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OBJECTIVE: To evaluate the efficacy and safety of hydroxychloroquine sulfate (HCQ) in the treatment of low risk phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN). METHODS: A total of 110 patients with low risk PLA2R-associated MN were included in the study. Patients who met the inclusion and exclusion criteria were assigned randomly to two groups: the HCQ treatment group and the control group. The control group received standard supportive treatment according to the guidelines, while the HCQ treatment group received HCQ in addition to the supportive treatment. The clinical data of the patients were analyzed, with comparisons made at baseline and during the six-month follow-up period. Any adverse reactions were recorded. RESULTS: The baseline data were comparable between the HCQ treatment group and the control group. At the end of the six-month follow-up period, the reductions in urine protein excretion and serum PLA2R antibody titer were more notable in the HCQ treatment group than those in the control group, with these differences being statistically significant (p < 0.05). Compared to the control group, the HCQ treatment group had fewer patients who were converted from low risk to moderate-to-high risk (p = 0.084). There were also no severe adverse reactions in the HCQ treatment group. CONCLUSION: In patients with low risk PLA2R-associated MN, adequate supportive therapy combined with HCQ is superior to supportive therapy alone in controlling proteinuria and reducing serum PLA2R antibody titers. Additionally, our study demonstrated that the incidence of adverse reactions did not increase. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (Registration No.: ChiCTR1900021757, Date of registration: 2019-03-08).
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Glomerulonefrite Membranosa , Hidroxicloroquina , Receptores da Fosfolipase A2 , Humanos , Hidroxicloroquina/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Receptores da Fosfolipase A2/imunologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Resultado do Tratamento , Autoanticorpos/sangue , ProteinúriaRESUMO
We report the discovery and functional characterization of a new bacterial tRNA species. The tRNA-Asp-AUC, from a fast-growing desert streptomycete, decodes GAU codons. In the absence of queuosine tRNA anticodon modification in streptomycetes, the new tRNA circumvents inefficient wobble base-pairing during translation. The tRNA, which is constitutively expressed, greatly enhances synthesis of 4 different antibiotics in the model mesophilic species Streptomyces coelicolor, including the product of a so-called cryptic pathway, and increases yields of medically-important antibiotics in other species. This can be rationalised due to increased expression of both pleiotropic and pathway-specific transcriptional activators of antibiotic biosynthesis whose genes generally possess one or more GAT codons; the frequency of this codon in these gene sets is significantly higher than the average for streptomycete genes. In addition, the tRNA enhances production of cobalamin, a precursor of S-adenosyl methionine, itself an essential cofactor for synthesis of many antibiotics. The results establish a new paradigm of inefficient wobble base-pairing involving GAU codons as an evolved strategy to regulate gene expression and, in particular, antibiotic biosynthesis. Circumventing this by expression of the new cognate tRNA offers a generic strategy to increase antibiotic yields and to expand the repertoire of much-needed new bioactive metabolites produced by these valuable bacteria.
