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Proton exchange membrane fuel cells (PEMFCs) for automotive applications are required to achieve mechanical reliability at various temperatures ranging from subfreezing to 80 °C. The thermal behavior of the electrode should be considered at the initial design stage to design a robust automotive fuel cell electrode. Recently, a behavior different from that of the bulk state has been reported for ionomers with a few nanometers of thickness. Therefore, the intrinsic thermal behavior of ionomer films with thicknesses from micrometers to nanometers is quantitatively investigated in this study. By introducing the fabrication of a pseudo-freestanding Nafion thin film and in-plane thermal strain measurement method on the water surface, the thermal expansion of the freestanding Nafion thin film was successfully measured with minimizing substrate constraints. Thermal strain measurement and X-ray scattering studies revealed that the weakening of intermolecular interaction within the hydrophobic and hydrophilic domains in the Nafion thin film caused thermal expansion, and well-structured hydrophobic domains could suppress thermal expansion. The thermal expansion behavior with different heat treatments provides evidence of the thin-film-to-bulk transition of the fully hydrated Nafion film. Intrinsic thermal behavior without substrate interactions can facilitate an understanding of the thermal behavior of electrodes and provide insight into designing a robust PEMFC in temperature-varying environments.
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BACKGROUND This subgroup analysis of prospective observational research, involving 71 participants, compared the effects of anesthesia on microvascular reactivity in obese vs lean individuals using near-infrared spectroscopy and vascular occlusion tests. The correlation between the body mass index (BMI) and microvascular reactivity under general anesthesia was also investigated. MATERIAL AND METHODS This study enrolled adult patients classified as American Society of Anesthesiologists physical status I or II, undergoing elective surgery under general anesthesia. The microcirculatory variables measured before (Tpre) and 30 min following the induction of anesthesia (Tpost) were as follows: baseline tissue oxygen saturation (StO2), occlusion slope (∇occl), and recovery slope (∇recov). The patients were grouped according to their BMI (lean [BMI <25 kg/m²] vs obese [BMI ≥25 kg/m²]). Data are presented as medians and interquartile ranges. RESULTS There were 43 patients in the lean group and 28 in the obese group. At Tpre, baseline StO2, ∇occl, and ∇recov were not different between the 2 groups (P=0.860, 0.659, and 0.518, respectively). At Tpost, the baseline StO2 and ∇occl were not different between the 2 groups (P=0.343 and 0.791); however, the ∇recov was lower in the obese group than in the lean group (3.245 [2.737, 3.977] vs 4.131 [3.491, 4.843], P=0.003). At Tpost, BMI showed a moderate correlation with ∇recov (correlation coefficient: -0.319, P=0.007). CONCLUSIONS In obese patients, capillary recruitment capacity during general anesthesia is compromised compared to lean patients.
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Obesidade , Doenças Vasculares , Adulto , Humanos , Anestesia Geral , Índice de Massa Corporal , Capilares , Microcirculação , Estudos Observacionais como AssuntoRESUMO
BACKGROUND/PURPOSE: This retrospective immunohistological pilot study aimed to investigate the influence of natural killer group 2, member D (NKG2D) ligand expression on ameloblastoma recurrence after surgical resection. It also aimed to elucidate additional clinical factors that could serve as predictors of ameloblastoma recurrence. MATERIALS AND METHODS: This study included 96 patients who were histologically diagnosed with ameloblastoma after surgical resection. The expression of NKG2D ligands, including UL16-binding proteins (ULBPs) 1-3 and major histocompatibility complex class I chain-related molecule (MIC) A/B, was evaluated in formalin-fixed paraffin-embedded tumor tissues via immunohistochemistry assays. Furthermore, the patients' electronic medical records were reviewed. Multivariate Cox regression analysis was conducted, and data were expressed as adjusted hazard ratios [HRs] with 95% confidence intervals [95% CIs]. RESULTS: Multivariate analysis revealed that recurrent tumors (ref.: primary; adjusted HR [95% CI]: 2.780 [1.136, 6.803], p = 0.025) and positive MICA/B expression (ref.: negative; adjusted HR [95% CI]: 0.223 [0.050, 0.989], p = 0.048) independently affected recurrence-free survival in ameloblastoma. CONCLUSION: This study identified recurrent cases and loss of MICA/B expression as independent predictors of early ameloblastoma recurrence following surgical resection. The findings suggest that decreased MICA/B expression might undermine NKG2D-mediated tumor immunosurveillance, thereby influencing early recurrence.
