RESUMO
The taste of sugar is one of the most basic sensory percepts for humans and other animals. Animals can develop a strong preference for sugar even if they lack sweet taste receptors, indicating a mechanism independent of taste1-3. Here we examined the neural basis for sugar preference and demonstrate that a population of neurons in the vagal ganglia and brainstem are activated via the gut-brain axis to create preference for sugar. These neurons are stimulated in response to sugar but not artificial sweeteners, and are activated by direct delivery of sugar to the gut. Using functional imaging we monitored activity of the gut-brain axis, and identified the vagal neurons activated by intestinal delivery of glucose. Next, we engineered mice in which synaptic activity in this gut-to-brain circuit was genetically silenced, and prevented the development of behavioural preference for sugar. Moreover, we show that co-opting this circuit by chemogenetic activation can create preferences to otherwise less-preferred stimuli. Together, these findings reveal a gut-to-brain post-ingestive sugar-sensing pathway critical for the development of sugar preference. In addition, they explain the neural basis for differences in the behavioural effects of sweeteners versus sugar, and uncover an essential circuit underlying the highly appetitive effects of sugar.
Assuntos
Encéfalo/fisiologia , Comportamento de Escolha/fisiologia , Açúcares da Dieta/metabolismo , Preferências Alimentares/fisiologia , Glucose/metabolismo , Intestinos/fisiologia , Animais , Encéfalo/citologia , Açúcares da Dieta/química , Glucose/análogos & derivados , Glucose/química , Masculino , Metilglucosídeos/química , Metilglucosídeos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/fisiologia , Paladar/fisiologia , Tiazinas/metabolismo , Água/metabolismoRESUMO
In eukaryotic protein N-glycosylation, a series of glycosyltransferases catalyse the biosynthesis of a dolichylpyrophosphate-linked oligosaccharide before its transfer onto acceptor proteins1. The final seven steps occur in the lumen of the endoplasmic reticulum (ER) and require dolichylphosphate-activated mannose and glucose as donor substrates2. The responsible enzymes-ALG3, ALG9, ALG12, ALG6, ALG8 and ALG10-are glycosyltransferases of the C-superfamily (GT-Cs), which are loosely defined as containing membrane-spanning helices and processing an isoprenoid-linked carbohydrate donor substrate3,4. Here we present the cryo-electron microscopy structure of yeast ALG6 at 3.0 Å resolution, which reveals a previously undescribed transmembrane protein fold. Comparison with reported GT-C structures suggests that GT-C enzymes contain a modular architecture with a conserved module and a variable module, each with distinct functional roles. We used synthetic analogues of dolichylphosphate-linked and dolichylpyrophosphate-linked sugars and enzymatic glycan extension to generate donor and acceptor substrates using purified enzymes of the ALG pathway to recapitulate the activity of ALG6 in vitro. A second cryo-electron microscopy structure of ALG6 bound to an analogue of dolichylphosphate-glucose at 3.9 Å resolution revealed the active site of the enzyme. Functional analysis of ALG6 variants identified a catalytic aspartate residue that probably acts as a general base. This residue is conserved in the GT-C superfamily. Our results define the architecture of ER-luminal GT-C enzymes and provide a structural basis for understanding their catalytic mechanisms.
Assuntos
Microscopia Crioeletrônica , Retículo Endoplasmático/enzimologia , Glicosiltransferases/genética , Glicosiltransferases/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/enzimologia , Biocatálise , Domínio Catalítico , Sequência Conservada , Dolicol Monofosfato Manose/metabolismo , Fosfatos de Dolicol/metabolismo , Glucose/análogos & derivados , Glucose/metabolismo , Glicosiltransferases/deficiência , Técnicas In Vitro , Lipídeos , Proteínas de Membrana/deficiência , Modelos Moleculares , Mutação , Monossacarídeos de Poli-Isoprenil Fosfato/química , Monossacarídeos de Poli-Isoprenil Fosfato/metabolismo , Ligação Proteica , Saccharomyces cerevisiae/genética , Especificidade por SubstratoRESUMO
This study focuses on the synthesis of fully renewable polycarbonates (PCs) starting from cellulose-based platform molecules levoglucosenone (LGO) and 2,5-bis(hydroxymethyl)furan (BHMF). These unique bio-based PCs are obtained through the reaction of a citronellol-containing triol (Triol-citro) derived from LGO, with a dimethyl carbonate derivative of BHMF (BHMF-DC). Solvent-free polymerizations are targeted to minimize waste generation and promote an eco-friendly approach with a favorable environmental factor (E-factor). The choice of metal catalyst during polymerization significantly influences the polymer properties, resulting in high molecular weight (up to 755 kDa) when Na2 CO3 is employed as an inexpensive catalyst. Characterization using nuclear magnetic resonance confirms the successful incorporation of the furan ring and the retention of the terminal double bond of the citronellol pendant chain. Furthermore, under UV irradiation, the presence of both citronellol and furanic moieties induces singular structural changes, triggering the formation of three distinct structures within the polymer network, a phenomenon herein occurs for the first time in this type of polymer. These findings pave the way to new functional materials prepared from renewable monomers with tunable properties.
