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1.
Artigo em Inglês | MEDLINE | ID: mdl-32198688

RESUMO

Anammox process was regarded to be one of the vital links to achieve energy-saving or energy-producing wastewater treatment plant. In the study, an anammox reactor with the nitrogen gas circulation was constructed to culture anammox granules, and the performance, granule size distribution, and microbial community were investigated. Dissolved oxygen loading is found to be an important factor for the start-up of the anammox process, and the nitrogen removal rate of 2.12 kg N m-3 day-1 was achieved under the average nitrogen loading rate of 2.6 kg N m-3 day-1. The activity test showed that the highest specific anammox activity of 345.9 mg N gVSS-1 day-1 was achieved for granules with size of 0.5-1.0 mm. The Illumina high-throughput sequencing analysis revealed the consistent variation of Candidatus Brocadia and Denitratisoma abundance in granues of all sizes, suggesting possible synergistic mechanism between heterotrophic bacteria Denitratisoma and anammox bacteria Ca. Brocadia. Furthermore, the results indicated the reactor with the nitrogen gas circulation is an efficient strategy to start-up anammox.

2.
Medicine (Baltimore) ; 99(11): e19244, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176048

RESUMO

A mutation in the epithelial morphogen gene ectodysplasin-A1 (EDA1) is responsible for the disorder X-linked hypohidrotic ectodermal dysplasia (XLHED), the most common form of ectodermal dysplasia. XLHED is characterized by impaired development of hair, eccrine sweat glands, and teeth. This study aimed to identify potentially pathogenic mutations in four Chinese XLHED families.Genomic DNA was extracted from the peripheral blood and sequenced. Sanger sequencing was used to carry out mutational analysis of the EDA1 gene, and the three-dimensional structure of the novel mutant residues in the EDA trimer was determined. Transcriptional activity of NF-κB was tested by Dual luciferin assay.We identified a novel EDA1 mutation (c.1046C>T) and detected 3 other previously-reported mutations (c.146T>A; c.457C>T; c.467G>A). Our findings demonstrated that novel mutation c.1046C>T (p.A349 V) resulted in XLHED. The novel mutation could cause volume repulsion in the protein due to enlargement of the amino acid side chain. Dual luciferase assay revealed that transcriptional NF-κB activation induced by XLHED EDA1 protein was significantly reduced compared with wild-type EDA1.These results extend the spectrum of EDA1 mutations in XLHED patients and suggest a functional role of the novel mutation in XLHED.


Assuntos
Displasia Ectodérmica Anidrótica Tipo 1/etnologia , Displasia Ectodérmica Anidrótica Tipo 1/genética , Ectodisplasinas/genética , Predisposição Genética para Doença , Luciferases/genética , Mutação de Sentido Incorreto/genética , Pré-Escolar , China , Displasia Ectodérmica Anidrótica Tipo 1/fisiopatologia , Feminino , Humanos , Masculino , Linhagem , Reação em Cadeia da Polimerase/métodos
3.
Sensors (Basel) ; 20(7)2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32218361

RESUMO

The high-speed three-dimensional (3-D) shape measurement technique has become more and more popular recently, because of the strong demand for dynamic scene measurement. The single-shot nature of Fourier Transform Profilometry (FTP) makes it highly suitable for the 3-D shape measurement of dynamic scenes. However, due to the band-pass filter, FTP method has limitations for measuring objects with sharp edges, abrupt change or non-uniform reflectivity. In this paper, an improved Temporal Fourier Transform Profilometry (TFTP) algorithm combined with the 3-D phase unwrapping algorithm based on a reference plane is presented, and the measurement of one deformed fringe pattern producing a new 3-D shape of an isolated abrupt objects has been achieved. Improved TFTP method avoids band-pass filter in spatial domain and unwraps 3-D phase distribution along the temporal axis based on the reference plane. The high-frequency information of the measured object can be well preserved, and each pixel is processed separately. Experiments verify that our method can be well applied to a dynamic 3-D shape measurement with isolated, sharp edges or abrupt change. A high-speed and low-cost structured light pattern sequence projection has also been presented, it is capable of projection frequencies in the kHz level. Using the proposed 3-D shape measurement algorithm with the self-made mechanical projector, we demonstrated dynamic 3-D reconstruction with a rate of 297 Hz, which is mainly limited by the speed of the camera.

