. However, the production cost of xylanase remains high, and the enzymatic characteristics of xylanases of most microorganisms are not suitable for industrial production. Therefore, it is of great significance to discover and develop new and efficient xylanases. In this study, the xylanase gene TAX1 (672 bp cDNA) was cloned from Trichoderma atroviride 3.3013 and expressed in Pichia pastoris. The TAX1 gene encoded a 223-amino acid protein (TAX1) with a molecular weight of 24.2 kDa which showed high similarity to glycoside hydrolase family 11. Enzyme activity assay verified that the recombinant xylanase TAX1 had optimal activity (215.3 IU/mL) at 50°C and pH 6.0. Stable working conditions were measured as pH 4.0-7.0 and 40-60°C. By adding Zn2+, the relative enzymatic activity of recombinant TAX1 was enhanced by 26%. The recombinant xylanase showed high activity toward birchwood xylan and corn stover. The Km and Kcat for xylan and corn stover were 0.36 mg/mL and 0.204 S-1 and 0.48 mg/mL and 0.149 S-1, respectively. The enzymatic activity of the TAX1 produced by P. pastoris was about 2.4-4 times higher that directly isolated from T. atroviride, so engineered P. pastoris for xylanase production could be an ideal candidate for industrial enzyme production.

8.
Environ Int ; 155: 106596, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33940391

RESUMO

BACKGROUND: Chlorinated polyfluorinated ether sulfonic acids (Cl-PFESAs), a group of perfluorooctane sulfonate (PFOS) alternatives, can be widely observed in humans and environmental matrices. However, associations between exposure to Cl-PFESAs and serum lipid levels in adults are unknown. OBJECTIVE: To explore the relationships between Cl-PFESA levels and serum lipid levels in adults. METHODS: We analyzed 1238 adults from the Isomers of C8 Health Project, a cross-sectional study conducted in China from July 2015 to October 2016. The average age of the participants was 61.98 ± 14.40 years. We quantified two select legacy per- and perfluoroalkyl substances [perfluorooctanoic acid (PFOA) and PFOS] and their alternatives (6:2 and 8:2 Cl-PFESAs). We also measured four serum lipids: low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), total cholesterol (TC), and triglycerides (TG). We used generalized linear models to estimate the associations between PFASs and serum lipids, with PFASs defined as either a categorical variable divided into quartiles or as a continuous variable. RESULTS: We found that 6:2 Cl-PFESA was positively associated with serum TC and LDL-C. For instance, LDL-C levels in the highest quartile of 6:2 Cl-PFESA exposure (Q4) were significantly higher than those in the lowest quartile (Q1) [ß: 0.19, 95% confidence interval (CI): 0.08, 0.30]. Further analysis showed that one ln-ng/mL increase in 6:2 Cl-PFESA exposure corresponded to a 0.10 mmol/L (95% CI: 0.05, 0.16) LDL-C increase, and that exposure to 8:2 Cl-PFESA was negatively correlated with HDL-C (ß: -0.03, 95% CI: -0.05, -0.01). TC had a similar relationship with both 6:2 Cl-PFESA and legacy PFASs. Participants with a BMI ≥ 25 kg/m2 exhibited a stronger association between 6:2 Cl-PFESA and TC. CONCLUSIONS: Our findings make the novel suggestion that exposure to Cl-PFESAs are adversely associated with serum lipid levels, and that such associations are also observed in legacy PFASs. Increased investigation into the effects of Cl-PFESAs exposure on human health is warranted.