Assuntos
Monoterpenos Acíclicos , Compostos Bicíclicos Heterocíclicos com Pontes , Furaldeído/análogos & derivados , Glucose/análogos & derivados , Cimento de Policarboxilato , Polímeros , Polímeros/químicaRESUMO
BACKGROUND AND AIM: Woodsmoke from household fireplaces contributes significantly to outdoor air pollution in the Netherlands. The current understanding of the respiratory health effects of exposure to smoke from residential wood burning is limited. This study investigated the association between short-term changes in outdoor woodsmoke exposure and lung function, respiratory symptoms, and medication use in adults in the Netherlands. METHODS: This study was co-created with citizen scientists and other relevant stakeholders. A panel study was conducted with repeated observations in 46 adults between February and May 2021 in four Dutch towns. Participants recorded their symptoms and medication use in daily diaries, and conducted morning and evening home spirometry measurements. Woodsmoke exposure was characterized by measuring levoglucosan (most specific marker for woodsmoke exposure), black/brown carbon, fine and ultrafine particulate matter at central monitoring sites. Individual woodsmoke perception (smell) was recorded in daily diaries. Linear and logistic regression models were used to investigate the association between respiratory health and woodsmoke exposure. Models were adjusted for time-varying confounders and accounted for repeated observations within participants. RESULTS: Consistent positive associations were found between levoglucosan and shortness of breath (SOB) during rest and extra respiratory medication use. Odds ratios for current day exposure to levoglucosan were 1.12 (95% CI: 0.97, 1.30) for SOB during rest and 1.19 (95% CI: 1.07, 1.33) for extra medication use, expressed per interquartile range of levoglucosan concentrations (69.16 ng/m3). Positive non-significant associations were found between levoglucosan and nasal symptoms, cough and waking up with SOB. No consistent association was found between levoglucosan and lung function. Associations found between woodsmoke markers, SOB during rest and extra medication use remained after the inclusion of PM2.5 and UFP in two-pollutant models. CONCLUSIONS: Adults experienced more SOB during rest, nasal symptoms and used more medication to treat respiratory symptoms on days with higher levels of outdoor woodsmoke concentrations.
Assuntos
Poluentes Atmosféricos , Fumaça , Madeira , Humanos , Países Baixos , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Fumaça/efeitos adversos , Fumaça/análise , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/efeitos adversos , Exposição Ambiental/análise , Idoso , Material Particulado/análise , Material Particulado/efeitos adversos , Doenças Respiratórias/epidemiologia , Glucose/análogos & derivadosRESUMO
We recently showed that site-specific incorporation of 2'-modifications or neutral linkages in the oligo-deoxynucleotide gap region of toxic phosphorothioate (PS) gapmer ASOs can enhance therapeutic index and safety. In this manuscript, we determined if introducing substitution at the 5'-position of deoxynucleotide monomers in the gap can also enhance therapeutic index. Introducing R- or S-configured 5'-Me DNA at positions 3 and 4 in the oligodeoxynucleotide gap enhanced the therapeutic profile of the modified ASOs suggesting a different positional preference as compared to the 2'-OMe gap modification strategy. The generality of these observations was demonstrated by evaluating R-5'-Me and R-5'-Ethyl DNA modifications in multiple ASOs targeting HDAC2, FXI and Dynamin2 mRNA in the liver. The current work adds to a growing body of evidence that small structural changes can modulate the therapeutic properties of PS ASOs and ushers a new era of chemical optimization with a focus on enhancing the therapeutic profile as opposed to nuclease stability, RNA-affinity and pharmacokinetic properties. The 5'-methyl DNA modified ASOs exhibited excellent safety and antisense activity in mice highlighting the therapeutic potential of this class of nucleic acid analogs for next generation ASO designs.