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Ameloblastoma , Recidiva Local de Neoplasia , Humanos , Estudos Retrospectivos , Masculino , Feminino , Recidiva Local de Neoplasia/patologia , Projetos Piloto , Pessoa de Meia-Idade , Ameloblastoma/patologia , Ameloblastoma/metabolismo , Ameloblastoma/cirurgia , Adulto , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Idoso , Imuno-Histoquímica , Adolescente , Neoplasias Maxilomandibulares/patologia , Neoplasias Maxilomandibulares/metabolismo , Neoplasias Maxilomandibulares/cirurgia , Adulto JovemRESUMO
Promotion of good mental health, prevention, and early intervention before/at the onset of mental disorders improve outcomes. However, the range and peak ages at onset for mental disorders are not fully established. To provide robust, global epidemiological estimates of age at onset for mental disorders, we conducted a PRISMA/MOOSE-compliant systematic review with meta-analysis of birth cohort/cross-sectional/cohort studies, representative of the general population, reporting age at onset for any ICD/DSM-mental disorders, identified in PubMed/Web of Science (up to 16/05/2020) (PROSPERO:CRD42019143015). Co-primary outcomes were the proportion of individuals with onset of mental disorders before age 14, 18, 25, and peak age at onset, for any mental disorder and across International Classification of Diseases 11 diagnostic blocks. Median age at onset of specific disorders was additionally investigated. Across 192 studies (n = 708,561) included, the proportion of individuals with onset of any mental disorders before the ages of 14, 18, 25 were 34.6%, 48.4%, 62.5%, and peak age was 14.5 years (k = 14, median = 18, interquartile range (IQR) = 11-34). For diagnostic blocks, the proportion of individuals with onset of disorder before the age of 14, 18, 25 and peak age were as follows: neurodevelopmental disorders: 61.5%, 83.2%, 95.8%, 5.5 years (k = 21, median=12, IQR = 7-16), anxiety/fear-related disorders: 38.1%, 51.8%, 73.3%, 5.5 years (k = 73, median = 17, IQR = 9-25), obsessive-compulsive/related disorders: 24.6%, 45.1%, 64.0%, 14.5 years (k = 20, median = 19, IQR = 14-29), feeding/eating disorders/problems: 15.8%, 48.1%, 82.4%, 15.5 years (k = 11, median = 18, IQR = 15-23), conditions specifically associated with stress disorders: 16.9%, 27.6%, 43.1%, 15.5 years (k = 16, median = 30, IQR = 17-48), substance use disorders/addictive behaviours: 2.9%, 15.2%, 48.8%, 19.5 years (k = 58, median = 25, IQR = 20-41), schizophrenia-spectrum disorders/primary psychotic states: 3%, 12.3%, 47.8%, 20.5 years (k = 36, median = 25, IQR = 20-34), personality disorders/related traits: 1.9%, 9.6%, 47.7%, 20.5 years (k = 6, median = 25, IQR = 20-33), and mood disorders: 2.5%, 11.5%, 34.5%, 20.5 years (k = 79, median = 31, IQR = 21-46). No significant difference emerged by sex, or definition of age of onset. Median age at onset for specific mental disorders mapped on a time continuum, from phobias/separation anxiety/autism spectrum disorder/attention deficit hyperactivity disorder/social anxiety (8-13 years) to anorexia nervosa/bulimia nervosa/obsessive-compulsive/binge eating/cannabis use disorders (17-22 years), followed by schizophrenia, personality, panic and alcohol use disorders (25-27 years), and finally post-traumatic/depressive/generalized anxiety/bipolar/acute and transient psychotic disorders (30-35 years), with overlap among groups and no significant clustering. These results inform the timing of good mental health promotion/preventive/early intervention, updating the current mental health system structured around a child/adult service schism at age 18.
