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1.
Chemosphere ; 240: 124903, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31563100

RESUMO

Excessive nitrogen has been a global concern to cause lake eutrophication. The denitrification and anammox processes are considered to be effective biological pathways for nitrogen removal. Submerged macrophytes also play a key role in the nitrogen cycle of lakes. However, the mechanism of submerged macrophytes on regulating biological nitrogen removal pathways has not been well quantified. Therefore, this study investigated the impacts of submerged macrophytes on the community structures and abundance of the nirS-type denitrifiers and anammox bacteria in the rhizospheres. The qPCR results indicated that the abundance of two bacteria in the near-rhizospheres of submerged macrophytes was significantly lower than the root compartments and non-rhizospheres, while the concentrations of organic acids in the near-rhizospheres were higher than those of the root compartments and non-rhizospheres. Redundancy analysis results illustrated that concentrations of NO3--N, NO2--N, citric acid and oxalic acid were the key environmental indicators which had the significant impact on the microbial community. The concentrations of citric acid and oxalic acid were negatively correlated with the nirS-type denitrifiers abundance, and the oxalic acid concentrations were negatively correlated with the anammox bacteria abundance. These results indicated that submerged macrophytes could reduce the abundance of nirS-type denitrifiers and anammox bacteria by releasing organic acids. In addition, the highest diversity of denitrifier community were found in the rhizosphere of the Hydrilla verticillata, while the highest diversity of anammox community were found in the Potamogeton maackianus rhizosphere. These results indicate that the impacts of submerged macrophytes on the biological nitrogen removal pathways were species-dependent.

2.
Int J Biol Macromol ; 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31715236

RESUMO

Alzheimer's disease (AD) is the most common degenerative disease of the central nervous system. It is associated with abnormal accumulation of amyloid-ß (Aß) plaques, impaired neurogenesis, and damaged cognitive functions. Wehaveknownfor a long timethatnatural compounds and their derivatives have gained increasing attention in AD drug research due to their multiple effects and inherently enormous chemicals. In this study, we will demonstrate that polysaccharides from L. barbarum (LBP1), a traditional natural compound, can reduce Aß level and improve the cognitive functions in APP/PS1 transgenic mouse. LBP1 can enhance neurogenesis as indicated by BrdU/NeuN double labeling. Furthermore, it can restore synaptic dysfunction at hippocampus CA3-CA1 pathway. Additionally, in vitro cell assay indicates that LBP1 may affect Aß processing. In conclusion, our study indicates that LBP1 might be a potential therapeutic agent for the treatment of AD against multiple targets that include synaptic plasticity, Aß pathology and neuropathology.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31691266

RESUMO

INTRODUCTION: Bishop score, the traditional method to assess cervical condition, is not a promising predictive tool of the outcome of labor induction. As an objective assessment tool, many cervical ultrasound measurements have been proposed to represent the individual components of the Bishop score, but none of them can measure the cervical stiffness. Cervical shear wave elastography is a novel tool to assess the cervical stiffness quantitatively. MATERIAL AND METHODS: A total of 475 women who required labor induction were studied prospectively. Prior to routine digital assessment of the Bishop score, transvaginal sonographic measurement of cervical length, posterior cervical angle, angle of progression and shear wave elastography was performed. Shear wave elastography measurement was made at the inner, middle and outer regions of the cervix to assess homogeneity. Association of labor induction outcomes including the overall cesarean section and subgroups of cesarean section for failure to enter active phase, with cervical sonographic parameters and the Bishop score, were assessed using multivariate regression analyses. The predictive accuracy of the outcomes using models based on ultrasound measurement and the Bishop score was compared using the area under the receiver-operating characteristics curves. RESULTS: Among 475 women, 82 (17.3%) required cesarean section. Shear wave elasticity was significantly higher in the inner cervical region than in other regions, indicating a greater stiffness (P < 0.001). Both inner cervical shear wave elasticity and cervical length were independent predictors of overall cesarean section (respective adjusted odds ratio [95% CI] 1.338 [1.001-1.598] and 1.717 [1.077-1.663]) and cesarean section for failure to enter active phase (respective adjusted odds ratio [95% CI] 1.689 [1.234-2.311] and 2.556 [1.462-4.467]), after adjusting for other covariates. Outcome prediction models using inner cervical shear wave elasticity and cervical length, had increased area under curve compared with models using the Bishop score (0.888 vs 0.819, P = 0.009). CONCLUSIONS: The cervix is not a homogenous structure, with the inner cervix having the highest stiffness, which is an independent predictor of overall cesarean section, and specifically for those indicated because of failure to enter active phase. Models based on shear wave elastography and cervical length had higher predictive accuracy than models based on the Bishop score.

