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1.
J Cell Biol ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31719114

RESUMO

Quantification of stable isotope tracers after metabolic labeling provides a snapshot of the dynamic state of living cells and tissue. A form of imaging mass spectrometry quantifies isotope ratios with a lateral resolution <50 nm, using a methodology that we refer to as multi-isotope imaging mass spectrometry (MIMS). Despite lateral resolution exceeding diffraction-limited light microscopy, lack of contrast has largely limited use of MIMS to large or specialized subcellular structures, such as the nucleus and stereocilia. In this study, we repurpose the engineered peroxidase APEX2 as the first genetically encoded marker for MIMS. Coupling APEX2 labeling of lysosomes and metabolic labeling of protein, we identify that individual lysosomes exhibit substantial heterogeneity in protein age, which is lost in iPSC-derived neurons lacking the lysosomal protein progranulin. This study expands the practical use of MIMS for cell biology by enabling measurements of metabolic function from stable isotope labeling within individual organelles in situ.

2.
Target Oncol ; 14(6): 719-728, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31691892

RESUMO

BACKGROUND: Droplet digital polymerase chain reaction (ddPCR) is an emerging technology for quantitative cell-free DNA oncology applications. However, a ddPCR assay for the epidermal growth factor receptor (EGFR) p.Thr790Met (T790M) mutation suitable for clinical use remains to be established with analytical and clinical validations. OBJECTIVE: We aimed to develop and validate a new ddPCR assay to quantify the T790M mutation in plasma for monitoring and predicting the progression of advanced non-small-cell lung cancer (NSCLC). METHODS: Specificity of the ddPCR assay was evaluated with genomic DNA samples from healthy individuals. The inter- and intraday variations of the assay were evaluated using mixtures of plasmid DNA containing wild-type EGFR and T790M mutation sequences. We assessed the clinical utility of the T790M assay in a multicenter prospective study in patients with advanced NSCLC receiving tyrosine kinase inhibitor (TKI) treatment by analyzing longitudinal plasma DNA samples. RESULTS: We set the criteria for a positive call when the following conditions were satisfied: (1) T790M mutation frequency > 0.098% (3 standard deviations above the background signal); (2) at least two positive droplets in duplicate ddPCR reactions. Among the 62 patients with advanced NSCLC exhibiting resistance to TKI treatment, 15 had one or more serial plasma samples that tested positive for T790M. T790M mutation was detected in the plasma as early as 205 days (median 95 days) before disease progression, determined by imaging analysis. Plasma T790M concentrations also correlated with intervention after disease progression. CONCLUSIONS: We developed a ddPCR assay to quantify the T790M mutation in plasma. Quantification of longitudinal plasma T790M mutation may allow noninvasive assessment of drug resistance and guide follow-up treatment in TKI-treated patients with NSCLC. TRIAL REGISTRATION: Clinical Trials.gov identifier: NCT02804100.

3.
Langmuir ; 35(47): 15106-15113, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31692357

RESUMO

Xanthate with low cost and strong collecting ability has great application in the recovery of sulfide mineral. Herein, a xanthate, sodium O-benzythioethyl xanthate (SBEX), with high collecting ability was prepared by introducing thioether structure, which was constructed by reactive 2-(benzylthio)ethanol, carbon disulfide, and sodium hydroxide. The flotation performance of SBEX to chalcopyrite is yet to be explored by flotation experimental, surface tension measurements, adsorption experimental, density functional theory (DFT) calculations, and X-ray photoelectron spectroscopy (XPS) analyses. It is found that the thioether structure can increase the hydrophobicity and adsorption amount of SBEX on chalcopyrite surface, and SBEX features a higher collecting recovery toward chalcopyrite than sodium isobutyl xanthate (SIBX) and sodium phenylethyl xanthate (SPEX). The adsorption mechanism analyses reveal that two S atoms in the structure of -C(═S)-S are the reactive sites that can donate their electrons to minerals, as confirmed by DFT calculations and XPS analyses.