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Alcoolismo , Transtorno do Espectro Autista , Transtornos Mentais , Transtorno Obsessivo-Compulsivo , Idade de Início , Alcoolismo/epidemiologia , Transtorno do Espectro Autista/epidemiologia , Comorbidade , Estudos Transversais , Humanos , Transtornos Mentais/epidemiologia , PrevalênciaRESUMO
The aim of this systematic review and network meta-analysis is to evaluate the comparative effectiveness of N95, surgical/medical and non-medical facemasks as personal protective equipment against respiratory virus infection. The study incorporated 35 published and unpublished randomized controlled trials and observational studies investigating specific mask effectiveness against influenza virus, SARS-CoV, MERS-CoV and SARS-CoV-2. We searched PubMed, Google Scholar and medRxiv databases for studies published up to 5 February 2021 (PROSPERO registration: CRD42020214729). The primary outcome of interest was the rate of respiratory viral infection. The quality of evidence was estimated using the GRADE approach. High compliance to mask-wearing conferred a significantly better protection (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.23-0.82) than low compliance. N95 or equivalent masks were the most effective in providing protection against coronavirus infections (OR, 0.30; CI, 0.20-0.44) consistently across subgroup analyses of causative viruses and clinical settings. Evidence supporting the use of medical or surgical masks against influenza or coronavirus infections (SARS, MERS and COVID-19) was weak. Our study confirmed that the use of facemasks provides protection against respiratory viral infections in general; however, the effectiveness may vary according to the type of facemask used. Our findings encourage the use of N95 respirators or their equivalents (e.g., P2) for best personal protection in healthcare settings until more evidence on surgical and medical masks is accrued. This study highlights a substantial lack of evidence on the comparative effectiveness of mask types in community settings.
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COVID-19 , Infecções Respiratórias , COVID-19/prevenção & controle , Humanos , Máscaras , Metanálise em Rede , Infecções Respiratórias/prevenção & controle , SARS-CoV-2RESUMO
Mammalian brain glycome remains a relatively poorly understood area compared to other large-scale "omics" studies, such as genomics and transcriptomics due to the inherent complexity and heterogeneity of glycan structure and properties. Here, we first performed spatial and temporal analysis of glycome expression patterns in the mammalian brain using a cutting-edge experimental tool based on liquid chromatography-mass spectrometry, with the ultimate aim to yield valuable implications on molecular events regarding brain functions and development. We observed an apparent diversity in the glycome expression patterns, which is spatially well-preserved among nine different brain regions in mouse. Next, we explored whether the glycome expression pattern changes temporally during postnatal brain development by examining the prefrontal cortex (PFC) at different time point across six postnatal stages in mouse. We found that glycan expression profiles were dynamically regulated during postnatal developments. A similar result was obtained in PFC samples from humans ranging in age from 39 d to 49 y. Novel glycans unique to the brain were also identified. Interestingly, changes primarily attributed to sialylated and fucosylated glycans were extensively observed during PFC development. Finally, based on the vast heterogeneity of glycans, we constructed a core glyco-synthesis map to delineate the glycosylation pathway responsible for the glycan diversity during the PFC development. Our findings reveal high levels of diversity in a glycosylation program underlying brain region specificity and age dependency, and may lead to new studies exploring the role of glycans in spatiotemporally diverse brain functions.
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Metabolismo dos Carboidratos , Polissacarídeos/biossíntese , Córtex Pré-Frontal/metabolismo , Adolescente , Adulto , Animais , Criança , Pré-Escolar , Glicômica , Humanos , Lactente , Recém-Nascido , Masculino , Camundongos , Córtex Pré-Frontal/crescimento & desenvolvimento , Adulto JovemRESUMO
Children and adolescents with autism spectrum disorder (ASD) experience various sleep problems. Sleep problems co-occur in a bidirectional relationship with ASD core symptoms and behavioral problems. However, studies on how these three factors are intricately linked to each other are limited. This meta-analysis examined the differential relationship between specific sleep problems, core symptoms, and behavioral problems in this population. This study was registered in PROSPERO (CRD42022339695). We systematically searched the PubMed/MEDLINE, Web of Science, and Scopus databases from inception to April 27, 2022. Observational studies that reported correlations between measures of sleep problems, ASD core symptoms, or ASD behavioral problems were included, and participants aged 18 years or below were enrolled. The correlation coefficient (r) was assessed as the primary effect metric. Total 22 cross-sectional studies were included, which comprised 2655 participants (mean age = 6.60 years old; mean percentage of boys = 80.64%). We found correlations between total sleep problems and total core symptoms (r 0.293 [95% confidence interval - 0.095 to 0.604]), total sleep problems and total behavioral problems (r 0.429 [0.299-0.544]), and total core symptoms and total behavioral problems (r - 0.050 [- 0.177 to 0.079]) and identified statistically significant correlations between specific components of sleep problems, ASD core symptoms, and ASD behavioral problems. Each specific sleep problem showed a unique association with core symptoms and behavioral problems. Sleep problems in ASD should be explored in detail, and the closely linked core symptoms and behavioral problems should be common therapeutic targets.