4.
Sci Signal ; 13(622)2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32156782

RESUMO

Mortalin [also known as heat shock protein family A (HSP70) member 9 (HSPA9) or glucose-regulated protein 75 (GRP75)] is a mitochondrial molecular chaperone that is often up-regulated and mislocalized in tumors with abnormal activation of the kinases MEK and ERK. Here, we found that mortalin depletion was selectively lethal to tumor and immortalized normal cells expressing the mutant kinase B-RafV600E or the chimeric protein ΔRaf-1:ER and that MEK-ERK-sensitive regulation of the peptide-binding domain in mortalin was critical to cell survival or death. Proteomics screening identified adenine nucleotide translocase 3 (ANT3) as a previously unknown mortalin substrate and cell survival/death effector. Mechanistically, increased MEK-ERK signaling activity and mortalin function converged opposingly on the regulation of mitochondrial permeability. Specifically, whereas MEK-ERK activity increased mitochondrial permeability by promoting the interaction between ANT3 and the peptidyl-prolyl isomerase cyclophilin D (CypD), mortalin decreased mitochondrial permeability by inhibiting this interaction. Hence, mortalin depletion increased mitochondrial permeability in MEK-ERK-deregulated cells to an extent that triggered cell death. HSP70 inhibitor derivatives that effectively inhibited mortalin suppressed the proliferation of B-RafV600E tumor cells in culture and in vivo, including their B-Raf inhibitor-resistant progenies. These findings suggest that targeting mortalin has potential as a selective therapeutic strategy in B-Raf-mutant or MEK-ERK-driven tumors.

5.
Chemosphere ; 251: 126361, 2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32143079

RESUMO

One of the challenges for the application of the ANAMMOX (anaerobic ammonium oxidation) process for nitrogen removal in the mainstream municipal wastewater treatment is the disturbances in the feeding influent, in terms of the organic material, ammonium concentration, flow rate and temperature. Past experimental and mathematical simulation researches were mainly carried out under stable feeding condition. It is not clear how the ANAMMOX responds to the feeding disturbances. In this study, a 1D (one-dimensional) biofilm model was used to examine the behavior of feeding disturbances in the single-stage granule PN-A (partial nitrification -ANAMMOX) process. The results indicated that the feeding disturbances could be mitigated by maintaining a small amount of ammonium in the bulk liquid. A cascade control strategy based on DO (dissolved oxygen) manipulation to derive the preset bulk ammonium set-point value (i.e., 2 mg N/L) was shown to be successful in achieving the maximum TN (total nitrogen) removal percentage of above 95% under dynamic feeding conditions. The long-term simulation showed that the small bulk ammonium accumulation could also suppress the NOB (nitrite-oxidizing bacteria) growth.

6.
Environ Pollut ; 262: 114332, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32182534

RESUMO

Dibutyl phthalate (DBP) is widely used as plasticizer and has been detected in the environment, posing a threat to animal health. However, the effects of DBP on agricultural microbiomes are not known. In this study, DBP levels in black soil were evaluated, and the impact of DBP contamination on the uptake and metabolism of sugars in microbes was assessed by glucose absorption tests, metaproteomics, metabolomics, enzyme activity assays and computational simulation analysis. The results indicated that DBP contamination accelerated glucose consumption and upregulated the expression of porins and periplasmic monosaccharide ATP-binding cassette (ABC) transporter solute-binding proteins (SBPs). DBP and its metabolic intermediates (carboxymuconate and butanol) may form a stable complex with sugar transporters and enhance the rigidity and stability of these proteins. Sugar metabolism resulting in the generation of ATP and reducing agent (NADPH), as well as the expression of some key enzymes (dehydrogenases) were also upregulated by DBP treatment. Moreover, a diverse bacterial community appears to utilize sugar, suggesting that there are widespread effects of DBP contamination on soil microbial ecosystems. The results of this study provide a theoretical basis for investigating the toxicological effects of DBP on microbes in black soil.