4.
Sensors (Basel) ; 19(15)2019 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-31382640

RESUMO

The expansion and improvement of synthetic aperture radar (SAR) technology have greatly enhanced its practicality. SAR imaging requires real-time processing with limited power consumption for large input images. Designing a specific heterogeneous array processor is an effective approach to meet the power consumption constraints and real-time processing requirements of an application system. In this paper, taking a commonly used algorithm for SAR imaging-the chirp scaling algorithm (CSA)-as an example, the characteristics of each calculation stage in the SAR imaging process is analyzed, and the data flow model of SAR imaging is extracted. A heterogeneous array architecture for SAR imaging that effectively supports Fast Fourier Transformation/Inverse Fast Fourier Transform (FFT/IFFT) and phase compensation operations is proposed. First, a heterogeneous array architecture consisting of fixed-point PE units and floating-point FPE units, which are respectively proposed for the FFT/IFFT and phase compensation operations, increasing energy efficiency by 50% compared with the architecture using floating-point units. Second, data cross-placement and simultaneous access strategies are proposed to support the intra-block parallel processing of SAR block imaging, achieving up to 115.2 GOPS throughput. Third, a resource management strategy for heterogeneous computing arrays is designed, which supports the pipeline processing of FFT/IFFT and phase compensation operation, improving PE utilization by a factor of 1.82 and increasing energy efficiency by a factor of 1.5. Implemented in 65-nm technology, the experimental results show that the processor can achieve energy efficiency of up to 254 GOPS/W. The imaging fidelity and accuracy of the proposed processor were verified by evaluating the image quality of the actual scene.

5.
Neurosci Bull ; 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31444652

RESUMO

Efficient viral vectors for mapping and manipulating long-projection neuronal circuits are crucial in structural and functional studies of the brain. The SAD strain rabies virus with the glycoprotein gene deleted pseudotyped with the N2C glycoprotein (SAD-RV(ΔG)-N2C(G)) shows strong neuro-tropism in cell culture, but its in vivo efficiency for retrograde gene transduction and neuro-tropism have not been systematically characterized. We compared these features in different mouse brain regions for SAD-RV-N2C(G) and two other widely-used retrograde tracers, SAD-RV(ΔG)-B19(G) and rAAV2-retro. We found that SAD-RV(ΔG)-N2C(G) enhanced the infection efficiency of long-projecting neurons by ~10 times but with very similar neuro-tropism, compared with SAD-RV(ΔG)-B19(G). On the other hand, SAD-RV(ΔG)-N2C(G) had an infection efficiency comparable with rAAV2-retro, but a more restricted diffusion range, and broader tropism to different types and regions of long-projecting neuronal populations. These results demonstrate that SAD-RV(ΔG)-N2C(G) can serve as an effective retrograde vector for studying neuronal circuits.

6.
Mar Pollut Bull ; 149: 110540, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31470210

RESUMO

Nutrient concentrations in porewater and their benthic fluxes were investigated in Daya Bay, South China, to study the accumulation and transfer of nutrients at sediment-water interface, as well as the impact of human activities on nutrients. The contributions of sediment to nutrients in water column and the potential influences on eutrophication were also discussed. Nutrients in porewater and overlying water changed in different seasons and areas, which was mainly attributed to human activities, hydrodynamic force and biogeochemical conditions. Mean concentrations of DIN (dissolved inorganic nitrogen), PO4 and SiO3 were 70 ±â€¯61, 3.1 ±â€¯4.3, 103 ±â€¯105 µmol/L, and 234 ±â€¯166, 15.6 ±â€¯4.0, 353 ±â€¯48 µmol/L in overlying water and porewater, respectively. Annual mean DIN, PO4 and SiO3 fluxes were 330 ±â€¯249, -1.3 ±â€¯16 and 549 ±â€¯301 µmol/(m2d), respectively, indicating that sediment was generally the source of DIN and SiO3, but was the sink of PO4. The mean exchange capacities were (7.8 ±â€¯5.5) × 107, (-1.2 ±â€¯34.0) × 105 and (1.2 ±â€¯0.6) × 108 mol/a for DIN, PO4 and SiO3, respectively, in Daya Bay.