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Introduction: Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide because of difficulties in early diagnosis. Aberrant glycosylation in serum proteins has been associated with many human diseases. Serum haptoglobin, a highly sialylated glycoprotein with four N-glycosylation sites, has gained considerable attention due to its potential as a signature molecule to display aberrant glycosylation in inflammatory disorders and various types of cancer. In particular, the relevance of haptoglobin glycosylation in GC has been investigated in a multifaceted way.Areas covered: The screening of haptoglobin glycosylation could offer an alternative approach toward GC diagnosis and detection. In this report, various assay platforms such as glycan profiling, site-specific glycopeptide profiling, and intact protein profiling are introduced for the detection of abnormal glycosylation of serum haptoglobin.Expert opinion: Although aberrant glycosylation of serum haptoglobin is associated with gastric cancer patients and might be a promising marker of GC screening, the development of a diagnosis platform to increase specificity and sensitivity for clinical use is still an analytical challenge. However, the continuous advancement of analytical technologies and methods will spur the paradigm shift from traditional serum markers, enabling the effective mining of human glycoproteome for GC diagnostic markers.
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Biomarcadores Tumorais/sangue , Haptoglobinas/metabolismo , Processamento de Proteína Pós-Traducional , Neoplasias Gástricas/sangue , Glicosilação , Humanos , Neoplasias Gástricas/diagnósticoRESUMO
Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide, largely because of difficulties in early diagnosis. Despite accumulating evidence indicating that aberrant glycosylation is associated with GC, site-specific localization of the glycosylation to increase specificity and sensitivity for clinical use is still an analytical challenge. Here, we created an analytical platform with a targeted glycoproteomic approach for GC biomarker discovery. Unlike the conventional glycomic approach with untargeted mass spectrometric profiling of released glycan, our platform is characterized by three key features: it is a target-protein-specific, glycosylation-site-specific, and structure-specific platform with a one-shot enzyme reaction. Serum haptoglobin enriched by immunoaffinity chromatography was subjected to multispecific proteolysis to generate site-specific glycopeptides and to investigate the macroheterogeneity and microheterogeneity. Glycopeptides were identified and quantified by nano liquid chromatography-mass spectrometry and nano liquid chromatography-tandem mass spectrometry. Ninety-six glycopeptides, each corresponding to a unique glycan/glycosite pairing, were tracked across all cancer and control samples. Differences in abundance between the two groups were marked by particularly high magnitudes. Three glycopeptides exhibited exceptionally high control-to-cancer fold changes along with receiver operating characteristic curve areas of 1.0, indicating perfect discrimination between the two groups. From the results taken together, our platform, which provides biological information as well as high sensitivity and reproducibility, may be useful for GC biomarker discovery. Graphical abstract á .
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Glicopeptídeos/análise , Haptoglobinas/química , Proteômica/métodos , Neoplasias Gástricas/diagnóstico , Espectrometria de Massas em Tandem/métodos , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Glicosilação , Humanos , Modelos Moleculares , Proteólise , Neoplasias Gástricas/sangue , Neoplasias Gástricas/químicaRESUMO
The main carbohydrate of red macroalgae is agarose, a heterogeneous polysaccharide composed of D-galactose and 3,6-anhydro-L-galactose. When saccharifying agarose by enzymes, the unique physical properties of agarose, namely the sol-gel transition and the near-insolubility of agarose in water, limit the accessibility of agarose to the enzymes. Due to the lower accessibility of agarose to enzymes in the gel state than to the sol state, it is important to prevent the sol-gel transition by performing the enzymatic liquefaction of agarose at a temperature higher than the sol-gel transition temperature of agarose. In this study, a thermostable endo-type ß-agarase, Aga16B, originating from Saccharophagus degradans 2-40T, was characterized and introduced in the liquefaction process. Aga16B was thermostable up to 50 °C and depolymerized agarose mainly into neoagarooligosaccharides with degrees of polymerization 4 and 6. Aga16B was applied to enzymatic liquefaction of agarose at 45 °C, which was above the sol-gel transition temperature of 1 % (w/v) agarose (â¼35 °C) when cooling agarose. This is the first systematic demonstration of enzymatic liquefaction of agarose, enabled by determining the sol-gel temperature of agarose under specific conditions and by characterizing the thermostability of an endo-type ß-agarase.
