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MOTIVATION: Functional profiling of metagenomic samples is essential to decipher the functional capabilities of microbial communities. Traditional and more widely used functional profilers in the context of metagenomics rely on aligning reads against a known reference database. However, aligning sequencing reads against a large and fast-growing database is computationally expensive. In general, k-mer-based sketching techniques have been successfully used in metagenomics to address this bottleneck, notably in taxonomic profiling. In this work, we describe leveraging FracMinHash (implemented in sourmash, a publicly available software), a k-mer-sketching algorithm, to obtain functional profiles of metagenome samples. RESULTS: We show how pieces of the sourmash software (and the resulting FracMinHash sketches) can be put together in a pipeline to functionally profile a metagenomic sample. We named our pipeline fmh-funprofiler. We report that the functional profiles obtained using this pipeline demonstrate comparable completeness and better purity compared to the profiles obtained using other alignment-based methods when applied to simulated metagenomic data. We also report that fmh-funprofiler is 39-99× faster in wall-clock time, and consumes up to 40-55× less memory. Coupled with the KEGG database, this method not only replicates fundamental biological insights but also highlights novel signals from the Human Microbiome Project datasets. AVAILABILITY AND IMPLEMENTATION: This fast and lightweight metagenomic functional profiler is freely available and can be accessed here: https://github.com/KoslickiLab/fmh-funprofiler. All scripts of the analyses we present in this manuscript can be found on GitHub.
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Algoritmos , Metagenoma , Metagenômica , Software , Metagenômica/métodos , Metagenoma/genética , Humanos , Microbiota/genética , Bases de Dados GenéticasRESUMO
Developing high-safety separators is a promising strategy to prevent thermal runaway in lithium-ion batteries (LIBs), which stems from the low melting temperatures and inadequate modulus of commercial polyolefin separators. However, achieving high modulus and thermal stability, along with uniform nanopores in these separators, poses significant challenges. Herein, the study presents ultrathin nanoporous aramid nanofiber (ANF) separators with high modulus and excellent thermal stability, enhancing the safety of LIBs. These separators are produced using a microfluidic-based continuous printing strategy, where the flow thickness can be meticulously controlled at the micrometer scale. This method allows for the continuous fabrication of nanoporous ANF separators with thicknesses ranging from 1.6 ± 0.1 µm to 2.7 ± 0.1 µm. Thanks to the double-side solvent diffusion, the separators exhibit controllably uniform pore sizes with a narrow distribution, spanning from 40 ± 5 nm to 105 ± 9 nm, and a high modulus of 3.3 ± 0.5 GPa. These nanoporous ANF separators effectively inhibit lithium dendrite formation, resulting in a high-capacity retention rate for the LIBs (80% after 240 cycles). Most notably, their robust structural and mechanical stability at elevated temperatures significantly enhances LIB safety under transient thermal abuse conditions, thus addressing critical safety concerns associated with LIBs.
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The development of thermally stable separators is a promising approach to address the safety issues of lithium-ion batteries (LIBs) owing to the serious shrinkage of commercial polyolefin separators at elevated temperatures. However, achieving controlled nanopores with a uniform size distribution in thermostable polymeric separators and high electrochemical performance is still a great challenge. In this study, nanoporous polyimide (PI) membranes with excellent thermal stability as high-safety separators is developed for LIBs using a superspreading strategy. The superspreading of polyamic acid solutions enables the generation of thin and uniform liquid layers, facilitating the formation of thin PI membranes with controllable and uniform nanopores with narrow size distribution ranging from 121 ± 5 nm to 86 ± 6 nm. Such nanoporous PI membranes display excellent structural stability at elevated temperatures up to 300 °C for at least 1 h. LIBs assembled with nanoporous PI membranes as separators show high specific capacity and Coulombic efficiency and can work normally after transient treatment at a high temperature (150 °C for 20 min) and high ambient temperature, indicating their promising application as high-safety separators for rechargeable batteries.