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Streptomyces , Streptomyces/genética , Antibacterianos , RNA de Transferência/genéticaRESUMO
BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is an orphan metabolic disease characterized by extremely elevated low-density lipoprotein cholesterol (LDL-C), xanthomas, aortic stenosis, and premature atherosclerotic cardiovascular disease (ASCVD). In addition to LDL-C, studies in experimental models and small clinical populations have suggested that other types of metabolic molecules might also be risk factors responsible for cardiovascular complications in HoFH, but definitive evidence from large-scale human studies is still lacking. Herein, we aimed to comprehensively characterize the metabolic features and risk factors of human HoFH by using metabolic systems strategies. METHODS: Two independent multi-center cohorts with a total of 868 individuals were included in the cross-sectional study. First, comprehensive serum metabolome/lipidome-wide analyses were employed to identify the metabolomic patterns for differentiating HoFH patients (n = 184) from heterozygous FH (HeFH, n = 376) and non-FH (n = 100) subjects in the discovery cohort. Then, the metabolomic patterns were verified in the validation cohort with 48 HoFH patients, 110 HeFH patients, and 50 non-FH individuals. Subsequently, correlation/regression analyses were performed to investigate the associations of clinical/metabolic alterations with typical phenotypes of HoFH. In the prospective study, a total of 84 HoFH patients with available follow-up were enrolled from the discovery cohort. Targeted metabolomics, deep proteomics, and random forest approaches were performed to investigate the ASCVD-associated biomarkers in HoFH patients. RESULTS: Beyond LDL-C, various bioactive metabolites in multiple pathways were discovered and validated for differentiating HoFH from HoFH and non-FH. Our results demonstrated that the inflammation and oxidative stress-related metabolites in the pathways of arachidonic acid and lipoprotein(a) metabolism were independently associated with the prevalence of corneal arcus, xanthomas, and supravalvular/valvular aortic stenosis in HoFH patients. Our results also identified a small marker panel consisting of high-density lipoprotein cholesterol, lipoprotein(a), apolipoprotein A1, and eight proinflammatory and proatherogenic metabolites in the pathways of arachidonic acid, phospholipid, carnitine, and sphingolipid metabolism that exhibited significant performances on predicting first ASCVD events in HoFH patients. CONCLUSIONS: Our findings demonstrate that human HoFH is associated with a variety of metabolic abnormalities and is more complex than previously known. Furthermore, this study provides additional metabolic alterations that hold promise as residual risk factors in HoFH population.
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Aterosclerose , Doenças Cardiovasculares , Hipercolesterolemia Familiar Homozigota , Hiperlipoproteinemia Tipo II , Xantomatose , Humanos , LDL-Colesterol , Hiperlipoproteinemia Tipo II/complicações , Hiperlipoproteinemia Tipo II/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/complicações , Estudos Prospectivos , Estudos Transversais , Ácido Araquidônico , Fatores de Risco , Fenótipo , Fatores de Risco de Doenças Cardíacas , Aterosclerose/epidemiologia , Aterosclerose/complicações , Lipoproteína(a) , Xantomatose/complicaçõesRESUMO
PURPOSE: Head rotation is an effective positional therapy for obstructive sleep apnea (OSA). However, not all OSA patients benefit from head rotation. This study aimed to explore the clinical phenotype of OSA patients who can benefit from head rotation. METHODS: We performed a retrospective review of 184 consecutive OSA patients who underwent polysomnography. Head rotation in supine position was determined by high-quality video recording. According to the changes in apnea-hypopnea index (AHI) after head rotation, OSA patients were divided into two groups: patients with response to head rotation(HR) and patients without response to head rotation(NHR). Demographic factors and overnight polysomnography were analyzed. RESULTS: Compared with NHR group, HR group showed significantly lower AHI (51.8 vs 31.5, p < 0.01), time spent with oxygen saturation below 90%(5.3% vs 0.51%, p < 0.01), and higher lowest oxygen saturation(80% vs 86%, p < 0.05). Logistic regression showed that AHI was an independent factor to predict the decrease of AHI in head rotation (OR 0.985, 95% CI 0.970-0.979, p < 0.05). Among mild to moderate group (AHI < 30/h), severe group (30/h ≤ AHI < 60/h), and extremely severe group (AHI ≥ 60/h), the percentage decrease of AHI in head rotation was 18.5%, 9.5%, and 2.6%, respectively. Surprisingly, the percentage decrease of AHI of 6 responders in mild to moderate group was more than 50%. CONCLUSION: OSA patients who respond well to head rotation have less severe disease, and patients with mild to moderate OSA are more likely to improve and benefit from this position. Our research provides potential strategies and insights into the individual treatment of OSA patients.
