Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 185
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-35007197

RESUMO

Lung cancer is a major cause of cancer deaths worldwide, and has a very low survival rate. Non-small cell lung cancer (NSCLC) is the largest subset of lung cancers, which accounts for about 85% of all cases. It has been well established that mutation in epidermal growth factor receptor (EGFR) can lead to lung cancer. EGFR Tyrosine Kinase Inhibitors are developed to target the kinase domain of EGFR. These TKIs produce promising results at initial stage of therapy, but the efficacy becomes limited due to the development of drug resistance. In this paper, we provide a comprehensive overview of computational methods, for understanding drug resistance mechanisms. Next, we evaluate the role of important EGFR parameters in drug resistance mechanism, including structural dynamics, stability, dimerization, binding free energies, and signaling pathways. Personalized drug resistance prediction models, drug response curves, drug synergy, and other data-driven methods are also discussed. We explore limitations in the current methodologies and discuss strategies to overcome them. We believe this review will serve as a reference for researchers; to apply computational techniques for precision medicine, analyzing structures of protein-drug complexes, drug discovery, and understanding the drug response and resistance mechanisms in lung cancer patients.

2.
J Colloid Interface Sci ; 610: 271-279, 2022 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-34923267

RESUMO

Low-dimensional noble-metal materials (LDNMs) with different structural advantages have been considered as the high-performance catalysts for C2 alcohol electrooxidation. However, it is still a great challenging to precisely construct nanomaterials with low-dimensional composite structure thus to take advantages of various dimension, especial without the surfactant participation. Most studies focus on the modulation of the single dimensional nanocatalysts, the correlation between electrocatalytic performances and low-dimension composite have been rarely reported. Herein, we engineered a simple one-step approach to design multi-low-dimensional PdPt nanomaterials by using different Pd precursors. The low-dimensional PdPt nanocrystals (NCs) composed of zero dimension (0D) dendrite-like nanoparticles and two dimension (2D) nanosheets were obtained by using Pd(OAc)2, and meanwhile the 2D PdPt nanosheet assemblies (NAs) were synthesized by the introduction of NaPdCl4. Specifically, benefitting from the unique low-dimension structures with fast electron/mass transfer, and optimized electronic and synergistic effect, the multi-low-dimensional 0D-2D PdPt NCs showed the highest ethanol oxidation reaction (EOR)/ethylene glycol oxidation reaction (EGOR) mass activities, which were much higher than 2D PdPt NAs. The 0D-2D PdPt NCs also exhibited the highest structural stability. Generally, this work could inspire more advanced designs for surfactant-free synthesis and promote the fundamental engineering on nanocatalysts with low-dimension composite structure for electrocatalytic fields.

3.
J Colloid Interface Sci ; 606(Pt 2): 1395-1409, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34492475

RESUMO

As an antioxidant, hindered phenol scavenges free radicals. Due to the oxidative degradation of black phosphorus (BP) in the presence of water and oxygen, free radical quenching of hindered phenol antioxidants can solve this issue and improve the environmental stability and flame retardant efficiency of BP. Herein, hydroxyl-modified BP (BP-OH) with active groups on the surface was obtained by hydroxylation, and then the hindered phenol antioxidant was grafted onto the surface of BP-OH through an isophorone diisocyanate bridging covalent reaction to obtain hindered phenol-modified BP (BP-HPL). The fire hazard of thermoplastic polyurethane (TPU) can be significantly reduced by introducing BP-HPL into TPU. Adding 2 wt% BP-HPL can reduce the heat release rate and total heat release values of TPU by 49.9% and 49.0%, respectively. In addition, the reductions in smoke volume and carbon monoxide production were also significant. Compared with BP-OH, the environmental stability of BP-HPL is significantly improved. This work provides a reference for the application of BP in the field of fire safety and simultaneously achieves the improvement of the environmental stability and flame retardant performance of BP.