Assuntos
Ácidos Alcanossulfônicos , Fluorcarbonetos , Adulto , Idoso , China , Estudos Transversais , Fluorcarbonetos/análise , Humanos , Pessoa de Meia-Idade
9.
Environ Pollut ; 283: 117078, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-33839621

RESUMO

Chlorinated polyfluoroalkyl ether sulfonates (Cl-PFESAs), are ubiquitous alternatives to perfluorooctane sulfonate (PFOS), a widely used poly- and perfluoroalkyl substance (PFAS). Despite in vivo and in vitro evidence of metabolic toxicity, no study has explored associations of Cl-PFESAs concentrations with metabolic syndrome (MetS) in a human population. To help address this data gap, we quantified 32 PFAS, including 2 PFOS alternative Cl-PFESAs (6:2 and 8:2 Cl-PFESAs) in serum from 1228 adults participating in the cross-sectional Isomers of C8 Health Project in China study. The odds ratios (ORs) and 95% confidence intervals (CIs) of MetS and its various components were estimated using individual PFAS as a continuous or categorical predictor in multivariate regression models. The association between the overall mixture of PFAS and MetS was examined using probit Bayesian Kernel Machine Regression (BKMR-P). Greater serum PFAS concentrations were associated with higher odds of MetS and demonstrated a statistically significant dose-response trend (P for trend < 0.001). For example, each ln-unit (ng/mL) increase in serum 6:2 Cl-PFESA was associated with a higher prevalence of MetS (OR = 1.52, 95% CI: 1.25, 1.85). MetS was also 2.26 (95% CI: 1.59, 3.23) times more common in the highest quartile of serum 6:2 Cl-PFESA concentration than the lowest, and particularly high among women (OR = 6.41, 95% CI: 3.65, 11.24). The BKMR-P analysis showed a positive association between the overall mixture of measured PFAS and the odds of MetS, but was only limited to women. While our results suggest that exposure to Cl-PFESAs was associated with MetS, additional longitudinal studies are needed to more definitively address the potential health concerns of these PFOS alternatives.


Assuntos
Ácidos Alcanossulfônicos , Fluorcarbonetos , Síndrome Metabólica , Adulto , Teorema de Bayes , China/epidemiologia , Estudos Transversais , Feminino , Fluorcarbonetos/análise , Humanos , Síndrome Metabólica/epidemiologia
10.
Antonie Van Leeuwenhoek ; 114(4): 465-477, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33638738

RESUMO

Cordyceps militaris is a traditional Chinese medicinal food that is challenging to quality maintaining while mass cultivation. Many studies have found that abundant microbes inhabit Ophiocordyceps sinensis and perform important functions for their host. In this study, our objective was to reveal the microbial communities that inhabit C. militaris and analyze their potential functions. High-throughput sequencing of 16S rRNA and ITS genes was used to compare the diversity and composition of the bacterial and fungal communities associated with naturally occurring C. militaris collected from Yunnan Province, southwestern China. The diversity and richness of the microbial communities and the number of function genes of the bacteria were significantly higher in the habitat soil than in the fruiting body. The sclerotia and stromata samples shared the same microbiota and functions. The main bacterial phyla were Proteobacteria, Acidobacteria, Bacteroidetes and Actinobacteria, and Ascomycota was the main fungal phylum. The growth-promoting bacteria Herbaspirillum and the plant probiotic Phyllobacterium, which may enhance C. militaris quality and facilitate its cultivation, were detected in the fruiting body samples. Genes related to metabolism were more abundant in the soil bacteria, while membrane transport genes were more abundant in the endophytic bacteria of C. militaris. Our study is the first to reveal the unexpectedly high diversity of the microbial communities and the bacterial functions inhabiting the natural C. militaris using high-throughput sequencing, and our results provide insights into mining the functions of microorganisms in the development and quality of C. militaris.


Assuntos
Cordyceps , Microbiota , China , Cordyceps/genética , RNA Ribossômico 16S/genética , Solo , Microbiologia do Solo
11.
Environ Res ; 196: 110430, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33181135