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Apneia Obstrutiva do Sono , Humanos , Estudos Transversais , Apneia Obstrutiva do Sono/diagnóstico , Gravidade do Paciente , Polissonografia , Estudos RetrospectivosRESUMO
The central region of MDM2 is critical for p53 activation and tumor suppression. Upon ribosomal stress, this region is bound by ribosomal proteins, particularly ribosomal protein L11 (RPL11), leading to MDM2 inactivation and subsequent p53 activation. Here, we solved the complex structure of human MDM2-RPL11 at 2.4 Å. MDM2 extensively interacts with RPL11 through an acidic domain and two zinc fingers. Formation of the MDM2-RPL11 complex induces substantial conformational changes in both proteins. RPL11, unable to bind MDM2 mutants, fails to induce the activation of p53 in cells. MDM2 mimics 28S rRNA binding to RPL11. The C4 zinc finger determines RPL11 binding to MDM2 but not its homolog, MDMX. Our results highlight the essential role of the RPL11-MDM2 interaction in p53 activation and tumor suppression and provide a structural basis for potential new anti-tumor drug development.
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Modelos Moleculares , Proteínas Proto-Oncogênicas c-mdm2/química , Proteínas Ribossômicas/química , Ativação Transcricional , Proteína Supressora de Tumor p53/metabolismo , Sequência de Aminoácidos , Cristalização , Inativação Gênica , Humanos , Dados de Sequência Molecular , Mutação , Ligação Proteica , Estrutura Quaternária de Proteína , Estrutura Terciária de Proteína , Proteínas Proto-Oncogênicas c-mdm2/genética , Alinhamento de SequênciaRESUMO
BACKGROUND: Kernel number per spike (KNS) and spike length (SL) are important spike-related traits in wheat variety improvement. Discovering genetic loci controlling these traits is necessary to elucidate the genetic basis of wheat yield traits and is very important for marker-assisted selection breeding. RESULTS: In the present study, we used a recombinant inbred line population with 248 lines derived from the two founder genotypes of wheat, Bima4 and BainongAK58, to construct a high-density genetic map using wheat 55 K genotyping assay. The final genetic linkage map consists of 2356 bin markers (14,812 SNPs) representing all 21 wheat chromosomes, and the entire map spanned 4141.24 cM. A total of 7 and 18 QTLs were identified for KNS and SL, respectively, and they were distributed on 11 chromosomes. The allele effects of the flanking markers for 12 stable QTLs, including four QTLs for KNS and eight QTLs for SL, were estimated based on phenotyping data collected from 15 environments in a diverse wheat panel including 384 elite cultivars and breeding lines. The positive alleles at seven loci, namely, QKns.his-7D2-1, QKns.his-7D2-2, QSl.his-4A-1, QSl.his-5D1, QSl.his-4D2-2, QSl.his-5B and QSl.his-5A-2, significantly increased KNS or SL in the diverse panel, suggesting they are more universal in their effects and are valuable for gene pyramiding in breeding programs. The transmission of Bima4 allele indicated that the favorite alleles at five loci (QKns.his-7D2-1, QSl.his-5A-2, QSl.his-2D1-1, QSl.his-3A-2 and QSl.his-3B) showed a relatively high frequency or an upward trend following the continuity of generations, suggesting that they underwent rigorous selection during breeding. At two loci (QKns.his-7D2-1 and QSl.his-5A-2) that the positive effects of the Bima4 alleles have been validated in the diverse panel, two and one kompetitive allele-specific PCR (KASP) markers were further developed, respectively, and they are valuable for marker-assisted selection breeding. CONCLUSION: Important chromosome regions controlling KNS and SL were identified in the founder parents. Our results are useful for knowing the molecular mechanisms of founder parents and future molecular breeding in wheat.