Assuntos
Antioxidantes , Fósforo , Radicais Livres , Fenóis , Poliuretanos
4.
Front Cell Dev Biol ; 9: 731867, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34900990

RESUMO

Background: Dry eye disease (DED) is a multifactorial inflammatory disease of the ocular surface. It is hypothesized that dysbiosis of the conjunctival microbiota contributes to the development of DED. However, species-level compositions of the conjunctival microbiota in DED and the potential dysbiosis involving microorganisms other than bacteria remain largely uncharacterized. Methods: We collected conjunctival impression samples from a cohort of 95 individuals, including 47 patients with DED and 48 healthy subjects. We examined the conjunctival microbiota of these samples using shotgun metagenomic sequencing and analyzed microbial dysbiosis in DED at the species level. Results: The conjunctival microbiota in DED exhibited a decreased α-diversity and an increased inter-individual variation. The α-diversity of female patients with DED was higher than that of male patients. Despite a decreased prevalence in DED, 23 microbial species were identified to show abnormally high abundance in DED samples positive for the species. Among these species, a fungal species Malassezia globosa was enriched female patients. In addition, distinct patterns of associations with disease status were observed for different species of the same genus. For DED subtypes, Staphylococcus aureus and S. capitis were associated with meibomian gland dysfunction (MGD), whereas S. hominis was enriched in patients solely with aqueous tear deficiency (ATD). The microbiota of patients with a mixed type of diagnosis was more similar to MGD patients than ATD patients. Conclusion: We demonstrated that the conjunctival microbiota dysbiosis in DED is characterized by significant heterogeneity. Microbial signatures may offer novel insights into the complicated etiology of DED and potentially promote the development of personalized treatment for DED in the future.

5.
Front Cell Dev Biol ; 9: 788422, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34926465

RESUMO

Congenital cataract is one of the leading causes of blindness in children worldwide. About one-third of congenital cataracts are caused by genetic defects. LSS, which encodes lanosterol synthase, is a causal gene for congenital cataracts. LSS is critical in preventing abnormal protein aggregation of various cataract-causing mutant crystallins; however, its roles in lens development remain largely unknown. In our study, we generated a mouse model harboring Lss G589S mutation, which is homologous to cataract-causing G588S mutation in human LSS. LssG589S/G589S mice exhibited neonatal lethality at postal day 0 (P0), whereas these mice showed severe opacity in eye lens. Also, we found that cataract was formed at E17.5 after we examined the opacity of embryonic lens from E13.5 to E18.5. Moreover, disrupted lens differentiation occurred at E14.5 prior to formation of the opacity of eye lens, shown as delayed differentiation of lens secondary fiber and disordered lens fiber organization. In addition, RNA-seq analysis indicated that cholesterol synthesis signaling pathways were significantly downregulated. Overall, our findings provide clear evidence that a mouse model harboring a homozygous Lss G589S mutation can recapitulate human congenital cataract. Our study points out that LSS functions as a critical determinant of lens development, which will contribute to better understanding LSS defects in cataractogenesis and developing therapies for cataracts.

6.
IEEE Trans Cybern ; PP2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34919528

RESUMO

The divide-and-conquer strategy is a very effective method of dealing with big data. Noisy samples in big data usually have a great impact on algorithmic performance. In this article, we introduce Markov sampling and different weights for distributed learning with the classical support vector machine (cSVM). We first estimate the generalization error of weighted distributed cSVM algorithm with uniformly ergodic Markov chain (u.e.M.c.) samples and obtain its optimal convergence rate. As applications, we obtain the generalization bounds of weighted distributed cSVM with strong mixing observations and independent and identically distributed (i.i.d.) samples, respectively. We also propose a novel weighted distributed cSVM based on Markov sampling (DM-cSVM). The numerical studies of benchmark datasets show that the DM-cSVM algorithm not only has better performance but also has less total time of sampling and training compared to other distributed algorithms.

