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1.
Proc Natl Acad Sci U S A ; 120(18): e2207537120, 2023 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-37098064

RESUMO

Policymakers must make management decisions despite incomplete knowledge and conflicting model projections. Little guidance exists for the rapid, representative, and unbiased collection of policy-relevant scientific input from independent modeling teams. Integrating approaches from decision analysis, expert judgment, and model aggregation, we convened multiple modeling teams to evaluate COVID-19 reopening strategies for a mid-sized United States county early in the pandemic. Projections from seventeen distinct models were inconsistent in magnitude but highly consistent in ranking interventions. The 6-mo-ahead aggregate projections were well in line with observed outbreaks in mid-sized US counties. The aggregate results showed that up to half the population could be infected with full workplace reopening, while workplace restrictions reduced median cumulative infections by 82%. Rankings of interventions were consistent across public health objectives, but there was a strong trade-off between public health outcomes and duration of workplace closures, and no win-win intermediate reopening strategies were identified. Between-model variation was high; the aggregate results thus provide valuable risk quantification for decision making. This approach can be applied to the evaluation of management interventions in any setting where models are used to inform decision making. This case study demonstrated the utility of our approach and was one of several multimodel efforts that laid the groundwork for the COVID-19 Scenario Modeling Hub, which has provided multiple rounds of real-time scenario projections for situational awareness and decision making to the Centers for Disease Control and Prevention since December 2020.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Incerteza , Surtos de Doenças/prevenção & controle , Saúde Pública , Pandemias/prevenção & controle
2.
J Am Chem Soc ; 146(25): 17189-17200, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38864358

RESUMO

Spatial immobilization of fragile enzymes using a nanocarrier is an efficient means to design heterogeneous biocatalysts, presenting superior stability and recyclability to pristine enzymes. An immobilized enzyme, however, usually compromises its catalytic activity because of inevasible mass transfer issues and the unfavorable conformation changes in a confined environment. Here, we describe a synergetic metal-organic framework pore-engineering strategy to trap lipase (an important hydrolase), which confers lipase-boosted stability and activity simultaneously. The hierarchically porous NU-1003, featuring interconnected mesopore and micropore channels, is precisely modified by chain-adjustable fatty acids on its mesopore channel, into which lipase is trapped. The interconnected pore structure ensures efficient communication between trapped lipase and exterior media, while the fatty acid-mediated hydrophobic pore can activate the opening conformation of lipase by interfacial interaction. Such dual pore compartmentalization and hydrophobization activation effects render the catalytic center of trapped lipase highly accessible, resulting in 1.57-fold and 2.46-fold activities as native lipase on ester hydrolysis and enantioselective catalysis. In addition, the feasibility of these heterogeneous biocatalysts for kinetic resolution of enantiomer is also validated, showing much higher efficiency than native lipase.


Assuntos
Estabilidade Enzimática , Enzimas Imobilizadas , Interações Hidrofóbicas e Hidrofílicas , Lipase , Lipase/química , Lipase/metabolismo , Porosidade , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Estruturas Metalorgânicas/química , Hidrólise , Biocatálise
3.
Toxicol Appl Pharmacol ; 487: 116957, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38735590

