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1.
Zhongguo Dang Dai Er Ke Za Zhi ; 26(8): 840-844, 2024 Aug 15.
Artigo em Chinês | MEDLINE | ID: mdl-39148389

RESUMO

OBJECTIVES: To investigate the clinical phenotypes and genotypes of children with congenital fibrinogen disorder (CFD). METHODS: A retrospective analysis was conducted on the clinical data of 16 children with CFD. Polymerase chain reaction was used to amplify all exons and flanking sequences of the FGA, FGB, and FGG genes, and sequencing was performed to analyze mutation characteristics. RESULTS: Among the 16 children, there were 9 boys (56%) and 7 girls (44%), with a median age of 4 years at the time of attending the hospital. Among these children, 9 (56%) attended the hospital due to bleeding events, and 7 (44%) were diagnosed based on preoperative examination. The children with bleeding events had a significantly lower fibrinogen activity than those without bleeding events (P<0.05). Genetic testing was conducted on 12 children and revealed a total of 12 mutations, among which there were 4 novel mutations, i.e., c.80T>C and c.1368delC in the FGA gene and c.1007T>A and C.1053C>A in the FGG gene. There were 2 cases of congenital afibrinogenemia caused by null mutations of the FGA gene, with relatively severe bleeding symptoms. There were 7 cases of congenital dysfibrinogenemia mainly caused by heterozygous missense mutations of the FGG and FGA genes, and their clinical phenotypes ranged from asymptomatic phenotype to varying degrees of bleeding. CONCLUSIONS: The clinical phenotypes of children with CFD are heterogeneous, and the severity of bleeding is associated with the level of fibrinogen activity, but there is a weak association between clinical phenotype and genotype.


Assuntos
Afibrinogenemia , Fibrinogênio , Genótipo , Mutação , Fenótipo , Humanos , Masculino , Feminino , Afibrinogenemia/genética , Pré-Escolar , Criança , Fibrinogênio/genética , Lactente , Estudos Retrospectivos , Adolescente , Hemorragia/genética , Hemorragia/etiologia
2.
Org Lett ; 26(27): 5670-5675, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38923904

RESUMO

Axially chiral carboxylic acids are important motifs in chiral catalysts and ligands. We herein reported the synthesis of axially chiral carboxylic acids via Pd(II)-catalyzed atroposelective C-H olefination using carboxylic acid as the native directing group. A broad range of axial chiral biaryl-2-carboxylic acids were synthesized in good yields with high enantioselectivities (up to 84% yield with 99% ee). Gram-scale reaction and further transformation reactions also provide a platform for synthetic applications of this method.

3.
Cell Rep ; 43(7): 114368, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38905100

RESUMO

DOT1L mediates the methylation of histone H3 at lysine 79 and, in turn, the transcriptional activation or repression in a context-dependent manner, yet the regulatory mechanisms and functions of DOT1L/H3K79me remain to be fully explored. Following peptide affinity purification and proteomic analysis, we identified that DCAF1-a component of the E3 ligase complex involved in HIV regulation-is associated with H3K79me2 and DOT1L. Interestingly, blocking the expression or catalytic activity of DOT1L or repressing the expression of DCAF1 significantly enhances the tumor necrosis factor alpha (TNF-α)/nuclear factor κB (NF-κB)-induced reactivation of the latent HIV-1 genome. Mechanistically, upon TNF-α/NF-κB activation, DCAF1 is recruited to the HIV-1 long terminal repeat (LTR) by DOT1L and H3K79me2. Recruited DCAF1 subsequently induces the ubiquitination of NF-κB and restricts its accumulation at the HIV-1 LTR. Altogether, our findings reveal a feedback modulation of HIV reactivation by DOT1L-mediated histone modification regulation and highlight the potential of targeting the DOT1L/DCAF1 axis as a therapeutic strategy for HIV treatment.