8.
Chem Commun (Camb) ; 57(97): 13198-13201, 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34816835

RESUMO

Herein, we developed a one-pot, surfactant-free approach to obtain a PdPtAu@Pd core@shell catalyst for the photocatalytic methanol oxidation reaction. By virtue of its dimensions, conjunction architecture and robust core@shell construction, 0D@2D PdPtAu@Pd exhibited a superior catalytic performance, with a mass activity 2.3- and 6.7-times higher than that of Pt/C and Pd/C catalysts, respectively.

9.
Front Cell Infect Microbiol ; 11: 759333, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746029

RESUMO

Recent advances have identified significant associations between the composition and function of the gut microbiota and various disorders in organ systems other than the digestive tract. Utilizing next-generation sequencing and multiomics approaches, the microbial community that possibly impacts ocular disease has been identified. This review provides an overview of the literature on approaches to microbiota analysis and the roles of commensal microbes in ophthalmic diseases, including autoimmune uveitis, age-related macular degeneration, glaucoma, and other ocular disorders. In addition, this review discusses the hypothesis of the "gut-eye axis" and evaluates the therapeutic potential of targeting commensal microbiota to alleviate ocular inflammation.


Assuntos
Microbioma Gastrointestinal , Microbiota , Uveíte , Olho , Humanos , Inflamação
10.
Bioengineered ; 12(1): 8583-8593, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34607526

RESUMO

Interleukin (IL)-13-associated inflammatory response is important for the pathogenesis of allergic rhinitis (AR). Apremilast is a phosphodiesterase-4 (PDE4) inhibitor approved for psoriasis treatment. Here, we investigated the potential effects of Apremilast against IL-13-induced injury in human nasal epithelial cells (hNECs). Firstly, Apremilast ameliorated oxidative stress in IL-13-challenged cells by decreasing the levels of reactive oxygen species (ROS) and the production of malondialdehyde (MDA). Secondly, Apremilast inhibited the expressions of IL-6 and IL-8. Moreover, Apremilast inhibited the expressions of the chemokines colony-stimulating factor 2 (CSF2) and chemokine ligand 11 (CCL11). Interestingly, exposure to IL-13 increased the expressions of mucin 4 and mucin 5AC (MUC5AC), which was ameliorated by treatment with Apremilast. Interestingly, we found that Apremilast inhibited the phosphorylation of c-Jun-N-terminal kinase (JNK). Importantly, Apremilast reduced the levels of c-fos and c-Jun, the two AP-1 subfamilies. The luciferase reporter assay demonstrates that Apremilast reduced the transcriptional activity of activator protein 1 (AP-1). Lastly, we found that Apremilast prevented the activation of nuclear factor kappa-B (NF-κB) by decreasing the levels of nuclear NF-κB p65 and the luciferase activity of the NF-κB reporter. In summary, we conclude that Apremilast possesses a protective effect against IL-13-induced inflammatory response and mucin production in hNECs by inhibiting the activity of AP-1 and NF-κB.