RESUMO

Heart failure is associated with histone deacetylase (HDAC) regulation of gene expression, the inhibition of which is thought to be beneficial for heart failure therapy. Here, we explored the cardioprotective effects and underlying mechanism of a novel selenium-containing HDAC inhibitor, Se-SAHA, on isoproterenol (ISO)-induced heart failure. We found that pretreatment with Se-SAHA attenuated ISO-induced cardiac hypertrophy and fibrosis in neonatal rat ventricular myocytes (NRVMs). Se-SAHA significantly attenuated the generation of ISO-induced reactive oxygen species (ROS) and restored the expression levels of superoxide dismutase 2 (SOD2) and heme oxygenase-1 (HO-1) in vitro. Furthermore, Se-SAHA pretreatment prevented the accumulation of autophagosomes. Se-SAHA reversed the high expression of HDAC1 and HDAC6 induced by ISO incubation. However, after the addition of the HDAC agonist, the effect of Se-SAHA on blocking autophagy was inhibited. Using ISO-induced mouse models, cardiac ventricular contractile dysfunction, hypertrophy, and fibrosis was reduced treated by Se-SAHA. In addition, Se-SAHA inhibited HDAC1 and HDAC6 overexpression in ISO-treated mice. Se-SAHA treatment significantly increased the activity of SOD2 and improved the ability to eliminate free radicals. Se-SAHA hindered the excessive levels of the microtubule-associated protein 1 light chain 3 (LC3)-II and Beclin-1 in heart failure mice. Collectively, our results indicate that Se-SAHA exerts cardio-protection against ISO-induced heart failure via antioxidative stress and autophagy inhibition.


Assuntos
Autofagia , Insuficiência Cardíaca , Inibidores de Histona Desacetilases , Isoproterenol , Camundongos Endogâmicos C57BL , Miócitos Cardíacos , Estresse Oxidativo , Ratos Sprague-Dawley , Animais , Isoproterenol/toxicidade , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/prevenção & controle , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/tratamento farmacológico , Autofagia/efeitos dos fármacos , Inibidores de Histona Desacetilases/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Miócitos Cardíacos/metabolismo , Masculino , Ratos , Camundongos , Superóxido Dismutase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/farmacologia , Fibrose , Células Cultivadas , Cardiomegalia/induzido quimicamente , Cardiomegalia/prevenção & controle , Cardiomegalia/patologia
4.
Appl Microbiol Biotechnol ; 108(1): 336, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38761182

RESUMO

To investigate the cell-cell interactions of intergeneric bacterial species, the study detected the survival of Enterococcus faecalis (Ef) under monospecies or coaggregation state with Fusobacterium nucleatum subsp. polymorphum (Fnp) in environmental stress. Ef and Fnp infected the human macrophages with different forms (Ef and Fnp monospecies, Ef-Fnp coaggregates, Ef + Fnp cocultures) for exploring the immunoregulatory effects and the relevant molecular mechanisms. Meanwhile, the transcriptomic profiles of coaggregated Ef and Fnp were analyzed. Ef was shown to coaggregate with Fnp strongly in CAB within 90 min by forming multiplexes clumps. Coaggregation with Fnp reinforced Ef resistance against unfavorable conditions including alkaline, hypertonic, nutrient-starvation, and antibiotic challenges. Compared with monospecies and coculture species, the coaggregation of Ef and Fnp significantly facilitates both species to invade dTHP-1 cells and aid Ef to survive within the cells. Compared with coculture species, dual-species interaction of Ef and Fnp significantly decreased the levels of pro-inflammatory cytokines IL-6, TNF-α, and chemokines MCP-1 secreted by dTHP-1 cells and lessened the phosphorylation of p38, JNK, and p65 signaling pathways. The transcriptome sequencing results showed that 111 genes were differentially expressed or Ef-Fnp coaggregated species compared to Ef monospecies; 651 genes were differentially expressed for Fnp when coaggregation with Ef. The analysis of KEGG pathway showed that Ef differentially expressed genes (DEGs) were enriched in quorum sensing and arginine biosynthesis pathway; Fnp DEGs were differentially concentrated in lipopolysaccharide (LPS) biosynthesis, biofilm formation, and lysine degradation pathway compared to monospecies. KEY POINTS: • Coaggregated with Fnp aids Ef's survival in environmental stress, especially in root canals after endodontic treatment. • The coaggregation of Ef and Fnp may weaken the pro-inflammatory response and facilitate Ef to evade killed by macrophages. • The coaggregation between Ef and Fnp altered interspecies transcriptional profiles.


