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1.
Small ; : e2402447, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940363

RESUMO

Lithium-carbon dioxide (Li-CO2) battery represents a high-energy density energy storage with excellent real-time CO2 enrichment and conversion, but its practical utilization is hampered by the development of an excellent catalytic cathode. Here, the synergistic catalytic strategy of designing CoRu bimetallic active sites achieves the electrocatalytic conversion of CO2 and the efficient decomposition of the discharge products, which in turn realizes the smooth operation of the Li-CO2 battery. Moreover, obtained support based on metal-organic frameworks precursors facilitates the convenient diffusion and adsorption of CO2, resulting in higher reaction concentration and lower mass transfer resistance. Meanwhile, the optimization of the interfacial electronic structure and the effective transfer of electrons are achieved by virtue of the strong interaction of CoRu at the support interface. As a result, the Li-CO2 cell assembled based on bimetallic CoRu active sites achieved a discharge capacity of 19,111 mA h g-1 and a steady-state discharge voltage of 2.58 V as well as a cycle life of >175 cycles at a rate of 100 mA g-1. Further experiments combined with density-functional theory calculations achieve a deeply view of the connection between cathode and electrochemical performance and pave a way for the subsequent development of advanced Li-CO2 catalytic cathodes.

2.
Stat Med ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38857904

RESUMO

The rise of cutting-edge precision cancer treatments has led to a growing significance of the optimal biological dose (OBD) in modern oncology trials. These trials now prioritize the consideration of both toxicity and efficacy simultaneously when determining the most desirable dosage for treatment. Traditional approaches in early-phase oncology trials have conventionally relied on the assumption of a monotone relationship between treatment efficacy and dosage. However, this assumption may not hold valid for novel oncology therapies. In reality, the dose-efficacy curve of such treatments may reach a plateau at a specific dose, posing challenges for conventional methods in accurately identifying the OBD. Furthermore, achieving reliable identification of the OBD is typically not possible based on a single small-sample trial. With data from multiple phase I and phase I/II trials, we propose a novel Bayesian random-effects dose-optimization meta-analysis (REDOMA) approach to identify the OBD by synthesizing toxicity and efficacy data from each trial. The REDOMA method can address trials with heterogeneous characteristics. We adopt a curve-free approach based on a Gamma process prior to model the average dose-toxicity relationship. In addition, we utilize a Bayesian model selection framework that uses the spike-and-slab prior as an automatic variable selection technique to eliminate monotonic constraints on the dose-efficacy curve. The good performance of the REDOMA method is confirmed by extensive simulation studies.

3.
Pharm Stat ; 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317370

RESUMO

The Bayesian logistic regression method (BLRM) is a widely adopted and flexible design for finding the maximum tolerated dose in oncology phase I studies. However, the BLRM design has been criticized in the literature for being overly conservative due to the use of the overdose control rule. Recently, a discussion paper titled "Improving the performance of Bayesian logistic regression model with overall control in oncology dose-finding studies" in Statistics in Medicine has proposed an overall control rule to address the "excessive conservativeness" of the standard BLRM design. In this short communication, we discuss the relative conservativeness of the standard BLRM design and also suggest a dose-switching rule to further enhance its performance.

4.
Angew Chem Int Ed Engl ; : e202404123, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38702953

RESUMO

One challenge confronting the Cu2O catalysts in the electrocatalysis of carbon dioxide reduction reaction (CO2RR) is the reduction of active Cu(I) species, resulting in low selectivity and quick deactivation. In this study, we for the first time introduce a bottom-up growth of convex sphere with adjustable Cu(0)/Cu(I) interfaces (Cux@Cu2O convex spheres). Interestingly, the interfaces are dynamically modulated by varying hydrothermal time, thus regulating the conversion of C1 and C2 products. In particular, the 4 h hydrothermal treatment applied to Cu0.25@Cu2O convex sphere with the favorable Cu(0)/Cu(I) interface results in the highest selectivity for C2 products (90.5 %). In situ Fourier-transform infrared spectroscopy measurements and density functional theory calculations reveal that the Cu(0)/Cu(I) interface lowers the energy barrier for the production of ethylene and ethanol while increasing the coverage of localized *CO adsorbate for increased dimerization. This work establishes a novel approach for transforming the state of valence-sensitive electrocatalysts into high-value energy-related engineering products.