7.
Sci Total Environ ; 694: 133702, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31386948

RESUMO

Coastal wetlands accumulate enormous quantities of nitrogen due to their position at the interface between land and sea and high trapping capacity. Fortunately, they have high nitrogen (N) purifying (removal) capacity, which means that they likely play an important role in mitigating against coastal eutrophication. However studies that empirically measure the degree to which wetlands purify nitrogen and their removal pathways (e.g. denitrification, anammox, plant uptake, microbial immobilization, etc.) are rare. In this study, the N purification potential (denitrification and anammox) and enzyme activities related to denitrification in different subtropical wetlands types were conducted in nitrogen-enriched wetlands of Daya Bay, Southern China. We found the average N purification rate was 11.4 µmol N·kg-1·h-1, with denitrification accounting for 84.2%-100% of the total N2 production in the wetlands of Daya Bay. The N purification potential in the wet season, subtidal areas and mangrove forests were generally observed to be higher than that in the dry season, high and low tidal areas, barren and estuary habitats, respectively. Correspondingly, these differences were mainly driven by the temperature, Eh and NH4-N, respectively. Additionally, the nitrate reductase (Nar) and nitrite reductase (Nir) activities tended to be similar among different seasons and tidal areas, however, Nir activity in mangrove forest was 1.5-fold and 2-fold of the estuarine and barren areas, respectively. Meanwhile, Nir showed a positive correlation with denitrification rate. These results indicate that NO2-N reduction, the key control mechanism for N purification, should be the rate-limiting step of the denitrification process in Daya Bay wetlands. Notably, mangroves could improve N removal rates by 48.0% compared to other wetlands. Therefore, protecting and restoring mangrove ecosystems could be an effective way to reduce the risk of coastal eutrophication.

8.
J Cell Biochem ; 120(8): 13562-13572, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30937952

RESUMO

Cervical carcinoma is the second most frequent gynecological malignancies in females worldwide. The objective of this study was to investigate the role of miR-199a-5p and protein inhibitor of activated signal transducer and activators of transcription 3 (PIAS3) in cervical carcinoma. Quantitative reverse transcription polymerase chain reaction was utilized to detect miR-199a-5p and PIAS3 expression in cervical carcinoma tissues and cells. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide Kit, transwell assay were used to explore the biological functions of miR-199a-5p in cervical carcinoma. Western blot analysis was applied to determine the expression level of epithelial-mesenchymal transition (EMT)-associated proteins and PIAS3 expression. The relationship between miR-199a-5p and PIAS3 was verified by luciferase activity reporter assay. We found that miR-199a-5p was upregulated in cervical carcinoma tissues and cell lines, and overexpression of miR-199a-5p promoted cell proliferation and metastasis in cervical carcinoma. In addition, Western blot analysis indicated that the enforced upregulation of miR-199a-5p enhanced mesenchymal markers vimentin and N-cadherin expressions, whereas reduced epithelial marker E-cadherin expressions. miR-199a-5p directly targeted PIAS3 and negatively regulated PIAS3 level in cervical carcinoma cells. And upregulation of PIAS3 reversed the effects of miR-199a-5p in cervical carcinoma. Collectively, our data provide evidence for miR-199a-5p function in cervical carcinoma growth, EMT, and metastasis; it may be act as a therapeutic strategy target for patients with cervical carcinoma.

9.
Sensors (Basel) ; 19(6)2019 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-30917494

RESUMO

Posture recognition has been widely applied in fields such as physical training, environmental awareness, human-computer-interaction, surveillance system and elderly health care. The traditional methods consist of two main variations: machine vision methods and acceleration sensor methods. The former has the disadvantages of privacy invasion, high cost and complex implementation processes, while the latter has low recognition rate for still postures. A new body posture recognition scheme based on indoor positioning technology is presented in this paper. A single deployed indoor positioning system is constructed by installing wearable receiving tags at key points of the human body. The distance measurement method with ultra-wide band (UWB) radio is applied to position the key points of human body. Posture recognition is implemented by positioning. In the posture recognition algorithm, least square estimation (LSE) method and the improved extended Kalman filtering (iEKF) algorithm are respectively adopted to suppress the noise of the distances measurement and to improve the accuracy of positioning and recognition. The comparison of simulation results with the two methods shows that the improved extended Kalman filtering algorithm is more effective in error performance.