11.
Environ Int ; 157: 106870, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34534788

RESUMO

BACKGROUND: Previous studies have revealed a significant association of fine particulate matter (PM2.5) with emotional disorders. However, as a crucial component of PM2.5, little is known about the potential effect of exposure to black carbon (BC) on the symptoms of depression and anxiety. OBJECTIVES: To explore the associations of long-term exposure to BC during the past six years with the current symptoms of depression and anxiety in a group of incoming college students. METHODS: This was a retrospective cohort study of incoming students in five universities of China. Symptoms of depression and anxiety during the past two weeks were measured by the Patient Health Questionnaire-2 (PHQ-2) and Generalized Anxiety Disorder Scale-2 (GAD-2), respectively. Levels of BC and other environmental factors during 2013 âˆ¼ 2018 (six years prior to the recruitment) was obtained from public repositories and linked to individual data by home addresses. Averagely daily dose of BC exposure was estimated according to the respiratory rate. Demographic and behavioral variables were collected through a questionnaire. The associations of BC with symptoms of depression and anxiety were estimated by mixed linear models adjusting for socioeconomic and behavioral characteristics, and the principal components of multiple environmental exposures. Subgroup analysis was conducted to assess the effect modification by covariates. Overall effect of environmental mixture was evaluated by weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR). RESULTS: A total of 20,079 participants was included in the current study. After adjustment for covariates, long-term BC exposure was significantly associated with symptoms of depression (ß = 0.17, P < 0.001) but not anxiety (ß = 0.07, P = 0.125). Effect modification by sex and parental educational level: BC was correlated with depressive symptoms in women (ß = 0.23, P < 0.001) but not in men (ß = 0.04, P = 0.581), and higher educational level was associated with decreased effect sizes of BC. Sensitivity analysis showed that the acute and short-term effects of BC on depression was consistent with its long-term exposure (ß varied from 0.18 to 0.20). WQS identified BC as the primary pollutant in association with symptoms of depression but not anxiety. BKMR identified no significant interaction between BC and other exposures. CONCLUSION: Exposure to BC is associated with symptoms of depression but not anxiety in college students, and the relationship is modified by sex and education.


Assuntos
Poluentes Atmosféricos , Depressão , Poluentes Atmosféricos/análise , Teorema de Bayes , Carbono , Depressão/epidemiologia , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , Feminino , Humanos , Masculino , Material Particulado/análise , Estudos Retrospectivos , Estudantes
12.
Front Genet ; 12: 708981, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34447413

RESUMO

It is well recognized that batch effect in single-cell RNA sequencing (scRNA-seq) data remains a big challenge when integrating different datasets. Here, we proposed deepMNN, a novel deep learning-based method to correct batch effect in scRNA-seq data. We first searched mutual nearest neighbor (MNN) pairs across different batches in a principal component analysis (PCA) subspace. Subsequently, a batch correction network was constructed by stacking two residual blocks and further applied for the removal of batch effects. The loss function of deepMNN was defined as the sum of a batch loss and a weighted regularization loss. The batch loss was used to compute the distance between cells in MNN pairs in the PCA subspace, while the regularization loss was to make the output of the network similar to the input. The experiment results showed that deepMNN can successfully remove batch effects across datasets with identical cell types, datasets with non-identical cell types, datasets with multiple batches, and large-scale datasets as well. We compared the performance of deepMNN with state-of-the-art batch correction methods, including the widely used methods of Harmony, Scanorama, and Seurat V4 as well as the recently developed deep learning-based methods of MMD-ResNet and scGen. The results demonstrated that deepMNN achieved a better or comparable performance in terms of both qualitative analysis using uniform manifold approximation and projection (UMAP) plots and quantitative metrics such as batch and cell entropies, ARI F1 score, and ASW F1 score under various scenarios. Additionally, deepMNN allowed for integrating scRNA-seq datasets with multiple batches in one step. Furthermore, deepMNN ran much faster than the other methods for large-scale datasets. These characteristics of deepMNN made it have the potential to be a new choice for large-scale single-cell gene expression data analysis.

13.
J Colloid Interface Sci ; 603: 844-855, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34237602

RESUMO

A sandwich-like melamine/phytic acid/silicon nitride hybrid (SW-Si3N4) sheets were prepared by supramolecular wrapping as the hybrid flame retardants for thermoplastic polyurethane (TPU). The introduction of Si3N4 sheets as a template could not only induce the generation of two-dimensional phytic/melamine (PAMA) capping layers, but also produce the synergistic flame-retardant effect on TPU composites. Cone test showed that heat release rate (HRR), smoke production rate (SPR) and total smoke production (TSP) values of TPU were decreased obviously by adding SW-Si3N4. TG-IR test indicated the dramatic inhibition of aromatic compound, hydrocarbons, CO and HCN release. Besides, the thermal conductivity of composites was obviously improved by adding SW-Si3N4. This work may provide better reference for developing multi-functional TPU composites for diverse application.