4.
World J Gastroenterol ; 25(40): 6116-6128, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31686767

RESUMO

BACKGROUND: For periampullary adenocarcinoma, the histological subtype is a better prognostic predictor than the site of tumor origin. Intestinal-type periampullary adenocarcinoma (IPAC) is reported to have a better prognosis than the pan-creatobiliary-type periampullary adenocarcinoma (PPAC). However, the classification of histological subtypes is difficult to determine before surgery. Apparent diffusion coefficient (ADC) histogram analysis is a noninvasive, non-enhanced method with high reproducibility that could help differentiate the two subtypes. AIM: To investigate whether volumetric ADC histogram analysis is helpful for distinguishing IPAC from PPAC. METHODS: Between January 2015 and October 2018, 476 consecutive patients who were suspected of having a periampullary tumor and underwent magnetic resonance imaging (MRI) were reviewed in this retrospective study. Only patients who underwent MRI at 3.0 T with different diffusion-weighted images (b-values = 800 and 1000 s/mm2) and who were confirmed with a periampullary adenocarcinoma were further analyzed. Then, the mean, 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles of ADC values and ADCmin, ADCmax, kurtosis, skewness, and entropy were obtained from the volumetric histogram analysis. Comparisons were made by an independent Student's t-test or Mann-Whitney U test. Multiple-class receiver operating characteristic curve analysis was performed to determine and compare the diagnostic value of each significant parameter. RESULTS: In total, 40 patients with histopathologically confirmed IPAC (n = 17) or PPAC (n = 23) were enrolled. The mean, 5th, 25th, 50th, 75th, 90th, and 95th percentiles and ADCmax derived from ADC1000 were significantly lower in the PPAC group than in the IPAC group (P < 0.05). However, values derived from ADC800 showed no significant difference between the two groups. The 75th percentile of ADC1000 values achieved the highest area under the curve (AUC) for differentiating IPAC from PPAC (AUC = 0.781; sensitivity, 91%; specificity, 59%; cut-off value, 1.50 × 10-3 mm2/s). CONCLUSION: Volumetric ADC histogram analysis at a b-value of 1000 s/mm2 might be helpful for differentiating the histological subtypes of periampullary adenocarcinoma before surgery.

5.
Sci Adv ; 5(10): eaay0352, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31692742

RESUMO

Boron carbide suffers from a loss of strength and toughness when subjected to high shear stresses due to amorphization. Here, we report that a small amount of Si doping (~1 atomic %) leads to a substantial decrease in stress-induced amorphization due to a noticeable change of the deformation mechanisms in boron carbide. In the undoped boron carbide, the Berkovich indentation-induced quasi-plasticity is dominated by amorphization and microcracking along the amorphous shear bands. This mechanism resulted in long, distinct, and single-variant shear faults. In contrast, substantial fragmentation with limited amorphization was activated in the Si-doped boron carbide, manifested by the short, diffuse, and multivariant shear faults. Microcracking via fragmentation competed with and subsequently mitigated amorphization. This work highlights the important roles that solute atoms play on the structural stability of boron carbide and opens up new avenues to tune deformation mechanisms of ceramics via doping.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31702508