5.
Microb Cell Fact ; 21(1): 238, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36376878

RESUMO

BACKGROUND: Our recent multi-omics analyses of glucoamylase biosynthesis in Aspergillus niger (A. niger) suggested that lipid catabolism was significantly up-regulated during high-yield period under oxygen limitation. Since the catabolism of fatty acids can provide energy compounds such as ATP and important precursors such as acetyl-CoA, we speculated that enhancement of this pathway might be beneficial to glucoamylase overproduction. RESULTS: Based on previous transcriptome data, we selected and individually overexpressed five candidate genes involved in fatty acid degradation under the control of the Tet-on gene switch in A. niger. Overexpression of the fadE, fadA and cyp genes increased the final specific enzyme activity and total secreted protein on shake flask by 21.3 ~ 31.3% and 16.0 ~ 24.2%, respectively. And a better inducible effect by doxycycline was obtained from early logarithmic growth phase (18 h) than stationary phase (42 h). Similar with flask-level results, the glucoamylase content and total extracellular protein in engineered strains OE-fadE (overexpressing fadE) and OE-fadA (overexpressing fadA) on maltose-limited chemostat cultivation were improved by 31.2 ~ 34.1% and 35.1 ~ 38.8% compared to parental strain B36. Meanwhile, intracellular free fatty acids were correspondingly decreased by 41.6 ~ 44.6%. The metabolomic analysis demonstrated intracellular amino acids pools increased 24.86% and 18.49% in two engineered strains OE-fadE and OE-fadA compared to B36. Flux simulation revealed that increased ATP, acetyl-CoA and NADH was supplied into TCA cycle to improve amino acids synthesis for glucoamylase overproduction. CONCLUSION: This study suggested for the first time that glucoamylase production was significantly improved in A. niger by overexpression of genes fadE and fadA involved in fatty acids degradation pathway. Harnessing the intracellular fatty acids could be a strategy to improve enzyme production in Aspergillus niger cell factory.


Assuntos
Aspergillus niger , Glucana 1,4-alfa-Glucosidase , Glucana 1,4-alfa-Glucosidase/metabolismo , Aspergillus niger/metabolismo , Acetilcoenzima A/metabolismo , Aminoácidos/metabolismo , Ácidos Graxos/metabolismo , Trifosfato de Adenosina/metabolismo
6.
PLoS Pathog ; 15(6): e1007826, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31220181

RESUMO

Vaccinia mature virus requires A26 envelope protein to mediate acid-dependent endocytosis into HeLa cells in which we hypothesized that A26 protein functions as an acid-sensitive membrane fusion suppressor. Here, we provide evidence showing that N-terminal domain (aa1-75) of A26 protein is an acid-sensitive region that regulates membrane fusion. Crystal structure of A26 protein revealed that His48 and His53 are in close contact with Lys47, Arg57, His314 and Arg312, suggesting that at low pH these His-cation pairs could initiate conformational changes through protonation of His48 and His53 and subsequent electrostatic repulsion. All the A26 mutant mature viruses that interrupted His-cation pair interactions of His48 and His 53 indeed have lost virion infectivity. Isolation of revertant viruses revealed that second site mutations caused frame shifts and premature termination of A26 protein such that reverent viruses regained cell entry through plasma membrane fusion. Together, we conclude that viral A26 protein functions as an acid-sensitive fusion suppressor during vaccinia mature virus endocytosis.


Assuntos
Endocitose , Fusão de Membrana , Vaccinia virus/metabolismo , Proteínas Virais/metabolismo , Internalização do Vírus , Animais , Chlorocebus aethiops , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Vaccinia virus/genética , Proteínas Virais/genética
7.
Clin Oral Investig ; 25(6): 4045-4058, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33411001