Assuntos
Enterococcus faecalis , Fusobacterium nucleatum , Macrófagos , Estresse Fisiológico , Fusobacterium nucleatum/fisiologia , Fusobacterium nucleatum/genética , Enterococcus faecalis/genética , Enterococcus faecalis/fisiologia , Humanos , Macrófagos/microbiologia , Macrófagos/imunologia , Citocinas/metabolismo , Citocinas/genética , Aderência Bacteriana , Técnicas de Cocultura , Perfilação da Expressão Gênica , Transcriptoma , Linhagem Celular , Interleucina-6/genética , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/genética , Inflamação
5.
Clin Exp Pharmacol Physiol ; 51(8): e13904, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38923060

RESUMO

Myocardial ischemia-reperfusion injury (MIRI) is a common clinic scenario that occurs in the context of reperfusion therapy for acute myocardial infarction. It has been shown that cocaine and amphetamine-regulated transcript (CART) can ameliorate cerebral ischemia-reperfusion (I/R) injury, but the effect of CART on MIRI has not been studied yet. Here, we revealed that CART protected the heart during I/R process by inhibiting apoptosis and excessive autophagy, indicating that CART would be a potential drug candidate for the treatment of MIRI. Further analysis showed that CART upregulated the activation of phospho-AKT, leading to downregulation of lactate dehydrogenase (LDH) release, apoptosis, oxidative stress and excessive autophagy after I/R, which was inhibited by PI3K inhibitor, LY294002. Collectively, CART attenuated MIRI through inhibition of cardiomyocytes apoptosis and excessive autophagy, and the protective effect was dependent on PI3K/AKT signalling pathway.


Assuntos
Apoptose , Autofagia , Traumatismo por Reperfusão Miocárdica , Proteínas do Tecido Nervoso , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Apoptose/efeitos dos fármacos , Proteínas do Tecido Nervoso/metabolismo , Masculino , Autofagia/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Ratos , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley
6.
Angew Chem Int Ed Engl ; 63(8): e202319876, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38183367

RESUMO

Utilizing covalent organic framework (COF) as a hypotoxic and porous scaffold to encapsulate enzyme (enzyme@COF) has inspired numerous interests at the intersection of chemistry, materials, and biological science. In this study, we report a convenient scheme for one-step, aqueous-phase synthesis of highly crystalline enzyme@COF biocatalysts. This facile approach relies on an ionic liquid (2 µL of imidazolium ionic liquid)-mediated dynamic polymerization mechanism, which can facilitate the in situ assembly of enzyme@COF under mild conditions. This green strategy is adaptive to synthesize different biocatalysts with highly crystalline COF "exoskeleton", as well evidenced by the low-dose cryo-EM and other characterizations. Attributing to the rigorous sieving effect of crystalline COF pore, the hosted lipase shows non-native selectivity for aliphatic acid hydrolysis. In addition, the highly crystalline linkage affords COF "exoskeleton" with higher photocatalytic activity for in situ production of H2 O2 , enabling us to construct a self-cascading photo-enzyme coupled reactor for pollutants degradation, with a 2.63-fold degradation rate as the poorly crystalline photo-enzyme reactor. This work showcases the great potentials of employing green and trace amounts of ionic liquid for one-step synthesis of crystalline enzyme@COF biocatalysts, and emphasizes the feasibility of diversifying enzyme functions by integrating the reticular chemistry of a COF.