RESUMO

BACKGROUND: Cancer is increasingly becoming the major cause leading to death in many countries, and digestive system malignant tumours account for the majority of cancer incidence and mortality. Metabolism has been identified as a core hallmark of cancer. Peroxisome proliferator activated receptor gamma coactivator alpha (PGC-1α) is a pivotal regulator of mitochondrial energy metabolism. Accumulating evidence reveals that PGC-1α is essential in cancer development. OBJECTIVE: We summarize the latest research progress of PGC-1α in common digestive system malignant tumours. Some related modulators and pathways are involved as well. METHODS: We conducted a literature review of the development about PGC-1α in common digestive system malignant tumours. RESULTS: In colorectal cancer, PGC-1α appears to provide growth advantages by different pathways, although it has also been reported to have opposite effects. The previous studies of PGC-1α on liver cancer also demonstrate different effects by sundry pathways. Concerning gastric cancer, PGC-1α promotes cell proliferation, apoptosis in vitro and tumour growth in vivo. AMPK/SIRT1/ PGC-1α is related to the inhibition of apoptosis in pancreatic cancer cells. Pancreatic cancer stem cells are strongly dependent on mitochondrial oxidative phosphorylation. PGC-1α is required to maintain the stemness property of pancreatic cancer stem cells. CONCLUSION: We expose diverse mechanisms that explain the dichotomous functions of PGC-1α on tumorigenesis, as well as discuss the latest research concerning digestive system malignant tumours. This review would supply better comprehension of the field and a basis for further studies associated with PGC-1α in digestive system cancers.

7.
Nano Lett ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31687827

RESUMO

Practical applications of lithium metal anodes are gravely impeded by inhomogeneous lithium deposition, which results in dendrite growth. Electrolyte additives are proven to be effective in improving performance but usually serve only a single function. Herein, nitrofullerene is introduced as a bifunctional additive with a smoothing effect and forms a protective solid electrolyte interphase (SEI) layer on stable lithium metal anodes. By design, nitro-C60 can gather on electrode protuberances via electrostatic interactions and then be reduced to NO2- and insoluble C60. Next, the C60 anchors on the uneven groove of the lithium surface, resulting in a homogeneous distribution of Li ions. Finally, NO2- anions can react with metallic Li to build a compact and stable SEI with high ion transport. With a 5 mM nitro-C60 additive, Li-Li symmetric cells show superior cycle stability in both carbonate and ether electrolytes, Li-sulfur batteries with a high cathode loading (10.6 mg cm-2, 6 mAh cm-2) can achieve improved cycle retention of 63.2% over 100 cycles in a carbonate electrolyte, and full cells paired with a high-areal-capacity LiNi0.6Co0.2Mn0.2O2 cathode (3.5 mAh cm-2) exhibit a significantly enhanced cycle lifespan even under lean electrolyte conditions.

8.
J Acoust Soc Am ; 146(4): 2590, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31671965

RESUMO

Online secondary path modeling is always appealing in active noise control due to the benefit of tracking the variations in the secondary path while exerting noise control simultaneously. However, the auxiliary noise usually utilized in online modeling contributes to the residual noise and deteriorates the noise control performance. This problem is more severe in multi-channel active control systems. Recently, it has been revealed that the secondary path can be identified using the output of the control source directly without injecting any auxiliary noise. In this letter, this strategy is extended to the multi-channel case. The reliability of the secondary path modeling is theoretically proven, and the effectiveness of the proposed multi-channel simultaneous modeling and control system is validated through simulations using measured impulse responses.

9.
Sci Total Environ ; : 134773, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31753491

RESUMO

In this study, corn straw biomass was co-pyrolyzed with a clay mineral (montmorillonite) in the presence of iron-bearing materials (FeCl3, magnetite and iron acetylacetone) and the prepared iron-montmorillonite biochars were characterized for their interfacial behavior. The results showed that, by adding iron to the pyrolysis process, organometallic complexes such as Fe-O-C were generated on the surface of biochars. All the iron-montmorillonite biochars were also shown to enhance the oxidation resistance likely by the increased relative contents of CO and COOH from 0% and 3.7% to 6.5-8.4% and 5.5-6.3%, respectively, compared with the iron-absent biochar. The measured carbon recalcitrance index (R50, bicohar) of iron-montmorillonite biochars in thermogravimetric analysis (TGA) also increased from 46.9% to 48.6-56.9%. Among the three types of added iron materials, magnetite showed the best performance in improving biochar stability. The study indicated that, when added together, montmorillonite and iron were effective in improving the stability of biochar, which displays an important environmental significance of carbon sequestration.