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Glicosídeo Hidrolases/metabolismo , Sefarose/química , Sefarose/metabolismo , Clonagem Molecular , Estabilidade Enzimática , Gammaproteobacteria/enzimologia , Glicosídeo Hidrolases/genética , Glicosídeo Hidrolases/isolamento & purificação , Cinética , Transição de Fase , Proteínas Recombinantes/metabolismo , Alga Marinha/química , Temperatura de TransiçãoRESUMO
UNLABELLED: In this study, we characterized Gly5M, originating from a marine bacterium, as a novel ß-1,3-1,6-endoglucanase in glycoside hydrolase family 5 (GH5) in the Carbohydrate-Active enZyme database. The gly5M gene encodes Gly5M, a newly characterized enzyme from GH5 subfamily 47 (GH5_47) in Saccharophagus degradans 2-40(T) The gly5M gene was cloned and overexpressed in Escherichia coli Through analysis of the enzymatic reaction products by thin-layer chromatography, high-performance liquid chromatography, and matrix-assisted laser desorption ionization-tandem time of flight mass spectrometry, Gly5M was identified as a novel ß-1,3-endoglucanase (EC 3.2.1.39) and bacterial ß-1,6-glucanase (EC 3.2.1.75) in GH5. The ß-1,3-endoglucanase and ß-1,6-endoglucanase activities were detected by using laminarin (a ß-1,3-glucan with ß-1,6-glycosidic linkages derived from brown macroalgae) and pustulan (a ß-1,6-glucan derived from fungal cell walls) as the substrates, respectively. This enzyme also showed transglycosylase activity toward ß-1,3-oligosaccharides when laminarioligosaccharides were used as the substrates. Since laminarin is the major form of glucan storage in brown macroalgae, Gly5M could be used to produce glucose and laminarioligosaccharides, using brown macroalgae, for industrial purposes. IMPORTANCE: In this study, we have discovered a novel ß-1,3-1,6-endoglucanase with a unique transglycosylase activity, namely, Gly5M, from a marine bacterium, Saccharophagus degradans 2-40(T) Gly5M was identified as the newly found ß-1,3-endoglucanase and bacterial ß-1,6-glucanase in GH5. Gly5M is capable of cleaving glycosidic linkages of both ß-1,3-glucans and ß-1,6-glucans. Gly5M also possesses a transglycosylase activity toward ß-1,3-oligosacchrides. Due to the broad specificity of Gly5M, this enzyme can be used to produce glucose or high-value ß-1,3- and/or ß-1,6-oligosaccharides.
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Celulase/genética , Celulase/metabolismo , Gammaproteobacteria/enzimologia , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Clonagem Molecular , Escherichia coli/genética , Escherichia coli/metabolismo , Gammaproteobacteria/genética , Expressão Gênica , Glucanos/metabolismo , Hidrólise , Polissacarídeos/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Especificidade por SubstratoRESUMO
2'-Fucosyllactose (2-FL) is one of the key oligosaccharides in human milk. In the present study, the salvage guanosine 5'-diphosphate (GDP)-l-fucose biosynthetic pathway from fucose was employed in engineered Escherichia coli BL21star(DE3) for efficient production of 2-FL. Introduction of the fkp gene coding for fucokinase/GDP-l-fucose pyrophosphorylase (Fkp) from Bacteroides fragilis and the fucT2 gene encoding α-1,2-fucosyltransferase from Helicobacter pylori allows the engineered E. coli to produce 2-FL from fucose, lactose and glycerol. To enhance the lactose flux to 2-FL production, the attenuated, and deleted mutants of ß-galactosidase were employed. Moreover, the 2-FL yield and productivity were further improved by deletion of the fucI-fucK gene cluster coding for fucose isomerase (FucI) and fuculose kinase (FucK). Finally, fed-batch fermentation of engineered E. coli BL21star(DE3) deleting lacZ and fucI-fucK, and expressing fkp and fucT2 resulted in 23.1 g/L of extracellular concentration of 2-FL and 0.39 g/L/h productivity. Biotechnol. Bioeng. 2016;113: 2443-2452. © 2016 Wiley Periodicals, Inc.