Assuntos
DNA/química , Oligonucleotídeos Antissenso/química , Animais , Glucose/análogos & derivados , Glucose/química , Células HeLa , Humanos , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Células NIH 3T3 , Oligonucleotídeos Antissenso/uso terapêutico , Oligonucleotídeos Antissenso/toxicidade , Compostos Organofosforados/síntese química , Ribonuclease HRESUMO
Thymineless death in Escherichia coli thyA mutants growing in the absence of thymidine (dT) is preceded by a substantial resistance phase, during which the culture titer remains static, as if the chromosome has to accumulate damage before ultimately failing. Significant chromosomal replication and fragmentation during the resistance phase could provide appropriate sources of this damage. Alternatively, the initial chromosomal replication in thymine (T)-starved cells could reflect a considerable endogenous dT source, making the resistance phase a delay of acute starvation, rather than an integral part of thymineless death. Here we identify such a low-molecular-weight (LMW)-dT source as mostly dTDP-glucose and its derivatives, used to synthesize enterobacterial common antigen (ECA). The thyA mutant, in which dTDP-glucose production is blocked by the rfbA rffH mutations, lacks a LMW-dT pool, the initial DNA synthesis during T-starvation and the resistance phase. Remarkably, the thyA mutant that makes dTDP-glucose and initiates ECA synthesis normally yet cannot complete it due to the rffC defect, maintains a regular LMW-dT pool, but cannot recover dTTP from it, and thus suffers T-hyperstarvation, dying precipitously, completely losing chromosomal DNA and eventually lysing, even without chromosomal replication. At the same time, its ECA+thyA parent does not lyse during T-starvation, while both the dramatic killing and chromosomal DNA loss in the ECA-deficient thyA mutants precede cell lysis. We conclude that: 1) the significant pool of dTDP-hexoses delays acute T-starvation; 2) T-starvation destabilizes even nonreplicating chromosomes, while T-hyperstarvation destroys them; and 3) beyond the chromosome, T-hyperstarvation also destabilizes the cell envelope.
Assuntos
Cromossomos Bacterianos/metabolismo , DNA Bacteriano/metabolismo , Escherichia coli/metabolismo , Viabilidade Microbiana , Polissacarídeos Bacterianos/farmacologia , Timina/metabolismo , Antígenos de Bactérias/metabolismo , Replicação do DNA/efeitos dos fármacos , Proteínas de Escherichia coli/metabolismo , Glucose/análogos & derivados , Glucose/metabolismo , Viabilidade Microbiana/efeitos dos fármacos , Peso Molecular , Mutação/genética , Estresse Fisiológico/efeitos dos fármacos , Timidina/metabolismo , Nucleotídeos de Timina/metabolismoRESUMO
Glycogen phosphorylase (GP) is a key regulator of glucose levels and, with that, an important target for the discovery of novel treatments against type 2 diabetes. ß-d-Glucopyranosyl derivatives have provided some of the most potent GP inhibitors discovered to date. In this regard, C-ß-d-glucopyranosyl azole type inhibitors proved to be particularly effective, with 2- and 4-ß-d-glucopyranosyl imidazoles among the most potent designed to date. His377 backbone C=O hydrogen bonding and ion-ion interactions of the protonated imidazole with Asp283 from the 280s loop, stabilizing the inactive state, were proposed as crucial to the observed potencies. Towards further exploring these features, 4-amino-3-(ß-d-glucopyranosyl)-5-phenyl-1H-pyrazole (3) and 3-(ß-d-glucopyranosyl)-4-guanidino-5-phenyl-1H-pyrazole (4) were designed and synthesized with the potential to exploit similar interactions. Binding assay experiments against rabbit muscle GPb revealed 3 as a moderate inhibitor (IC50 = 565 µM), but 4 displayed no inhibition at 625 µM concentration. Towards understanding the observed inhibitions, docking and post-docking molecular mechanics-generalized Born surface area (MM-GBSA) binding free energy calculations were performed, together with Monte Carlo and density functional theory (DFT) calculations on the free unbound ligands. The computations revealed that while 3 was predicted to hydrogen bond with His377 C=O in its favoured tautomeric state, the interactions with Asp283 were not direct and there were no ion-ion interactions; for 4, the most stable tautomer did not have the His377 backbone C=O interaction and while ion-ion interactions and direct hydrogen bonding with Asp283 were predicted, the conformational strain and entropy loss of the ligand in the bound state was significant. The importance of consideration of tautomeric states and ligand strain for glucose analogues in the confined space of the catalytic site with the 280s loop in the closed position was highlighted.