10.
Artigo em Inglês | MEDLINE | ID: mdl-31743318

RESUMO

OBJECTIVE: Current evidence regarding the association between paternal smoking before conception or during pregnancy and the risk of childhood acute lymphoblastic leukemia (ALL) are inconsistent. We aimed to systematically summarize the current evidence regarding this potential association. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the Meta-analysis of Observational Studies in Epidemiology (MOOSE), we systematically retrieved PubMed, Embase, Web of Science, and Scopus, screened relevant literature, and assessed the methodological quality of the included studies. We calculated the pooled estimates using random-effects models. We assessed statistical heterogeneity by I values and χ tests for the Cochrane Q statistic. We further investigate the dose-response relation using 2-stage nonlinear models. RESULTS: A total of 17 case-control studies were identified, and the synthesized risk ratios (RRs) for smoking before conception (RR=1.15, 95% confidence interval: 1.04-1.27) and during pregnancy (RR=1.20, 95% confidence interval: 1.12-1.28) were both statistically significant. Moreover, the dose-response analysis showed a positive association as well. CONCLUSION: Current evidence from observational studies suggests the association between paternal smoking before conception or during pregnancy and the increased risk of childhood ALL, which needs to be confirmed in prospective studies.

11.
Physiol Genomics ; 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31682178

RESUMO

Long non-coding RNAs have been implicated in the development and progression of atherosclerosis. However, the expression and mechanism of action of lncRNAs in atherosclerosis are still unclear. We implemented microarray analysis in human advanced atherosclerotic plaques and normal arterial intimae to detect the lncRNA and mRNA expression profile. Gene Ontology functional enrichment and pathway analyses were applied to explore the potential functions and pathways involved in the pathogenesis of atherosclerosis. A total of 236 lncRNAs and 488 mRNAs were selected for further Ingenuity Pathway Analysis. Moreover, qRT-PCR tests of most selected lncRNAs and mRNAs with high fold changes were consistent with the microarray data. We also performed ELISA to investigate the corresponding proteins levels of selected genes and showed that serum levels of SPP1, CD36, ATP6V0D2, CHI3L1, MYH11 and BDNF were differentially expressed in patients with coronary heart disease compared with healthy subjects.These proteins correlated with some biochemical parameters used in the diagnosis of cardiovascular diseases. Furthermore, receiver operating characteristic analysis showed a favorable diagnostic performance.The microarray profiling analysis and validation of differentially-expressed lncRNAs and mRNAs in atherosclerosis not only provide new insights into the pathogenesis of this disease, but may also reveal new biomarkers for its diagnosis and treatment.

12.
Medicine (Baltimore) ; 98(47): e18086, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764843

RESUMO

Acute poisoning in children is a clinical emergency. Prompt and effective treatment is critical for life-threatening poisoning. Extracorporeal treatment (ECTR) is a practical option for enhancing the elimination of poisons.We conducted a retrospective observational study on 338 children with severe acute poisoning who received ECTR during hospitalization from January 2010 to December 2017. The poisonous substances, utilization of ECTR, adverse reactions to ECTR, and outcomes were recorded.The top 3 poisoning categories, in order of frequency, were found to be pesticides (57.99%), biotoxins (25.15%), and pharmaceuticals (14.20%). Paraquat (35.21%), an organic heterocyclic herbicide with high toxicity to humans, was the most common toxic substance. The main modalities of ECTR use were hemoperfusion (50.59%) and therapeutic plasma exchange (42.60%), followed by continuous renal replacement therapy (4.44%) and hemodialysis (1.18%). There were also 4 patients (1.18%) with a combination of ECTR performed. Adverse events of ECTR included errhysis and hematomas around the catheter exit site, oral cavity bleeding, allergic reactions, hypothermia, hypotension, and blood coagulation. The adverse reactions were mostly mild to moderate and were manageable. During the study period, there were 295 patients (87.28%) who were cured, 9 (2.66%) who experienced some improvement, and 34 (10.06%) who died.ECTR modalities were found to be clinically effective approaches to the treatment of poisoning by pesticides, biotoxins, and pharmaceuticals, indicating they are important modalities in toxicology and treatment, and are well tolerated by children.