Assuntos
Retardadores de Chama , Poliuretanos , Temperatura Alta , Condutividade Térmica
14.
Small ; 17(32): e2101428, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34213824

RESUMO

The core@shell structure dimension of the Pd-based nanocrystals deeply impacts their catalytic properties for C1 and C2 alcohol oxidation reactions. However, the precise simultaneous control on the synthesis of core@shell nanocrystals with different shell dimensions is difficult, and most synthesis on Pd-based core@shell nanocatalysts involves the surfactants participation by multiple steps, thus leads to limited catalytic properties. Herein, for the first time, a facile one-step surfactant-free strategy is developed for shell dimension reconstruction of PdAu@Pd core@shell nanocrystals by altering volume ratios of mixed solvents. The Pd-based sunflower-like (SL) and coral grass-like (CGL) nanocrystals are obtained with different 2D hexagonal nanosheet assembles and 3D network shells, respectively. Benefitting from the clean surface shell of 2D ultrathin nanosheets structure, high atom utilization efficiency, and robust electronic effect. The PdAu@Pd SL achieves the ascendant methanol/ethanol/ethylene glycol oxidation reaction (MOR/EOR/EGOR) activities, much higher than Pd/C catalysts, as well as the improved antipoisoning ability. Notably, this one-step construction shell dimension of PdAu@Pd core@shell catalysts not only provide a significant reference for the improvement of surfactant-free synthetic routes, but also shed light on the advanced engineering on shell dimensions in core@shell nanostructures for electrocatalysis and so forth.


Assuntos
Nanopartículas , Paládio , Catálise , Etanol , Solventes
15.
Inorg Chem ; 60(13): 9977-9986, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34133159

RESUMO

Pt-based catalysts with core@shell structures are widely used in alcohol oxidations due to their excellent catalytic performance. In this work, we synthesized a series of core@shell PtAuAg@PtAg hollow nanodendrites (HNDs) with different compositions by a simple seed-mediated method. The PtAuAg@PtAg HNDs with a hollow core and dendritic shell exhibit excellent catalytic performance for ethylene glycol oxidation reaction (EGOR) and methanol oxidation reaction (MOR). Among these, Pt38Au29Ag33 HNDs have the highest mass activity (12364.0 mA mgPt-1/3278.0 mA mgPt-1) for EGOR and MOR, which is 4.2 times and 5.3 times higher than that of commercial Pt/C (2941.0 mA mgPt-1/617.6 mA mgPt-1), respectively. More importantly, after successive cyclic voltammetry tests, the retained mass activities of Pt38Au29Ag33 HNDs are 3913.8 mA mgPt-1 and 348.3 mA mgPt-1, which are much higher than that of commercial Pt/C as well. The excellent catalytic performance of PtAuAg@PtAg HNDs can be attributed to the structure of HNDs, which can greatly increase the surface area and active sites, as well as the electronic and synergistic effects among Pt, Au, and Ag. This research may provide new ideas for the development of high-efficiency hollow catalytic materials for EGOR and MOR.