Assuntos
Glicogênio Fosforilase , Pirazóis , Pirazóis/síntese química , Pirazóis/química , Pirazóis/farmacologia , Glicogênio Fosforilase/antagonistas & inibidores , Glicogênio Fosforilase/metabolismo , Teoria da Densidade Funcional , Simulação de Acoplamento Molecular , Método de Monte Carlo , Conformação Molecular , Glucose/análogos & derivados , Glucose/química , Glucose/metabolismo , Glucose/farmacologia , Diabetes Mellitus Tipo 2RESUMO
Bacteria were isolated from wastewater and soil containing charred wood remnants based on their ability to use levoglucosan as a sole carbon source and on their levoglucosan dehydrogenase (LGDH) activity. On the basis of their 16S rRNA gene sequences, these bacteria represented the diverse genera Microbacterium, Paenibacillus, Shinella, and Klebsiella. Genomic sequencing of the isolates verified that two isolates represented novel species, Paenibacillus athensensis MEC069T and Shinella sumterensis MEC087T, while the remaining isolates were closely related to Microbacterium lacusdiani or Klebsiella pneumoniae. The genetic sequence of LGDH, lgdA, was found in the genomes of these four isolates as well as Pseudarthrobacter phenanthrenivorans Sphe3. The identity of the P. phenanthrenivorans LGDH was experimentally verified following recombinant expression in Escherichia coli. Comparison of the putative genes surrounding lgdA in the isolate genomes indicated that several other gene products facilitate the bacterial catabolism of levoglucosan, including a putative sugar isomerase and several transport proteins. IMPORTANCE Levoglucosan is the most prevalent soluble carbohydrate remaining after high-temperature pyrolysis of lignocellulosic biomass, but it is not fermented by typical production microbes such as Escherichia coli and Saccharomyces cerevisiae. A few fungi metabolize levoglucosan via the enzyme levoglucosan kinase, while several bacteria metabolize levoglucosan via levoglucosan dehydrogenase. This study describes the isolation and characterization of four bacterial species that degrade levoglucosan. Each isolate is shown to contain several genes within an operon involved in levoglucosan degradation, furthering our understanding of bacteria that metabolize levoglucosan.
Assuntos
Glucose , Paenibacillus , Biomassa , Glucose/análogos & derivados , Glucose/metabolismo , Paenibacillus/genética , RNA Ribossômico 16S/genéticaRESUMO
Breast cancer is the leading cause of cancer death among women worldwide. For this reason, the development of new therapies is still essential. In this work we have analyzed the antitumor potential of levoglucosenone, a chiral building block derived from the pyrolysis of cellulose-containing materials such as soybean hulls, and three structurally related analogues. Employing human and murine mammary cancer models, we have evaluated the effect of our compounds on cell viability through MTS assay, apoptosis induction by acridine orange/ethidium bromide staining and/or flow cytometry and the loss of mitochondrial potential by tetramethylrhodamine methyl ester staining. Autophagy and senescence induction were also evaluated by Western blot and ß-galactosidase activity respectively. Secreted metalloproteases activity was determined by quantitative zymography. Migratory capacity was assessed by wound healing assays while invasive potential was analyzed using Matrigel-coated transwell chambers. In vivo studies were also performed to evaluate subcutaneous tumor growth and experimental lung colonization. All compounds impaired in vitro proliferation with IC50 values in a range of low micromolar. Apoptosis was identified as the main mechanism responsible for the reduction of monolayer cell content induced by the compounds without detecting modulations of autophagy or senescence processes. Two of the four compounds (levoglucosenone and its brominated variant) were able to modulate in vitro events associated with tumor progression, such as migratory potential, invasiveness, and proteases secretion. Furthermore, tumor volume and metastatic spread were significantly reduced in vivo after the treatment these two compounds. Here, we could obtain from soybean hulls, a material with almost no commercial value, a variety of chemical compounds useful for breast cancer treatment.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias da Mama/patologia , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Glucose/análogos & derivados , Animais , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Compostos Bicíclicos Heterocíclicos com Pontes/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Celulose/química , Relação Dose-Resposta a Droga , Glucose/química , Glucose/farmacologia , Humanos , Concentração Inibidora 50 , Camundongos , Camundongos Endogâmicos BALB C , Carga Tumoral/efeitos dos fármacosRESUMO