RESUMO

OBJECTIVES: The tongue is identified as a high-risk site for oral leukoplakia and malignant transformation. The purpose of this study is to investigate the clinicopathological characteristics and treatment outcomes of tongue leukoplakia and assess the factors related to recurrence and malignant transformation. MATERIALS AND METHODS: One hundred and forty-four patients who received carbon dioxide laser surgery for tongue leukoplakia from 2002 to 2019 were analyzed statistically. RESULTS: The follow-up period was 54.90 ± 54.41 months. Thirty patients showed postoperative recurrence (20.83%), and 12 patients developed malignant transformation (8.33%). The annual transformation rate was 2.28%. Univariate analysis showed that a history of head and neck cancer, size of lesion area, clinical appearance, and pathology were significant factors for both recurrence and malignant transformation. In the multivariate logistic regression, a history of head and neck cancer and size of lesion area were independent prognostic factors for recurrence, and a history of head and neck cancer was the only independent factor for postoperative malignant change. CONCLUSIONS: Clinicians should adopt more aggressive strategies for tongue leukoplakia patients with a history of head and neck cancer. CLINICAL RELEVANCE: These results may help clinicians gain a better understanding of oral tongue leukoplakia.


Assuntos
Leucoplasia Oral , Recidiva Local de Neoplasia , Transformação Celular Neoplásica , Humanos , Leucoplasia Oral/cirurgia , Estudos Retrospectivos , Língua , Resultado do Tratamento
8.
Int J Mol Sci ; 22(7)2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33917452

RESUMO

Due to the increasing incidence of malignant gliomas, particularly glioblastoma multiforme (GBM), a simple and reliable GBM diagnosis is needed to screen early the death-threaten patients. This study aimed to identify a protein that can be used to discriminate GBM from low-grade astrocytoma and elucidate further that it has a functional role during malignant glioma progressions. To identify proteins that display low or no expression in low-grade astrocytoma but elevated levels in GBM, glycoprotein fibronectin (FN) was particularly examined according to the mining of the Human Protein Atlas. Web-based open megadata minings revealed that FN was mainly mutated in the cBio Cancer Genomic Portal but dominantly overexpressed in the ONCOMINE (a cancer microarray database and integrated data-mining platform) in distinct tumor types. Furthermore, numerous different cancer patients with high FN indeed exhibited a poor prognosis in the PrognoScan mining, indicating that FN involves in tumor malignancy. To investigate further the significance of FN expression in glioma progression, tumor specimens from five malignant gliomas with recurrences that received at least two surgeries were enrolled and examined. The immunohistochemical staining showed that FN expression indeed determined the distinct progressions of malignant gliomas. Furthermore, the expression of vimentin (VIM), a mesenchymal protein that is strongly expressed in malignant cancers, was similar to the FN pattern. Moreover, the level of epithelial-mesenchymal transition (EMT) inducer transforming growth factor-beta (TGF-ß) was almost recapitulated with the FN expression. Together, this study identifies a protein FN that can be used to diagnose GBM from low-grade astrocytoma; moreover, its expression functionally determines the malignant glioma progressions via TGF-ß-induced EMT pathway.


Assuntos
Neoplasias Encefálicas/metabolismo , Fibronectinas/biossíntese , Regulação Neoplásica da Expressão Gênica , Glioblastoma/metabolismo , Proteínas de Neoplasias/biossíntese , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Adulto , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Bases de Dados de Ácidos Nucleicos , Feminino , Fibronectinas/genética , Glioblastoma/diagnóstico , Glioblastoma/diagnóstico por imagem , Glioblastoma/genética , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Prognóstico , Fator de Crescimento Transformador beta/genética
9.
BMC Oral Health ; 21(1): 45, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33509189

RESUMO

BACKGROUND: The tongue has been identified as a high-risk site for malignant transformation of oral leukoplakia. The purpose of this study was to investigate the clinicopathological characteristics and treatment outcomes of the dorsal and ventrolateral tongue leukoplakia. METHODS: Demographic data and pathological results of patients who underwent carbon dioxide laser surgery for tongue leukoplakia from 2002 to 2019 were retrospectively reviewed and analyzed statistically. RESULTS: Of the 111 patients enrolled, 80 were males and 31 females, with a mean age of 51.86 ± 11.84 years. The follow-up time was 3.74 ± 4.19 years. Fifteen patients had a postoperative recurrence (13.51%). Four (3.6%) patients developed malignant transformation. Annual transformation rate was 4.03%. There were no differences in the time to develop carcinoma (3.19 ± 1.94 vs. 3.51 ± 2.12 years, P = 0.83), overall cumulative malignant transformation rates (7.41% vs. 2.25%, P = 0.12), and annual transformation rates (2.32% vs. 0.64%, P = 0.099). The prevalence of the ventrolateral tongue leukoplakia was higher than that of the dorsal tongue leukoplakia (P < 0.001). The results of multivariate logistic regression analysis showed that the degree of pathology was the only independent prognostic factor related to postoperative malignant transformation (P = 0.045). CONCLUSIONS: Dorsal tongue leukoplakia is not as frequently encountered clinically as ventrolateral tongue leukoplakia. The response of the dorsal tongue and ventrolateral tongue leukoplakia to laser therapy of are comparable in postoperative recurrence and postoperative malignant transformation. Clinicians should take a more aggressive attitude toward oral tongue leukoplakia with higher grade of dysplasia.