Assuntos
Disciplinas das Ciências Biológicas , Líquidos Iônicos , Estruturas Metalorgânicas , Polimerização , Lipase
7.
Arch Insect Biochem Physiol ; 107(1): e21781, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33687102

RESUMO

The Chinese white wax scale insect, Ericerus pela, is an important resource insect in China. The rapid response of E. pela to decreasing temperatures plays key roles in the population distribution. In this study, we analyzed the gene expression of E. pela treated with low temperature using transcriptome analyses and weighted gene coexpression network analysis (WGCNA). The results showed that the cold resistance of E. pela involved changes in the expression of many genes. The genes were mainly involved in alcohol formation activity, lipid metabolism, membrane and structure, and oxidoreductase activity. According to the WGCNA results, some pathways related to cold resistance were found in the genes in the modules, such as cytoskeleton proteins, cytoskeleton protein pathway, biosynthesis of unsaturated fatty acids, glycerophospholipid metabolism, ether lipid metabolism, and thermogenesis. Some of the hub genes were nonspecific lipid-transfer proteins, DnaJ homolog subfamily C member 13, paramyosin, tropomodulin, and tubulin beta chain. In particular, the hub genes of the tan module included the heat shock protein (hsp) 10, hsp 60, hsp 70, and hsp 90 genes. Thirty-five antifreeze protein (afp) genes were identified according to the annotation results. Three afp genes were further identified among the hub genes. Six of these genes were selected for heterogeneous protein expression. One of them was expressed successfully. The thermal hysteresis activity (THA) analyses showed that the THA was 1.73°C. These results showed that the cytoskeleton, lipid metabolism, thermogenesis, HSPs and AFPs may play important roles in the cold resistance of E. pela.


Assuntos
Proteínas Anticongelantes , Temperatura Baixa/efeitos adversos , Expressão Gênica , Hemípteros , Adaptação Biológica/genética , Animais , Proteínas Anticongelantes/genética , Proteínas Anticongelantes/metabolismo , Clonagem Molecular , Perfilação da Expressão Gênica , Genes de Insetos , Hemípteros/genética , Hemípteros/metabolismo , Proteínas de Insetos/metabolismo
8.
Sensors (Basel) ; 21(17)2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34502693

RESUMO

Capability assessment plays a crucial role in the demonstration and construction of equipment. To improve the accuracy and stability of capability assessment, we study the neural network learning algorithms in the field of capability assessment and index sensitivity. Aiming at the problem of overfitting and parameter optimization in neural network learning, the paper proposes an improved machine learning algorithm-the Ensemble Learning Based on Policy Optimization Neural Networks (ELPONN) with the policy optimization and ensemble learning. This algorithm presents an optimized neural network learning algorithm through different strategies evolution, and builds an ensemble learning model of multi-intelligent algorithms to assess the capability and analyze the sensitivity of the indexes. Through the assessment of capabilities, the algorithm effectively avoids parameter optimization from entering the minimum point in performance to improve the accuracy of equipment capability assessment, which is significantly better than previous neural network assessment methods. The experimental results show that the mean relative error is 4.10%, which is better than BP, GABP, and early stopping. The ELPONN algorithm has better accuracy and stability performance, and meets the requirements of capability assessment.


Assuntos
Algoritmos , Redes Neurais de Computação , Aprendizado de Máquina , Políticas
9.
BMC Oral Health ; 21(1): 294, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34107959