L-ido-Deoxynojirimycin (L-ido-DNJ) itself showed no affinity for human lysosomal acid α-glucosidase (GAA), whereas 5-C-methyl-L-ido-DNJ showed a strong affinity for GAA, comparable to the glucose analog DNJ, with a Ki value of 0.060 µM. This excellent affinity for GAA and enzyme stabilization was observed only when methyl and ethyl groups were introduced. Docking simulation analysis revealed that the alkyl chains of 5-C-alkyl-L-ido-DNJs were stored in three different pockets, depending on their length, thereby the molecular orientation was changed. Comparison of the binding poses of DNJ and 5-C-methyl-L-ido-DNJ showed that they formed a common ionic interaction with Asp404, Asp518, and Asp616, but both the binding orientation and the distance between the ligand and each amino acid residue were different. 5-C-Methyl-L-ido-DNJ dose-dependently increased intracellular GAA activity in Pompe patient fibroblasts with the M519V mutation and also promoted enzyme transport to lysosomes. This study provides the first example of a strategy to design high-affinity ligands by introducing alkyl branches into rare sugars and L-sugar-type iminosugars to change the orientation of binding.
Assuntos
1-Desoxinojirimicina , Inibidores de Glicosídeo Hidrolases , Imino Açúcares , alfa-Glucosidases , 1-Desoxinojirimicina/química , 1-Desoxinojirimicina/farmacologia , Aminoácidos , Domínio Catalítico , Glucose/análogos & derivados , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Humanos , Imino Açúcares/química , Imino Açúcares/farmacologia , Ligantes , Ligação Proteica , alfa-Glucosidases/químicaRESUMO
Selective conversion of lignocellulosic biomass-derived chemicals is of critical significance for sustainable fine and commodity chemical industries. Cellulose-derived levoglucosenone (LGO) has a promising potential for producing 5-hydroxymethylfurfural (HMF) with a substantial yield under acid conditions, but the mechanism is unidentified. Herein, we disclose the mechanism of LGO conversion to HMF in the aqueous phase without and with H2SO4 as a catalyst by density functional theory (DFT) calculations for the first time. Results showed that LGO first forms 6,8-dioxabicyclo[3.2.1]-octane-2,4,4-triol (DH) via two sequential hydration reactions occurring at the CâC bond and then the ketone group. The use of H2SO4 as a catalyst significantly reduced the free energy barriers of LGO and DH conversion to HMF, with a free energy barrier of 115 kJ/mol for LGO â HMF compared to that of 91 kJ/mol for DH â HMF, demonstrating that DH is easier for HMF formation.
Assuntos
Furaldeído , Compostos Bicíclicos Heterocíclicos com Pontes , Teoria da Densidade Funcional , Furaldeído/análogos & derivados , Furaldeído/química , Glucose/análogos & derivados , HidróliseRESUMO
H2S and H2O2 are two redox regulating molecules that play important roles in many physiological and pathological processes. While each of them has distinct biosynthetic pathways and signaling mechanisms, the crosstalk between these two species is also known to cause critical biological responses such as protein S-persulfidation. So far, many chemical tools for the studies of H2S and H2O2 have been developed, such as the donors and sensors for H2S and H2O2. However, these tools are normally targeting single species (e.g., only H2S or only H2O2). As such, the crosstalk and synergetic effects between H2S and H2O2 have hardly been studied with those tools. In this work, we report a unique H2S/H2O2 dual donor system by employing 1-thio-ß-d-glucose and glucose oxidase (GOx) as the substrates. This enzymatic system can simultaneously produce H2S and H2O2 in a slow and controllable fashion, without generating any bio-unfriendly byproducts. This system was demonstrated to cause efficient S-persulfidation on proteins. In addition, we expanded the system to thiolactose and thioglucose-disulfide; therefore, additional factors (ß-galactosidase and cellular reductants) could be introduced to further control the release of H2S/H2O2. This dual release system should be useful for future research on H2S and H2O2.