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Cromossomos de Plantas , Triticum , Mapeamento Cromossômico , Genótipo , Melhoramento Vegetal , Triticum/genéticaRESUMO
Pseudarthrobacter sulfonivorans strain Ar51 can degrade crude oil and multi-substituted benzene compounds efficiently at low temperatures. However, it cannot degrade hydroquinone, which is a key intermediate in the degradation of several other compounds of environmental importance, such as 4-nitrophenol, g-hexachlorocyclohexane, 4-hydroxyacetophenone and 4-aminophenol. Here we co-expressed the two subunits of hydroquinone dioxygenase from Sphingomonas sp. strain TTNP3 with different promoters in the strain Ar51. The strain with 2 hdnO promoters exhibited the strongest hydroquinone catabolic activity. However, in the absence of antibiotic selection this ability to degrade hydroquinone was lost due to plasmid instability. Consequently, we constructed a hisD knockout strain, which was unable to synthesise histidine. By introducing the hisD gene onto the plasmid, the ability to degrade hydroquinone in the absence of antibiotic selection was stabilised. In addition, to make the strain more stable for industrial applications, we knocked out the recA gene and integrated the hydroquinone dioxygenase genes at this chromosomal locus. This strain exhibited the strongest activity in catabolizing hydroquinone, up to 470 mg/L in 16 h without antibiotic selection. In addition, this activity was shown to be stable when the strain has cultured in medium without antibiotic selection after 20 passages.
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Dioxigenases , Sphingomonas , Antibacterianos/metabolismo , Biodegradação Ambiental , Dioxigenases/genética , Dioxigenases/metabolismo , Hidroquinonas/metabolismo , Micrococcaceae , Sphingomonas/genética , Sphingomonas/metabolismoRESUMO
PURPOSE: Obstructive sleep apnea (OSA) increases the risk for olfactory dysfunction. However, the relationship between olfactory function and cognition in OSA patients is unclear. The present study aimed to investigate the relationship between cognition and olfactory dysfunction (OD) in patients with OSA. METHOD: This was a cross-sectional study in which 74 patients with OSA and 22 controls were recruited. All subjects completed polysomnography, Sniffin' Sticks, and -neurocognitive assessments. According to results of Sniffin' Sticks, OSA patients were divided into two groups: OSA with OD (53 cases) and OSA without OD (21 cases). Neurocognitive function was assessed by Montreal Cognitive Assessment (MoCA), Memory and Executive Screening (MES), and Shape Trail Test (STT). Cognition was compared between OSA with and without OD. Correlation between olfactory parameters and respiratory sleep parameters and neurocognitive assessments was analyzed. RESULTS: Compared with OSA without OD, OSA with OD showed significantly decreased neurocognitive scores of MoCA (29-27 vs 27-23, p < 0.01), MES-5R (45-40.1 vs 43-33.5, p < 0.01) and increased consuming time of STT-B (91.66 vs 121.63, p < 0.01). A positive correlation was found between the scores of MoCA and MES-5R and all olfactory parameters. In addition, a negative correlation was present between the time consumed for STT-B and odor thresholds (r = - 0.344, p < 0.01), odor identification (r = - 0.335, p < 0.01), and threshold-discrimination-identification scores (r = - 0.448, p < 0.01). CONCLUSION: Olfactory function is associated cognitive function in patients with OSA and may provide a new direction for early treatment interventions in OSA patients at risk for cognitive impairment.
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Disfunção Cognitiva , Transtornos do Olfato , Apneia Obstrutiva do Sono , Disfunção Cognitiva/complicações , Disfunção Cognitiva/diagnóstico , Estudos Transversais , Humanos , Transtornos do Olfato/complicações , Transtornos do Olfato/etiologia , PolissonografiaRESUMO
There are a lot of review papers of sample pretreatment, but the comprehensive review on pipette-tip solid-phase extraction (PT-SPE) is lacking. This review (133 references) is mainly devoted to the development of different types of micro- and nanosorbent-based PT-SPE, including silica materials, carbon materials, organic polymers, molecularly imprinted polymers, and metal-organic frameworks. Each section mainly introduces and discusses the preparation methods, advantages and limitations of adsorbents, and their applications to environmental, biological, and food samples. This review also demonstrates the advantages of PT-SPE like convenience, speed, less organic solvent, and low cost. Finally, the future application and development trend of PT-SPE are prospected.