RESUMO

BACKGROUND: Exposure to perfluoroalkyl acids (PFAAs) is known to be associated with metabolic disorders. However, whether PFAAs isomers are associated with metabolic syndrome (MetS) still remains unknown. OBJECTIVES: To explore the associations between serum PFAAs isomers and MetS. METHODS: We recruited 1,501 adults from a cross-sectional study, the "Isomers of C8 Health Project in China" to investigate the associations between PFAAs isomers and MetS. A total of 20 PFAAs including the isomers of PFOS and PFOA were detected. Logistic regression models and restricted cubic spline models were used to evaluate the relationship of serum PFAAs isomers exposure with MetS and its components as well after adjusting for covariates. RESULTS: The MetS prevalence in our study was 43.0%. The serum levels of both PFOS and PFOA isomers were higher in participants with MetS than that with non-MetS (p < 0.05). We found positive associations for per natural log-transformed ng/mL of branched perfluorooctane sulfonate (br-PFOS) (odds ratio (OR) = 1.18, 95% confidence interval (CI): 1.01, 1.38)) linear perfluoronanoic acid (n-PFOA) (OR = 1.35, 95% CI: 1.16, 1.58) and perfluoro-6-methylpheptanoic acid (6 m-PFOA) (OR = 1.32, 95% CI: 1.11, 1.57) with higher odds of MetS after covariates adjustment, while null association was observed for linear isomers of PFOS (OR = 1.09, 95% CI: 0.94, 1.25). We found a nonlinear dose-response relationship with a "threshold" effect in serum br-PFOS isomers with MetS, in which the odds of MetS increased quickly with increasing serum br-PFOS isomers under low exposure (p for nonlinearity = 0.030). CONCLUSION: We report new evidence of associations between PFAAs isomers and MetS and the nonlinearity of dose-response relationship with br-PFOS isomers. Our findings indicate that more attention is needed to pay on the nonlinearity of dose-response relationship when investigate the association of PFAAs isomers with human health.


Assuntos
Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorcarbonetos , Síndrome Metabólica , Adulto , Caprilatos , China/epidemiologia , Estudos Transversais , Fluorcarbonetos/análise , Humanos , Síndrome Metabólica/induzido quimicamente , Síndrome Metabólica/epidemiologia
12.
Chem Biodivers ; 17(12): e2000520, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33184961

RESUMO

Panax notoginseng (Burkill) F.H.Chen (Araliaceae), of which the dry root and rhizome are precious traditional Chinese medicine, suffers severely from diseases during planting. Essential oils (EOs) with antimicrobial activity are a possibility for the development of green pesticides. We extracted EOs from Pogostemon cablin (Blanco) Benth. and Eupatorium fortunei Turcz., respectively and tested their inhibitory rates on fungi isolated from diseased P. notoginseng by the Oxford cup method. The compounds of the EO were identified by GC/MS and the minimum inhibitory concentrations (MICs) of the EOs and their main components were evaluated by the 96-well plate method. We also mixed P. cablin EO, E. fortunei EO and hymexazol in pairs to explore whether their combinations produce stronger antifungal effects than individual components. Finally, we evaluated the effects of the EOs against Fusarium oxysporum in vivo. P. cablin EO and E. fortunei EO exhibited different antifungal activities against fungi, with the inhibitory rates of 21.02 %-100 % and 54.84 %-100 % and MICs of 0.07-0.88 mg/mL and 0.20-1.17 mg/mL, respectively. Pogostone (24.96 %) and thymol (15.64 %) were the major compounds of P. cablin EO and E. fortunei EO, respectively, and they exhibited stronger antifungal activities than EOs, with MICs of 0.008-0.078 mg/mL and 0.12-0.31 mg/mL, respectively. Moreover, hymexazol was mixed with E. fortunei EO, and the inhibitory effect against Cylindrocarpon destructans was enhanced with a synergistic effect. The disease incidence and disease index of EO treatments decreased significantly in vivo. Based on our study, P. cablin EO and E. fortunei EO have great potential to be developed into green fungicides for use in agriculture to control diseases of P. notoginseng.