RESUMO

BACKGROUND: XP-Endo Finisher (XPF) and passive ultrasonic irrigation (PUI) are commonly used in intracanal medicament removal. The effectiveness of these two techniques needs to be compared, and evidence-based research should be conducted. METHODS: A comprehensive literature search was conducted in PubMed, Web of Science, Embase, Cochrane Library, and Google Scholar up to December 20th, 2020. The outcomes of the included trials were pooled into the Cochrane Collaboration's Review Manager 5.3 software. Cochrane's risk-of-bias tool 2.0 was applied to assess the risk of bias. RESULTS: Nine articles were included in this systematic review and processed for data extraction, and eight studies were identified for meta-analysis. In general, the use of PUI showed better medicament removal effectiveness than XPF (odds ratio [OR]: 3.09; 95% confidence interval [CI], 1.96-4.86; P < 0.001). PUI was also significantly more efficient than XPF in the apical third (OR: 3.42; 95% CI, 1.32-8.84; P = 0.01). For trials using sodium hypochlorite (NaOCl) alone, PUI was also significantly more effective than XPF on intracanal medicaments removal (OR: 5.23; 95% CI, 2.79-9.82; P < 0.001). However, there was no significant difference between PUI and XPF when NaOCl and ethylenediaminetetraacetic acid (EDTA) were used in combination (OR: 1.51; 95% CI, 0.74-3.09; P = 0.26). In addition, for studies whose intracanal medicament periods were two weeks, the effectiveness of PUI was statistically better than the XPF (OR: 7.73; 95% CI, 3.71-16.07; P < 0.001). Nevertheless, for trials whose intracanal medicament time was one week or over two weeks, no differences between the XPF and PUI were found (OR: 1.54; 95% CI, 0.74-3.22; P = 0.25) (OR: 1.42; 95% CI, 0.44-4.61; P = 0.56). CONCLUSIONS: The meta-analysis is the first study to quantitatively compare the effectiveness of XPF and PUI techniques on intracanal medicaments removal. With rigorous eligibility criteria, the study only included high-quality randomised controlled trials. The study indicated that PUI might be superior over XPF techniques for removing intracanal medicaments from artificial standardized grooves and cavities in the root canal system. The anatomical areas, irrigation protocol, and intracanal medicaments time may influence the cleaning efficacy.


Assuntos
Cavidade Pulpar , Ultrassom , Humanos , Irrigantes do Canal Radicular , Preparo de Canal Radicular , Hipoclorito de Sódio , Irrigação Terapêutica
10.
J Am Chem Soc ; 142(9): 4438-4444, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-31976663

RESUMO

CrGeTe3 has recently emerged as a new class of two-dimensional (2D) materials due to its intrinsic long-range ferromagnetic order. However, almost all the reported synthesis methods for CrGeTe3 nanosheets are based on the conventional mechanical exfoliation from single-crystalline CrGeTe3, which is prepared by the complicated self-flux technique. Here we report a solution-processed synthesis of CrGeTe3 nanosheets from a non-van der Waals (vdW) Cr2Te3 template. This structure evolution from non-vdW to vdW is originated from the substitution of Ge atoms on the Cr sites surrounded by fewer Te atoms in the Cr2Te3 lattice due to their smaller steric hindrance and lower energy barrier. These CrGeTe3 nanosheets present regular hexagonal structures with a diameter larger than 1 µm and excellent stability. They exhibit soft magnetic behavior with a Curie temperature lower than 67.5 K. This non-vdW to vdW synthesis strategy promotes the development of CrGeTe3 in ferromagnetism while providing an effective route to synthesize other 2D materials.

11.
Appl Microbiol Biotechnol ; 104(22): 9733-9748, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33064184

RESUMO

Bacterial membrane vesicles (MVs) are used as a tool for intercellular communication and seem essential for bacterial survival. However, few data are available on MVs generated by Streptococcus mutans, which is the main aetiological agent of dental caries. The present study presents an integrated proteomics and metabolomics analysis of MVs isolated from S. mutans at initial pH values of 7.5 and 5.5 and explores their function. The results showed that S. mutans releases more MVs with smaller diameters under acidic conditions than under neutral conditions. Proteomic analysis showed 344 common vesicular proteins, including various virulence factors. The expressions of 140 individual proteins and 37 metabolites were altered as a result of culturing S. mutans at different pH values. Co-analyses of proteomic and metabolomics data indicated that ABC transporters underwent significant changes under acid pressure. We concluded that S. mutans produced MVs at different pH values to carry proteins associated with cariogenesis. Moreover, the alterations of S. mutans MVs under acid pressure were associated with ABC transporters. These results increase our knowledge of S. mutans MVs and imply that S. mutans MVs may play a functional role in carious infection. KEY POINTS: • S. mutans MVs contained virulence factor-related proteins, even at low pH values. • Integrated proteomics and metabolomics analysis showed that S. mutans MVs alterations under acidic conditions were associated with ABC transporters.