7.
Artigo em Inglês | MEDLINE | ID: mdl-32204590

RESUMO

Stability is becoming a main issue for perovskite light-emitting diodes (PeLEDs), as their external quantum efficiency (EQE) has been boosted to above 20%. An all-inorganic perovskite, cesium lead iodide (CsPbI3), has better stability than organic-inorganic hybrid perovskites but suffers from a transition to yellow δ-CsPbI3 phase at room temperature. Herein, we report stabilization of the α-CsPbI3 phase by in situ formation of perovskite nanocrystals (NCs). By incorporation of a proper ratio of bulky organoammonium halides, 4-fluoro-phenylmethylammonium iodide (4-F-PMAI), stable α-CsPbI3 films with nanometer-sized crystals can be obtained using a one-step spin-coating approach. The PeLEDs using α-CsPbI3 NC films as emitters show a pure red emission at 692 nm and a high EQE of 14.8%. The EQE is further boosted to 18.6% using CsPbI2.8Br0.2 as the emissive layer. Furthermore, the PeLEDs show a very decent half-lifetime of over 1200 min and a shelf stability of over 2 months, much longer than that of hybrid PeLEDs.

8.
Acta Otolaryngol ; 140(4): 258-261, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32031482

RESUMO

Background: Endolymphatic sac decompression surgery (ESDS) is commonly used for intractable Meniere's disease, but its effect remains controversial because of the low rate of vertigo control.Objectives: In the present study, we examined ESDS combined with posterior tympanotomy with local steroids as a new therapeutic strategy for intractable Meniere's disease.Materials and methods: This retrospective study enrolled 19 patients with Meniere's disease using ESDS combined with posterior tympanotomy with local steroids between 2015 and 2018. Postoperatively we recorded and evaluated changes in vertigo attack frequency and hearing level.Results: Vertigo episodes decreased from 3.6 ± 3.2 times preoperatively to 0.2 ± 0.5 times postoperatively, with 89.5% complete vertigo control rate. Mean PTA decreased from 40.5 ± 21.3 dB to 39.5 ± 17.5 dB postoperatively, with 21.1% improvement rate.Conclusions and significance: The present findings suggest that ESDS combined with posterior tympanotomy with local steroids could improve clinical results of hearing as well as vertigo control for intractable Meniere's disease.

9.
J Environ Manage ; 260: 110103, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-31941634

RESUMO

The nitrogen removal in the aerobic granular sludge sequential batch reactor (AGS-SBR) can be achieved by the simultaneous nitrification and denitrification (SND) mode, or by the separated nitrification and denitrification stages. The SND offers a simpler operation structure than the separated nitrification and denitrification. Based on the mathematical simulation, a novel control strategy was put forward to adjust the DO (dissolved oxygen) concentration to achieve the SND under dynamic fluctuated influent conditions in AGS-SBR. The control strategy aimed to achieve a small accumulation of NH4+ at the end of the aeration cycle (NH4+ setpoint value), as previous research has indicated that keeping the small NH4+ setpoint value would guarantee the optimal condition for total nitrogen (TN) removal. The SBR aeration cycle was divided into several equal control intervals. The DO was adjusted in every control interval to reach the NH4+ set point. The results revealed that the control strategy was able to maintain the NH4+ setpoint value and achieve satisfactory TN removal. The control interval should be less than 30 min to prevent deviation of NH4+ concentration from its setpoint value. A minimum aeration duration of 3 h was required to achieve satisfactory SND.


Assuntos
Desnitrificação , Nitrificação , Reatores Biológicos , Nitrogênio , Esgotos
10.
Int J Biol Sci ; 16(1): 181-193, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31892855

RESUMO

Tooth development is a complex process that is regulated precisely by several signalling pathways and transcription factors. GATA-binding protein 4 (GATA4) is a DNA binding transcription factor, and our previous study showed that GATA4 is a novel regulator of root development. However, it remains unclear whether GATA4 is necessary for odontoblast differentiation and dentin formation. Here, we evaluated the phenotypic changes of Wnt1-Cre;GATA4fl/fl mice. The mutant mice showed defective dentin and short root deformity. The odontoblasts lost polarity instead of exhibiting a shorter height and flattened morphology. Moreover, the expression of several molecules, such as DSPP, COL-1, DCN, and PCNA, were downregulated during mutant tooth development. In vivo, we injected lentivirus to overexpress GATA4 in mice root. The dentin formation and the expression of odonto/osteogenic markers (DSPP, COL-1, DCN) were enhanced in the GATA4 overexpression group. During the in vitro study, the ability of proliferation, migration and odonto/osteogenic differentiation was declined by GATA4 knockdown approach in human dental pulp stem cells (DPSCs). The expression of odonto/osteogenic markers (DSPP, BMP4, RUNX2, OSX, OPN, OCN) was reduced in the shGATA4 group, while overexpressing GATA4 in DPSCs promoted mineralization. Furthermore, an immunoprecipitation-mass spectrometry procedure was used to confirm the interaction between GATA4 and Fructose-1, 6-bisphosphatase 1 (FBP1). We used gain and lose-of-function to delineated the role of GATA4 in regulating FBP1 expression. Knocking down GATA4 in DPSCs resulted in decreased glucose consumption and lactate production. We used small hairpin RNA targeting FBP1 to reduce the expression of FBP1 in DPSCs, which significantly increased glucose consumption and lactate production. Together, the results suggested that GATA4 is important for root formation and odontoblast polarity, as it promotes the growth and differentiation of dental mesenchymal cells around the root and affects the glucose metabolism of DPSCs via the negative regulation of FBP1.