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MOTIVATION: With the rapidly growing volume of knowledge and data in biomedical databases, improved methods for knowledge-graph-based computational reasoning are needed in order to answer translational questions. Previous efforts to solve such challenging computational reasoning problems have contributed tools and approaches, but progress has been hindered by the lack of an expressive analysis workflow language for translational reasoning and by the lack of a reasoning engine-supporting that language-that federates semantically integrated knowledge-bases. RESULTS: We introduce ARAX, a new reasoning system for translational biomedicine that provides a web browser user interface and an application programming interface (API). ARAX enables users to encode translational biomedical questions and to integrate knowledge across sources to answer the user's query and facilitate exploration of results. For ARAX, we developed new approaches to query planning, knowledge-gathering, reasoning and result ranking and dynamically integrate knowledge providers for answering biomedical questions. To illustrate ARAX's application and utility in specific disease contexts, we present several use-case examples. AVAILABILITY AND IMPLEMENTATION: The source code and technical documentation for building the ARAX server-side software and its built-in knowledge database are freely available online (https://github.com/RTXteam/RTX). We provide a hosted ARAX service with a web browser interface at arax.rtx.ai and a web API endpoint at arax.rtx.ai/api/arax/v1.3/ui/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Bases de Conhecimento , Software , Bases de Dados Factuais , Idioma , NavegadorRESUMO
Adjuvant whole-breast radiotherapy is essential for breast cancer patients who adopted breast-conserving surgery (BCS) to reduce the risk of local recurrences, which however suffer from large-area and highly destructive ionizing radiation-induced adverse events. To tackle this issue, an afterglow/photothermal bifunctional polymeric nanoparticle (APPN) is developed that utilizes nonionizing light for precise afterglow imaging-guided post-BCS adjuvant second near-infrared (NIR-II) photothermal therapy. APPN consists of a tumor cell targeting afterglow agent, which is doped with a NIR dye as an afterglow initiator and a NIR-II light-absorbing semiconducting polymer as a photothermal transducer. Such a design realizes precise afterglow imaging-guided NIR-II photothermal ablation of minimal residual breast tumor foci after BCS, thus achieving complete inhibition of local recurrences. Moreover, APPN enables early diagnosis and treatment of local recurrence after BCS. This study thus provides a nonionizing modality for precision post-BCS adjuvant therapy and early recurrence theranostic.
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Nanopartículas , Medicina de Precisão , Humanos , Fototerapia , Polímeros , Recidiva , Linhagem Celular TumoralRESUMO
MOTIVATION: K-mer-based methods are used ubiquitously in the field of computational biology. However, determining the optimal value of k for a specific application often remains heuristic. Simply reconstructing a new k-mer set with another k-mer size is computationally expensive, especially in metagenomic analysis where datasets are large. Here, we introduce a hashing-based technique that leverages a kind of bottom-m sketch as well as a k-mer ternary search tree (KTST) to obtain k-mer-based similarity estimates for a range of k values. By truncating k-mers stored in a pre-built KTST with a large k=kmax value, we can simultaneously obtain k-mer-based estimates for all k values up to kmax. This truncation approach circumvents the reconstruction of new k-mer sets when changing k values, making analysis more time and space-efficient. RESULTS: We derived the theoretical expression of the bias factor due to truncation. And we showed that the biases are negligible in practice: when using a KTST to estimate the containment index between a RefSeq-based microbial reference database and simulated metagenome data for 10 values of k, the running time was close to 10× faster compared to a classic MinHash approach while using less than one-fifth the space to store the data structure. AVAILABILITY AND IMPLEMENTATION: A python implementation of this method, CMash, is available at https://github.com/dkoslicki/CMash. The reproduction of all experiments presented herein can be accessed via https://github.com/KoslickiLab/CMASH-reproducibles. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Algoritmos , Software , Biologia Computacional/métodos , Metagenômica , Análise de Sequência de DNA/métodosRESUMO
The construction of allylic quaternary sp3 -carbon centers has long been a formidable challenge in transition-metal-catalyzed alkyl-allyl coupling reactions due to the severe steric hindrance. Herein, we report an effective carbene strategy that employs well-defined vinyl-N-triftosylhydrazones as a versatile allylating reagent to enable direct assembly of these medicinally desirable structural elements from low-cost alkane feedstocks. The reaction exhibited excellent site selectivity for tertiary C-H bonds, broad scope (>60â examples and >20 : 1:0 r. r.) and good efficiency, even on a gram-scale, making it a convenient alternative to the well-known Trost-Tsuji allylation reaction for the formation of alkyl-allyl bonds. Combined experimental and computational studies were employed to unravel the mechanism and origin of site- and chemoselectivity of the reaction.
