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1.
CNS Neurosci Ther ; 30(5): e14742, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38715283

RESUMO

BACKGROUND: Adenosine A3 receptor (ADORA3) belongs to the adenosine receptor families and the role of ADORA3 in vascular dementia (VaD) is largely unexplored. The present study sought to determine the therapeutic role of ADORA3 antagonist in a mouse model of VaD. METHODS: The GSE122063 dataset was selected to screen the differential expression genes and pathways between VaD patients and controls. A mouse model of bilateral carotid artery stenosis (BCAS) was established. The cognitive functions were examined by the novel object recognition test, Y maze test, and fear of conditioning test. The white matter injury (WMI) was examined by 9.4 T MRI, western blot, and immunofluorescence staining. The mechanisms of ADORA3-regulated phagocytosis by microglia were examined using qPCR, western blot, dual immunofluorescence staining, and flow cytometry. RESULTS: The expression of ADORA3 was elevated in brain tissues of VaD patients and ADORA3 was indicated as a key gene for VaD in the GSE122063. In BCAS mice, the expression of ADORA3 was predominantly elevated in microglia in the corpus callosum. ADORA3 antagonist promotes microglial phagocytosis to myelin debris by facilitating cAMP/PKA/p-CREB pathway and thereby ameliorates WMI and cognitive impairment in BCAS mice. The therapeutic effect of ADORA3 antagonist was partially reversed by the inhibition of the cAMP/PKA pathway. CONCLUSIONS: ADORA3 antagonist alleviates chronic ischemic WMI by modulating myelin clearance of microglia, which may be a potential therapeutic target for the treatment of VaD.


Assuntos
Demência Vascular , Camundongos Endogâmicos C57BL , Microglia , Fagocitose , Receptor A3 de Adenosina , Animais , Humanos , Masculino , Camundongos , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Estenose das Carótidas , Demência Vascular/patologia , Demência Vascular/metabolismo , Microglia/metabolismo , Microglia/efeitos dos fármacos , Microglia/patologia , Compostos Orgânicos , Fagocitose/efeitos dos fármacos , Fagocitose/fisiologia , Receptor A3 de Adenosina/metabolismo , Receptor A3 de Adenosina/genética , Substância Branca/patologia , Substância Branca/metabolismo , Substância Branca/efeitos dos fármacos
2.
Food Res Int ; 186: 114350, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38729698

RESUMO

In this study, three types of ß-sitosterol-based oleogels (ß-sitosterol + Î³-oryzanol oleogels, ß-sitosterol + lecithin, oleogels and ß-sitosterol + monostearate oleogels), loaded with astaxanthin, were employed as the oil phase to create oleogel-based emulsions (SO, SL, and SM) using high-pressure homogenization. The microstructure revealed that fine-scale crystals were dispersed within the oil phase of the droplets in the ß-sitosterol oleogel-based emulsion. The bioaccessibility of astaxanthin was found to be 58.13 %, 51.24 %, 36.57 %, and 45.72 % for SM, SL, SO, and the control group, respectively. Interestingly, the release of fatty acids was positively correlated with the availability of astaxanthin (P = 0.981). Further analysis of FFAs release and kinetics indicated that the structural strength of the oil-phase in the emulsions influenced the degree and rate of lipolysis. Additionally, the micellar fraction analysis suggested that the nature and composition of the oleogelators in SM and SL also impacted lipolysis and the bioaccessibility of astaxanthin. Furthermore, interfacial binding of lipase and isothermal titration calorimetry (ITC) measurements revealed that the oleogel network within the oil phase of the emulsion acted as a physical barrier, hindering the interaction between lipase and lipid. Overall, ß-sitosterol oleogel-based emulsions offer a versatile platform for delivering hydrophobic molecules, enhancing the bioavailability of active compounds, and achieving sustained release.


Assuntos
Emulsões , Compostos Orgânicos , Sitosteroides , Xantofilas , Sitosteroides/química , Xantofilas/química , Compostos Orgânicos/química , Disponibilidade Biológica , Lipólise , Lecitinas/química , Ácidos Graxos/química , Fenilpropionatos
3.
Anim Sci J ; 95(1): e13949, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38705592

RESUMO

Excess moisture content in cow manure inhibits the process of composting. This study examined the effects of introducing a slatted frame on temperature development, organic matter degradation, and moisture content during high-moisture composting. Twelve tons of cow manure was piled individually, and an iron slatted frame with a pipe and a plain frame filled inside with styrofoam was introduced in the treatment and control piles, respectively. Two hours after the start, running leachate via the pipe in the treatment pile was observed, but not in the control pile. The maximum temperatures as well as durations of the temperatures above 55°C of the treatment piles at all seven positions were higher than those of the control piles. In particular, four of the seven positions in the treatment pile exhibited more than twice the duration. Installing the slatted frame improved the organic matter degradation; the values of organic matter loss in the control and treatment were 48.0% and 58.4%, respectively. The final moisture content in the treated compost was 5% lower than that in the control. Overall, the introduction of a slatted frame generated higher temperatures and produced relatively dried and well-degraded compost.


