RESUMEN
COP1 is a critical repressor of plant photomorphogenesis in darkness. However, COP1 plays distinct roles in the photoreceptor UVR8 pathway in Arabidopsis thaliana. COP1 interacts with ultraviolet B (UV-B)-activated UVR8 monomers and promotes their retention and accumulation in the nucleus. Moreover, COP1 has a function in UV-B signaling, which involves the binding of its WD40 domain to UVR8 and HY5 via conserved Val-Pro (VP) motifs of these proteins. UV-B-activated UVR8 interacts with COP1 via both the core domain and the VP motif, leading to the displacement of HY5 from COP1 and HY5 stabilization. However, it remains unclear whether the function of COP1 in UV-B signaling is solely dependent on its VP motif binding capacity and whether UV-B regulates the subcellular localization of COP1. Based on published structures of the COP1 WD40 domain, we generated a COP1 variant with a single amino acid substitution, COP1C509S , which cannot bind to VP motifs but retains the ability to interact with the UVR8 core domain. UV-B only marginally increased nuclear YFP-COP1 levels and significantly promoted YFP-COP1 accumulation in the cytosol, but did not exert the same effects on YFP-COP1C509S . Thus, the full UVR8-COP1 interaction is important for COP1 accumulation in the cytosol. Notably, UV-B signaling including activation of HY5 transcription was obviously inhibited in the Arabidopsis lines expressing YFP-COP1C509S , which cannot bind VP motifs. We conclude that the full binding of UVR8 to COP1 leads to the predominant accumulation of COP1 in the cytosol and that COP1 has an additional function in UV-B signaling besides VP binding-mediated protein destabilization.
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Proteínas de Arabidopsis , Arabidopsis , Transducción de Señal , Ubiquitina-Proteína Ligasas , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Núcleo Celular/metabolismo , Proteínas Cromosómicas no Histona/genética , Proteínas Cromosómicas no Histona/metabolismo , Regulación de la Expresión Génica de las Plantas , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Rayos UltravioletaRESUMEN
Both non-rapid eye movement (NonREM) sleep and rapid eye movement (REM) sleep, as well as sleep spindle and ripple oscillations, are important for memory formation. Through cortical EEG recordings of prefrontal cortex and hippocampus during and after an inhibitory avoidance task, we analysed the dynamic changes in the amounts of sleep, spindle and ripple oscillations related to memory formation. The total amount of NonREM sleep was reduced during the first hour after learning. Moreover, significant decrease of the total spindle and ripple counts was observed at the first hour after learning as well. In addition, foot shock alone, with no associated learning, produced little effect on the dynamics of sleep oscillations, indicating that the learning experience is necessary for these changes to occur.
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Reacción de Prevención , Sueño de Onda Lenta , Sueño , Sueño REM , Hipocampo , ElectroencefalografíaRESUMEN
Protein S-nitrosylation, which is defined by the covalent attachment of nitric oxide (NO) to the thiol group of cysteine residues, is known to play critical roles in plant development and stress responses. NO promotes seedling photomorphogenesis and NO emission is enhanced by light. However, the function of protein S-nitrosylation in plant photomorphogenesis is largely unknown. E3 ligase CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) and transcription factor ELONGATED HYPOCOTYL 5 (HY5) antagonistically regulate seedling photomorphogenesis. COP1 inhibits plant photomorphogenesis by targeting photomorphogenic promoters like HY5 for 26S proteasome degradation. Here, we report that COP1 is S-nitrosylated in vitro. Mass spectrometry analyses revealed that two evolutionarily well conserved residues, cysteine 425 and cysteine 607, in the WD40 domain of COP1 are S-nitrosylated. S-nitrosylated glutathione (GSNO) is an important physiological NO donor for protein S-nitrosylation. The Arabidopsis (Arabidopsis thaliana) gsnor1-3 mutant, which accumulates higher level of GSNO, accumulated higher HY5 levels than wildtype (WT), indicating that COP1 activity is inhibited. Protein S-nitrosylation can be reversed by Thioredoxin-h5 (TRXh5) in plants. Indeed, COP1 interacts directly with TRXh5 and its close homolog TRXh3. Moreover, catalase 3 (CAT3) acts as a transnitrosylase that transfers NO to its target proteins like GSNO reductase (GSNOR). We found that CAT3 interacts with COP1 in plants. Taken together, our data indicate that the activity of COP1 is likely inhibited by NO via S-nitrosylation to promote the accumulation of HY5 and photomorphogenesis.