Assuntos
Eupatorium/química , Fungos/efeitos dos fármacos , Óleos Voláteis/farmacologia , Panax notoginseng/química , Pogostemon/química , Cromatografia Gasosa-Espectrometria de Massas , Testes de Sensibilidade Microbiana
13.
J Bone Miner Res ; 35(10): 2015-2031, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32460388

RESUMO

Despite the best treatment, approximately 10% of fractures still face undesirable repair. Recently, many studies have focused on the importance of macrophages in bone repair; however, the cellular mechanisms by which they work are not yet fully understood. In this study, we explored the functions of macrophage G-protein-coupled receptor interacting protein 1 (GIT1) in healing a tibial monocortical defect model. Using GIT1flox/flox Lyz2-Cre (GIT1 CKO) mice, we observed that a GIT1 deficiency in the macrophages led to an exacerbation of interleukin 1ß (IL1ß) production, more M1-like macrophage infiltration, and impaired intramembranous ossification in vivo. The results of in vitro assays further indicated that the macrophage GIT1 plays a critical role in several cellular processes in response to lipopolysaccharide (LPS), such as anti-oxidation, IL1ß production alleviation, and glycolysis control. Although GIT1 has been recognized as a scaffold protein, our data clarified that GIT1-mediated extracellular-signal-regulated kinase (ERK) phosphorylation could activate nuclear factor (erythroid-derived 2)-like 2 (NRF2) in macrophages after LPS treatment. Moreover, we demonstrated that macrophage GIT1-activated ERK/NRF2 negatively regulates the 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3 (PFKFB3), facilitating the decrease of glycolysis. Our findings uncovered a previously unrecognized role of GIT1 in regulating ERK/NRF2 in macrophages to control the inflammatory response, suggesting that macrophage GIT1 could be a potential target to improve bone regeneration. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research..


Assuntos
Regeneração Óssea , Proteínas de Ciclo Celular/fisiologia , MAP Quinases Reguladas por Sinal Extracelular , Proteínas Ativadoras de GTPase/fisiologia , Macrófagos , Fator 2 Relacionado a NF-E2 , Animais , Inflamação , Camundongos
14.
ACS Appl Mater Interfaces ; 12(10): 11789-11796, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32091874

RESUMO

Electroreduction of N2 represents a promising technique for ambient NH3 synthesis, but exploring efficient electrocatalysts for nitrogen reduction reaction (NRR) remains a key challenge. Herein, we reported our experimental and theoretical findings that FeMoO4 could be a new candidate for effective and durable NRR in neutral solution. The developed FeMoO4 nanorods exhibited a fascinating NRR activity with an NH3 yield of 45.8 µg h-1 mg-1 (-0.5 V) and a Faradaic efficiency of 13.2% (-0.3 V). Mechanistic studies disclosed that Fe and Mo synergistically promoted the N2 adsorption and accelerated the electron transfer on FeMoO4, whereas the unsaturated 3-fold coordinated Mo (Mo3c) sites served as the main active centers for stabilizing the key *N2H intermediate and reducing the reaction energy barrier.

15.
FASEB J ; 34(2): 2055-2074, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31908016

RESUMO

In spinal cord ischemia-reperfusion (I/R) injury, large amounts of reactive oxygen species can cause mitochondrial damage. Therefore, mitophagy acts as the main mechanism for removing damaged mitochondria and protects nerve cells. This study aimed to illustrate the important role of GPCR kinase 2-interacting protein-1 (GIT1) in mitophagy in vivo and in vitro. The level of mitophagy in the neurons of Git1 knockout mice was significantly reduced after ischemia-reperfusion. However, the overexpression of adeno-associated virus with Git1 promoted mitophagy and inhibited the apoptosis of neurons. GIT1 regulated the phosphorylation of Beclin-1 in Thr119, which could promote the translocation of Parkin to the mitochondrial outer membrane. This process was independent of PTEN-induced kinase 1 (PINK1), but it could not rescue the role in the absence of PINK1. Overall, GIT1 enhanced mitophagy and protected neurons against ischemia-reperfusion injury and, hence, might serve as a new research site for the protection of ischemia-reperfusion injury.