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Nanotubos de Carbono/química , Extração em Fase Sólida/métodos , Adsorção , Animais , Grafite/química , Humanos , Estruturas Metalorgânicas/química , Polímeros Molecularmente Impressos/química , Dióxido de Silício/química , Extração em Fase Sólida/instrumentaçãoRESUMO
Using poly(ionic liquid) (PIL) and tetraethyl orthosilicate (TEOS) as the co-precursors, PIL-hybridized silica aerogel was prepared via sol-gel method for solid-phase microextraction (SPME). The ratio between PIL and TEOS was regulated to achieve the best extraction effect. The aerogel was coated onto the surface of stainless steel wire to get SPME fiber. Coupled to gas chromatography-flame ionization detector (GC-FID), the fiber was separately evaluated by the determination of alkanes, polycyclic aromatic hydrocarbons (PAHs), as well as BTEX (benzene, toluene, ethylbenzene, and xylenes) in immersion mode. The extraction performance of PAHs was attributed to π stacking and hydrophobic effect. After optimization of main extraction and desorption conditions, the SPME-GC-FID method was established towards eight PAHs, and it provided low detection limits (0.005 µg L-1, 0.010 µg L-1) and wide linear ranges (0.016-20.00 µg L-1, 0.033-20.00 µg L-1) with good linear coefficients (0.9991-0.9998). The method was applied to detect trace PAHs in real water samples, with relative recoveries of 86.2-119.2%. Furthermore, PIL-hybridized silica aerogel exhibits some superiorities like higher sensitivity, shorter extraction time, and better repeatability over other extraction coatings. The present work not only extends the range of aerogel materials but also promoted their further applications in sample preparation. Graphical abstract.
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Efficient, high-precision, and automatic measurement of tunnel structural changes is the key to ensuring the safe operation of subways. Conventional manual, static, and discrete measurements cannot meet the requirements of rapid and full-section detection in subway construction and operation. Mobile laser scanning technology is the primary method for tunnel detection. Herein, we propose a method to calculate shield tunnel displacements of a full cross-section tunnel. The point cloud data, obtained via a mobile tunnel deformation detection system, were fitted, projected, and interpolated to generate an orthophoto image. Combined with the cumulative characteristics of the tunnel gray gradient, the longitudinal ring seam of the tunnel was identified, while the Canny algorithm and Hough line detection algorithm identified the transverse seam. The symmetrical vertical foot method and cross-section superposition analysis were used to calculate the circumferential and radial displacements, respectively. The proposed displacement calculation method achieves automatic recognition of a ring seam, reduces human-computer interaction, and is fast, intelligent, and accurate. Furthermore, the description of the tunnel deformation location and deformation amount is more quantitative and specific. These results confirm the significance of shield tunnel displacement monitoring based on mobile monitoring systems in tunnel disease monitoring.
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Algoritmos , Computadores , Eletrocardiografia , HumanosRESUMO
Traditional precision measurement adopts discrete artificial static observation, which cannot meet the demands of the dynamic, continuous, fine and high-precision holographic measurement of large-scale infrastructure construction and complex operation and maintenance management. Due to its advantages of fast, accurate and convenient measurement, mobile laser scanning technology is becoming a popular technology in the maintenance and measurement of infrastructure construction such as tunnels. However, in some environments without satellite signals, such as indoor areas and underground spaces, it is difficult to obtain 3D data by means of mobile measurement technology. This paper proposes a method to restore the linear of the point cloud obtained by mobile laser scanning based on the measured track center line. In this paper, the measured track position is interpolated with a cubic spline to calculate the translations, and the rotation parameters are calculated by combining the simulation design data. The point cloud of the cross-section of the tunnel under the local coordinate system is converted to the absolute coordinate system to calculate the tunnel line. In addition, the method is verified by experiments combined with the subway tunnel data, and the overall point error can be controlled to within 0.1 m. The average deviation in the horizontal direction is 0.0551 m, and that in the vertical direction is 0.0274 m. Compared with the previous methods, this method can effectively avoid the obvious deformation of the tunnel and the sharp increase in the error, and can process the tunnel point cloud data more accurately and quickly. It also provides better data support for subsequent tunnel analysis such as 3D display, completion survey, systematic hazard management and so on.