Assuntos
Lasers de Gás , Adulto , Transformação Celular Neoplásica , Feminino , Humanos , Lasers de Gás/uso terapêutico , Leucoplasia Oral/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estudos Retrospectivos , Língua/cirurgia , Resultado do Tratamento
10.
Metab Eng ; 47: 445-452, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29704653

RESUMO

Rubisco-based engineered Escherichia coli MZLFB (E. coli BL21(DE3) Δzwf, Δldh, Δfrd) containing heterologous phosphoribulokinase (Prk) and Ribulose-1,5- bisphosphate carboxylase/oxygenase (Rubisco) was constructed for the mixotrophic growth. However, in situ CO2 recycling was hindered by clogs of pyruvate during glucose metabolism, which consequently resulted in an insufficient regeneration of NAD+ through the pflB-mediated ethanol production. Recombinant plasmid pLOI295 (encodes pyruvate decarboxylase and alcohol dehydrogenase II, referred to as the Pdc-based carbon tap valve (CTV) for convenience) was introduced into E. coli MZLFB + CTV to bypass the pflB-mediated ethanol production. Results show that while the C-2/C-1 ratio (i.e., the molar ratio of ethanol and acetate to formate and total CO2) for parental strain MZLFB was 1.0 ±â€¯0.1, the C-2/C-1 for MZLFB + CTV increased to 1.6 ±â€¯0.1. This indicates that the Pdc-based CTV enhanced the performance of in situ CO2 recycling. By simultaneously utilizing glucose and CO2, the fermentation product yield of MZLFB + CTV exceeded the normal theoretical yield and reached 2.2 ±â€¯0.0 (mol/mol). In silico analysis shows that 61% of the glucose consumption went through the Rubisco-based engineered pathway when the CTV was equipped. Also shown are the average CO2 consumption rate of 55.3 mg L-1·h-1 and an average ethanol production rate of 144.8 mg L-1·h-1. The conversion of CO2 to ethanol through the Rubisco-based engineered pathway and the Pdc-based carbon tap valve is important for mixotrophic growth, since these two modules serve as the energy sink to achieve intracellular energy balance. Also, during mixotrophic growth, ATP production from a certain percentage (39% in this study) of the EMP pathway activity is needed for mixotrophic growth.


Assuntos
Dióxido de Carbono/metabolismo , Escherichia coli , Microrganismos Geneticamente Modificados , Modelos Biológicos , Ribulose-Bifosfato Carboxilase , Escherichia coli/genética , Escherichia coli/crescimento & desenvolvimento , Microrganismos Geneticamente Modificados/genética , Microrganismos Geneticamente Modificados/crescimento & desenvolvimento , Ribulose-Bifosfato Carboxilase/genética , Ribulose-Bifosfato Carboxilase/metabolismo
11.
Histopathology ; 72(3): 500-508, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28881050

RESUMO

AIMS: Using intraoperative frozen sections to diagnose pulmonary sclerosing pneumocytoma is always challenging. However, an accurate diagnosis is needed to guide surgical management and prevent unnecessary treatment. The aim of this study was to investigate the most frequently misdiagnosed histological patterns and evaluate the potential diagnostic pitfalls of using frozen sections. METHODS AND RESULTS: We reviewed retrospectively 59 cases of sclerosing pneumocytoma that underwent an intraoperative frozen section examination. All original frozen section slides and permanent section slides were reviewed. The rate of accurate diagnosis using frozen sections was 44.1%, the deferral rate was 15.3% and 10 cases (16.9%) were misdiagnosed as malignancy. A solid-predominant pattern is misdiagnosed more frequently than other growth patterns. We also summarised the five major diagnostic pitfalls, including hypercellularity, glandular spaces, desmoplasia-like sclerosis, cellular atypia and coagulative necrosis. CONCLUSIONS: In addition to evaluating the tumour circumscription and identifying the various growth patterns, we propose that the key to avoiding a misdiagnosis is to recognise the dual-cell populations in a tumour, i.e. cuboidal surface cells and stromal round cells.