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Escherichia coli/fisiologia , Fucosiltransferases/genética , Guanosina Difosfato Fucose/metabolismo , Engenharia Metabólica/métodos , Trissacarídeos/biossíntese , Fucosiltransferases/metabolismo , Regulação Bacteriana da Expressão Gênica/fisiologia , Guanosina Difosfato Fucose/genética , Lactose/metabolismo , Transdução de Sinais/fisiologia , Trissacarídeos/genéticaRESUMO
This study was performed to evaluate the effectiveness of acidic pretreatment in increasing the enzymatic digestibility of alginate from brown macroalgae. Pretreatment with 1 % (w/v) sulfuric acid at 120 °C for 30 min produced oligosaccharides, mannuronic acid, and guluronic acid. Enzymatic saccharification of pretreated alginate by alginate lyases produced 52.2 % of the theoretical maximal sugar yield, which was only 7.5 % higher than the sugar yield obtained with unpretreated alginate. Mass spectrometric analyses of products of the two reactions revealed that acidic pretreatment and enzymatic saccharification produced saturated monomers (i.e., mannuronic and guluronic acid) with saturated oligosaccharides and unsaturated monomers (i.e., 4-deoxy-L-erythro-5-hexoseulose uronic acid; DEH), respectively. While DEH is further metabolized by microorganisms, mannuronic acid and guluronic acid are not metabolizable. Because of the poor efficacy in increasing enzymatic digestibility and owing to the formation of non-fermentable saturated monomers, acidic pretreatment cannot be recommended for enzymatic saccharification and fermentation of alginate.
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Alginatos/metabolismo , Metabolismo dos Carboidratos , Fermentação , Phaeophyceae/metabolismo , Alga Marinha/metabolismo , Cromatografia em Gel , Ácido Glucurônico/metabolismo , Ácidos Hexurônicos/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
BACKGROUND: Comparative proteomics in bacteria are often hampered by the differential nature of dataset quality and/or inherent biological deviations. Although common practice compensates by reproducing and normalizing datasets from a single sample, the degree of certainty is limited in comparison of multiple dataset. To surmount these limitations, we introduce a two-step assessment criterion using: (1) the relative number of total spectra (R TS ) to determine if two LC-MS/MS datasets are comparable and (2) nine glycolytic enzymes as internal standards for a more accurate calculation of relative amount of proteins. Lactococcus lactis HR279 and JHK24 strains expressing high or low levels (respectively) of green fluorescent protein (GFP) were used for the model system. GFP abundance was determined by spectral counting and direct fluorescence measurements. Statistical analysis determined relative GFP quantity obtained from our approach matched values obtained from fluorescence measurements. RESULTS: L. lactis HR279 and JHK24 demonstrates two datasets with an R TS value less than 1.4 accurately reflects relative differences in GFP levels between high and low expression strains. Without prior consideration of R TS and the use of internal standards, the relative increase in GFP calculated by spectral counting method was 3.92 ± 1.14 fold, which is not correlated with the value determined by the direct fluorescence measurement (2.86 ± 0.42 fold) with the p = 0.024. In contrast, 2.88 ± 0.92 fold was obtained by our approach showing a statistically insignificant difference (p = 0.95). CONCLUSIONS: Our two-step assessment demonstrates a useful approach to: (1) validate the comparability of two mass spectrometric datasets and (2) accurately calculate the relative amount of proteins between proteomic datasets.
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Proteínas de Bactérias/metabolismo , Bases de Dados de Proteínas , Lactobacillus/metabolismo , Proteômica/métodos , Cromatografia Líquida , Proteínas de Fluorescência Verde/metabolismo , Lactobacillus/crescimento & desenvolvimento , Padrões de Referência , Espectrometria de Massas em TandemRESUMO
In clinical settings, biopsies are routinely used to determine cancer type and grade based on tumor cell morphology, as determined via histochemical or immunohistochemical staining. Unfortunately, in a significant number of cases, traditional biopsy results are either inconclusive or do not provide full subtype differentiation, possibly leading to inefficient or ineffective treatment. Glycomic profiling of the cell membrane offers an alternate route toward cancer diagnosis. In this study, isomer-sensitive nano-LC/MS was used to directly obtain detailed profiles of the different N-glycan structures present on cancer cell membranes. Membrane N-glycans were extracted from cells representing various subtypes of breast, lung, cervical, ovarian, and lymphatic cancer. Chip-based porous graphitized carbon nano-LC/MS was used to separate, identify, and quantify the native N-glycans. Structure-sensitive N-glycan profiling identified hundreds of glycan peaks per cell line, including multiple isomers for most compositions. Hierarchical clusterings based on Pearson correlation coefficients were used to quickly compare and separate each cell line according to originating organ and disease subtype. Based simply on the relative abundances of broad glycan classes (e.g., high mannose, complex/hybrid fucosylated, complex/hybrid sialylated, etc.), most cell lines were readily differentiated. More closely related cell lines were differentiated based on several-fold differences in the abundances of individual glycans. Based on characteristic N-glycan profiles, primary cancer origins and molecular subtypes could be distinguished. These results demonstrate that stark differences in cancer cell membrane glycosylation can be exploited to create an MS-based biopsy, with potential applications toward cancer diagnosis and direction of treatment.