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Proteínas de Arabidopsis , Arabidopsis , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico , Óxido Nítrico , Ubiquitina-Proteína Ligasas , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Arabidopsis/metabolismo , Arabidopsis/crecimiento & desarrollo , Arabidopsis/genética , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Óxido Nítrico/metabolismo , Luz , Cisteína/metabolismo , Plantones/metabolismo , Plantones/crecimiento & desarrollo , Plantones/genética , Aldehído Oxidorreductasas/metabolismo , Aldehído Oxidorreductasas/genética , Regulación de la Expresión Génica de las PlantasRESUMEN
BACKGROUND: ABCC8 variants can cause hyperinsulinemia by activating or deactivating gene expression. This study used targeted exon sequencing to investigate genetic variants of ABCC8 and the associated phenotypic features in Chinese patients with hyperinsulinemic hypoglycemia (HH). METHODS: We enrolled eight Chinese children with HH and analyzed their clinical characteristics, laboratory results, and genetic variations. RESULTS: The age at presentation among the patients ranged from neonates to 0.6 years old, and the age at diagnosis ranged from 1 month to 5 years, with an average of 1.3 ± 0.7 years. Among these patients, three presented with seizures, and five with hypoglycemia. One patient (Patient 7) also had microcephaly. All eight patients exhibited ABCC8 abnormalities, including six missense mutations (c. 2521 C > G, c. 3784G > A, c. 4478G > A, c. 4532T > C, c. 2669T > C, and c. 331G > A), two deletion-insertion mutations (c. 3126_3129delinsTC and c. 3124_3126delins13), and one splicing mutation (c. 1332 + 2T > C). Two of these mutations (c. 3126_3129delinsTC and c. 4532T > C) are novel. Six variations were paternal, two were maternal, and one was de novo. Three patients responded to diazoxide and one patient responded to octreotide treatment. All there patients had diazoxide withdrawal with age. Two patients (patients 3 and 7) were unresponsive to both diazoxide and octreotide and had mental retardation. CONCLUSIONS: Gene analysis can aid in the classification, treatment, and prognosis of children with HH. In this study, the identification of seven known and two novel variants in the ABCC8 gene further enriched the variation spectrum of the gene.
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Hiperinsulinismo Congénito , Recién Nacido , Niño , Humanos , Hiperinsulinismo Congénito/tratamiento farmacológico , Hiperinsulinismo Congénito/genética , Hiperinsulinismo Congénito/diagnóstico , Diazóxido/uso terapéutico , Octreótido/uso terapéutico , Mutación , China/epidemiología , Receptores de Sulfonilureas/genéticaRESUMEN
Obesity-related ciliopathies, as a group of ciliopathies including Alström Syndrome and Bardet-Biedl Syndrome, exhibit distinct genetic and phenotypic variability. The understanding of these diseases is highly significant for understanding the functions of primary cilia in the human body, particularly regarding the relationship between obesity and primary cilia. The diagnosis of these diseases primarily relies on clinical presentation and genetic testing. However, there is a significant lack of research on biomarkers to elucidate the variability in clinical manifestations, disease progression, prognosis, and treatment responses. Through an extensive literature review, the paper focuses on obesity-related ciliopathies, reviewing the advancements in the field and highlighting the potential roles of biomarkers in the clinical presentation, diagnosis, and prognosis of these diseases.