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BACKGROUND: Single-balloon enteroscopy (SBE) is a valuable but difficult modality for the diagnosis and treatment of small-bowel disease. The water exchange method has the advantage of facilitating intubation during colonoscopy. Here, we evaluated the effects of water exchange on procedure-related variables related to SBE. METHODS: This randomized controlled trial was conducted in a tertiary-care referral center in China. Patients due for attempted total enteroscopy were randomly allocated to undergo water exchange-assisted (water exchange group) or carbon dioxide-insufflated enteroscopy (CO2 group). All patients were planned to undergo both anterograde and retrograde procedures. The primary outcome was the total enteroscopy rate. Secondary outcomes included the maximal insertion depth, positive findings, procedural time, and adverse events. RESULTS: In total, 110 patients were enrolled, with 55 in each group.âBaseline characteristics between the two groups were comparable. Total enteroscopy was achieved in 58.2â% (32/55) of the water exchange group and 36.4â% (20/55) of the control group (Pâ=â0.02). The mean (standard deviation) estimated intubation depth was 521.2 (101.4) cm in the water exchange group and 481.6 (95.2) cm in the CO2 group (Pâ=â0.04). The insertion time was prolonged in the water exchange group compared with the CO2 group (178.9 [45.1] minutes vs. 154.2 [27.6] minutes; Pâ<â0.001). Endoscopic findings and adverse events were comparable between the two groups. CONCLUSIONS: The water exchange method improved the total enteroscopy rate and increased the intubation depth during SBE. The use of water exchange did not increase the complications of enteroscopy.
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Enteropatias , Enteroscopia de Balão Único , Dióxido de Carbono , Enteroscopia de Duplo Balão/efeitos adversos , Endoscopia Gastrointestinal/métodos , Humanos , Enteropatias/diagnóstico , Enteropatias/etiologia , Enteropatias/terapia , ÁguaRESUMO
Polymer flooding is drawing lots of attention because of the technical maturity in some reservoirs. The first commercial polymer flooding in China was performed in the Daqing oilfield and is one of the largest applications in the world. Some laboratory tests from Daqing researchers in China showed that the viscoelasticity of high molecular weight polymers plays a significant role in increasing displacement efficiency. Hence, encouraged by the conventional field applications and new findings on the viscoelasticity effect of polymers on residual oil saturation (ROS), some high-concentration high-molecular-weight (HCHMW) polymer-flooding field tests have been conducted. Although some field tests were well-documented, subsequent progress was seldom reported. It was recently reported that HCHMW has a limited application in Daqing, which does not agree with observations from laboratory core flooding and early field tests. However, the cause of this discrepancy is unclear. Thus, a systematic summary of polymer-flooding mechanisms and field tests in China is necessary. This paper explained why HCHMW is not widely used when considering new understandings of polymer-flooding mechanisms. Different opinions on the viscoelasticity effect of polymers on ROS reduction were critically reviewed. Other mechanisms of polymer flooding, such as wettability change and gravity stability effect, were discussed with regard to widely reported laboratory tests, which were explained in terms of the viscoelasticity effects of polymers on ROS. Recent findings from Chinese field tests were also summarized. Salt-resistance polymers (SRPs) with good economic performance using produced water to prepare polymer solutions were very economically and environmentally promising. Notable progress in SRP flooding and new amphiphilic polymer field tests in China were summarized, and lessons learned were given. Formation blockage, represented by high injection pressure and produced productivity ability, was reported in several oil fields due to misunderstanding of polymers' injectivity. Although the influence of viscoelastic polymers on reservoir conditions is unknown, the injection of very viscous polymers to displace medium-to-high viscosity oils is not recommended. This is especially important for old wells that could cause damage. This paper clarified misleading notions on polymer-flooding implementations based on theory and practices in China.