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Neoplasias/patologia , Polissacarídeos/metabolismo , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Cromatografia Líquida , Glicômica , Humanos , Espectrometria de Massas , Neoplasias/classificação , Neoplasias/metabolismoRESUMO
Marine red macroalgae have emerged to be renewable biomass for the production of chemicals and biofuels, because carbohydrates that form the major component of red macroalgae can be hydrolyzed into fermentable sugars. The main carbohydrate in red algae is agarose, and it is composed of D-galactose and 3,6-anhydro-L-galactose (AHG), which are alternately bonded by ß1-4 and α1-3 linkages. In this study, a novel ß-galactosidase that can act on agarooligosaccharides (AOSs) to release galactose was discovered in a marine bacterium (Vibrio sp. strain EJY3); the enzyme is annotated as Vibrio sp. EJY3 agarolytic ß-galactosidase (VejABG). Unlike the lacZ-encoded ß-galactosidase from Escherichia coli, VejABG does not hydrolyze common substrates like lactose and can act only on the galactose moiety at the nonreducing end of AOS. The optimum pH and temperature of VejABG on an agarotriose substrate were 7 and 35°C, respectively. Its catalytic efficiency with agarotriose was also similar to that with agaropentaose or agaroheptaose. Since agarotriose lingers as the unreacted residual oligomer in the currently available saccharification system using ß-agarases and acid prehydrolysis, the agarotriose-hydrolyzing capability of this novel ß-galactosidase offers an enormous advantage in the saccharification of agarose or agar in red macroalgae for its use as a biomass feedstock for fermentable sugar production.
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Ágar/metabolismo , Sefarose/metabolismo , Vibrio/enzimologia , beta-Galactosidase/metabolismo , Ágar/química , Sequência de Aminoácidos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Metabolismo dos Carboidratos , Carboidratos/química , Clonagem Molecular , Fermentação , Galactose/química , Galactose/metabolismo , Concentração de Íons de Hidrogênio , Hidrólise , Oligossacarídeos/química , Oligossacarídeos/metabolismo , Filogenia , Rodófitas/química , Especificidade por Substrato , Temperatura , Vibrio/genética , beta-Galactosidase/genéticaRESUMO
The vibrational spectrum of a pyrimidine cation in the ground electronic state was obtained using vacuum ultraviolet mass-analyzed threshold ionization (VUV-MATI) spectroscopy. Accurate ionization energy of pyrimidine was determined from the 0-0 band position in the VUV-MATI spectrum and was measured by varying the PFI field to the zero field limit, which is 75,258 ± 7 cm(-1) (9.3308 eV). The spectrum displayed a large number of vibrational peaks, which could be nearly completely assigned through Franck-Condon analysis performed with variations of geometrical parameters at the B3LYP/cc-pVTZ level. Based on the excellent agreement between experimental and calculated results, the definite geometry of the pyrimidine cation in the ground electronic state was determined to be a planar structure with C2v symmetry with a decreased N-N distance in the ring.
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Pirimidinas/química , Cátions/química , Espectrometria de Massas , Estrutura Molecular , Teoria Quântica , Espectrofotometria Ultravioleta , VácuoRESUMO
The association between self-rated health (SRH) and the development of atrial fibrillation (AF) in the general population remains underexplored. We reviewed the data of 9,895 participants in the Ansung-Ansan cohort study, a community-based Korean study. SRH was categorised as 'poor', 'fair', or 'good'. A newly developed AF was identified through biennial electrocardiography examinations and/or a self-reported history of physician-determined diagnoses. Over a median follow-up of 11 years, 149 patients (1.5%) developed AF. Compared with the 'good' group, the 'poor' group exhibited a higher risk of incident AF (adjusted hazard ratio, 1.85; 95% confidence interval, 1.19-2.87). Old age, female sex, lower educational level, smoking, cardiovascular diseases (hypertension, diabetes mellitus, and coronary artery disease), and inflammation were associated with 'poor' SRH. Along with SRH, age, male sex, urban residence, hypertension, and myocardial infarction were also associated with a higher risk of incidental AF. The combined model, which included conventional risk factors and SRH, demonstrated a marginally improved performance in predicting incident AF (concordance index: 0.704 vs. 0.714, P = 0.058). Poor SRH is independently associated with the development of AF in Korean adults. However, it plays a limited role in AF surveillance when combined with conventional AF risk factors.