11.
Biomater Sci ; 8(2): 657-672, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31769455

RESUMO

Sericin has been exploited as a biomaterial due to its biocompatibility, biodegradability, and low-immunogenicity as an isolated polymer and support for cell adhesion. In the present study, human platelet-derived growth factor (PDGF-BB)-functionalized sericin hydrogels were generated using transgenic silkworms, where the as-spun silk incorporated engineered PDGF-BB (termed PDGFM) in the sericin layers of the cocoons. Sericin and PDGFM were simultaneously extracted from the silk fibroin cocoon fibers, and the soluble extract was then formed into a hydrogel via thermal exposure. The PDGFM sericin hydrogels exhibited increased ß-sheet content and a compressive modulus of 74.91 ± 2.9 kPa comparable to chemically crosslinked sericin hydrogels (1.68-55.53 kPa) and a porous microstructure, which contributed to cell adhesion and growth. A 13.1% of total extracted PDGFM from the initial silk fibers was incorporated and immobilized in the sericin hydrogels during material processing, and 1.33% of PDGFM was released over 30 days from the hydrogels in vitro. The remaining PDGFM achieved long-term storage/stability in the sericin hydrogels for more than 42 days at 37 °C. In addition, the PDGFM sericin hydrogels were not immunogenic, were biocompatible and bioactive in promoting the support of cell proliferation. When combined with BMP-9, the PDGFM sericin hydrogels provided synergy to support the osteoblastic differentiation of mesenchymal stem cells (hMSCs) in vitro and in vivo. This study demonstrates that genetically functionalized PDGFM sericin hydrogels can provide useful biomaterials to support cell and tissue outcomes, here with a focus on osteogenesis.

12.
Inorg Chem ; 59(1): 748-758, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31808678

RESUMO

The rational design by the introduction of fluorine into a compound has achieved success in the development of organic anticancer drugs. However, the fluorine effect in metal-based anticancer complexes has rarely been reported. In this contribution, we report the synthesis, characterization, chemical reactivity, and biological activity of a series of half-sandwich zwitterionic iridium(III) complexes containing different substituents in the η5-CpR ring. The molecular structures for complexes Ir1-Ir4 and Ir7 were determined by single-crystal X-ray crystallography techniques. Notably, the asymmetrically substituted fluoro complexes Ir4 and Ir6 in solution show two conformational isomers. These complexes have sufficient stability, exhibit fluorescence emission, and show potent catalytic activity in converting NADH to NAD+. The effect of the substituents in the η5-CpR ring for these zwitterionic complexes on their anticancer activity was systematically investigated. Surprisingly, the presence of fluorinated substituents gives rise to a significant increase in the anticancer activity. The lipophilicity and cellular uptake levels of these complexes appeared to be the primary factors for their cytotoxicity in this system. A microscopic mechanism study showed that the typical complex Ir4 entered A549 cancer cells through an energy-dependent pathway and was mainly located in lysosomes. Furthermore, an increase in ROS level, apoptosis induction, and cell-cycle perturbation together contribute to the anticancer potency of these zwitterionic complexes.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Flúor/química , Irídio/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/química , Cisplatino/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Irídio/química , Modelos Moleculares , Estrutura Molecular , Espécies Reativas de Oxigênio/análise
13.
Sci Total Environ ; 702: 135049, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31715398