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Petróleo , Polímeros , Espécies Reativas de Oxigênio , Água , ÓleosRESUMO
BACKGROUND: Targeted optical imaging offers a noninvasive and accurate method for the early detection of gastrointestinal tumors, especially for flat appearances. In our previous study, a sequence of SNFYMPL (SNF) was identified as a specific peptide to bind to esophageal carcinoma using phage-display technology. This study aimed to evaluate the tumor-targeting efficacy of Cy5.5-conjugated SNF probe for imaging of esophageal carcinoma in vitro and in vivo. METHODS: The SNF-Cy5.5 probe was synthesized and then identified using High Performance Liquid Chromatography (HPLC) and mass spectrometry (MS). Confocal fluorescence imaging and Flow cytometry analysis were performed to evaluate the binding specificity and the receptor binding affinity of SNF-Cy5.5 to OE33. In vivo imaging was performed to evaluate the targeting ability of SNF-Cy5.5 to esophageal carcinoma. RESULTS: The confocal imaging and flow cytometry analysis showed that SNF-Cy5.5 bound specifically to the plasma membrane of OE33 cells with a high affinity. In vivo, for non-block group, SNF-Cy5.5 probe exhibited rapid OE33 tumor targeting during 24 h p.i. and excellent tumor-to-background contrast at 2 h p.i. For the block group, SNF-Cy5.5 was not observed in the mice after 4 h p.i. Ex vivo imaging also revealed that a higher fluorescent signal intensity value of the tumors was clearly observed in the non-block group than that in the block group (2.6 ± 0.32 × 109 vs. 0.8 ± 0.08 × 109, p < 0.05). CONCLUSIONS: SNF-Cy5.5 was synthesized and characterized with a high efficiency and purity. The higher affinity, specificity, and tumor targeting efficacy of SNF-Cy5.5 were confirmed by in vitro and in vivo tests. SNF-Cy5.5 is a promising optical probe for the imaging of esophageal adenocarcinoma.
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Adenocarcinoma , Espectroscopia de Luz Próxima ao Infravermelho , Adenocarcinoma/diagnóstico por imagem , Animais , Linhagem Celular Tumoral , Corantes Fluorescentes , Camundongos , Camundongos Nus , PeptídeosRESUMO
PURPOSE: The lingual-based mucoperiosteal flap, a novel flap, was unclear about the effects on the prognosis of surgery for impacted mandibular third molars. This study aimed to compare the lingual- and buccal-based mucoperiosteal flaps with respect to postoperative responses and complications. MATERIALS AND METHODS: A systematic review with a meta-analysis was designed and the PubMed, Cochrane Library, EMBASE, and Web of Science databases and Google Scholar from January 1, 2000 to April 30, 2020 were searched for randomized clinical trials. The predictor variable was buccal- or lingual-based flap in the surgery, and the outcome variables were pain, swelling, trismus, operative time, and wound dehiscence. Other study variables were sex and retention depth of impacted teeth. RevMan 5.3 software was used for data analysis. Mean differences or standardized mean differences and risk ratios were computed to assess associations between 2 variables, where statistical significance was set at P < .05. RESULTS: Seven publications met the inclusion criteria, contributing 370 subjects who had 590 teeth removed to sample. The lingual-based flap failed to significantly reduce postoperative discomfort. However, subgroup analysis revealed that subjects who underwent comma flap (a type of lingual-based flap) surgeries complained of milder pain than those who underwent buccal-based flap surgeries on day 1 (mean difference = -1.18, 95% confidence interval [CI] [-1.53, -0.83], P < .001) and day 7 (mean difference = -1.80, 95% CI [-2.13, -1.48], P < .001) after surgery. Significant differences were also observed on days 1, 3, and 7 regarding postoperative swelling and trismus (P < .01). In addition, the lingual-based flap was reported to cause a significantly lower rate of wound dehiscence (relative risk = 0.46, 95% CI [0.30, 0.69], P = .0002). CONCLUSIONS: The lingual-based flap was associated with better primary wound closure in third molar removal. The comma flap, as a subtype, was preferable for relieving postoperative pain, swelling, and trismus over the buccal-based flap.