Assuntos
Cárie Dentária , Proteômica , Streptococcus mutans , Proteínas de Bactérias , Biofilmes , Humanos , Concentração de Íons de Hidrogênio
12.
Sensors (Basel) ; 20(16)2020 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-32823783

RESUMO

Multiple unmanned aerial vehicle (UAV) collaboration has great potential. To increase the intelligence and environmental adaptability of multi-UAV control, we study the application of deep reinforcement learning algorithms in the field of multi-UAV cooperative control. Aiming at the problem of a non-stationary environment caused by the change of learning agent strategy in reinforcement learning in a multi-agent environment, the paper presents an improved multiagent reinforcement learning algorithm-the multiagent joint proximal policy optimization (MAJPPO) algorithm with the centralized learning and decentralized execution. This algorithm uses the moving window averaging method to make each agent obtain a centralized state value function, so that the agents can achieve better collaboration. The improved algorithm enhances the collaboration and increases the sum of reward values obtained by the multiagent system. To evaluate the performance of the algorithm, we use the MAJPPO algorithm to complete the task of multi-UAV formation and the crossing of multiple-obstacle environments. To simplify the control complexity of the UAV, we use the six-degree of freedom and 12-state equations of the dynamics model of the UAV with an attitude control loop. The experimental results show that the MAJPPO algorithm has better performance and better environmental adaptability.

13.
Proc Natl Acad Sci U S A ; 112(24): 7569-74, 2015 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-26034276

RESUMO

One major challenge to studying human microbiome and its associated diseases is the lack of effective tools to achieve targeted modulation of individual species and study its ecological function within multispecies communities. Here, we show that C16G2, a specifically targeted antimicrobial peptide, was able to selectively kill cariogenic pathogen Streptococcus mutans with high efficacy within a human saliva-derived in vitro oral multispecies community. Importantly, a significant shift in the overall microbial structure of the C16G2-treated community was revealed after a 24-h recovery period: several bacterial species with metabolic dependency or physical interactions with S. mutans suffered drastic reduction in their abundance, whereas S. mutans' natural competitors, including health-associated Streptococci, became dominant. This study demonstrates the use of targeted antimicrobials to modulate the microbiome structure allowing insights into the key community role of specific bacterial species and also indicates the therapeutic potential of C16G2 to achieve a healthy oral microbiome.


Assuntos
Peptídeos Catiônicos Antimicrobianos/farmacologia , Microbiota/efeitos dos fármacos , Streptococcus mutans/efeitos dos fármacos , Streptococcus mutans/fisiologia , Adulto , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Cárie Dentária/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Boca/microbiologia , Saliva/microbiologia , Streptococcus mutans/patogenicidade
14.
Sensors (Basel) ; 18(12)2018 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-30558334

RESUMO

Electromechanical actuator (EMA) systems are widely employed in missiles. Due to the influence of the nonlinearities, there is a flat-top of about 64 ms when tracking the small-angle sinusoidal signals, which significantly reduces the performance of the EMA system and even causes the missile trajectory to oscillate. Aiming to solve these problems, this paper presents a hybrid control for flat-top situations. In contrast to the traditional PID or sliding mode controllers that missiles usually use, this paper utilizes improved sliding mode control based on a novel reaching law to eliminate the flat-top during the steering of the input signal, and utilizes the PID control to replace discontinuous control and improve the performance of EMA system. In addition, boundary layer and switching function are employed to solve the high-frequency chattering problem caused by traditional sliding mode control. Experiments indicate that the hybrid control can evidently reduce the flat-top time from 64 ms to 12 ms and eliminate the trajectory limit cycle oscillation. Compared with PID controllers, the proposed controller provides better performance-less chattering, less flat-top, higher precision, and no oscillation.