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Síndrome de Bardet-Biedl , Biomarcadores , Ciliopatías , Obesidad , Humanos , Obesidad/metabolismo , Obesidad/genética , Ciliopatías/genética , Ciliopatías/metabolismo , Síndrome de Bardet-Biedl/genética , Síndrome de Bardet-Biedl/metabolismo , Cilios/metabolismo , Cilios/patología , Síndrome de Alstrom/genética , Síndrome de Alstrom/metabolismo , AnimalesRESUMEN
BACKGROUND: The emergence of carbapenem-resistant Klebsiella pneumoniae (CRKP) attracted extensive attention. Information on CRKP from hospital wastewater (HWW) is limited. The aims of this study were to investigate the genomic characteristics and to evaluate the survivability characteristics of 11 CRKP from HWW in a Chinese teaching hospital in Fujian province. RESULTS: A total of 11 CRKP from HWW were recovered in this study. All CRKP from HWW were resistant to most antibiotics. Comparative genetic analysis demonstrated that all CRKP isolates were clustered into the three distinct phylogenetic clades and clade 2 and clade 3 were mixtures of samples collected from both HWW and clinical settings. Varieties of resistance genes, virulence genes and plasmid replicon types were detected in CRKP from HWW. In vitro transfer of blaKPC-2 was successful for 3 blaKPC-2-positive CRKP from HWW with high conjugation frequency. Our study demonstrated that the genetic environments of blaKPC-2 shared core structure with ISKpn27-blaKPC-2-ISKpn6. Group analysis showed that CRKP from HWW had a lower survivability in serum compared to clinical CRKP (p < 005); and CRKP from HWW had no significant difference in survivability in HWW compared to clinical CRKP (p > 005). CONCLUSIONS: We analyzed the genomic and survivability characteristics of CRKP from HWW in a Chinese teaching hospital. These genomes represent a significant addition of genomic data from the genus and could serve as a valuable resource for future genomic studies about CRKP from HWW.
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Enterobacteriaceae Resistentes a los Carbapenémicos , Infecciones por Klebsiella , Humanos , Carbapenémicos , Klebsiella pneumoniae/genética , Aguas Residuales , Filogenia , Infecciones por Klebsiella/tratamiento farmacológico , Antibacterianos/uso terapéutico , Genómica , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Hospitales de Enseñanza , Pruebas de Sensibilidad Microbiana , beta-Lactamasas/genéticaRESUMEN
Since its outbreak in late 2021, the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widely reported to be able to evade neutralizing antibodies, becoming more transmissible while causing milder symptoms than previous SARS-CoV-2 strains. Understanding the underlying molecular changes of Omicron SARS-CoV-2 infection and corresponding host responses are important to the control of Omicron COVID-19 pandemic. In this study, we report an integrative proteomics and metabolomics investigation of serum samples from 80 COVID-19 patients infected with Omicron SARS-CoV-2, as well as 160 control serum samples from 80 healthy individuals and 80 patients who had flu-like symptoms but were negative for SARS-CoV-2 infection. The multiomics results indicated that Omicron SARS-CoV-2 infection caused significant changes to host serum proteome and metabolome comparing to the healthy controls and patients who had flu-like symptoms without COVID-19. Protein and metabolite changes also pointed to liver dysfunctions and potential damage to other host organs by Omicron SARS-CoV-2 infection. The Omicron COVID-19 patients could be roughly divided into two subgroups based on their proteome differences. Interestingly, the subgroup who mostly had received full vaccination with booster shot had fewer coughing symptom, changed sphingomyelin lipid metabolism, and stronger immune responses including higher numbers of lymphocytes, monocytes, neutrophils, and upregulated proteins related to CD4+ T cells, CD8+ effector memory T cells (Tem), and conventional dendritic cells, revealing beneficial effects of full COVID-19 vaccination against Omicron SARS-CoV-2 infection through molecular changes.