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Dente Serotino , Dente Impactado , Humanos , Mandíbula/cirurgia , Dente Serotino/cirurgia , Morbidade , Dor Pós-Operatória/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Extração Dentária/efeitos adversos , Dente Impactado/cirurgiaRESUMO
Cortical interneurons (cINs) modulate excitatory neuronal activity by providing local inhibition. During fetal development, several cIN subtypes derive from the medial ganglionic eminence (MGE), a transient ventral telencephalic structure. While altered cIN development contributes to neurodevelopmental disorders, the inaccessibility of human fetal brain tissue during development has hampered efforts to define molecular networks controlling this process. Here, we modified protocols for directed differentiation of human embryonic stem cells, obtaining efficient, accelerated production of MGE-like progenitors and MGE-derived cIN subtypes with the expected electrophysiological properties. We defined transcriptome changes accompanying this process and integrated these data with direct transcriptional targets of NKX2-1, a transcription factor controlling MGE specification. This analysis defined NKX2-1-associated genes with enriched expression during MGE specification and cIN differentiation, including known and previously unreported transcription factor targets with likely roles in MGE specification, and other target classes regulating cIN migration and function. NKX2-1-associated peaks were enriched for consensus binding motifs for NKX2-1, LHX, and SOX transcription factors, suggesting roles in coregulating MGE gene expression. Among the NKX2-1 direct target genes with cIN-enriched expression was CHD2, which encodes a chromatin remodeling protein mutated to cause human epilepsies. Accordingly, CHD2 deficiency impaired cIN specification and altered later electrophysiological function, while CHD2 coassociated with NKX2-1 at cis-regulatory elements and was required for their transactivation by NKX2-1 in MGE-like progenitors. This analysis identified several aspects of gene-regulatory networks underlying human MGE specification and suggested mechanisms by which NKX2-1 acts with chromatin remodeling activities to regulate gene expression programs underlying cIN development.
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Diferenciação Celular , Córtex Cerebral/metabolismo , Proteínas de Ligação a DNA/metabolismo , Células-Tronco Embrionárias Humanas/metabolismo , Interneurônios/metabolismo , Linhagem Celular , Córtex Cerebral/citologia , Proteínas de Ligação a DNA/genética , Células-Tronco Embrionárias Humanas/citologia , Humanos , Interneurônios/citologia , Fator Nuclear 1 de Tireoide/genética , Fator Nuclear 1 de Tireoide/metabolismoRESUMO
Huntington's disease (HD) is a fatal neurodegenerative disorder caused by an abnormal expansion of polyglutamine repeats in the huntingtin protein (Htt). Transcriptional dysregulation is an early event in the course of HD progression and is thought to contribute to disease pathogenesis, but how mutant Htt causes transcriptional alterations and subsequent cell death in neurons is not well understood. RNA-Seq analysis revealed that expression of a mutant Htt fragment in primary cortical neurons leads to robust gene expression changes before neuronal death. Basic helix-loop-helix transcription factor Twist1, which is essential for embryogenesis and is normally expressed at low levels in mature neurons, was substantially up-regulated in mutant Htt-expressing neurons in culture and in the brains of HD mouse models. Knockdown of Twist1 by RNAi in mutant Htt-expressing primary cortical neurons reversed the altered expression of a subset of genes involved in neuronal function and, importantly, abrogated neurotoxicity. Using brain-derived neurotrophic factor (Bdnf), which is known to be involved in HD pathogenesis, as a model gene, we found that Twist1 knockdown could reverse mutant Htt-induced DNA hypermethylation at the Bdnf regulatory region and reactivate Bdnf expression. Together, these results suggest that Twist1 is an important upstream mediator of mutant Htt-induced neuronal death and may in part operate through epigenetic mechanisms.