Assuntos
Postura , Algoritmos , Humanos , Análise dos Mínimos Quadrados , Dispositivos Eletrônicos Vestíveis , Tecnologia sem Fio
10.
Mol Genet Metab ; 126(4): 368-376, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30718057

RESUMO

BACKGROUND: GALT deficiency is a rare genetic disorder of carbohydrate metabolism. Due to the decreased activity or absence of the enzyme galactose-1-phosphate uridylyltransferase (GALT), cells from affected individuals are unable to metabolize galactose normally. Lactose consumption in the newborn period could potentially lead to a lethal disease process with multi-organ involvement. In contrast to the newborn-stage disease, however, a galactose-restricted diet does not prevent long-term complications such as central nervous system (CNS) dysfunction with speech defects, learning disability and neurological disease in addition to hypergonadotropic hypogonadism or primary ovarian insufficiency (POI) in females. As the literature suggests an association between GALT enzyme activity and the long-term complications, it is of importance to have a highly sensitive assay to quantify the GALT enzyme activity. To that end, we had developed a sensitive and accurate LC-MS/MS method to measure GALT enzyme activity. Its ability to predict outcome is the subject of this report. MATERIALS AND METHODS: The GALT enzyme activity in erythrocytes from 160 individuals, in which 135 with classic, clinical variant or biochemical variant galactosemia, was quantified by LC-MS/MS. Individuals with GALT deficiency were evaluated for the long-term complications of speech defects, dysarthria, ataxia, dystonia, tremor, POI, as well as intellectual functioning (full scale IQ). The LC-MS/MS results were compared to a variety of assays: radioactive, [14C]-galactose-1-phosphate, paper chromatography with scintillation counting, enzyme-coupled assays with spectrophotometric or fluorometric readout or high-pressure liquid chromatography with UV detection of UDP-galactose. RESULTS: The LC-MS/MS method measured GALT activity as low as 0.2%, whereas other methods showed no detectable activity. Largely due to GALT activities that were over 1%, the LC-MS/MS measurements were not significantly different than values obtained in other laboratories using other methodologies. Severe long-term complications were less frequently noted in subjects with >1% activity. Patients with a p.Q188R/p.Q188R genotype have no residual enzyme activity in erythrocytes. CONCLUSION: Our LC-MS/MS assay may be necessary to accurately quantify residual GALT activities below 5%. The data suggest that patients with >1% residual activity are less likely to develop diet-independent long-term complications. However, much larger sample sizes are needed to properly assess the clinical phenotype in patients with residual enzyme activities between 0.1 and 5%.


Assuntos
Eritrócitos/enzimologia , Galactosemias/diagnóstico , UTP-Hexose-1-Fosfato Uridililtransferase/sangue , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Ensaios Enzimáticos , Feminino , Galactose/metabolismo , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Retrospectivos , Sensibilidade e Especificidade , Espectrometria de Massas em Tandem , Adulto Jovem
11.
J Phys Chem Lett ; 10(3): 610-616, 2019 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-30668125

RESUMO

Nanolasers are expected to be integrated on chips as miniaturized coherent light sources, and their application is strongly dependent on their lasing behavior. In this work, the lasing behavior of a single hexagonal ZnO pyramid (HZOP) is tailored by tuning the electronic bandgap with pressure. The lasing of the HZOP nanolaser is dominated by a helical whispering-gallery-like mode, and the lasing threshold varies little with increasing pressure. All lasing peaks of HZOP are limited in a spectral prescreen window on the right shoulder of the fluorescence emission and gradually blue-shift accompanied by several abrupt hops with increasing pressure. This feature of a spectral prescreen window originates from the strong coupling between excitons, and the coupling is described by a dispersive complex refractive index. These results provide a new perspective to tune and switch the lasing mode of a nanolaser with precision by the pressure-induced bandgap broadening of a semiconductor.

12.
Mar Pollut Bull ; 138: 598-603, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30660311

RESUMO

Seagrass meadows are experiencing worldwide declines mainly because of nutrient enrichment, which always result in macroalgae bloom and consequently periodic collapse and decomposition. However, effects of macroalgae decay on the sediment organic carbon (SOC) sequestration capacity remain unknown. Depending on the macroalgae biomass in eutrophic seagrass meadows of South China Sea, we carried out a laboratory chamber experiment to investigate the sediment labile organic carbon (OC) compositions and the influencing SOC transformation enzyme activity variations of seagrass meadows in response to common macroalgae bloom species (Cladophora spp.) decomposition. Although the dehydrogenase and ß-glucosidase activities were not affected by macroalgae decomposition, the macroalgae decomposition significantly elevated the salt-extractable carbon (SEC) content, SEC/SOC, levels of invertase and polyphenol oxidase activities, and the CO2 release. Overall, this study indicates that macroalgae decomposition stimulates the SOC transformation, and therefore, it is not benefit for SOC sequestration within seagrass meadows of the South China Sea.