RESUMO

Based on their differences in the kinetic values, the nitrifiers could be classified into the fast-growing "r-strategists" and the slow-growing "K-strategists" bacteria. However, the difference in the kinetic values originated not only from the intrinsic differences among the nitrifier species, but also from other factors, i.e. sludge floc morphology, and the environment in which the nitrifiers were cultivated. It is not clear how these factors interact and affect the measured kinetic parameters and the competition among the "r-strategists" and the "K-strategists" bacteria. In this study, the kinetic parameters of nitrifiers cultivated in the SBR (sequencing batch reactor) under different substrate concentrations were monitored, together with the identification of nitrifier species and sludge floc morphology characterization. The results showed that the r-AOB and r-NOB ("r-strategists" ammonium-oxidizing bacteria and nitrite-oxidizing bacteria, i.e., Nitrosomonas and Nitrospira) were the dominant nitrifiers in the SBR reactor. A mathematical model describing the competition between r/K AOB and NOB showed that r-AOB and r-NOB could be enriched in the SBR. The experimental investigation supported the model simulation results. The model simulation also revealed that the different r/K AOB and NOB species could be enriched in different DO concentrations and SRT conditions, which could be manipulated to promote the growth of r-AOB and NO2- accumulation for the autotrophic nitrogen removal using ANAMMX.


Assuntos
Modelos Teóricos , Nitrificação , Eliminação de Resíduos Líquidos , Amônia , Compostos de Amônio/metabolismo , Processos Autotróficos , Bactérias/metabolismo , Cinética , Nitritos , Nitrogênio , Oxirredução , Esgotos
14.
BMC Infect Dis ; 19(1): 1017, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31791265

RESUMO

BACKGROUND: Early diagnosis and treatment of neurosyphilis is of great significance for regression. There is no gold standard for the diagnosis of neurosyphilis. We did this study to explore the factors associated with the clinical diagnosis of neurosyphilis and assess their accuracy for the diagnosis of neurosyphilis. METHODS: We retrospectively reviewed 100 cases of syphilis patients who underwent lumbar puncture at a major dermatology hospital in Guangzhou, China between April 2013 and November 2016. Fifty patients who were clinically diagnosed with neurosyphilis were selected as case group. Control group consisted of 50 general syphilis patients who were matched with age and gender. The records of patients were reviewed to collect data of socio-demographic information, clinical symptom, and laboratory indicators. Multivariable logistic regression was used to explore diagnostic indictors, and ROC analysis was used to assess diagnostic accuracy. RESULTS: Neurological symptoms (odds ratio (OR) = 59.281, 95% CI:5.215-662.910, P = 0.001), cerebrospinal fluid (CSF) Treponema pallidum particle agglutination (TPPA) titer (OR = 1.004, 95% CI:1.002-1.006, P < 0.001), CSF protein (OR = 1.005, 95% CI:1.000-1.009, P = 0.041), and CSF white blood cell (WBC) (OR = 1.120, 95% CI:1.017-1.233, P = 0.021) were found to be statistically associated with neurosyphilis. In ROC analysis, CSF TPPA titer had a sensitivity of 90%, a specificity of 84%, and an area under curve (AUC) of 0.941. CONCLUSION: CSF TPPA can potentially be considered as an alternative test for diagnosis of neurosyphilis. Combining with neurological symptoms, CSF protein, CSF WBC, the diagnosis would have a higher sensitivity.


Assuntos
Soronegatividade para HIV , Neurossífilis/diagnóstico , Adulto , Estudos de Casos e Controles , China/epidemiologia , Testes Diagnósticos de Rotina/métodos , Testes Diagnósticos de Rotina/normas , Feminino , Infecções por HIV/líquido cefalorraquidiano , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neurossífilis/líquido cefalorraquidiano , Neurossífilis/complicações , Neurossífilis/epidemiologia , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Sensibilidade e Especificidade , Sífilis/líquido cefalorraquidiano , Sífilis/complicações , Sífilis/diagnóstico , Sífilis/epidemiologia , Treponema pallidum
15.
PeerJ ; 7: e8090, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772842