16.
Sci Total Environ ; 793: 148540, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34171802

RESUMO

Reliable estimation of exposure to black carbon (BC) and sub-micrometer particles (PM1) within a city is challenging because of limited monitoring data as well as the lack of models suitable for assessing the intra-urban environment. In this study, to estimate exposure levels in the inner-city area, we developed land use regression (LUR) models for BC and PM1 based on specially designed mobile monitoring surveys conducted in 2019 and 2020 for three seasons. The daytime and nighttime LUR models were developed separately to capture additional details on the variation in pollutants. The results of mobile monitoring indicated similar temporal variation characteristics of BC and PM1. The mean concentrations of pollutants were higher in winter (BC: 4.72 µg/m3; PM1: 56.97 µg/m3) than in fall (BC: 3.74 µg/m3; PM1: 33.29 µg/m3) and summer (BC: 2.77 µg/m3; PM1: 27.04 µg/m3). For both BC and PM1, higher nighttime concentrations were found in winter and fall, whereas higher daytime concentrations were observed in the summer. A supervised forward stepwise regression method was used to select the predictors for the LUR models. The adjusted R2 of the LUR models for BC and PM1 ranged from 0.39 to 0.66 and 0.45 to 0.80, respectively. Traffic-related predictors were incorporated into all the models for BC. In contrast, more meteorology-related predictors were incorporated into the PM1 models. The concentration surface based on the LUR models was mapped at a spatial resolution of 100 m, and significant seasonal and diurnal trends were observed. PM1 was dominated by seasonal variations, whereas BC showed more spatial variation. In conclusion, the development of season-dependent diurnal LUR models based on mobile monitoring could provide a methodology for the estimation of exposure and screening of influencing factors of BC and PM1 in typical inner-city environments, and support pollution management.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Monitoramento Ambiental , Material Particulado/análise , Estações do Ano
17.
Sci Total Environ ; 793: 148470, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34166901

RESUMO

Estuary and coastal environments have essential ecosystem functions in greenhouse gas sinks and removal of nitrogen pollution. Methane-oxidizing bacteria (MOB) and ammonia-oxidizing bacteria (AOB) communities play critical functions in the estuary's tidal flat sediments. Therefore, the effects of ammonium on MOB communities and methane on AOB communities need to be further explained. In this study, microcosm incubations with different contents of ammonium or methane were conducted for a relatively short (24 h) or long (28 days) period with tidal flat sediments from the Yangtze River estuary. Subsequently, the tagged highly degenerate primer PCR and DNA-based stable isotope probing method were employed to demonstrate the effects on MOB and AOB populations. The results indicated that the methane consumption was enhanced with ammonium supplements within 24 h of incubation. Supplement of 2 µmol/g d.w.s (µmol per gram dry weight soil) NH4+ increased the amount of MOB and its proportion to the total bacteria (p < 0.05) for 28 days incubation. The ammonium supplement increased the proportion of Methylomonas and Methylobacter based on the 16S rRNA gene. According to the functional gene analysis, the MOB primarily engaged in methane oxidation include Methylomonas, Methylobacter, Methylomicrobium, and Methylosarcina, which were associated with Type Ia MOB. It suggested that ammonium supplement may promote methane oxidation by stimulating the Type Ia MOB in tidal flat sediments of the Yangtze River estuary. The current research helps understand the effect of ammonium on methane consumption in the estuary and coastal environments.


Assuntos
Compostos de Amônio , Methylococcaceae , Ecossistema , Estuários , Metano , Oxirredução , Filogenia , RNA Ribossômico 16S/genética , Rios
18.
J Colloid Interface Sci ; 601: 42-49, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34052725

RESUMO

Recently, intensive attention has been attracted to the two-dimensional metal nanosheets, owing to their excellent electrocatalytic performance for direct alcohol fuel cells (DAFCs). Herein, PdRu nanosheets have been synthesized successfully by a facile one-pot method. The rugged nanosheet structure provided plentiful surface active sites to enhance the electrocatalytic activity. Moreover, benefiting from the synergistic effect and improved electronic structure, PdRu NSs exhibited splendid electrocatalytic performance in ethylene glycol oxidation reaction (EGOR) and glycerol oxidation reaction (GOR). Specifically, the mass activity of PdRu NSs was 1.72 and 3.69 times over those of Pd NSs and Pd/C catalysts in EGOR. Moreover, PdRu NSs displayed the largest mass activity in GOR, 1.48 and 2.47 times as large as Pd NSs and Pd/C catalysts. The results of stability tests demonstrated that the durability of PdRu NSs was the highest among the obtained catalysts. This work plays a directive role on the in-depth engineering on Pd-based catalysts with nanosheet architectures.