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COVID-19 , Humanos , COVID-19/prevención & control , SARS-CoV-2 , Vacunas contra la COVID-19 , Pandemias , Proteoma , Proteómica , Anticuerpos Neutralizantes , Anticuerpos AntiviralesRESUMEN
Perovskite materials with excellent optical and electronic properties have huge potential in the research field of photodetectors. Constructing heterojunctions and promoting carrier transportation are significant for the development of perovskite-based optoelectronics devices with high performances. Herein, we demonstrated a CsPbBr3/SnO2heterojunction photodetector and improved the device performances through post-annealing treatment of SnO2film. The results indicated that the electrical properties of SnO2films will make an important impact on carrier extraction, especially for type-II heterojunction. As the electrons transfer layer in CsPbBr3/SnO2type-II heterojunction, defects related to oxygen vacancy should be the key factor to affect carrier concentration, induce carriers' limitation and recombination rate. Under proper annealing temperature for SnO2layer, the recombination rate can decrease to 1.37 × 1021cm3s and the spectral responsivity will be highly increased. This work can enhance the understanding on the photoresponse of perovskite photodetectors, and will be helpful for the further optimization and design of optoelectronic devices based on the perovskite heterojunction.
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MicroRNAs (miRNAs) control liver diseases, but the role of microRNA-181a-5p in acute liver failure (ALF) is unclear. In this study, the ALF model was generated by injection of D-galactosamine (D-GalN) and lipopolysaccharide (LPS). The levels of miRNAs were assessed by microarray and qRT-PCR. The expression of caspase 3 was detected as the marker of cell apoptosis in ALF by immunohistochemistry and western blot. The targeting of microRNA-181a-5p on the high mobility group box 1 (HMGB1) was verified by dual luciferase assay. The impact of microRNA-181a-5p and HMGB1 was explored by flow cytometry. Results showed that microRNA-181a-5p was significantly down-regulated by D-GalN/LPS in vivo and in vitro, while the level of HMGB1 was up-regulated after the challenge. Furthermore, microRNA-181a-5p overexpression attenuated cell apoptosis in D-GalN/TNF-treated BNLCL2 cells. MicroRNA-181a-5p could directly target HMGB1 mRNA and repress its expressions, in further HMGB1 is involved in microRNA-181a-5p effect on cell apoptosis of ALF. In conclusion, these findings demonstrate that microRNA-181a-5p regulates hepatocyte apoptosis via HMGB1 in the development of ALF, which may provide potential therapeutic targets for ALF. However, the precise underlying mechanism that connects microRNA-181a-5p and HMGB1 remains to be explored.
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Proteína HMGB1 , Fallo Hepático Agudo , MicroARNs , Animales , Ratones , Apoptosis/genética , Galactosamina , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Lipopolisacáridos , Fallo Hepático Agudo/genética , Fallo Hepático Agudo/metabolismo , Análisis por Micromatrices , MicroARNs/genética , MicroARNs/metabolismoRESUMEN
BACKGROUND: Dyslipidemia, especially hypercholesterolemia is of significant clinical interest. Precise diagnosis is not paid enough attention to about the management of pediatric patients with hypercholesterolemia, which is especially apparent in China. Given this, we designed this study to confirm the specific molecular defects associated with hypercholesterolemia using whole-exome sequencing (WES) to be helpful for precise diagnosis and treatment. METHODS: Pediatric patients were enrolled using specific criteria and their clinical information were recorded for later evaluation in conjunction with the WES completed for each of these patients. RESULTS: Our criteria allowed for the initial enrollment of 35 patients, 30 of whom (aged 1.02-12.99 years) underwent successful genetic sequencing and clinical investment. Positive results were obtained in 63.33% (19/30) of these patients. We identified 25 variants in 30 pediatric patients with persistent hypercholesterolemia, seven of them were novel and variants in LDLR and ABCG5/ABCG8 ranks first and second, respectively. Further analysis revealed that the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB) and lipoprotein (a) were higher in patients with positive genetic results. CONCLUSION: Our study enriched the genetic and phenotypic spectra for hypercholesterolemia in young patients. Genetic testing is important for the prognostics and treatment of pediatric patients. Heterozygous ABCG5/8 variants may be underestimated in pediatric patients with hypercholesterolemia.