Assuntos
Sequestro de Carbono , Alga Marinha/fisiologia , Carbono/metabolismo , Dióxido de Carbono/metabolismo , Catecol Oxidase/metabolismo , Celulases/metabolismo , China , Ecossistema , Eutrofização , Sedimentos Geológicos , Oxirredutases/metabolismo , Alga Marinha/crescimento & desenvolvimento , beta-Frutofuranosidase/metabolismo
13.
Mar Pollut Bull ; 139: 32-39, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30686433

RESUMO

The origins of sediment organic matter (SOM) and their contributions were studied in three contrasting wetlands (mudflat, estuarine and mangrove) of Daya Bay, South China Sea. Lower sediment δ13C but higher δ15N values were observed in coastal wetland than in offshore water of the bay. Greater terrigenous organic matter (TOM) contribution to SOM was observed in lower tidal area in mudflat and estuarine wetland. Higher concentrations of total organic carbon and total nitrogen in the three wetlands, as well as lower sediment δ13C, were found in the wet season. Extremely lower sediment δ15N with higher seawater ammonia were observed in estuarine wetland than in mudflat and mangrove, which was caused by the input of 15N-depleted ammonia from petrochemical industrial wastewater. Mangrove contributed substantially to SOM, with a larger contribution in mangrove area than in non-mangrove area. The mean contribution of TOM to SOM was lower in mangrove than in mudflat.


Assuntos
Monitoramento Ambiental/métodos , Estuários , Sedimentos Geológicos/química , Nitrogênio/análise , Compostos Orgânicos/análise , Áreas Alagadas , China , Salinidade , Estações do Ano , Água do Mar/química
14.
Sci Total Environ ; 662: 151-159, 2019 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-30690350

RESUMO

Due to distinct human disturbances and sediment type, seagrasses growing in offshore carbonate and onshore terrigenous sediments may show contrasting characteristics. A comparison of seagrass morphology, nutrient content and sediment carbon pools was taken for seagrass beds inhabiting offshore carbonate sediments in Xuande Atoll and onshore terrigenous sediments in Hainan Island, South China Sea. Lower nitrogen (N) content was observed in the aboveground (1.1%-2.8%) and belowground (0.4%-1.5%) tissue of seagrasses in Xuande Atoll than in the same species (aboveground: 2.7%-3.6%; belowground: 1.2%-2.8%) in Hainan Island. Greater depletion of leaf δ15N of Thalassia hemprichii (T. hemprichii) and Halodule pinifolia (H. pinifolia) in Xuande Atoll indicated nitrogen fixation might be the major source of nitrogen in oligotrophic reef environments. The root lengths of the seagrass species in Xuande Atoll were longer than the same species in Hainan Island. Sediment inorganic carbon (SIC) was considerably higher than sediment organic carbon (SOC) in the carbonate sediment, while the opposite trend was found in the terrigenous sediments. The SOC stock in the carbonate and terrigenous sediments was 2.41 ±â€¯0.78 Mg C ha-1 and 2.20 ±â€¯0.34 Mg C ha-1 in the top 5 cm, respectively, while the corresponding SIC was 84.38 ±â€¯21.65 Mg C ha-1 and 1.27 ±â€¯0.51 Mg C ha-1, respectively. The average CO2 net sequestered in the carbonate sediment in Xuande Atoll and the terrigenous sediment in Hainan Island were -48.22 ±â€¯-12.21 Mg C ha-1 and 1.44 ±â€¯0.03 Mg C ha-1, respectively. This suggested seagrass sediment was a source of CO2 during sediment production in the carbonate sediment but a sink of CO2 in the terrigenous sediment. Thus, the N concentration in seagrass leaf, root length, sediment carbon composition and pools were contrasted between offshore carbonate sediments and onshore terrigenous sediments.