Assuntos
Glucose Oxidase/metabolismo , Glucose/análogos & derivados , Peróxido de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/metabolismo , Proteína S/metabolismo , Glucose/química , Glucose/metabolismo , Glucose Oxidase/química , Humanos , Peróxido de Hidrogênio/química , Sulfeto de Hidrogênio/química , Proteína S/químicaRESUMO
Levoglucosan has been widely used to quantitatively assess biomass burning's contribution to ambient aerosols, but previous such assessments have not accounted for levoglucosan's degradation in the atmosphere. We develop the first global simulation of atmospheric levoglucosan, explicitly accounting for its chemical degradation, to evaluate the impacts on levoglucosan's use in quantitative aerosol source apportionment. Levoglucosan is emitted into the atmosphere from the burning of plant matter in open fires (1.7 Tg yr-1) and as biofuels (2.1 Tg yr-1). Sinks of atmospheric levoglucosan include aqueous-phase oxidation (2.9 Tg yr-1), heterogeneous oxidation (0.16 Tg yr-1), gas-phase oxidation (1.4 × 10-4 Tg yr-1), and dry and wet deposition (0.27 and 0.43 Tg yr -1). The global atmospheric burden of levoglucosan is 19 Gg with a lifetime of 1.8 days. Observations show a sharp decline in levoglucosan's concentrations and its relative abundance to organic carbon aerosol (OC) and particulate K+ from near-source to remote sites. We show that such features can only be reproduced when levoglucosan's chemical degradation is included in the model. Using model results, we develop statistical parametrizations to account for the atmospheric degradation in levoglucosan measurements, improving their use for quantitative aerosol source apportionment.
Assuntos
Poluentes Atmosféricos , Monitoramento Ambiental , Aerossóis/análise , Poluentes Atmosféricos/análise , Atmosfera , Biomassa , Glucose/análogos & derivados , Glucose/análise , Material Particulado/análise , Estações do AnoRESUMO
Levoglucosan (LG) emitted from non-biomass burning (non-BB) sources has given rise to biased or even unreasonable source identification results when adopting LG as a distinct marker of biomass burning (BB). The estimation of LG emission and its spatiotemporal variation for various sources are the keys to reducing uncertainty. This study first developed a LG emission inventory for China from 25 sub-type sources belonging to eight categories, with a 3 km × 3 km spatial resolution and monthly distribution. The total LG emission in 2014 was 145.7 Gg. Domestic BB and open BB contributed 39.2 and 34.3% of the total emission. Non-BB sources, including municipal solid waste burning (9.7%), firework burning (9.6%), meat cooking (5.4%), domestic coal burning (1.5%), ritual item burning (0.2%), and industrial coal burning (0.1%), contributed to 26.5% of the total emission. LG emission varied spatially and temporally. Non-BB sources have a significant spatiotemporal impact on BB source contributions, even in high BB emission regions or in sowing, harvesting, and winter heating seasons. The local BB contributions have been substantially overestimated by 4.28-369% in previous studies, wherein LG was solely referred to as the BB source. By 2018, LG emission from BB might decrease to 63.9% of its total emission. This high-resolution LG emission inventory can be greatly useful for source identification studies in China. It also supports future research on the modeling of smoke aging and pollution control.
Assuntos
Poluentes Atmosféricos , Material Particulado , Aerossóis/análise , Poluentes Atmosféricos/análise , Biomassa , China , Monitoramento Ambiental , Glucose/análogos & derivados , Material Particulado/análise , Estações do AnoRESUMO
The homopolymerization in basic conditions of the recently reported bis(γ-lactone), 2H-HBO-HBO, is herein described for the first time. The solvent-free polymerization of this pentafunctional levoglucosenone (LGO) derivative affords fully renewable poly(vinyl-ether lactone) copolymers with a highly hyperbranched structure. This investigation stems from the polycondensation trials between 2H-HBO-HBO and di(methyl carbonate) isosorbide (DCI) that fails to give the anticipated polycarbonates. Such unexpected behavior is ascribed to the higher reactivity of the 2H-HBO-HBO hydroxy groups toward its α,ß-conjugated endocyclic CâC, rather than the DCI methylcarbonate moieties. The different mechanistic scenarios involved in 2H-HBO-HBO homopolymerization are addressed and a possible structure of poly(2H-HBO-HBO) is suggested. Furthermore, the readily accessible (S)-γ-hydroxymethyl-α,ß-butenolide (HBO) is also polymerized for the first time at a relatively large scale, without any prior modification, resulting in a new hyperbranched polymer with an environmental factor (E factor) ≈0. These new HBO-based polymers have a great potential for industrial-scale production due to their interesting properties and easy preparation via a low-cost, green, and efficient process.
Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , Polímeros , Glucose/análogos & derivados , Substâncias Macromoleculares , PolimerizaçãoRESUMO
The COVID-19 disease caused by the virus SARS-CoV-2, first detected in December 2019, is still emerging through virus mutations. Although almost under control in some countries due to effective vaccines that are mitigating the worldwide pandemic, the urgency to develop additional vaccines and therapeutic treatments is imperative. In this work, the natural polyphenols corilagin and 1,3,6-tri-O-galloy-ß-d-glucose (TGG) are investigated to determine the structural basis of inhibitor interactions as potential candidates to inhibit SARS-CoV-2 viral entry into target cells. First, the therapeutic potential of the ligands are assessed on the ACE2/wild-type RBD. We first use molecular docking followed by molecular dynamics, to take into account the conformational flexibility that plays a significant role in ligand binding and that cannot be captured using only docking, and then analyze more precisely the affinity of these ligands using MMPBSA binding free energy. We show that both ligands bind to the ACE2/wild-type RBD interface with good affinities which might prevent the ACE2/RBD association. Second, we confirm the potency of these ligands to block the ACE2/RBD association using a combination of surface plasmon resonance and biochemical inhibition assays. These experiments confirm that TGG and, to a lesser extent, corilagin, inhibit the binding of RBD to ACE2. Both experiments and simulations show that the ligands interact preferentially with RBD, while weak binding is observed with ACE2, hence, avoiding potential physiological side-effects induced by the inhibition of ACE2. In addition to the wild-type RBD, we also study numerically three RBD mutations (E484K, N501Y and E484K/N501Y) found in the main SARS-CoV-2 variants of concerns. We find that corilagin could be as effective for RBD/E484K but less effective for the RBD/N501Y and RBD/E484K-N501Y mutants, while TGG strongly binds at relevant locations to all three mutants, demonstrating the significant interest of these molecules as potential inhibitors for variants of SARS-CoV-2.
Assuntos
Antivirais/química , Ácido Gálico/análogos & derivados , Glucose/análogos & derivados , Glucosídeos/química , Taninos Hidrolisáveis/química , SARS-CoV-2/efeitos dos fármacos , Enzima de Conversão de Angiotensina 2/química , Enzima de Conversão de Angiotensina 2/metabolismo , Sítios de Ligação , Ácido Gálico/química , Glucose/química , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Mutação , Ligação Proteica/efeitos dos fármacos , Domínios e Motivos de Interação entre Proteínas/genética , SARS-CoV-2/química , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Internalização do Vírus/efeitos dos fármacosRESUMO
The composition of PM10, including molecular markers of biomass burning (levoglucosan, mannosan and galactosan), was determined at a residential site in southeastern Spain during winter and early spring. The average PM10 concentration was 25.0 µg m-3, being organic carbon (OC, 6.77 µg m-3), NO3- (2.02 µg m-3), SO42- (1.36 µg m-3) and Ca2+ (1.01 µg m-3) the main components. Levoglucosan was the dominant anhydrosugar (143 ng m-3), accounting for 81% of the total concentration of monosaccharide anhydrides. The average contribution of biomass combustion to OC, estimated from the levoglucosan data, was 23%. This value agreed well with that calculated by Positive Matrix Factorization (PMF, 25%). The PMF model resolved six factors that were assigned to road traffic (28%), secondary aerosols (27%), soil dust (14%), fresh sea salt (13%), aged sea salt (10%) and biomass burning (8%). This model was used to estimate the OC/Levoglucosan and PM10/Levoglucosan emission ratios for the study area.