13.
Sci Rep ; 9(1): 17552, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31772181

RESUMO

Aeschynanthus (Gesneriaceae), a genus comprising approximately 160 species in subtropical Southeast Asia, has red, tubular flowers, typical of a sunbird pollination syndrome. A. acuminatus, the species that is distributed extending to the northern edge of the genus, where the specialized nectarivorous sunbirds are absent, possesses reddish-green flowers and a wide-open corolla tube, flowering time shifts from summer to winter and the species achieves high fruiting success. This atypical flower led us to investigate the pollination biology of this species. Three species of generalist passerines, Grey-cheeked Fulvetta (Alcippe morrisonia, Sylviidae), White-eared Sibia (Heterophasia auricularis, Leiothrichidae) and Taiwan Yuhina (Yuhina brunneiceps, Zosteropidae), were recorded visiting A. acuminatus flowers. Pollination effectiveness was quantified via conspecific pollen presence on stigmas and natural fruit set. The significantly high natural fruit set (60%) and conspecific pollen transfer rate (94%) indicate high reproductive success facilitated by the accurate pollen placement on the birds. The existence of copious (61 µL) and highly diluted (7%) hexose-dominant nectar, together with a major reflectance peak of corolla lobe in the long-wavelength red color spectrum, is consistent with the pollination syndrome of generalist passerines. The high pollination effectiveness of A. acuminatus due to the recruitment of generalist passerines as pollinators, and the specializations of floral traits to match generalist bird pollination, appear crucial in the successful colonization on islands such as Taiwan that lack specialized bird pollinators.

14.
Bioresour Technol ; 294: 122231, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31606596

RESUMO

In this study, the effects of salt stress on the physiological, lipidomic and transcriptomic profiles of halophilic microalga Schizochytrium sp. were investigated. In general, Schizochytrium sp. could survive under high osmotic fermentation medium containing 30 g/L NaCl, and showed a significant increase in C14:0 percentage in total fatty acids. In lipidomic analysis, C14:0 was specifically enriched in phosphatidylcholine (PC), and membrane phospholipids participated in the salt stress response mostly. Specially, one novel signal lipid N-acylphosphatidylethanolamine (NAPE) (18:0/20:3/14:0) was upregulated significantly. Transcriptomic analysis revealed glycerol-3-phosphate acyltransferase (GPAT) and phospholipase ABHD3 (PLABDH3) were involved in C14:0 metabolism and NAPE biosynthesis. Signalling pathways they mediated were activated as evident by high expression level of Myristoyl-CoA: protein N-myristoyltransferase (NMT) and NAPE-hydrolyzing PLD (NAPE-PLD). This study gives us an insight in specific responses to salt stress in Schizochytrium sp. and provides a considerable proportion of novel genes that could commendably be used for engineering modification.


Assuntos
Estresse Salino , Transcriptoma , Ácidos Graxos , Fosfolipídeos , Transdução de Sinais
15.
Appl Microbiol Biotechnol ; 103(21-22): 8963-8975, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31630240

RESUMO

Candida albicans is the most common clinical pathogenic fungus, which is highly susceptible to immunodeficiency. Development of novel antifungal agents has become a growing trend in the treatment of Candida infections. C16-Fengycin A, a lipopeptide isolated from Bacillus amyloliquefaciens fmb60 showed significant fungicidal activity against C. albicans. In the study, we explored the possible antifungal mode of C16-Fengycin A. It was predicted that C16-Fengycin A had the ability to disrupt the cell wall due to its alterations of cell ultrastructure, and reduction of cell wall hydrophobicity. This was further confirmed by the changes in the exposure of the cell wall components and down-regulation of the genes related in the cell wall synthesis. Meanwhile, with the treatment of C16-Fengycin A, the levels of reactive oxygen species (ROS) increased, resulting in mitochondrial dysfunction in the cells. We hypothesized that the antifungal mechanism of C16-Fengycin A might be via the destruction of the cell wall and the accumulation of ROS, which could activate the High-Osmolarity Glycerol Mitogen-Activated Protein Kinase (HOG-MAPK) pathway. Our findings indicated that C16-Fengycin A could be a potential antifungal agent that could be used to treat candida infections.