Assuntos
Alismatales/química , Alismatales/crescimento & desenvolvimento , Sequestro de Carbono , Carbono/análise , Sedimentos Geológicos/análise , Nutrientes/análise , Raízes de Plantas/crescimento & desenvolvimento , China , Oceanos e Mares
15.
Gynecol Endocrinol ; 35(2): 179-183, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30614300

RESUMO

The purpose of this meta-analysis was to investigate the relationship between bile salt export pump (BSEP) polymorphisms and intrahepatic cholestasis of pregnancy (ICP) susceptibility. Retrieved studies from Pubmed, EMBASE, Web of Science, Cochrane Library and CBM databases about BSEP polymorphisms and ICP susceptibility were included. Odds ratio (OR) and 95% confidence interval (CI) and publication bias were calculated. Ten related case-control studies on BSEP polymorphisms and ICP susceptibility were included. The pooled results showed a significant association between BSEP rs2287622 polymorphism and ICP risk in Asian population (OR >1, p < .01 for A vs. a and AA vs. Aa/aa) and general population (OR >1, p < .05 for A vs. a, Aa vs. aa, AA/Aa vs. aa), and a borderline statistical significance was found between BSEP rs473351 polymorphism and ICP susceptibility (OR = 1.66, p < .05), and no statistical significance was found in D482G or rs853782 polymorphisms and ICP risk (all p > .05). Additionally, no publication bias was found in these studies (all p > .05). Our current meta-analysis indicated that BSEP rs2287622 polymorphism could increase the susceptibility of ICP in Asians and in general populations, while rs473351, D482G, and rs853782 polymorphisms were not obviously associated with ICP risk, but it needs further larger study with ethnicity and various etiologies.


Assuntos
Membro 11 da Subfamília B de Transportadores de Cassetes de Ligação de ATP/genética , Colestase Intra-Hepática/genética , Complicações na Gravidez/genética , Grupo com Ancestrais do Continente Asiático/genética , Feminino , Predisposição Genética para Doença , Humanos , Polimorfismo de Nucleotídeo Único , Gravidez
16.
Orphanet J Rare Dis ; 13(1): 212, 2018 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-30477550

RESUMO

BACKGROUND: Classic galactosemia is a rare genetic metabolic disease with an unmet treatment need. Current standard of care fails to prevent chronically-debilitating brain and gonadal complications. Many mutations in the GALT gene responsible for classic galactosemia have been described to give rise to variants with conformational abnormalities. This pathogenic mechanism is highly amenable to a therapeutic strategy based on chemical/pharmacological chaperones. Arginine, a chemical chaperone, has shown beneficial effect in other inherited metabolic disorders, as well as in a prokaryotic model of classic galactosemia. The p.Q188R mutation presents a high prevalence in the Caucasian population, making it a very clinically relevant mutation. This mutation gives rise to a protein with lower conformational stability and lower catalytic activity. The aim of this study is to assess the potential therapeutic role of arginine for this mutation. METHODS: Arginine aspartate administration to four patients with the p.Q188R/p.Q188R mutation, in vitro studies with three fibroblast cell lines derived from classic galactosemia patients as well as recombinant protein experiments were used to evaluate the effect of arginine in galactose metabolism. This study has been registered at https://clinicaltrials.gov (NCT03580122) on 09 July 2018. Retrospectively registered. RESULTS: Following a month of arginine administration, patients did not show a significant improvement of whole-body galactose oxidative capacity (p = 0.22), erythrocyte GALT activity (p = 0.87), urinary galactose (p = 0.52) and urinary galactitol levels (p = 0.41). Patients' fibroblasts exposed to arginine did not show changes in GALT activity. Thermal shift analysis of recombinant p.Q188R GALT protein in the presence of arginine did not exhibit a positive effect. CONCLUSIONS: This short pilot study in four patients homozygous for the p.Q188R/p.Q188R mutation reveals that arginine has no potential therapeutic role for galactosemia patients homozygous for the p.Q188R mutation.