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Epigênese Genética , Proteína Huntingtina/genética , Doença de Huntington/genética , Proteína 1 Relacionada a Twist/genética , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Células Cultivadas , Metilação de DNA , Feminino , Redes Reguladoras de Genes , Humanos , Proteína Huntingtina/metabolismo , Doença de Huntington/metabolismo , Masculino , Camundongos , Mutação , Neurônios/metabolismo , Ativação Transcricional , Proteína 1 Relacionada a Twist/metabolismoRESUMO
We present a theoretical scheme to realize high-sensitive mass detection in a dispersive optomechanical system (DOMS) via nonlinear sum-sideband. In this scheme, DOMS assisted by a degenerate parametric amplifier (DPA) provides a well-established optomechanical circumstance, where nonlinear optomechanical interaction between cavity mode and mechanical mode of dielectric membrane is expected for creating the frequency components at optical sum-sideband. Such a scheme for mass detection mainly relies on monitoring the conversion efficiency of generated sum-sideband after the added mass is absorbed on the dielectric membrane. Using experimentally achievable parameters, we find that the conversion efficiency of sum-sideband and the sensitivity of mass detection can be simultaneously improved when the nonlinear gain of DPA increases. Furthermore, our results also demonstrate that this mass detection of DOMS can reach femtogram (fg) level resolution, when the method of mass detection relies on a direct relationship between maximum efficiency of sum-sideband and mass-change of membrane.
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Cancer is a major disease that seriously threatens human health and is a leading cause of human death. At present, the commonly used cancer treatment methods are surgical therapy, chemical drug therapy and radiation therapy (RT). However, these treatments all have their own shortcomings and cannot perfectly meet the needs of clinical diagnosis and treatment. It is of great significance to improve the diagnosis and treatment level, so that the curative effect and quality of life of tumor patients can be improved. The rapid development of nanotechnology has brought hope to the diagnosis and treatment of cancer and the appearance of biofunctional magnetic hybrid nanomaterials (MHNs) has provided a new possibilities for the integration of cancer diagnosis and treatment. As a promising research direction, the multifunctional nanoplatform integrates imaging diagnosis, drug therapy and drug delivery. Better treatment effects and fewer side effects can be achieved by optimizing materials to build stable, efficient, and safe MHNs with combined functions of multimodal imaging and various treatments. This review focuses on not only the research progress of MHNs but also their applications and development trend in the integration of cancer diagnosis and treatment. A description of the applications of MHN structure optimization for both magnetic resonance imaging-based multimodal diagnosis and cancer therapy is given. Furthermore, RT is introduced and the development of MHNs for diagnosis and treatment system is investigated.
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Numerous signal transduction pathways are closely associated with the occurrence, development, and prognosis of ameloblastoma (AM). Mitogen-activated protein kinase (MAPK) is a serine/threonine-specific protein kinase that transduces intracellular signals in critical cellular phenomena. A number of recent analyses have reported that the MAPK signaling pathway contributes significantly to AM. High-throughput DNA sequencing methods, such as next-generation sequencing using Illumina have yielded advancements in studies on MAPK signaling pathways and their association with AM; in particular, BRAF V600E is mediated by the activation of the Ras/Raf/MAPK pathway. This review discusses advancements in studies on MAPK signaling pathways and MAPK-targeted inhibitors or antibodies, along with the merits and demerits of MAPK-targeted therapies, finally followed by a discussion regarding more efficient potential MAPK-targeted therapies to treat AM with few side effects, thereby providing novel insights into targeted therapy for AM.