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Hipercolesterolemia , Hiperlipoproteinemia Tipo II , Humanos , Niño , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/genética , Hiperlipoproteinemia Tipo II/genética , Fenotipo , Genotipo , LDL-Colesterol , MutaciónRESUMEN
In this study, we introduced H-terminated diamond solution-gate field-effect transistor (H-diamond SGFET) to detect trace SARS-CoV-2 N-protein, which plays an important role in replication and transcription of viral RNA. 1-Pyrenebutyric acid-N-hydroxy succinimide ester (Pyr-NHS) was modified on H-diamond surface as linker, on which the specific antibody of SARS-CoV-2 N-protein was catenated. Fourier transform infrared spectrum, scanning electron microscope and energy dispersive spectrum were utilized to demonstrate the modification of H-diamond with Pyr-NHS and antibody. Shifts of IDS(max) at VGS = -500 mV in transfer characteristics of H-diamond SGFET was observed to determine N-protein concentration in phosphate buffer solution. Good linear relationship between IDS(max) and log10(N-protein) was observed from 10-14 to 10-5 g/mL with goodness of fit R2 = 0.90 and sensitivity of 1.98 µA/Log10 [concentration of N-protein] at VDS = -500 mV, VGS = -500 mV. Consequently, this prepared H-diamond SGFET biosensor may provide a new idea for diagnosis of SARS-CoV-2 due to a wide detection range from 10-14 to 10-5 g/mL and low limit of detection 10-14 g/mL.
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Research demonstrated that folate deficiency in either the mother or father could impact the biological functions of the offspring's of neural cells. Folate deficiency can also impair the methionine cycle, thus contributing to the conversion of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH), which could potentially cause damage to the central nervous system. The study focused on the effect of parental folate deficiency on neural cell apoptosis in offspring neonatal rats and whether it is mediated by the levels of SAM and SAH in brains. The experimental design was conducted by feeding female and male Sprague Dawley (SD) rats with either folate-deficient or folate-normal diets, sacrificing the offspring within 24 h and isolating their brain tissue. Rats were divided into four groups: the maternal-folate-deficient and paternal-folate-deficient (D-D) group; the maternal-folate-deficient and paternal-folate-normal (D-N) group; the maternal-folate-normal and paternal-folate-deficient (N-D) group; and the maternal-folate-normal and paternal-folate-normal (N-N) group. There was down-regulation of B-cell lymphoma 2 (Bcl-2) expression, up-regulation of Bcl-2-associated X protein (Bax) and Caspase-3 expression of neural cells, and pathological changes in the brain ultrastructure, as well as decreased SAM levels, increased SAH levels, and a decreased SAM/SAH ratio in the rat fetal brain via parental folate deficiency. In conclusion, parental folate deficiency could induce the apoptosis of neural cells in neonatal offspring rats, while biparental folate deficiency had the greatest effect on offspring, and the unilateral effect was greater in mothers than in fathers. This process may be mediated by the levels of SAM and SAH in the rat fetal brain.