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A Gram-staining-positive and aerobic coccus with the ability to degrade petroleum bacterium, designated Y42T, was isolated from the Lenghu oil field located in the northern margin of the Qaidam Basin. Phylogenetic and signature nucleotides analyses revealed that strain Y42T belongs to the genus Planococcus. The multiple sequence alignments of 16S rRNA and housekeeping genes showed that strain Y42T formed a distinct lineage with the other Planococcus clade. The average nucleotide identity (ANI) and DNA-DNA hybridization values (DDH) between strain Y42T and the reference strains were 69.5-70.1 and 19.4-21.7%, respectively, which values were below the threshold for species delineation. The major fatty acids of strain Y42T were anteiso-C15:0. The respiratory quinone was MK-7 (71.8%) as the predominant menaquinone followed the MK-6 (28.2%) and the cell-wall hydrolysates contained LL-diaminopimelic acid. The polar lipid was composed of diphosphatidyl glycerol, phosphatidyl glycerol, phosphoglycolipid, aminophospholipid and four unidentified lipids. The peptidoglycan type was A4α (L-Lys-D-Glu). The strain Y42T possessed larger genome (approximately 4 MB) and revealed obvious differences for the abundance of the COG categories compared with the other Planococcus bacteria. Also, the strain Y42T also possessed more unique orthologous proteins. The structural characteristics of the strain Y42T genome provided a competitive advantage for better survival in petroleum-polluted environments. Combined with the 16S rRNA gene and genome sequence, phenotypic as well as chemotaxonomic characterisations, strain Y42T is considered to represent a novel species of the genus Planococcus, for which the name Planococcus lenghuensis sp. nov. be proposed. The type strain is Y42T (= CGMCC 1.15921T = JCM 32719T).
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Planococcus (Bactéria) , Biodegradação Ambiental , Poluentes Ambientais/metabolismo , Ácidos Graxos/análise , Genes Bacterianos , Genoma Bacteriano , Óleos/metabolismo , Peptidoglicano/análise , Petróleo/metabolismo , Fenótipo , Fosfolipídeos/análise , Filogenia , Planococcus (Bactéria)/classificação , Planococcus (Bactéria)/genética , Planococcus (Bactéria)/isolamento & purificação , RNA Ribossômico 16S/genética , Solo/química , Microbiologia do Solo , Vitamina K 2/análiseRESUMO
A facile method was introduced for preparing a biocharcoal aerogel, which was derived from pomelo peel as the only raw material. The inner spongy layer of pomelo peel was freeze-dried for maintaining three-dimensional structure and then carbonized under high temperature and oxygen-limited conditions. The morphological structure and graphitization degree of biocharcoal aerogel were characterized using a scanning electron microscope and Raman spectrum. After sifting and grinding, the biocharcoal aerogel as an adsorbent was coated onto the surface of stainless steel wires. Through placing the wires into a polyetheretherketone tube, the in-tube solid-phase microextraction device was obtained. Coupled with high-performance liquid chromatography, it exhibited good extraction performance for polycyclic aromatic hydrocarbons, then an online analytical method was established with low limits of detection (0.005-0.050 ng/mL), wide linear ranges (0.017-15 ng/mL) with superior correlation coefficients higher than 0.9990, high enrichment factors (1128-3425), and acceptable intra- and inter-day repeatabilities (relative standard deviations ≤ 6.7%, n = 3). The method was applied to detect polycyclic aromatic hydrocarbons in bottled water samples, environmental water samples, and soft drinks with satisfactory recoveries (83.3-120.9%). This research not only developed a new carbon aerogel but also evaluated its adsorption performance in sample preparation.