16.
Invest Ophthalmol Vis Sci ; 60(13): 4328-4335, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31622469

RESUMO

Purpose: We evaluate the effect of choroidal vessel density on the residual length of the ellipsoid zone (EZ) and visual function in patients with retinitis pigmentosa (RP) using optical coherence tomography angiography (OCTA). Methods: Fifty-three patients with RP (n = 101 eyes) and 53 normal participants (n = 76 eyes) were enrolled in this study. Patients with RP were assigned to three groups according to their best-corrected visual acuity (BCVA). All patients underwent ophthalmologic examinations, including BCVA, fundus examination performed with a slit-lamp using an indirect 90 diopter (D) lens, OCTA, full-field electroretinogram (ERG), and visual field. The choroidal vessel density in the choriocapillaris-Sattler's layer (DC-S), Haller's layer (DH), horizontal length of the ellipsoid (HEL), and vertical length of the ellipsoid (VEL) were assessed using OCTA and Adobe Photoshop CS3 extended software. Results: A significantly increasing impairment of choroidal vessel density (DC-S and DH) was characterized in the RP groups compared to those of the controls (P < 0.05 for all). The magnitude of the reduction in the DC-S and DH was much easier to identify for more severely impaired BCVA in the RP groups (P < 0.05 for all). The DC-S had the strongest correlation with the HEL, VEL, BCVA, visual field, and b-wave amplitude (r = 0.735, r = 0.753, r = -0.843, r = 0.579, and r = 0.671, respectively). Conclusions: Using noninvasive OCTA, choroidal microcirculation, especially in the small/middle choroidal vessel layers, was a prominent factor affecting the EZ, visual acuity, visual field, and recordable ERG b-wave amplitude of patients with RP. This may provide new insights into the progress mechanism and treatment of RP.

17.
Food Chem Toxicol ; : 110890, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31628963

RESUMO

Alcoholic liver disease is a major cause of morbidity and mortality worldwide. In this work, a food-grade recombinant Bacillus subtilis co-expressing both alcohol dehydrogenase from Saccharomyces cerevisiae (scADH) and aldehyde dehydrogenase from Issatchenkia terricola (istALDH) were successfully constructed via double-crossover homologous recombination. When cultured at 37 °C for 48 h, the activities of scADH and istALDH were 57.56 ±â€¯7.44 and 81.41 ±â€¯8.26 U/mL, respectively. In pH 4.0, the alcohol degradation rate of recombinant B. subtilis fmb8 was 33% and the ΔLog10 was 0.1, indicating that fmb8 could be used as whole-cell biocatalysts for biodegradation of alcohols under low pH conditions. Mice experiments indicated that recombinant B. subtilis significantly alleviate recombinant alcohol-induced increases of mouse liver index, blood alcohol content, and serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase activities. Furthermore, recombinant B. subtilis significantly reduced liver malondialdehyde levels and increased total antioxidant capacity and superoxide dismutase levels in mouse liver. Overall, our findings suggested that food-grade B. subtilis fmb8 co-expressing scADH and istALDH could be used as a potential probiotic for alcohol detoxification and alleviation of alcoholic liver injury.