Assuntos
Proteína Beclina-1/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas Ativadoras de GTPase/metabolismo , Mitofagia , Traumatismo por Reperfusão , Doenças da Medula Espinal , Ubiquitina-Proteína Ligases/metabolismo , Animais , Proteína Beclina-1/genética , Proteínas de Ciclo Celular/genética , Proteínas Ativadoras de GTPase/genética , Camundongos , Camundongos Knockout , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/prevenção & controle , Doenças da Medula Espinal/genética , Doenças da Medula Espinal/metabolismo , Doenças da Medula Espinal/patologia , Doenças da Medula Espinal/prevenção & controle , Ubiquitina-Proteína Ligases/genética
16.
Environ Pollut ; 259: 113857, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31918137

RESUMO

Previous epidemiological and experimental studies have shown that legacy perfluoroalkyl acids (PFAAs) are immunotoxic. However, whether the immunosuppressive effects in PFAA alternatives which recently have been widely detected in the environment are unknown. To address this knowledge gap, we investigated the relationship of serum legacy PFAAs and PFAA alternatives with the antibody of hepatitis B virus in adults. We recruited 605 participants from a cross-sectional study, the Isomer of C8 Health Project in China. We measured two representative legacy PFAAs (perfluorooctane sulfonate, PFOS and perfluorooctanoic acid, PFOA), and three PFAA alternatives (two chlorinated polyfluorinated ether sulfonic acids, Cl-PFESAs and perfluorobutanoic acid, PFBA) in serum using ultra-performance liquid chromatograph-tandem mass spectrometry (UPLC-MS/MS). We applied linear and logistic regression models to analyze associations between serum PFAAs and hepatitis B surface antibody (HBsAb) with multivariable adjustments. We found negative associations between serum PFAAs concentrations and HBsAb. Lower serum HBsAb levels (log mIU/mL) were observed for each log-unit increase in linear PFOS (ß = -0.31, 95% confidential interval: 0.84, -0.18), 6:2 PFESA (ß = -0.81, 95% CI: 1.20, -0.42), 8:2 PFESA (ß = -0.29, 95% CI: 0.43, -0.14) and PFBA (ß = -0.18, 95% CI: 0.28, -0.08). The association between PFAAs and HBsAb seronegative seemed to be higher for 6:2 PFESA (odds ratio = 3.32, 95% CI: 2.16, 5.10) than its predecessors, linear PFOS (OR = 1.96, 95% CI: 1.37, 2.81) and branched PFOS isomers (OR = 1.64, 95% CI: 1.05, 2.56). We report new evidence that exposure to PFAA alternatives are associated with lower HBsAb in adults. This association seems to be stronger in 6:2 PFESA than PFOS. Our results suggest that more studies are needed to clarify the potential toxicity of PFAA alternatives in human which will facilitate better chemical regulations for PFAAs.


Assuntos
Anticorpos Antivirais , Fluorcarbonetos , Adulto , Ácidos Alcanossulfônicos/sangue , Anticorpos Antivirais/sangue , Caprilatos/sangue , China , Cromatografia Líquida , Estudos Transversais , Fluorcarbonetos/sangue , Fluorcarbonetos/toxicidade , Vírus da Hepatite B/imunologia , Humanos , Sistema Imunitário/efeitos dos fármacos , Espectrometria de Massas em Tandem
17.
Int J Syst Evol Microbiol ; 70(2): 1071-1078, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31755854