15.
Biofouling ; 33(6): 481-493, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28587519

RESUMO

Efflux pumps are a mechanism associated with biofilm formation and resistance. There is limited information regarding efflux pumps in Streptococcus mutans, a major pathogen in dental caries. The aim of this study was to investigate potential roles of a putative efflux pump (LmrB) in S. mutans biofilm formation and susceptibility. Upon lmrB inactivation and antimicrobial exposure, the biofilm structure and expression of other efflux pumps were examined using confocal laser scanning microscopy (CLSM) and qRT-PCR. lmrB inactivation resulted in biofilm structural changes, increased EPS formation and EPS-related gene transcription (p < 0.05), but no improvement in susceptibility was observed. The expression of most efflux pump genes increased upon lmrB inactivation when exposed to antimicrobials (p < 0.05), suggesting a feedback mechanism that activated the transcription of other efflux pumps to compensate for the loss of lmrB. These observations imply that sole inactivation of lmrB is not an effective solution to control biofilms.


Assuntos
Anti-Infecciosos/farmacologia , Biofilmes/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Expressão Gênica/efeitos dos fármacos , Genes Bacterianos , Polissacarídeos Bacterianos/biossíntese , Streptococcus mutans/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Cárie Dentária/microbiologia , Bombas de Íon/genética , Microscopia Confocal , Mutação , Streptococcus mutans/genética , Streptococcus mutans/fisiologia
16.
Int Endod J ; 55(1): 139-140, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34882811
17.
Tumour Biol ; 37(9): 12525-12533, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27344157

RESUMO

Recent studies have demonstrated the prognostic value of the C-reactive protein/albumin (CRP/Alb) ratio in cancer. However, the role of the CRP/Alb ratio in advanced pancreatic cancer (PC) has not been examined. A retrospective study of 233 patients with advanced PC was conducted. We investigated the relationship between the CRP/Alb ratio, clinicopathological variables, and overall survival (OS). The optimal cutoff point of the CRP/Alb ratio was 0.54. A higher CRP/Alb ratio was significantly associated with an elevated neutrophil-lymphocyte ratio (NLR) (P < 0.001) and higher modified Glasgow prognostic score (mGPS) (P < 0.001). Using univariate analyses, we found that the age (P = 0.009), disease stage (P < 0.001), NLR (P < 0.001), mGPS (P < 0.001), and CRP/Alb ratio (P < 0.001) were significant predictors of OS. Patients with a higher CRP/Alb ratio had a worse OS than patients with a lower CRP/Alb ratio (hazard ratio (HR) 3.619; 95 % CI 2.681-4.886; P < 0.001). However, the CRP/Alb ratio was identified as the only inflammation-based parameter with an independent prognostic ability in the multivariate analyses (P < 0.001). The pretreatment CRP/Alb ratio is a superior prognostic and therapeutic predictor of OS in advanced PC.


Assuntos
Proteína C-Reativa/análise , Neoplasias Pancreáticas/mortalidade , Albumina Sérica/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/patologia , Prognóstico
18.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 41(5): 471-6, 2016 May.
Artigo em Zh | MEDLINE | ID: mdl-27269920

RESUMO

OBJECTIVE: To investigate the correlation between cyclin-dependent kinase inhibitor p27kip1 and trastuzumab-resistance in gastric cancer.
 METHODS: We selected HER2-overexpressed human gastric cancer cell line NCI-N87 to establish trastuzumab-resistant NCI-N87/TR cell line by stepwise exposure to different doses of trastuzumab. The 50% inhibitory concentration (IC(50)) of trastuzumab and resistance index (RI) were calculated or analyzed by MTT assay. The expression levels of cdk2 and p27kip1 were detected by Western blot. After the treatment with cdk2 inhibitor (Purvalanol A), the expression levels of relevant proteins in NCI-N87/TR cells were detected by Western blot, and the sensitivity to trastuzumab was analyzed by MTT assay. 
 RESULTS: Compared with NCI-N87 cells, the expression of cdk2 was significantly increased in NCI-N87/TR cells (P<0.001), while the expression of p27kip1 showed a significant decrease (P<0.001). Restoration of the p27kip1 protein expression by cdk2 inhibitor (Purvalanol A) increased the sensitivity of NCI-N87/TR to trastuzumab.
 CONCLUSION: Down-regulation of p27kip1 might be a mechanism for triggering trastuzumab resistance to gastric cancer cell line NCI-N87.