17.
J Environ Manage ; 231: 329-335, 2018 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-30366311

RESUMO

Seagrass ecosystems have received a great deal of attention recently for their ability to capture and store carbon, thereby helping to mitigate climate change. However, their carbon-sink capacity could be offset somewhat if exported plant material - which accounts for ∼90% of total leaf production - undergoes microbial breakdown and is emitted into the atmosphere as a greenhouse gas. Here we measured emissions (CO2 and CH4) from the breakdown of exported seagrass plant material, focusing on beach-cast 'wrack'. We tested two seagrass species; Zostera nigricaulis and Amphibolis antarctica, which have contrasting morphologies and chemistries. We found that both species of wrack were substantial sources of CO2, but not CH4, during the decomposition process. Biomass loss and the coinciding CO2 emissions occurred over the 30-day experiment, and the pattern of CO2 emissions over this time followed a double exponential model (R2 > 0.92). The initial flux rate was relatively high, most likely due to rapid leaching of labile compounds, then decreased substantially within the 2-9 days, and stabilizing at < 3 µmol g-1 d-1 during the remaining decomposition period. Additionally, seagrass wrack cast high up on beaches that remained dry had 72% lower emissions than wrack that was subjected to repeated wetting in the intertidal zone. This implies that relocation of seagrass wrack by coastal resource managers (e.g. from water's edge to drier dune areas) could help to reduce atmospheric CO2 emissions. Scaling up, we estimate the annual CO2-C flux from seagrass wrack globally is between 1.31 and 19.04 Tg C yr-1, which is equivalent to annual emissions of 0.63-9.19 million Chinese citizens. With climate change and increasing coastal development expected to accelerate the rate of wrack accumulation on beaches, this study provides timely information for developing coastal carbon budgets.

19.
J Int Med Res ; 46(11): 4837-4844, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30270705

RESUMO

Linezolid (LZD) is the first oxazolidinone with excellent safety and efficacy profiles against refractory infections caused by gram-positive organisms. Hematological toxicities such as thrombocytopenia, anemia, and leukocytopenia are common in LZD therapy; however, LZD-induced pure red cell aplasia (PRCA) is rare. An 83-year-old man diagnosed with pleural empyema caused by Staphylococcus aureus received LZD after developing resistance to multiple antibiotics. Although his infection-related symptoms were improved by LZD, progressive anemia was noticed after LZD therapy was initiated. Eight weeks after LZD administration began, his hemoglobin level was 5.7 g/dL and reticulocyte proportion was 0.36%, while his white blood cell and platelet counts remained unchanged since admission. Bone marrow examination revealed markedly decreased erythropoiesis with cytoplasmic vacuolation of erythroblasts. Anemia resolved by 14 days after cessation of LZD. It is important to increase the awareness among clinicians about the potential for the hematological effects associated with LZD, particularly for older patients with pre-existing anemia and treatment courses longer than 14 days. To detect bone marrow suppression, including PRCA, we suggest monitoring the complete blood count and reticulocyte count periodically in patients receiving long-term LZD therapy.

20.
Biochem Biophys Res Commun ; 504(4): 834-842, 2018 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-30219229

RESUMO

AIMS: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific hepatic disorder with potentially deleterious consequences of fetuses. Although the intimate relationship between ICP and peroxisome proliferator-activated receptor γ (PPARγ) has been previously reported in physiological and pathological conditions, the detailed mechanisms in the process of intrahepatic cholestasis of pregnancy has been unclear. The aims of this study are to assess the role of PPARγ regulating the reactive oxygen species (ROS) and inflammation in the process of the ICP. METHODS: Clinical data of the pregnant women were collected. And the serum of cytokines, hepatic function, the expression of PPARγ and NF-κB were measured. The rat and fetal rat ICP model were constructed and detection of the expression of PPARγ and NF-κB, evaluation the level of ROS and inflammation. RESULTS: The clinical data showed that the new-born information in severe ICP group were significantly different as compared to that in control group (P < 0.05), and part of information in mild ICP group were also difference to that in control group (P < 0.05). The expression of PPARγ and NF-κB were significantly higher in clinical pregnant women, rat, fetal rat ICP model groups and taurocholate acid (TCA) treated HTR-8/SVneo cell (P < 0.01). PPARγ inhibited the production of ROS and decreased the level of inflammation. PPARγ down-regulated the NF-κB pathway. CONCLUSIONS: PPARγ provides the anti-inflammatory and protective effects in intrahepatic cholestasis of pregnancy through NF-κB pathway, which might be a probably one of the mechanisms of ICP.

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