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Ameloblastoma/tratamento farmacológico , Ameloblastoma/genética , Neoplasias Maxilomandibulares/tratamento farmacológico , Neoplasias Maxilomandibulares/genética , Sistema de Sinalização das MAP Quinases/fisiologia , Proteínas Quinases Ativadas por Mitógeno/fisiologia , Terapia de Alvo Molecular , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Proteínas Proto-Oncogênicas B-rafRESUMO
BACKGROUND: Carbonylation is an oxidative modification of the proteins and a marker of oxidative stress. The accumulation of toxic carbonylated proteins might be one of the onsets of pathogenesis in hippocampal aging or neurodegeneration. Enormous evidence indicates that regular aerobic exercise might alleviate the dysfunction of carbonylated proteins, but the adaptational mechanisms in response to exercise are unclear. OBJECTIVE: This study explored the carbonyl stress mechanism in the hippocampus using proteomics and the role of calmodulin-dependent protein kinases (CAMK)-AMP-activated protein kinase (AMPK)-Beclin1 signaling pathways in alleviating aging or improving function with regular aerobic exercise. METHODS: Twenty-four healthy 13-month-old male Sprague-Dawley rats (average 693.21 ± 68.85 g) were randomly divided into middle-aged sedentary control group (M-SED, n = 12) and middle-aged aerobic exercise runner group (M-EX, n = 12). The M-EX group participated in regular aerobic exercise - treadmill running - with exercise intensity increasing gradually from 50-55% to 65-70% of maximum oxygen consumption (VËO2max) over 10 weeks. The targeted proteins of oxidative modification were profiled by avidin magnetic beads and electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-Q-TOF-MS). Western blots were used to test for molecular targets. RESULTS: Regular aerobic exercise restores the intersessional habituation and rescues the hippocampus morphological structure in middle-aged rats. -ESI-Q-TOF-MS screened 56 carbonylated proteins only found in M-SED and 16 carbonylated proteins only found in M-EX, indicating aerobic exercise decreased carbonyl stress. Intriguingly, Ca2+/CAMK II alpha (CAMKIIα) was carbonylated only in the M-SED group at the oxidative modification site of 4-hydroxynonenal adducts, while regular aerobic exercise alleviated CAMKIIα carbonylation. Regular aerobic exercise significantly increased the expression and phosphorylated, active levels of CAMKIIα and AMPKα1. It also upregulated the expression of Beclin1 and microtubule-associated protein1-light chain 3 in the hippocampus. CONCLUSION: Quantification of CAMKIIα carbonylation may be a potential biomarker of the hippocampal senescence. Additionally, regular aerobic exercise-induced autophagy via the activation of CAMK-AMPK-Beclin1 signaling pathway may mitigate the hippocampal neurodegeneration or pathological changes by alleviating protein carbonylation (carbonyl stress).
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Autofagia , Hipocampo/metabolismo , Hipocampo/patologia , Condicionamento Físico Animal , Carbonilação Proteica , Animais , Proteína Beclina-1/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Espectrometria de Massas , Proteínas Associadas aos Microtúbulos/metabolismo , Proteômica , Distribuição Aleatória , Ratos Sprague-Dawley , Transdução de Sinais , Regulação para CimaRESUMO
PURPOSE: The purpose of this study was to evaluate whether bromelain can decrease trismus, pain, and facial swelling in patients undergoing impacted third molar surgery. MATERIALS AND METHODS: Three databases were searched to identify relevant studies through November 1, 2017. Randomized controlled trials (RCTs) that compared the effect of bromelain versus placebo after mandibular third molar surgery were included. The main outcome measures, pain, facial swelling, and trismus, were assessed in the early stage (2 to 3 days) and the late stage (7 days) after surgery. Standardized mean differences (SMDs) and weighted mean differences (WMDs) were calculated using fixed-effect models. All statistical analyses were implemented using Review Manager 5.3. RESULT: Six RCTs were included in this meta-analysis. The pooled results suggested that bromelain appears to be effective for decreasing facial swelling in the early and late stages after surgery (early-stage SMD, -0.24; 95% confidence interval [CI], -0.46 to -0.02; P = .03; late-stage SMD, -0.54; 95% CI, -0.84 to -0.24; P = .0004). Bromelain alleviated postoperative pain 7 days after surgery (SMD, -0.54; 95% CI, -0.87 to -0.20; P = .002), but there was no significant difference in pain levels at the early stage. For trismus, analyses showed that bromelain had no apparent effect on early or late trismus. CONCLUSION: Bromelain conferred moderate relief of postoperative discomfort after third molar surgery.