Assuntos
Secções Congeladas , Hemangioma Esclerosante Pulmonar/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
12.
Biophys J ; 110(8): 1732-1743, 2016 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-27119634

RESUMO

Dynamic water solvation is crucial to protein conformational reorganization and hence to protein structure and functionality. We report here the characterization of water dynamics on the L-asparaginase structural homology isozymes L-asparaginases I (AnsA) and II (AnsB), which are shown via fluorescence spectroscopy and dynamics in combination with molecular dynamics simulation to have distinct catalytic activity. By use of the tryptophan (Trp) analog probe 2,7-diaza-tryptophan ((2,7-aza)Trp), which exhibits unique water-catalyzed proton-transfer properties, AnsA and AnsB are shown to have drastically different local water environments surrounding the single Trp. In AnsA, (2,7-aza)Trp exhibits prominent green N(7)-H emission resulting from water-catalyzed excited-state proton transfer. In stark contrast, the N(7)-H emission is virtually absent in AnsB, which supports a water-accessible and a water-scant environment in the proximity of Trp for AnsA and AnsB, respectively. In addition, careful analysis of the emission spectra and corresponding relaxation dynamics, together with the results of molecular dynamics simulations, led us to propose two structural states associated with the rearrangement of the hydrogen-bond network in the vicinity of Trp for the two Ans. The water molecules revealed in the proximity of the Trp residue have semiquantitative correlation with the observed emission spectral variations of (2,7-aza)Trp between AnsA and AnsB. Titration of aspartate, a competitive inhibitor of Ans, revealed an increase in N(7)-H emission intensity in AnsA but no obvious spectral changes in AnsB. The changes in the emission profiles reflect the modulation of structural states by locally confined environment and trapped-water collective motions.


Assuntos
Asparaginase/química , Triptofano/química , Asparaginase/metabolismo , Biocatálise , Isoenzimas/química , Isoenzimas/metabolismo , Simulação de Dinâmica Molecular , Conformação Proteica , Homologia de Sequência de Aminoácidos , Espectrometria de Fluorescência , Água/química
13.
Microb Cell Fact ; 15(1): 133, 2016 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-27485110

RESUMO

BACKGROUND: In our previous study, the feasibility of Rubisco-based engineered E. coli (that contains heterologous phosphoribulokinase (PrkA) and Rubisco) for in situ CO2 recycling during the fermentation of pentoses or hexoses was demonstrated. Nevertheless, it is perplexing to see that only roughly 70 % of the carbon fed to the bacterial culture could be accounted for in the standard metabolic products. This low carbon recovery during fermentation occurred even though CO2 emission was effectively reduced by Rubisco-based engineered pathway. RESULTS: In this study, the heterologous expression of form I Rubisco was found to enhance the accumulation of pyruvate in Escherichia coli MZLF [E. coli BL21(DE3) Δzwf, Δldh, Δfrd]. This may be attributed to the enhanced glycolytic reaction supported by the increased biomass and the ethanol/acetate ratio. Besides, it was found that the transcription of arcA (encodes the redox-dependent transcriptional activators ArcA that positively regulates the transcription of pyruvate formate-lyase) was down-regulated in the presence of Rubisco. The enhanced accumulation of pyruvate also occurs when PrkA is co-expressed with Rubisco in E. coli MZLF. Furthermore, E. coli containing Rubisco-based engineered pathway has a distinct profile of the fermentation products, indicating CO2 was converted into fermentation products. By analyzing the ratio of total C-2 (2-carbon fermentation products) to total C-1 (1-carbon fermentation product) of MZLFB (MZLF containing Rubisco-based engineered pathway), it is estimated that 9 % of carbon is directed into Rubisco-based engineered pathway. CONCLUSIONS: Here, we report for the first time the complete profile of fermentation products using E. coli MZLF and its derived strains. It has been shown that the expression of Rubisco alone in MZLF enhances the accumulation of pyruvate. By including the contribution of pyruvate accumulation, the perplexing problem of low carbon recovery during fermentation by E. coli containing Rubisco-based engineered pathway has been solved. 9 % of glucose consumption is directed from glycolysis to Rubisco-based engineered pathway in MZLFB. The principle characteristics of mixotroph MZLFB are the high bacterial growth and the low CO2 emission.