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Deficiencia de Ácido Fólico , Ratas , Animales , Masculino , Femenino , Animales Recién Nacidos , Proteína X Asociada a bcl-2/genética , Caspasa 3 , Ratas Sprague-Dawley , Deficiencia de Ácido Fólico/metabolismo , Ácido Fólico , Apoptosis/fisiología , S-Adenosilmetionina/metabolismoRESUMEN
The current worldwide spread of carbapenem resistance genes (CRGs) has posed a major public health threat, which continues to grow in severity. Hospital wastewaters (HWWs) are major reservoirs for antibiotic resistance genes, while resistomes in HWWs are still poorly characterized when it comes to CRGs. We comprehensively characterized the profile and actual transmissibility of extracellular CRGs (eCRGs) and intracellular CRGs (iCRGs) in HWWs for the first time. In this study, CRGs showed similar relative abundance in treated and untreated HWWs. Meanwhile, HWWs treatments led to the enrichment of blaIMP-8, probably attributed to the promotion of Novosphingobium and Prosthecobacter after treatment. To evaluate the transmission potential of CRGs, extracellular and intracellular carbapenem-resistant plasmids were captured from HWWs by transformation and conjugation, respectively. We found an interesting phenomenon regarding the transmission characteristics of CRGs: blaKPC-carrying plasmids could only be captured by transformation, while blaNDM-carrying plasmids were captured by conjugation. Further experiments showed that HWW treatments increased the conjugation ability of blaNDM. In conclusion, our study demonstrated that HWWs are significant reservoirs of CRGs and various CRGs exhibit different modes of transmission in HWWs. CRGs cannot be removed by membrane bioreactor and chlorine disinfection. An urgent need is to develop more efficient wastewater treatments to limit CRG dissemination.
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Antibacterianos , Aguas Residuales , ADN , beta-Lactamasas/genética , Plásmidos/genética , Carbapenémicos/farmacología , Hospitales , Pruebas de Sensibilidad MicrobianaRESUMEN
OBJECTIVE: To investigate the clinical and genetic characteristics of a patient with STISS syndrome due to variant of PSMD12 gene. METHODS: Clinical data and result of genetic testing of a patient who was admitted to Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine on October 4, 2020 were analyzed, together with a review of relevant literature. RESULTS: The patient was found to harbor a heterozygous c.601C>T (p.Arg201*) nonsense variant of the PSMD12 gene, which was unreported previously. Clinically, the height of the patient has differed significantly from reported in the literature. An extremely rare case of STISS syndrome due to variant of the PSMD12 gene has been diagnosed. CONCLUSION: Whether the severely short stature is part of the clinical spectrum for PSMD12 gene variants needs to be further explored, and the efficacy and safety of growth hormone therapy has yet to be determined.
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Enanismo , Niño , Humanos , China , Pruebas Genéticas , Heterocigoto , SíndromeRESUMEN
OBJECTIVE: This study aims to assess the short- and long-term changes in the upper airway and alar width after mini-implant -assisted rapid palatal expansion (MARPE) in nongrowing patients. METHODS: Five electronic databases (PubMed, Scopus, Embase, Web of Science, and Cochrane Library) were searched up to 2 August, 2023 based on the PICOS principles. The main outcomes were classified into three groups: 1) nasal cavity changes, 2) upper airway changes and 3) alar changes. The mean difference (MD) and 95% confidence intervals (CI) were used to assess these changes. Heterogeneity tests, subgroup analyses, sensitivity analyses, and publication bias were also analyzed. RESULT: Overall, 22 articles were included for data analysis. Nasal cavity width (WMD: 2.05 mm; 95% CI: 1.10, 3.00) and nasal floor width (WMD: 2.13 mm; 95% CI: 1.16, 3.11) increased significantly. While palatopharyngeal volume (WMD: 0.29 cm3, 95% CI: -0.44, 1.01), glossopharyngeal volume (WMD: 0.30 cm3, 95% CI: -0.29, 0.89) and hypopharyngeal volume (WMD: -0.90 cm3; 95% CI: -1.86, 0.06) remained unchanged, nasal cavity volume (WMD: 1.24 cm3, 95% CI: 0.68, 1.81), nasopharyngeal volume (MD: 0.75 cm3, 95% CI: 0.44, 1.06), oropharyngeal volume (WMD: 0.61 cm3, 95% CI: 0.35, 0.87), and total volume of the upper airway (WMD: 1.67 cm3, 95% CI: 0.68, 2.66) increased significantly. Alar width (WMD: 1.47 mm; 95% CI: 0.40, 2.55) and alar base width (WMD: 1.54 mm; 95% CI: 1.21, 1.87) also increased. CONCLUSION: MARPE can increase nasal cavity width, nasal cavity volume, nasopharyngeal volume and oropharyngeal volume for nongrowing patients, but has no significant effect on hypopharyngeal volume. In addition, the alar width also increased. However, the studies included in this meta-analysis were mainly retrospective, nonrandomized and small in number, so the findings should be interpreted with caution and high-quality RCTs need to be studied.