RESUMO

A Gram-stain-negative, facultative anaerobic, motile and straight rod-shaped bacterium, designated strain C1-9T, was isolated from rhizosphere soil of Camellia sinensis (L.) O. Ktze collected from a tea garden in Huize, south-western PR China. Cells were oxidase-positive and catalase-negative. Growth occurred at 20-40 °C and pH 6.0-10.0, with an optimal growth at 30 °C and pH 7.0. The respiratory quinone was detected as ubiquinone-8 (Q-8). The major fatty acids were identified as summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), C16 : 0 and summed feature 8 (C18 : 1ω7c or C18 : 1ω6c). The cellular polar lipids contained phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, three unidentified phospholipids, two unidentified lipids, one unidentified aminophospholipid and one unidentified aminolipid. The polyamine types were detected as 1,8-diaminooctane and 2-hydroxyputrescine. The genomic DNA G+C content was 68.6 mol%. Based on the results of 16S rRNA gene sequence analysis, strain C1-9T (MF687442) showed highest sequence similarity to Rivibacter subsaxonicus DSM 19570T (97.1 %). The phylogenetic tree based on 16S rRNA gene sequences showed that strain C1-9T clustered close to R. subsaxonicus DSM 19570T, Methylibium petroleiphilum CCTCC AB 2014193T and species belonging to the genera Rhizobacter and Piscinibacter. The phylogenomic tree indicated that strain C1-9T formed a clade with R. subsaxonicus. The average nucleotide identity value was 76.0 % between strain C1-9T and R. subsaxonicus DSM 19570T, which is lower than the prokaryotic species delineation threshold of 95.0-96.0 %. The polyphasic taxonomic characteristics indicated that strain C1-9T represents a novel species of a new genus within the order Burkholderiales, for which the name Pseudorivibacter rhizosphaerae gen. nov., sp. nov. (type strain C1-9T = KCTC 62325T=CGMCC 1.13864T) is proposed.


Assuntos
Burkholderiales/classificação , Camellia sinensis/microbiologia , Filogenia , Rizosfera , Microbiologia do Solo , Técnicas de Tipagem Bacteriana , Composição de Bases , Burkholderiales/isolamento & purificação , China , DNA Bacteriano/genética , Ácidos Graxos/química , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Ubiquinona/química
18.
Environ Int ; 135: 105365, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31830731

RESUMO

BACKGROUND: Experimental studies show that chlorinated polyfluorinated ether sulfonic acids (Cl-PFESA 6:2 and 8:2), one of perfluoroalkyl substances (PFAS) used as perfluorooctane sulfonate (PFOS) alternatives, are reproductive toxicants in vivo and in vitro. However, the associations between gestational exposure to Cl-PFESAs and birth outcomes are unknown. OBJECTIVES: We investigated associations between 6:2 Cl-PFESA and 8:2 Cl-PFESA in maternal serum and birth outcomes. METHODS: We measured four PFAS, including 6:2 Cl-PFESA, 8:2 Cl-PFESA, PFOS, and perfluorooctanoic acid (PFOA) in third-trimester maternal serum collected from 372 mother-child dyads participating in the Guangzhou Birth Cohort Study. Characteristics of mothers and infants were gathered from medical records and by interviewer-administered questionnaires. RESULTS: PFOS was the most abundant PFAS in maternal serum (median: 7.15 ng/mL), followed by 6:2 Cl-PFESA (median: 2.41 ng/mL). Greater maternal serum levels of all PFAS alternatives were significantly associated with lower birth weight, adjusted for confounding variables. For example, each ln-ng/mL greater concentration of 6:2 Cl-PFESA and 8:2 Cl-PFESA was associated with a 54.44 g [95% confidence interval (CI): -95.66, -13.22] and 21.15 g (95% CI: -41.44, -0.86) lower birth weight, respectively. Greater continuous maternal serum 6:2 Cl-PFESA (OR: 2.67, 95% CI: 1.73, 4.15) and PFOS (OR: 2.03, 95% CI: 1.24, 3.32) were also associated with higher risks for preterm birth, adjusted for confounders, with a possible threshold effect at the highest quartile of 6:2 Cl-PFESA. CONCLUSIONS: For the first time, we report associations between maternal serum 6:2 Cl-PFESA and 8:2 Cl-PFESA concentrations and adverse birth outcomes. Our findings suggest that PFOS alternatives may be reproductive toxicants in human populations and should be considered with caution before widespread use. Given the preliminary nature of our results, additional epidemiological and toxicological investigations are needed to more definitively assess the risks.