Assuntos
Dióxido de Carbono/metabolismo , Escherichia coli/metabolismo , Metaboloma , Ribulose-Bifosfato Carboxilase/metabolismo , Escherichia coli/genética , Estudos de Viabilidade , Fermentação , Engenharia Genética , Piruvatos/metabolismo , Recombinação Genética , Ribulose-Bifosfato Carboxilase/genética
15.
Chemistry ; 21(13): 5161-72, 2015 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-25702928

RESUMO

Pt(II) complexes with one bulky, sterically demanding, tertiary phosphite ancillary ligand and a coordinating chromophore are herein presented. The phosphite ligand, tris(2,4-di-tert-butylphenyl) acts as a bidentate ligand coordinating the platinum ion through the central phosphorus atom and a cyclometalating carbon atom of one of the substituents. The two free phenoxy moieties lie above and below the coordination plane, leading to steric hindrance that avoids aggregation and provides solubility in organic solvents. The other two coordination sites on the central metal ion are occupied by a chromophoric ligand, which is responsible for the energy of the luminescent excited state. This separation of functions, on the two coordinated ligands, allows the use of a wider range of luminophores with good luminescent properties, maintaining the control of the intermolecular interactions with the non-chromophoric ligand. Based on this approach we were able to achieve a bright deep blue emission (λ=444 nm, Φem =0.38) from a complex with a tailored ligand, which was then used for the fabrication of an electroluminescent device. In addition commercially available luminophores were also employed to synthesize green emitters.

16.
Inorg Chem ; 53(20): 10944-51, 2014 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-25272317

RESUMO

The synthesis and the photophysics of three dinuclear copper(I) complexes containing bis(bidentate)phosphine ligands are described. The steric constraint imposed by tetrakis(di(2-methoxyphenyl)phosphanyl)cyclobutane) (o-MeO-dppcb) in combination with 2,9-dimethyl-1,10-phenanthroline in one of the complexes leads to interesting photophysical properties. The compound shows an intense emission at room temperature in deoxygenated acetonitrile solution (Φ = 49%) and a long excited-state lifetime (13.8 µs). Interestingly, at low temperature, 77 K, the emission maximum shifts to lower energy, and the excited-state lifetime increases. This observation leads to the conclusion that a mixing between the excited triplet and singlet states is possible and that the degree of mixing and population of state strongly depends on temperature, as the energy difference is quite small. The electroluminescent properties of this compound were therefore tested in light-emitting electrochemical cells (LEECs), proving that the bright emission can also be obtained by electrically driven population of the singlet state.


Assuntos
Cobre/química , Luminescência , Substâncias Luminescentes/química , Compostos Organometálicos/química , Fosfinas/química , Cristalografia por Raios X , Ligantes , Substâncias Luminescentes/síntese química , Modelos Moleculares , Conformação Molecular , Compostos Organometálicos/síntese química , Espectrofotometria Ultravioleta , Temperatura
17.
Commun Chem ; 7(1): 45, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38418525

RESUMO

The theories for substrate recognition in enzyme catalysis have evolved from lock-key to induced fit, then conformational selection, and conformational selection followed by induced fit. However, the prevalence and consensus of these theories require further examination. Here we use cryogenic electron microscopy and African swine fever virus type 2 topoisomerase (AsfvTop2) to demonstrate substrate binding theories in a joint and ordered manner: catalytic selection by the enzyme, conformational selection by the substrates, then induced fit. The apo-AsfvTop2 pre-exists in six conformers that comply with the two-gate mechanism directing DNA passage and release in the Top2 catalytic cycle. The structures of AsfvTop2-DNA-inhibitor complexes show that substantial induced-fit changes occur locally from the closed apo-conformer that however is too far-fetched for the open apo-conformer. Furthermore, the ATPase domain of AsfvTop2 in the MgAMP-PNP-bound crystal structures coexist in reduced and oxidized forms involving a disulfide bond, which can regulate the AsfvTop2 function.