RESUMO

Background: The major landscape in the hilly-gully region of the Loess Plateau is greatly affected by vegetation rehabilitation on abandoned cropland. Although many studies have shown that the rehabilitation have greatly improved soil conditions and protected them from erosion, these effectiveness were not always in consensus possibly due to the land type of vegetation or to the rehabilitation time. To close this gap, we conducted a long term experiment as follows. Methods: In this study, we analysed four land types of vegetation rehabilitation (shrub land, woodland, naturally revegetated grassland, and orchard land) with different rehabilitation times and investigated the mechanical composition and erodibility of the soil. Areas of slope croplandand natural forest were selected as controls. Results: The results showed that soil depth, rehabilitation time and rehabilitation land type had strong impacts on soil mechanical composition, micro-aggregation and erodibility. Following rehabilitation, naturally revegetated grassland and shrub land had lower fractal dimensions of particle size distribution (fractal dimensions of PSD), fractal dimensions of micro-aggregation, and erodibility (K factor) than did cropland. Compared to the positive effects of rehabilitation mainly happened in the topsoil layer at other rehabilitation land type, that of woodland happened in the deeper soil layer. Besides, the indispensable rehabilitation time for the significant improvement of soil condition was shorter at naturally revegetated grassland than that at shrub land and woodland. Discussion: Although rehabilitation time was more influential than was rehabilitation land type or soil depth, the differences among the rehabilitation land types showed that naturally revegetated grassland with native plants is the most time-saving rehabilitation vegetation for the Loess Plateau in the conversion from slope cropland. The success of rehabilitation in this forestry practice was mainly contributed by the suited species of rehabilitation land type to the local climate and soil. Based on the differences of rehabilitation effectiveness resulting from land type, we should be cautious to choose land types for the rehabilitation of soil conditions in the Loess Plateau.

16.
Int J Neurosci ; : 1-7, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31665950

RESUMO

Background: Treatment of neonatal seizures includes etiotropic and anticonvulsant treatments. However, anticonvulsant use in neonates is off-label and requires ethical review.Objective: To investigate the efficacy and safety of levetiracetam for neonatal seizures and to establish a predictive model.Methods: We retrospectively analyzed 125 neonatal seizure cases (phenobarbital 66 cases, levetiracetam 59 cases). The efficacy, safety and tolerability of levetiracetam were evaluated by cox regression survival analysis and a regression tree prediction model for the 16-week time point.Results: There was no significant difference between phenobarbital and levetiracetam treatment group in short-term efficacy (p > 0.05). But the cumulative survival function suggested that levetiracetam treatment group was better than phenobarbital (p = 0.026) in long-term efficacy evaluation. Neurodevelopmental assessments at 16 weeks showed that levetiracetam had better effect on the neurodevelopmental level (Gesell scores in response) than phenobarbital (p = 0.011). The main adverse events with levetiracetam were irritability and anorexia. According to the regression tree prediction model, the top three factors influencing the therapeutic effect were pre-treatment seizure frequency, age of onset and etiological classification.Conclusion: Levetiracetam shows good efficacy, safety and tolerability for the long-term neonatal seizure treatment.

17.
Oncol Lett ; 18(5): 5499-5507, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31612058

RESUMO

The biological characteristics and clinical outcomes of gastric cancer (GC) are largely dependent on the histopathological type and degree of differentiation. The identification of the molecular mechanisms underlying the histological grade of GC may provide information about tumorigenesis and tumor progression, and may subsequently be used to develop novel therapeutic agents. The present study obtained the RNA sequencing data and clinical characteristics of patients with GC from The Cancer Genome Atlas. A total of 1,400 differentially expressed genes (DEGs) were screened between two histological grades. Weighted gene co-expression network analysis (WGCNA) was subsequently used to identify nine co-expressed gene modules, and the black module was found to be the most significant for prognosis prediction of tumor. Additionally, the black module was associated with overall survival time, death event, N stage and tumor-node-metastasis (TNM) stage. Functional enrichment analysis revealed that the biological processes of the genes in the black module included 'Wnt signaling pathway' and 'structural molecule activity'. Additionally, 10 network hub genes that were significantly associated with the progression of GC were identified from the black module, and the significance of each hub gene was determined across different TNM stages. Kaplan-Meier survival curves revealed that keratin 40 and glycine decarboxylase were significantly associated with patient prognosis (P<0.05), suggesting that these genes may serve as potential progression and prognosis biomarkers in GC. The present study identified molecular markers that correlated with histological grade in GC. Therefore, the results obtained in the present study may have important clinical implications on treatment selection, risk stratification and prognosis prediction in patients with GC.