Assuntos
Etilenoglicol , Glicerol , Catálise , Etanol , Oxirredução
19.
Front Pharmacol ; 12: 611610, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33935705

RESUMO

Cholestasis is a pathological state that leads to serious liver disease; however, therapeutic options remain limited. Yinchen and Gancao are often used in combination at different ratios in traditional Chinese formulae for the treatment of jaundice and cholestasis. In the present study, we investigated the effect of decoctions containing different ratios of Yinchen and Gancao (YGD) on alpha-naphthyl isothiocyanate (ANIT)-treated intrahepatic cholestasis (IC) in mice, and further explored the underlying mechanism. Treatment with 0:4 and 1:4 YGD significantly reduced plasma total bile acid (TBA), total bilirubin (TBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) activities; decreased unconjugated and conjugated bile acid levels; and improved hepatocyte necrosis and inflammatory cells recruitment to hepatic sinusoids. Moreover, the expression levels of Toll-like receptor 4 (TLR4), interleukin-1ß (IL-1ß), IL-6, tumor necrosis factor alpha (TNF-α), C-C ligand 2 (CCL2), and C-X-C ligand 2 (CXCL2) in the liver were significantly reduced. However, treatment with 4:1 and 4:0 YGD increased plasma TBA, TBIL, AST, ALT, and ALP activities and aggravated liver cell injury and inflammation. Moreover, the mRNA expression of the bile salt export pump (BSEP) in the liver was significantly increased in mice treated with 4:0 YGD. The present study demonstrates that YGD containing a high proportion of Gancao, which inhibits the TLR4/NF-κB pathway and reduces the inflammatory response, had protective effects against ANIT-treated IC in mice. However, YGD containing a high proportion of Yinchen aggravated the ANIT-treated IC in mice, which may be related to upregulation of BSEP and boosting bile acid regurgitation from damage cholangiocytes to liver in ANIT-treated IC mice.

20.
Appl Environ Microbiol ; 87(14): e0022721, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-33962978

RESUMO

The families of copper-containing membrane-bound monooxygenases (CuMMOs) and soluble di-iron monooxygenases (SDIMOs) are involved not only in methane oxidation but also in short-chain alkane oxidation. Here, we describe Rhodococcus sp. strain ZPP, a bacterium able to grow with ethane or propane as the sole carbon and energy source, and report on the horizontal gene transfer (HGT) of actinobacterial hydrocarbon monooxygenases (HMOs) of the CuMMO family and the sMMO (soluble methane monooxygenase)-like SDIMO in the genus Rhodococcus. The key function of HMO in strain ZPP for propane oxidation was verified by allylthiourea inhibition. The HMO genes (designated hmoCAB) and those encoding sMMO-like SDIMO (designated smoXYB1C1Z) are located on a linear megaplasmid (pRZP1) of strain ZPP. Comparative genomic analysis of similar plasmids indicated the mobility of these plasmids within the genus Rhodococcus. The plasmid pRZP1 in strain ZPP could be conjugatively transferred to a recipient Rhodococcus erythropolis strain in a mating experiment and showed similar ethane- and propane-consuming activities. Finally, our findings demonstrate that the horizontal transfer of plasmid-based CuMMO and SDIMO genes confers the ability to use ethane and propane on the recipient. IMPORTANCE CuMMOs and SDIMOs initiate the aerobic oxidation of alkanes in bacteria. Here, the supposition that horizontally transferred plasmid-based CuMMO and SDIMO genes confer on the recipient similar abilities to use ethane and propane was proposed and confirmed in Rhodococcus. This study is a living example of HGT of CuMMOs and SDIMOs and outlines the plasmid-borne properties responsible for gaseous alkane degradation. Our results indicate that plasmids can support the rapid evolution of enzyme-mediated biogeochemical processes.


Assuntos
Proteínas de Bactérias/genética , Oxigenases de Função Mista/genética , Rhodococcus/genética , Etano/metabolismo , Transferência Genética Horizontal , Genes Bacterianos , Oxirredução , Plasmídeos , Propano/metabolismo , Rhodococcus/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...