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Carvão Vegetal/química , Hidrocarbonetos Policíclicos Aromáticos/análise , Microextração em Fase Sólida , Poluentes Químicos da Água/química , Adsorção , Géis/química , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
PURPOSE: Obstructive sleep apnea (OSA) is a common disorder characterized by recurrent episodes of partial or complete upper airway obstruction. OSA susceptibility is associated with multiple genetic, environmental, and developmental factors. The PPARG rs1801282 (G/C) polymorphism has been associated with OSA in obese Indian subjects, whereas no such association has been reported in Chinese Han subjects. Potential associations between other PPARG variants and OSA have not been investigated in Chinese Han populations. The aim of this study was to identify genetic variants of PPARG in unrelated Chinese Han patients with OSA and to investigate potential associations between these variants and OSA. METHODS: We performed a cross-sectional study of 233 individuals with OSA and 93 control individuals. A portable diagnostic device was used to diagnose OSA. Targeted sequencing was conducted to identify PPARG variants. Associations between PPARG variants and OSA were analyzed using multivariate regression. RESULTS: Three PPARG single-nucleotide polymorphisms were identified and the genotype frequencies of the rs1801282 polymorphism differed significantly. Subjects with the PPARG rs1801282 CG genotype had decreased risk of having OSA compared with subjects with the CC genotype after adjusting for confounding effects. CONCLUSIONS: We identified a variant of PPARG associated with the occurrence of OSA in Chinese Han populations.
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Povo Asiático/genética , Predisposição Genética para Doença/genética , PPAR gama/genética , Apneia Obstrutiva do Sono/genética , Variação Biológica da População/genética , Estudos de Casos e Controles , Estudos Transversais , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único/genética , Risco , Análise de Sequência , Apneia Obstrutiva do Sono/diagnósticoRESUMO
The dissacharide trehalose is an important intracellular osmoprotectant and the OtsA/B pathway is the principal pathway for trehalose biosynthesis in a wide range of bacterial species. Scaffolding proteins and other cytoskeletal elements play an essential role in morphogenetic processes in bacteria. Here we describe how OtsA, in addition to its role in trehalose biosynthesis, functions as an osmotic stress sensor to regulate cell morphology in Arthrobacter strain A3. In response to osmotic stress, this and other Arthrobacter species undergo a transition from bacillary to myceloid growth. An otsA null mutant exhibits constitutive myceloid growth. Osmotic stress leads to a depletion of trehalose-6-phosphate, the product of the OtsA enzyme, and experimental depletion of this metabolite also leads to constitutive myceloid growth independent of OtsA function. In vitro analyses indicate that OtsA can self-assemble into protein networks, promoted by trehalose-6-phosphate, a property that is not shared by the equivalent enzyme from E. coli, despite the latter's enzymatic activity when expressed in Arthrobacter. This, and the localization of the protein in non-stressed cells at the mid-cell and poles, indicates that OtsA from Arthrobacter likely functions as a cytoskeletal element regulating cell morphology. Recruiting a biosynthetic enzyme for this morphogenetic function represents an intriguing adaptation in bacteria that can survive in extreme environments.
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Arthrobacter/crescimento & desenvolvimento , Proteínas de Bactérias/metabolismo , Escherichia coli/crescimento & desenvolvimento , Regulação Bacteriana da Expressão Gênica , Fosfatos Açúcares/metabolismo , Trealose/análogos & derivados , Arthrobacter/enzimologia , Arthrobacter/genética , Proteínas de Bactérias/genética , Citocinese/efeitos dos fármacos , Escherichia coli/enzimologia , Escherichia coli/genética , Genes Bacterianos , Glucosiltransferases/genética , Glucosiltransferases/metabolismo , Pressão Osmótica , Trealose/metabolismoRESUMO