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Analgésicos , Bromelaínas , Dor Pós-Operatória , Extração Dentária , Dente Impactado , Trismo , Analgésicos/uso terapêutico , Bromelaínas/uso terapêutico , Edema/tratamento farmacológico , Humanos , Dente Serotino , Dor Pós-Operatória/tratamento farmacológico , Dente Impactado/cirurgia , Trismo/tratamento farmacológicoRESUMO
PURPOSE: The purpose of this study was to evaluate whether the anesthetic efficiency of articaine is superior to that of lidocaine during lower third molar extraction (LTME). MATERIALS AND METHODS: Three electronic databases (PubMed, Cochrane, and Web of Science) were searched to identify randomized controlled trials up to December, 31 2017. Five evaluation indexes were extracted, namely success rate of anesthesia, subjective onset time of anesthesia, objective onset time of anesthesia, duration time of anesthesia, and intraoperative pain assessment, to assess the anesthesia efficiency of the 2 solutions. All data analyses were conducted using Review Manager (version 5.3; The Cochrane Collaboration, London, United Kingdom). RESULTS: Nine studies were included in this review. The sample was composed of 770 LTMEs from 493 patients, with 382 LTMEs in the lidocaine group and 388 LTMEs in the articaine group. Compared with lidocaine, 4% articaine with 1:100,000 epinephrine showed a higher success rate of anesthesia (risk ratio, 1.10; 95% confidence interval [CI], 1.01 to 1.21; P = .03), shorter subjective onset time of anesthesia (standardized mean difference, 1.20; 95% CI, 0.50 to 1.89; P = .0007), and longer duration time of anesthesia (mean difference, 0.83 hours; 95% CI, 0.59 to 1.07 hours; P < .00001); however, for intraoperative pain assessment (mean difference, 3.12 mm; 95% CI, -0.13 to 6.37 mm; P = .06) and objective onset time of anesthesia (standardized mean difference, 0.44; 95% CI, -0.39 to 1.26; P = .30), there was no significant difference between the 2 solutions. CONCLUSIONS: The results of this study suggest that 4% articaine with 1:100,000 epinephrine possesses superior anesthetic efficiency relative to lidocaine for inferior alveolar nerve blocks during LTME.
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Anestesia Dentária , Dente Serotino , Anestésicos Locais , Carticaína , Método Duplo-Cego , Humanos , LidocaínaRESUMO
Surface sediment samples (nâ¯=â¯92) were collected from Hangzhou Bay to investigate the transport and deposition of polybrominated diphenyl ethers (PBDEs) and to assess the ecological risks in Hangzhou Bay. The concentrations of ∑7PBDEs (sum of BDE-28, 47, 99, 100, 153, 154, 183) and BDE-209 ranged from 3.61 to 91.09â¯pgâ¯g-1 and from non-detectable to 2007.52â¯pgâ¯g-1 (dry weight), respectively. The high values of ∑7PBDEs and BDE-209 were commonly occurred at the northeast of Hangzhou Bay and the Nanhui Spit coast of Shanghai. Compared with the south part of the bay, the dominance of BDE-209 was more prominent and the linear correlations between PBDEs concentrations and TOCs as well as median grain size were more significant in the northern Hangzhou Bay. Hydrodynamic forcing on the transport and deposition of PBDEs is primarily responsible for the discrepancy of this spatial distribution in these two parts. In addition to BDE-209, BDEs-153, 99, 47, and 100 were also the abundant congeners. Three principal components were extracted using principal component analysis (PCA), mainly attributed to human activities, erosion of polluted soils via surface runoff and release from products for PC1, PC2 and PC3, respectively. The calculation results of mass inventories, hazard quotients (HQs) and risk quotients (RQs) indicated that the ecological risk of PBDEs in Hangzhou Bay was low. The multiple effect of hydrodynamic forcing with complicated and large-scope tidal currents made it hard to deposit for organic matters and contaminants in Hangzhou Bay.