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Fibrilação Atrial , Humanos , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etiologia , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Idoso , República da Coreia/epidemiologia , Incidência , Autorrelato , Adulto , Nível de Saúde , Estudos de CoortesRESUMO
Background: Autistic individuals frequently experience psychiatric co-occurring conditions, but the association with self-harm/suicidality according to these conditions was not yet elucidated. We aimed to summarize the association between self-harm/suicidality and psychiatric co-occurring conditions in autistic people. Methods: We systematically searched PubMed, Scopus, Embase, Web of Science, and Cochrane Database of Systematic Reviews until June 4, 2024 (PROSPERO registration number: CRD42023412860). Observational studies were included that provided information to calculate the odds ratio (OR) regarding the association between self-harm/suicidality and psychiatric co-occurring conditions in autistic individuals. We summarized the identified associations by presenting OR range or meta-analyzing when 7 or more estimates are available. Findings: The systematic search found 20 eligible studies with 301,841 participants. Our findings suggested that autistic individuals with any psychiatric disorder (k = 1; OR 3.55; 95% CI 1.27-9.98), ADHD (k = 3; OR range: 1.07-1.65), or mood disorder (k = 1; OR 1.26; 95% CI 1.05-1.51) may be associated with higher odds of self-harm than those without these conditions. We identified potential positive associations between suicidality and the following co-occurring conditions: any psychiatric disorder (k = 1; OR 11.65; 95% CI 10.68-12.71), psychotic disorder (k = 4; OR range: 1.95-10.97), mood disorder (k = 3; OR range: 1.75-9.82), bipolar disorder (k = 2; OR range: 2.55-4.95), depressive disorder (k = 10; pooled OR 2.29; 95% CI 1.39-3.77), trauma- and stress-related disorder (k = 2; OR range: 1.28-10.47), and adjustment disorder (k = 1; OR 3.52; 95% CI 2.89-4.28). Interpretation: We found psychiatric co-occurring conditions that may be associated with higher odds of self-harm/suicidality in autistic individuals. However, our findings should be interpreted with caution considering the limited number of included studies. We suggested that clinicians should remain vigilant for autistic individuals with psychiatric co-occurring conditions for their potentially higher likelihood of self-harm and suicidality. Funding: This research was supported by a grant of the R&D project, funded by the National Center for Mental Health (grant number: MHER22A01).
RESUMO
INTRODUCTION: Antibiotic use for acute otitis media (AOM) is one of the major sources of antimicrobial resistance. However, the effective minimal antibiotic duration for AOM remains unclear. Moreover, guidelines often recommend broad ranges (5-10 days) of antibiotic use, yet the clinical impact of such a wide window has not been assessed. METHODS: We systematically searched PubMed/MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library from database inception to 6 October 2021. Network meta-analysis was conducted on randomized controlled trials that assessed antibiotic treatment for AOM in children (PROSPERO CRD42020196107). RESULTS: For amoxicillin and amoxicillin-clavulanate, 7-day regimens were noninferior to 10-day regimens in clinical responses [amoxicillin: risk ratio (RR) 0.919 (95% CI 0.820-1.031), amoxicillin-clavulanate: RR 1.108 (0.957-1.282)], except for ≤ 2 years. For the third-generation cephalosporins, 7-day and 10-day regimens had similar clinical responses compared to placebo [7-day: RR 1.420 (1.190-1.694), 10-day: RR 1.238 (1.125-1.362) compared to placebo]. However, 5-day regimens of amoxicillin-clavulanate and third-generation cephalosporins were inferior to 10-day regimens. Compared to amoxicillin, a shorter treatment duration was tolerable with amoxicillin-clavulanate. CONCLUSIONS: Our findings indicated that 10 days of antibiotic use may be unnecessarily long, while the treatment duration should be longer than 5 days. Otherwise, 5-day regimens would be sufficient for a modest treatment goal. Our findings revealed that the current wide range of recommended antibiotic durations may have influenced the clinical outcome of AOM, and a narrower antibiotic duration window should be re-established.