18.
Sci Rep ; 9(1): 14022, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31575919

RESUMO

Human metapneumovirus (hMPV), first identified in 2001, is a major viral respiratory pathogen that worldwide reported. Fundamental questions concerning the dynamics of viral evolution and transmission at both regional and global scales remain unanswered. In this study, we obtained 32 G gene and 51 F gene sequences of hMPV in Guangzhou, China in 2013-2017. Temporal and spatial phylogenetic analyses were undertaken by incorporating publicly available hMPV G gene (978) and F gene (767) sequences. The phylogenetic results show different global distribution patterns of hMPV before 1990, 1990-2005, and 2006-2017. A sharply increasing hMPV positive rate (11%) was detected in Guangzhou 2017, mainly caused by the B1 lineage of hMPV. A close phylogenetic relation was observed between hMPV strains from China and Japan, suggesting frequent hMPV transmissions between these regions. These results provide new insights into hMPV evolution, transmission, and spatial distribution and highlight Asia as a new epicenter for viral transmission and novel variant seeding after the year 2005. Conducting molecular surveillance of hMPV in Asian countries is critical for understanding the global circulation of hMPV and future vaccine design.

19.
Curr Alzheimer Res ; 16(10): 934-949, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31642778

RESUMO

BACKGROUND: Amyloid-ß42 oligomers (Aß42O), the proximate effectors of neurotoxicity observed in Alzheimer's disease (AD), can induce mitochondrial oxidative stress and impair mitochondrial function besides causing mitochondrial DNA (mtDNA) damage. Aß42O also regulate the proliferative and differentiative properties of stem cells. OBJECTIVE: We aimed to study whether Aß42O-induced mtDNA damage is involved in the regulation of stem cell differentiation. METHOD: Human iPSCs-derived neural stem cell (NSC) was applied to investigate the effect of Aß42O on reactive oxygen species (ROS) production and DNA damage using mitoSOX staining and long-range PCR lesion assay, respectively. mtDNA repair activity was measured by non-homologous end joining (NHEJ) in vitro assay using mitochondria isolates and the expression and localization of NHEJ components were determined by Western blot and immunofluorescence assay. The expressions of Tuj-1 and GFAP, detected by immunofluorescence and qPCR, respectively, were examined as an index of neurons and astrocytes production. RESULTS: We show that in NSC Aß42O treatment induces ROS production and mtDNA damage and impairs DNA end joining activity. NHEJ components, such as Ku70/80, DNA-PKcs, and XRCC4, are localized in mitochondria and silencing of XRCC4 significantly exacerbates the effect of Aß42O on mtDNA integrity. On the contrary, pre-treatment with Phytic Acid (IP6), which specifically stimulates DNA-PK-dependent end-joining, inhibits Aß42O-induced mtDNA damage and neuronal differentiation alteration. CONCLUSION: Aß42O-induced mtDNA repair impairment may change cell fate thus shifting human NSC differentiation toward an astrocytic lineage. Repair stimulation counteracts Aß42O neurotoxicity, suggesting mtDNA repair pathway as a potential target for the treatment of neurodegenerative disorders like AD.

20.
PLoS Negl Trop Dis ; 13(10): e0007764, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31600201

RESUMO

Reversal reactions (RRs) in leprosy are characterized by a reduction in the number of bacilli in lesions associated with an increase in cell-mediated immunity against the intracellular bacterium Mycobacterium leprae, the causative pathogen of leprosy. To identify the mechanisms that contribute to cell-mediated immunity in leprosy, we measured changes in the whole blood-derived transcriptome of patients with leprosy before, during and after RR. We identified an 'RR signature' of 1017 genes that were upregulated at the time of the clinical diagnosis of RR. Using weighted gene correlated network analysis (WGCNA), we detected a module of 794 genes, bisque4, that was significantly correlated with RR, of which 434 genes were part of the RR signature. An enrichment for both IFN-γ and IFN-ß downstream gene pathways was present in the RR signature as well as the RR upregulated genes in the bisque4 module, including those encoding proteins of the guanylate binding protein (GBP) family that contributes to antimicrobial responses against mycobacteria. Specifically, GBP1, GBP2, GBP3 and GBP5 mRNAs were upregulated in the RR peripheral blood transcriptome, with GBP1, GBP2 and GBP5 mRNAs also upregulated in the RR disease lesion transcriptome. These data indicate that RRs involve a systemic upregulation of IFN-γ downstream genes including GBP family members as part of the host antimicrobial response against mycobacteria.

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