Assuntos
Poluentes Atmosféricos , Material Particulado , Aerossóis/análise , Poluentes Atmosféricos/análise , Biomassa , Monitoramento Ambiental , Glucose/análogos & derivados , Material Particulado/análise , Estações do Ano , EspanhaRESUMO
Red cabbage (Brassica oleracea L. var. capitata) continues to receive increasing attention on its health-promoting properties because of its high glucosinolate content. Glucosinolates are an unstable active substance; however, there are few studies on their changes in different cooking processes. In this study, we investigated the effects of processing methods (boiling, steaming, microwave heating, frying, stir-frying) and boiling time on glucosinolates in red cabbage. Ten glucosinolates, including 4-methoxyglucobrassicin, neoglucobrassicin, glucoalyssin, glucobrassicin, glucoraphanin, glucoiberin, progoitrin, gluconapin and sinigrin, in red cabbage were detected. Decreases of 32.36%, 24.83%, 25.27%, 81.11% and 84.29% for total glucosinolates were observed after boiling, microwaving, steaming, frying and stir-frying. Indole glucosinolates were more efficiently lost compared to aliphatic glucosinolates after boiling, while microwaving, steaming, frying and stir-frying also resulted in a greater reduction in indole glucosinolates than aliphatic glucosinolates. Glucoalyssin, glucoerucin and sinigrin were more thermal sensitive than other glucosinolates. It was confirmed that microwaving and steaming retained higher levels of glucosinolates than other methods and may be better for cooking red cabbage.
Assuntos
Brassica/química , Glucosinolatos/química , Cromatografia Líquida/métodos , Culinária/métodos , Glucose/análogos & derivados , Glucose/química , Imidoésteres/química , Indóis/química , Micro-Ondas , Oximas/química , Sulfóxidos/química , Espectrometria de Massas em Tandem/métodosRESUMO
Broccoli microgreens have shown potential health benefits due to their high glucosinolate (GL) levels. Previously, we observed that postharvest UVB treatment did not have much effect on increasing GLs in broccoli microgreens. In this study, we investigated the influence of preharvest UVB irradiation on GL levels in broccoli microgreens. UHPLC-ESI/ITMS analysis showed that preharvest UVB treatments with UVB 0.09 and 0.27 Wh/m2 significantly increased the glucoraphanin (GLR), glucoerucin (GLE), and total aliphatic GL levels by 13.7 and 16.9%, respectively, in broccoli microgreens when measured on harvest day. The nutritional qualities of UVB-treated microgreens were stable during 21-day storage, with only small changes in their GL levels. Broccoli microgreens treated before harvest with UVB 0.27 Wh/m2 and 10 mM CaCl2 spray maintained their overall quality, and had the lowest tissue electrolyte leakage and off-odor values during the storage. Furthermore, preharvest UVB 0.27 Wh/m2 treatment significantly increased GL biosynthesis genes when evaluated before harvest, and reduced the expression level of myrosinase, a gene responsible for GL breakdown during postharvest storage. Overall, preharvest UVB treatment, together with calcium chloride spray, can increase and maintain health-beneficial compound levels such as GLs and prolong the postharvest quality of broccoli microgreens.
Assuntos
Brassica/metabolismo , Glucosinolatos/química , Raios Ultravioleta , Antioxidantes/química , Cálcio/química , Cloreto de Cálcio/química , Cromatografia Líquida de Alta Pressão , Glucose/análogos & derivados , Glucose/química , Imidoésteres/química , Valor Nutritivo , Estresse Oxidativo , Oximas/química , Fenol , Sementes , Espectrometria de Massas por Ionização por Electrospray , Sulfóxidos/químicaRESUMO
Lung cancer is one of the most commonly occurring cancer mortality worldwide. The epidermal growth factor receptor (EGFR) plays an important role in cellular functions and has become the new promising target. Natural products and their derivatives with various structures, unique biological activities, and specific selectivity have served as lead compounds for EGFR. D-glucose and EGCG were used as starting materials. A series of glucoside derivatives of EGCG (7-12) were synthesized and evaluated for their in vitro anticancer activity against five human cancer cell lines, including HL-60, SMMC-7721, A-549, MCF-7, and SW480. In addition, we investigated the structure-activity relationship and physicochemical property-activity relationship of EGCG derivatives. Compounds 11 and 12 showed better growth inhibition than others in four cancer cell lines (HL-60, SMMC-7721, A-549, and MCF), with IC50 values in the range of 22.90-37.87 µM. Compounds 11 and 12 decreased phosphorylation of EGFR and downstream signaling protein, which also have more hydrophobic interactions than EGCG by docking study. The most active compounds 11 and 12, both having perbutyrylated glucose residue, we found that perbutyrylation of the glucose residue leads to increased cytotoxic activity and suggested that their potential as anticancer agents for further development.