Assuntos
HIV-1 , Histona-Lisina N-Metiltransferase , Histonas , NF-kappa B , Ubiquitina-Proteína Ligases , Humanos , HIV-1/fisiologia , HIV-1/metabolismo , Histona-Lisina N-Metiltransferase/metabolismo , Histona-Lisina N-Metiltransferase/genética , Histonas/metabolismo , NF-kappa B/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , Repetição Terminal Longa de HIV/genética , Células HEK293 , Ativação Viral , Metilação , Fator de Necrose Tumoral alfa/metabolismo , Infecções por HIV/virologia , Infecções por HIV/metabolismo , Lisina/metabolismo , Proteínas Serina-Treonina Quinases
4.
Nanomaterials (Basel) ; 14(12)2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38921904

RESUMO

Large-area oriented ZnO nanoarrays (including nanowire, nanorod, and nanotube) on ITO glass substrates are synthesized via the simple hydrothermal, electrodeposition, and electrochemical etching approach. The morphology of ZnO nanoarrays is controlled by adjusting the reaction temperature, reaction time, and current density. The scanning and transmission electron microscopy (SEM and TEM) results indicate the successful preparation of large-area oriented ZnO nanoarrays with different types, and the energy-dispersive X-microanalysis spectrum (EDS) and X-ray diffraction (XRD) results confirm that the composition of the obtained nanoarrays is ZnO. More importantly, the as-prepared ZnO nanotube arrays are observed with about a 40% increase in ultraviolet absorption intensity compared to the ZnO nanowire/nanorod arrays, due to having larger specific surface areas. The as-prepared different types of ZnO nanoarrays have great potential for applications in low-cost and high-performance optoelectronic devices.

5.
N Biotechnol ; 82: 85-91, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-38777090

RESUMO

Suppressor tRNAs, notable for their capability of reading through the stop codon while maintaining normal peptide synthesis, are promising in treating diseases caused by premature termination codons (PTC). However, the lack of effective engineering methods for suppressor tRNAs has curtailed their application potential. Here, we introduce a directed evolution technology that employs phage-assisted continuous evolution (PACE), combined with gradient biosensors featuring various PTCs in the M13 gene III. Utilizing this novel methodology, we have successfully evolved tRNATrp (UGG) reading through the UGA stop codon in Escherichia coli. Massively parallel sequencing revealed that these mutations predominantly occurred in the anticodon loop. Finally, two suppressor tRNATrp (UGA) mutants exhibited over fivefold increases in readthrough efficiency.


Assuntos
Escherichia coli , RNA de Transferência , Escherichia coli/genética , RNA de Transferência/genética , Evolução Molecular Direcionada , Códon de Terminação/genética , Mutação , Bacteriófago M13/genética
6.
Food Chem ; 449: 139226, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38608603

RESUMO

The ripening characteristics after capping of honey are favourable for improving its quality. However, research on the variation and formation of aroma characteristics of honey in this process is lacking. Therefore, the present study was carried out with different stages of Rhus chinensis honeys (RCHs) after capping and identified 192 volatiles with varying levels of concentration. "Fruity" was the main aroma characteristic of RCHs at different stages after capping, mainly contributed by (E)-ß-damascenone. Methyl salicylate might be a potential indicator for differentiating RCHs at different stages after capping. The metabolic pathway analyses revealed that the aroma compounds in RCHs undergo transformation at different stages after capping, which subsequently affects its aroma characteristics formation. This work is the first to study the dynamic changes in honey aroma characteristics after capping from multiple perspectives, and the results are of great significance for understanding the aroma characteristics after capping and quality control of honey.


Assuntos
Mel , Odorantes , Rhus , Compostos Orgânicos Voláteis , Mel/análise , Odorantes/análise , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/análise , Rhus/química , Cromatografia Gasosa-Espectrometria de Massas , Manipulação de Alimentos , Controle de Qualidade
7.
Sci Total Environ ; 922: 171288, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38423309

RESUMO

Plant litter decomposition is critical for carbon and nutrient cycling globally. However, the effect of large herbivore grazing on litter decomposition and its mechanisms remain less explored. Here, 1203 paired observations and 381 independent experiments were analyzed to determine how litter decomposition and nutrient cycling respond to changes in grazing intensity. Grazing significantly increased litter decomposition rate by 14.08 % and litter carbon release by 5.03 %, and this effect was observed in grasslands and croplands but not in forests. The positive grazing effect was also found under sheep and cattle/yak grazing. Moderate grazing advanced the home-field advantage effect but inhibited under heavy grazing for grazed litters. The grazing effect was larger for high quality litter than for low quality litter. Litter decomposition slowed under >10 years heavy grazing but accelerated under moderate grazing. The effects of large herbivore grazing on litter decomposition were jointly influenced by grazing intensity, livestock type, climate condition, decomposition duration, litter quality, and soil properties. Our results demonstrated that large herbivore grazing accelerates litter decomposition globally and emphasized the significance and importance of grazing intensity on litter decomposition, which should be integrated into terrestrial ecosystem models.