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Implantes Dentales , Técnica de Expansión Palatina , Humanos , Estudios Retrospectivos , Técnica de Expansión Palatina/efectos adversos , Nariz , Cavidad Nasal , Maxilar , Tomografía Computarizada de Haz CónicoRESUMEN
A 2-year-old boy was admitted to Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine in Nov 30th, 2018, due to polydipsia, polyphagia, polyuria accompanied with increased glucose levels for more than 2 weeks. He presented with symmetrical short stature [height 81 cm (ï¼2.2 SD), weight 9.8 kg (ï¼2.1 SD), body mass index 14.94 kg/m2 (P10-P15)], and with no special facial or physical features. Laboratory results showed that the glycated hemoglobin A1c was 14%, the fasting C-peptide was 0.3 ng/mL, and the islet autoantibodies were all negative. Oral glucose tolerance test showed significant increases in both fasting and postprandial glucose, but partial islet functions remained (post-load C-peptide increased 1.43 times compared to baseline). A heterozygous variant c.1366C>T (p.R456C) was detected in GATA6 gene, thereby the boy was diagnosed with a specific type of diabetes mellitus. The boy had congenital heart disease and suffered from transient hyperosmolar hyperglycemia after a patent ductus arteriosus surgery at 11 months of age. Insulin replacement therapy was prescribed, but without regular follow-up thereafter. The latest follow-up was about 3.5 years after the diagnosis of diabetes when the child was 5 years and 11 months old, with the fasting blood glucose of 6.0-10.0 mmol/L, and the 2 h postprandial glucose of 17.0-20.0 mmol/L.
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Diabetes Mellitus Tipo 2 , Masculino , Niño , Humanos , Preescolar , Lactante , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/complicaciones , Mutación Missense , Péptido C/genética , China , Insulina/genética , Glucosa , Glucemia , Factor de Transcripción GATA6/genéticaRESUMEN
Simultaneous electrochemical ring contraction and expansion reactions remain unexplored to date. Herein, the reductive electrosynthesis of heterocycle-fused fulleroids from fullerotetrahydropyridazines and electrophiles in the presence of a trace amount of oxygen has been achieved with concurrent ring contraction and ring expansion. When trifluoroacetic acid and alkyl bromides are employed as electrophiles, heterocycle-fused fulleroids with a 1,1,2,6-configuration are regioselectively formed. In contrast, heterocycle-fused fulleroids with a 1,1,4,6-configuration are regioselectively produced as two separable stereoisomers if phthaloyl chloride is used as the electrophile. The reaction proceeds through multiple steps of electroreduction, heterocycle ring-opening, oxygen oxidation, heterocycle contraction, fullerene cage expansion, and nucleophilic addition. The structures of these fulleroids have been determined by spectroscopic data and single-crystal X-ray diffraction analyses. The observed high regioselectivities have been rationalized by theoretical calculations. Representative fulleroids have been applied in organic solar cells as the third component and exhibit good performance.