18.
Onco Targets Ther ; 12: 7337-7345, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31564916

RESUMO

Purpose: To investigate the role of zinc finger E­box­binding homeobox 2 antisense RNA 1 (ZEB2-AS1) in regulating laryngeal squamous cell carcinoma (LSCC) progression. Patients and methods: In this retrospective study, we included all patients who underwent a surgical operation at The First Hospital of Qiqihaer City for LSCC. Then, we compared the expression of ZEB2-AS1 in LSCC tissues and paired healthy tissues. Besides, we also performed a series of functional assays, CCK8 assays, colony formation assays, and transwell assays to examine the functions of LSCC cells after knockdown of ZEB2-AS1. Through bioinformatics analysis, we predicted that ZEB2-AS1 binds to miR-6840-3p and targets PLXNB1. Results: We indicated that the expression of ZEB2-AS1 was higher in LSCC tissues compared to the paired adjacent tissues, and ZEB2-AS1 was also highly expressed in LSCC cell lines. Furthermore, we discovered that ZEB2-AS1 promoted cell proliferation, migration and invasion and was associated with poor prognosis. To find the mechanism, we performed bioinformatics analysis. We identified that ZEB2-AS1 binds to miR-6840-3p and targets PLXNB1. Additionally, miR-6840-3p overexpression or knockdown of PLXNB1 decreased the abilities of cell migration and invasion. Conclusion: These findings demonstrated that overexpression of ZEB2-AS1 promotes LSCC progression. Overexpression of miR-6840-3p or downregulation of PLXNB1 can abrogate ZEB2-AS1-mediated LSCC malignant development.

19.
Circ Res ; 125(12): 1087-1102, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31625810

RESUMO

RATIONALE: A hallmark of chronic inflammatory disorders is persistence of proinflammatory macrophages in diseased tissues. In atherosclerosis, this is associated with dyslipidemia and oxidative stress, but mechanisms linking these phenomena to macrophage activation remain incompletely understood. OBJECTIVE: To investigate mechanisms linking dyslipidemia, oxidative stress, and macrophage activation through modulation of immunometabolism and to explore therapeutic potential targeting specific metabolic pathways. METHODS AND RESULTS: Using a combination of biochemical, immunologic, and ex vivo cell metabolic studies, we report that CD36 mediates a mitochondrial metabolic switch from oxidative phosphorylation to superoxide production in response to its ligand, oxidized LDL (low-density lipoprotein). Mitochondrial-specific inhibition of superoxide inhibited oxidized LDL-induced NF-κB (nuclear factor-κB) activation and inflammatory cytokine generation. RNA sequencing, flow cytometry, 3H-labeled palmitic acid uptake, lipidomic analysis, confocal and electron microscopy imaging, and functional energetics revealed that oxidized LDL upregulated effectors of long-chain fatty acid uptake and mitochondrial import, while downregulating fatty acid oxidation and inhibiting ATP5A (ATP synthase F1 subunit alpha)-an electron transport chain component. The combined effect is long-chain fatty acid accumulation, alteration of mitochondrial structure and function, repurposing of the electron transport chain to superoxide production, and NF-κB activation. Apoe null mice challenged with high-fat diet showed similar metabolic changes in circulating Ly6C+ monocytes and peritoneal macrophages, along with increased CD36 expression. Moreover, mitochondrial reactive oxygen species were positively correlated with CD36 expression in aortic lesional macrophages. CONCLUSIONS: These findings reveal that oxidized LDL/CD36 signaling in macrophages links dysregulated fatty acid metabolism to oxidative stress from the mitochondria, which drives chronic inflammation. Thus, targeting to CD36 and its downstream effectors may serve as potential new strategies against chronic inflammatory diseases such as atherosclerosis.

20.
Biomater Sci ; 7(11): 4536-4546, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31536077

RESUMO

Functional silk mats with improved cell proliferation activity are promising medical materials to accelerate damaged wound healing and tissue repair. In this study, novel functional silk mats were fabricated from human fibroblast growth factor (FGF)-containing cocoons generated by expressing human acid FGF1 and basic FGF2 in silkworms. First, functional silk mats containing FGF1 and FGF2 proteins alone or in combination were fabricated by physically cutting genetically engineered cocoons. Compared to those of normal silk mats, the physical properties of these functional silk mats such as silk fibre diameter, internal secondary structure, and mechanical properties were significantly changed. The expressed FGF1 and FGF2 proteins in these silk mats were efficiently and gradually released over 15 days. Moreover, these silk mats significantly promoted NIH/3T3 cell proliferation and growth by activating the extracellular signal-regulated kinase (ERK) pathway, and the silk mat containing FGF1 and FGF2 proteins showed higher cell proliferation. Importantly, this silk mat caused no obvious cytotoxicity or cell inflammation. These results suggest that these functional silk mats have potential medical applications.

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