Assuntos
Ecossistema , Herbivoria , Bovinos , Animais , Ovinos , Nitrogênio , Florestas , Solo , Carbono , Folhas de Planta
8.
Small Methods ; 8(8): e2301385, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38415955

RESUMO

Sugar substitutes are popular due to their akin taste and low calories. However, excessive use of aspartame and erythritol can have varying effects. While D-allulose is presently deemed a secure alternative to sugar, its excessive consumption is not devoid of cellular stress implications. In this study, the evolution of Escherichia coli Nissle 1917 (EcN) is directed to utilize allulose as sole carbon source through a combination of adaptive laboratory evolution (ALE) and fluorescence-activated droplet sorting (FADS) techniques. Employing whole genome sequencing (WGS) and clustered regularly interspaced short palindromic repeats interference (CRISPRi) in conjunction with compensatory expression displayed those genetic mutations in sugar and amino acid metabolic pathways, including glnP, glpF, gmpA, nagE, pgmB, ybaN, etc., increased allulose assimilation. Enzyme-substrate dynamics simulations and deep learning predict enhanced substrate specificity and catalytic efficiency in nagE A247E and pgmB G12R mutants. The findings evince that these mutations hold considerable promise in enhancing allulose uptake and facilitating its conversion into glycolysis, thus signifying the emergence of a novel metabolic pathway for allulose utilization. These revelations bear immense potential for the sustainable utilization of D-allulose in promoting health and well-being.


Assuntos
Evolução Molecular Direcionada , Escherichia coli , Escherichia coli/genética , Escherichia coli/metabolismo , Evolução Molecular Direcionada/métodos , Frutose/metabolismo , Carbono/metabolismo , Mutação , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Sequenciamento Completo do Genoma , Redes e Vias Metabólicas
9.
Angew Chem Int Ed Engl ; 63(15): e202319871, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38289019

RESUMO

The combination of achiral Cp*Rh(III) with chiral carboxylic acids (CCAs) represents an efficient catalytic system in transition metal-catalyzed enantioselective C-H activation. However, this hybrid catalysis is limited to redox-neutral C-H activation reactions and the adopt to oxidative enantioselective C-H activation remains elusive and pose a significant challenge. Herein, we describe the development of an electrochemical Cp*Rh(III)-catalyzed enantioselective C-H annulation of sulfoximines with alkynes enabled by chiral carboxylic acid (CCA) in an operationally friendly undivided cell at room temperature. A broad range of enantioenriched 1,2-benzothiazines are obtained in high yields with excellent enantioselectivities (up to 99 % yield and 98 : 2 er). The practicality of this method is demonstrated by scale-up reaction in a batch reactor with external circulation. A crucial chiral Cp*Rh(III) intermediate is isolated, characterized, and transformed, providing rational support for a Rh(III)/Rh(I) electrocatalytic cycle.

10.
Food Res Int ; 175: 113677, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38129024

RESUMO

Dendropanax dentiger honey (DDH) is a specialty herbal honey from China. Previous research on DDH has mostly focused on its composition and potential chemical markers, no studies have been conducted on the changes in aroma characteristics and chiral odorants during its maturation. Therefore, the present study aims to address the missing parts. The proportions and total concentrations of 185 volatile compounds identified in different classes varied with DDHs ripening. Fourteen common odor-active compounds were identified by odor activity values (OAVs) and GC-olfactometry (GC-O) analysis. The aroma profiles of DDHs were observed to vary at different ripening stages, although the dominant aroma characteristic was "fruity" aroma, which became more pronounced with increasing maturity. The enantiomeric contents and distributions of 7 volatile enantiomers were related to specific physicochemical indicators and the maturity of DDHs, among which the enantiomers of linalool oxide A may be a potential indicator to identify its maturity. Furthermore, precise quantification and OAVs calculation showed that the enantiomer (2S, 5S)-linalool oxide A presented the highest concentration (8.83-27.39 ng/mL) and only the enantiomer R-linalool (OAVs: 5.56-6.14) was an important contributor to the aroma profiles of DDHs at different stages of maturity. These results provided a new research idea for quality control and identification of DDHs at different maturity stages.


Assuntos
Mel , Compostos Orgânicos Voláteis , Cromatografia Gasosa-Espectrometria de Massas/métodos , Mel/análise , Compostos Orgânicos Voláteis/análise , Odorantes/análise
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