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Fulerenos , Cristalografía por Rayos X , Fulerenos/química , Estereoisomerismo , HalógenosRESUMEN
Light regulates the subcellular localization of plant photoreceptors, a key step in light signaling. Ultraviolet-B radiation (UV-B) induces the plant photoreceptor UV RESISTANCE LOCUS 8 (UVR8) nuclear accumulation, where it regulates photomorphogenesis. However, the molecular mechanism for the UV-B-regulated UVR8 nuclear localization dynamics is unknown. With fluorescence recovery after photobleaching (FRAP), cell fractionation followed by immunoblotting and co-immunoprecipitation (Co-IP) assays we tested the function of UVR8-interacting proteins including CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1), REPRESSOR OF UV-B PHOTOMORPHOGENESIS 1 (RUP1) and RUP2 in the regulation of UVR8 nuclear dynamics in Arabidopsis thaliana. We showed that UV-B-induced rapid UVR8 nuclear translocation is independent of COP1, which previously was shown to be required for UV-B-induced UVR8 nuclear accumulation. Instead, we provide evidence that the UV-B-induced UVR8 homodimer-to-monomer photo-switch and the concurrent size reduction of UVR8 enables its monomer nuclear translocation, most likely via free diffusion. Nuclear COP1 interacts with UV-B-activated UVR8 monomer, thereby promoting UVR8 nuclear retention. Conversely, RUP1and RUP2, whose expressions are induced by UV-B, inhibit UVR8 nuclear retention via attenuating the UVR8-COP1 interaction, allowing UVR8 to exit the nucleus. Collectively, our data suggest that UV-B-induced monomerization of UVR8 promotes its nuclear translocation via free diffusion. In the nucleus, COP1 binding promotes UVR8 monomer nuclear retention, which is counterbalanced by the major negative regulators RUP1 and RUP2.
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Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Transducción de Señal , Arabidopsis/metabolismo , Fotorreceptores de Plantas/metabolismo , Rayos Ultravioleta , Ubiquitina-Proteína Ligasas/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
Wine is a high-value alcoholic beverage welcomed by consumers because of its flavor and nutritional value. The key information on wine bottle label is the basis of consumers' choice, which also becomes a target for manufacturers to adulterate, including geographical origin, grape variety and vintage. With the improvement of wine adulteration technology, modern technological means are needed to solve the above mentioned problems. The chemical basis of wine determines the type of technique used. Detection technology can be subdivided into four groups: mass spectrometry techniques, spectroscopic techniques, chromatography techniques, and other techniques. Multivariate statistical analysis of the data was performed by means of chemometrics methods. This paper outlines a series of procedures for wine classification and identification, and classified the analytical techniques and data processing methods used in recent years with listing their principles, advantages and disadvantages to help wine researchers choose appropriate methods to meet the challenge and ensure wine traceability and authenticity.
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Vitis , Vino , Bebidas Alcohólicas/análisis , Espectrometría de Masas/métodos , Análisis Multivariante , Vitis/química , Vino/análisisRESUMEN
Polygonaceae is a large family of medicinal herbs that includes many species used as traditional Chinese medicine, such as Per sicaria per foliata. Here, we sequenced the complete chloroplast genome of P. per foliata using Illumina sequencing technology with the purpose of providing a method to facilitate accurate identification. After being annotated, the complete chloroplast genome of P. per foliata was compared with those of Fagopyrum tataricum, Per sicaria chinensis, Fagopyrum dibotrys, and Fallopia multiflora. The complete chloroplast genome of P. per foliata is 160 730 bp in length, containing a small single-copy region of 12 927 bp, a large single-copy region of 85 433 bp, and a pair of inverted repeat regions of 62 370 bp. A total of 131 genes were annotated, including 8 rRNA genes, 34 tRNA genes, and 84 protein-coding genes. Forty-two simple sequence repeats and 55 repeat sequences were identified. Mutational hotspot analyses indicated that five genes (matK, ndhF, ccsA, cemA, and rpl20) could be selected as candidates for molecular markers. Moreover, phylogenetic analysis showed that all the Polygonaceae species formed a monophyletic clade, and P. per foliata showed the closest relationship with P. chinense. The study provides valuable molecular information to accurately identify P. per foliata and assist in its development and application.