Assuntos
Ácidos Alcanossulfônicos/análise , Fluorcarbonetos/análise , Caprilatos , Estudos de Coortes , Humanos , Recém-Nascido , Ácidos Sulfônicos
19.
Sci Total Environ ; 705: 135885, 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-31841927

RESUMO

BACKGROUND: Recent studies suggest that perfluoroalkyl substances (PFAS) and PFAS alternatives can cross the placental barrier. However, little is known on the differential patterns of trans-placental transfer (TPT) among conventional PFAS and PFAS alternatives in epidemiological study. OBJECTIVES: We aimed to characterize comprehensive TPT patterns in conventional PFAS and PFAS alternatives using matched maternal-cord blood serum from a birth cohort. METHODS: A total of 424 mother-fetus pairs were recruited from the Maoming Birth Cohort during 2015-2018. We detected 20 PFAS in cord and maternal serum using an ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). TPT of PFAS was calculated via cord to maternal serum concentration ratios. RESULTS: Both of PFOS alternatives (chlorinated polyfluorinated ether sulfonates, Cl-PFESAs) and PFOA short-chain alternative (perfluorobutanoic acid, PFBA) were widely detected in the cord and maternal serum. In cord serum, the predominant PFAS was PFOS (1.93 ng/mL), followed by PFBA (1.45 ng/mL), PFOA (0.75 ng/mL) and 6:2 Cl-PFESA (0.32 ng/mL). We found that the PFAS alternatives had higher TPT than PFOS and PFOA, such as PFBA vs. PFOA (median: 1.41 vs. 0.73, P < 0.001) and 8:2 Cl-PFESA vs. PFOS (median: 0.98 vs. 0.42, P < 0.001). Moreover, the TPT of 8:2 Cl-PFESA was higher than the precursor, linear and isomeric PFOS, respectively (P < 0.01). Furthermore, we found a U-shaped pattern for TPT in perfluorocarboxylic acid compounds (PFCAs) across different length of carbon chain. CONCLUSION: Our findings suggest that PFAS alternatives may be more easily across the placenta than conventional PFAS. Given the widespread usage of PFAS alternatives, our results indicate that more research is needed to assess the potential health risks of prenatal exposure to PFAS alternatives in children.


Assuntos
Placenta , Ácidos Alcanossulfônicos , Cromatografia Líquida , Estudos de Coortes , Feminino , Sangue Fetal , Fluorcarbonetos , Humanos , Gravidez , Soro , Espectrometria de Massas em Tandem
20.
J Nematol ; 522020.
Artigo em Inglês | MEDLINE | ID: mdl-33829164

RESUMO

The southern root-knot nematode (RKN), Meloidogyne incognita, causes significant damage to vegetable production and is a major problem in greenhouse tomatoes. The effect of a combination of fluopyram and abamectin, at a mass ratio of 1:5, was studied for RKN control. Pot trials showed that fluopyram, abamectin, and their combination at three dosages increased the height, stem diameter, root fresh weight, shoot fresh weight, and the root length of tomato plants. The RKN control efficacy of the 1:5 combination at 450 g a.i./ha was 74.06% at 30 days after transplanting (DAT), and the control efficacy of the combination at 337.5 and 450 g a.i./ha differed significantly from those of other treatments at 60 DAT. The root-galling index (RGI) control efficacy of the combination at 450 g a.i./ha and of fluopyram (41.7% SC) only at 450 g a.i./ha were better than the control efficacies of other treatments, and these two treatments significantly increased root activity. Field trial results showed that the soil nematode control efficacy was similar to that of the pot trials at 30 and 60 DAT. The RGI control efficacy of the combination at 337.5 and 450 g a.i./ha and of fluopyram (41.7% SC) only at 450 g a.i./ha differed significantly from those of the two other treatments. The tomato yields of the 1:5 combination at 450 g a.i./ha were increased by 24.07 and 23.22% compared to the control in field trials during two successive years. The combination of fluopyram and abamectin provides good nematode measure, and it can increase tomato yields. It provides an effective solution for the integrated management of southern RKN.

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