BACKGROUND: Olfactory dysfunction secondary to chronic rhinosinusitis (CRS) has been highly associated with impaired quality of life. Asian CRS patients showed a distinct inflammatory profile, with less type 2 endotype compared with European and North American. This study aimed to explore the pattern of the inflammatory cytokines in CRS patients from China and their association with olfactory function. METHODS: Institutional review board-approved prospective study in which the olfactory function of 71 CRS patients was assessed with Sniffin' Sticks before the nasal endoscopic surgery. A set of cytokines and inflammatory mediators including type 1 and type 2 inflammatory cytokines were measured in nasal mucus by using a multiplex flow cytometric bead assay (CBA). Baseline characteristics in CRS patients were collected and the Spearman r statistic was performed to assess the association of olfactory function with cytokines and inflammatory mediators. RESULTS: A total of 71 nasal mucus samples of CRS patients, including 25 chronic rhinosinusitis without nasal polyposis (CRSsNP) patients and 46 chronic rhinosinusitis with nasal polyposis (CRSwNP) patients, were evaluated in this study. The nasal mucus levels of type 1 inflammatory cytokine IFN-γ (interferon-γ), type 2 inflammatory cytokines including IL-4, IL-5 and GM-CSF (granulocyte-macrophage colony-stimulating factor) and anti-inflammatory cytokine IL-10 were significantly and inversely correlated with olfactory function in total patients with CRS (r = -0.308, p = 0.009; r = -0.250, p = 0.036; r = -0.399, p = 0.001; r = -0.269, p = 0.023; r = -0.273, p = 0.021, respectively). In CRSsNP, the olfactory function was inversely correlated with levels of type 1 inflammatory cytokine TNF-α (tumor necrosis factor-α) (r = -0.637, p = 0.001) and IL-10 (r = -0.468, p = 0.018). Nevertheless, the olfactory function in CRSwNP was inversely correlated with type 2 inflammatory cytokines including IL-4 (r = -0.303, p = 0.041) and IL-5 (r = -0.383, p = 0.009). CONCLUSION: Both type 1 and type 2 inflammatory cytokines may contribute to the pathogenesis of CRS-associated olfactory dysfunction in the Chinese population.
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Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Mediadores da Inflamação/metabolismo , Interferon gama/metabolismo , Interleucina-10/metabolismo , Interleucina-4/metabolismo , Interleucina-5/metabolismo , Rinite/etiologia , Rinite/fisiopatologia , Sinusite/etiologia , Sinusite/fisiopatologia , Olfato , Adulto , Povo Asiático , Doença Crônica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rinite/metabolismo , Sinusite/metabolismoRESUMO
Subway structure safety detection is an important method to ensure the safe operation of trains. Efficient, high-precision, and automatic tunnel clearance detection is the key to ensure safe operations. This study introduces a mobile tunnel scanning system that integrates a scanner, an inertial measurement unit (IMU), and a rail car. Global Navigation Satellite System (GNSS) time and system hardware calibration are used to synchronize time and space information of the system; the attitude and speed are corrected using the control points from the tunnel to improve the accuracy of absolute positioning. The section coordinate system is converted using the control points and system calibration parameters to complete the tunnel clearance inspection, and the distance between the nearest point of the section and the clear height of the vault is given. Taking Fengxi Road's Bashan tunnel section of Chongqing Metro Line 5 as an example, the overall system accuracy was tested. The accuracy of chord line measurements was within 1 mm, the internal coincidence accuracy of repeated measurements of the vault clear height was 1.1 mm, the internal coincidence accuracy of repeated measurements of the closest gauge point was 4.8 mm, and the system calibration accuracy was approximately 2 mm. Compared with the existing scheme, the system combines absolute measurement and relative measurement mode to judge the structural safety of tunnel section from multiple angles, high precision, and high efficiency.
RESUMO
With the ongoing developments in laser scanning technology, applications for describing tunnel deformation using rich point cloud data have become a significant topic of investigation. This study describes the independently developed CNU-TS-2 mobile tunnel monitoring system for data acquisition, which has an electric system to control its forward speed and is compatible with various laser scanners such as the Faro and Leica models. A comparison with corresponding data acquired by total station data demonstrates that the data collected by CNU-TS-2 is accurate. Following data acquisition, the overall and local deformation of the tunnel is determined by denoising and 360° deformation analysis of the point cloud data. To enhance the expression of the analysis results, this study proposes an expansion of the tunnel point cloud data into a two-dimensional image via cylindrical projection, followed by an expression of the tunnel deformation through color difference to visualize the deformation. Compared with the three-dimensional modeling method of visualization, this method is easier to implement and facilitates storage. In addition, it is conducive to the performance of comprehensive analysis of problems such as water leakage in the tunnel, thereby achieving the effect of multiple uses for a single image.