18.
Biotechnol J ; 19(4): e2300740, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38581087

RESUMO

ß-Phenylethanol (2-PE), as an important flavor component in wine, is widely used in the fields of flavor chemistry and food health. 2-PE can be sustainably produced through Saccharomyces cerevisiae. Although significant progress has been made in obtaining high-yield strains, as well as improving the synthesis pathways of 2-PE, there still lies a gap between these two fields to unpin. In this study, the macroscopic metabolic characteristics of high-yield and low-yield 2-PE strains were systematically compared and analyzed. The results indicated that the production potential of the high-yield strain might be contributed to the enhancement of respiratory metabolism and the high tolerance to 2-PE. Furthermore, this hypothesis was confirmed through comparative genomics. Meanwhile, transcriptome analysis at key specific growth rates revealed that the collective upregulation of mitochondrial functional gene clusters plays a more prominent role in the production process of 2-PE. Finally, findings from untargeted metabolomics suggested that by enhancing respiratory metabolism and reducing the Crabtree effect, the accumulation of metabolites resisting high 2-PE stress was observed, such as intracellular amino acids and purines. Hence, this strategy provided a richer supply of precursors and cofactors, effectively promoting the synthesis of 2-PE. In short, this study provides a bridge for studying the metabolic mechanism of high-yield 2-PE strains with the subsequent targeted strengthening of relevant synthetic pathways. It also provides insights for the synthesis of nonalcoholic products in S. cerevisiae.


Assuntos
Álcool Feniletílico , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Álcool Feniletílico/metabolismo , Multiômica , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Vias Biossintéticas , Fermentação
19.
Inorg Chem ; 52(19): 10756-65, 2013 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-24093480

RESUMO

We report on the photophysical studies of two cationic near-UV emitters based on bis-pincer Ir(III) carbene complexes: [Ir(nBu)(C(NHC)(Me)CC(NHC))2]X, where Ir(nBu)(C(NHC)(Me)CC(NHC)) is (4,6-dimethyl-1,3-phenylene-κC(2))bis(1-butylimidazol-2-ylidene) and X = I(-) or PF6(-)). The compounds are highly emitting in deaerated CH3CN solution with emission maxima at 384 and 406 nm, and photoluminescence quantum yields of 0.41 and 0.38, for [Ir(nBu)(C(NHC)(Me)CC(NHC))2]I and Ir(nBu)(C(NHC)(Me)CC(NHC))2]PF6, respectively. In order to gain deeper understandings into their structural and electronic features, as well as to ascertain the nature of the excited states involved into the electronic absorption processes, density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations have been performed on the ground and excited states of the closely related complex [Ir(Me)(C(NHC)(Me)CC(NHC))2](+). In the solid state, an emission at low energy is observed (λ(max) = 500 nm) for both complexes. However, the intensity of the emission at high energy versus the intensity of the new emission at low energy is dependent on the nature of counterions. The origin of this emission is not completely clear, but the experimental data point to the formation of trapping sites induced by aggregation processes involving the interaction between the cationic emitter and the counterion.


Assuntos
Complexos de Coordenação/química , Irídio/química , Metano/análogos & derivados , Raios Ultravioleta , Cátions , Cristalografia por Raios X , Metano/química
20.
J Colloid Interface Sci ; 642: 283-291, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37004262

RESUMO

Covalent organic frameworks (COFs) are excellent candidates for rationally designed metal-coordinated catalysts due to their porous structures and adjustable organic building blocks. In this work, a two-dimensional (2D) COF with novel fxt topology was synthesized. The newly devised COF had been fully characterized by a range of spectroscopic and microscopic techniques. The COF was further metallized by the gold species to form a heterogeneous catalyst that enabled the one-pot synthesis of flavone and its derivatives. The Au@COF catalyst showed high catalytic activity and good recyclability. This work demonstrates the great potential of metallized COFs with unique well-defined pores in organic catalysis.

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