Assuntos
Antineoplásicos/farmacologia , Quinase 2 Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Resistencia a Medicamentos Antineoplásicos , Neoplasias Gástricas/metabolismo , Trastuzumab/farmacologia , Linhagem Celular Tumoral , Quinase 2 Dependente de Ciclina/antagonistas & inibidores , Quinase 2 Dependente de Ciclina/genética , Inibidor de Quinase Dependente de Ciclina p27/genética , Humanos , Purinas/farmacologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
19.
Wei Sheng Wu Xue Bao ; 55(7): 826-33, 2015 Jul 04.
Artigo em Zh | MEDLINE | ID: mdl-26710601

RESUMO

OBJECTIVE: To screen efficient molecular markers suitable for genetic diversity analysis of Cordyceps militaris from mitochondrial DNA. METHODS: We amplified 12 mitochondrial DNA fragments and 3 nuclear DNA fragments from each of 20 C. militaris isolates and analyzed nucleotide variations on these DNA fragments. RESULTS: We revealed a greatly higher genetic variation in mitochondrial DNA fragments than in nuclear DNA fragments. Specifically, C. militaris isolates exhibited intron presence/absence diversity in some mitochondrial fragments, and more variable sites were found in mitochondrial fragments than in nuclear fragments. The extent of nucleotide variations also varied by mitochondrial fragment, and intronic proteins seemed to be more vulnerable to amino acid changes than exonic proteins. Genetic diversity increased with the number of molecular markers used. CONCLUSION: We recommended using (in order) nad3-cox2. cox2-nad5, cox2, cox3, cob, and cox1 for future genetic diversity and population genetic studies of C. militaris.


Assuntos
Cordyceps/genética , Variação Genética , Mitocôndrias/genética , Biomarcadores/análise , Cordyceps/classificação , Cordyceps/isolamento & purificação , Proteínas Fúngicas/genética , Filogenia
20.
Microbiology (Reading) ; 160(Pt 7): 1466-1473, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24763427

RESUMO

A major aetiological factor of dental caries is the pathology of the dental plaque biofilms. The amino acid L-arginine (Arg) is found naturally in saliva as a free molecule or as a part of salivary peptides and proteins. Plaque bacteria metabolize Arg to produce alkali and neutralize glycolytic acids, promoting a less cariogenous oral microbiome. Here, we explored an alternative and complementary mechanism of action of Arg using atomic force microscopy. The nanomechanical properties of Streptococcus mutans biofilm extracellular matrix were characterized under physiological buffer conditions. We report the effect of Arg on the adhesive behaviour and structural properties of extracellular polysaccharides in S. mutans biofilms. High-resolution imaging of biofilm surfaces can reveal additional structural information on bacterial cells embedded within the surrounding extracellular matrix. A dense extracellular matrix was observed in biofilms without Arg compared to those grown in the presence of Arg. S. mutans biofilms grown in the presence of Arg could influence the production and/or composition of extracellular membrane glucans and thereby affect their adhesion properties. Our results suggest that the presence of Arg in the oral cavity could influence the adhesion properties of S. mutans to the tooth surface.


Assuntos
Arginina/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Streptococcus mutans/efeitos dos fármacos , Cárie Dentária/microbiologia , Placa Dentária/microbiologia , Placa Dentária/ultraestrutura , Matriz Extracelular/ultraestrutura , Glucanos/metabolismo , Microscopia de Força Atômica , Boca , Polissacarídeos Bacterianos/metabolismo , Saliva/microbiologia , Streptococcus mutans/fisiologia , Streptococcus mutans/ultraestrutura
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