Assuntos
Compostagem , Temperatura Alta , Esterco , Esterco/análise , Animais , Compostagem/métodos , Bovinos , Água , Temperatura , Compostos Orgânicos/análise , Solo/química
4.
Water Sci Technol ; 89(9): 2290-2310, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38747950

RESUMO

In the face of growing global freshwater scarcity, the imperative to recycle and reuse water becomes increasingly apparent across industrial, agricultural, and domestic sectors. Eliminating a range of organic pollutants in wastewater, from pesticides to industrial byproducts, presents a formidable challenge. Among the potential solutions, membrane technologies emerge as promising contenders for treating diverse organic contaminants from industrial, agricultural, and household origins. This paper explores cutting-edge membrane-based approaches, including reverse osmosis, nanofiltration, ultrafiltration, microfiltration, gas separation membranes, and pervaporation. Each technology's efficacy in removing distinct organic pollutants while producing purified water is scrutinized. This review delves into membrane fouling, discussing its influencing factors and preventative strategies. It sheds light on the merits, limitations, and prospects of these various membrane techniques, contributing to the advancement of wastewater treatment. It advocates for future research in membrane technology with a focus on fouling control and the development of energy-efficient devices. Interdisciplinary collaboration among researchers, engineers, policymakers, and industry players is vital for shaping water purification innovation. Ongoing research and collaboration position us to fulfill the promise of accessible, clean water for all.


Assuntos
Membranas Artificiais , Poluentes Químicos da Água , Purificação da Água , Purificação da Água/métodos , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação , Eliminação de Resíduos Líquidos/métodos , Filtração/métodos , Filtração/instrumentação , Ultrafiltração/métodos , Compostos Orgânicos/isolamento & purificação
5.
Environ Sci Technol ; 58(19): 8380-8392, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38691504

RESUMO

A comprehensive understanding of the full volatility spectrum of organic oxidation products from the benzene series precursors is important to quantify the air quality and climate effects of secondary organic aerosol (SOA) and new particle formation (NPF). However, current models fail to capture the full volatility spectrum due to the absence of important reaction pathways. Here, we develop a novel unified model framework, the integrated two-dimensional volatility basis set (I2D-VBS), to simulate the full volatility spectrum of products from benzene series precursors by simultaneously representing first-generational oxidation, multigenerational aging, autoxidation, dimerization, nitrate formation, etc. The model successfully reproduces the volatility and O/C distributions of oxygenated organic molecules (OOMs) as well as the concentrations and the O/C of SOA over wide-ranging experimental conditions. In typical urban environments, autoxidation and multigenerational oxidation are the two main pathways for the formation of OOMs and SOA with similar contributions, but autoxidation contributes more to low-volatility products. NOx can reduce about two-thirds of OOMs and SOA, and most of the extremely low-volatility products compared to clean conditions, by suppressing dimerization and autoxidation. The I2D-VBS facilitates a holistic understanding of full volatility product formation, which helps fill the large gap in the predictions of organic NPF, particle growth, and SOA formation.


Assuntos
Benzeno , Benzeno/química , Compostos Orgânicos/química , Oxirredução , Aerossóis , Volatilização , Poluentes Atmosféricos , Modelos Teóricos
6.
Bioresour Technol ; 401: 130730, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38657825

RESUMO

Achieving partial denitrification (PD) by using fermentation products extracted from waste activated sludge (WAS) rather than commercial organic matters is a promising approach for providing nitrite for anammox, while sludge reduction could also be realized by WAS reutilization. This study proposed an In-situ Sludge Fermentation coupled with Partial Denitrification (ISFPD) system and explored its performance under different conditions, including initial pH, nitrate concentrations, and organic matters. Results showed that nitrite production increased with the elevation of initial pH (from 6 to 9), and the highest nitrate-to-nitrite transformation ratio (NTR) reached 77% at initial pH 9. The PD rates and NTR were observed to be minimally influenced by initial nitrate concentrations. Acetate was preferred by denitrifying bacteria, while macromolecules such as proteins necessitated be hydrolyzed to be suitable for further utilization. The insights gained through this study paved the way for efficient nitrite production and sustainable WAS reutilization in harmony.


Assuntos
Desnitrificação , Fermentação , Nitratos , Nitritos , Esgotos , Esgotos/microbiologia , Concentração de Íons de Hidrogênio , Nitritos/metabolismo , Nitratos/metabolismo , Estudos de Viabilidade , Compostos Orgânicos , Reatores Biológicos , Álcalis/química
7.
Bioresour Technol ; 401: 130736, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38670289

RESUMO

Oxygenic photogranules (OPGs) have great potential for the aeration-free treatment of various wastewater, however, the effects of wastewater carbon composition on OPGs remain unknown. This study investigated the hydrodynamic photogranulation in three types of wastewater with the same total carbon concentration but different inorganic/organic carbon compositions, each operated at two replicated reactors. Results showed that photogranulation failed in reactors fed with only inorganic carbon. In reactors with equal inorganic and organic carbon, loose-structured OPGs formed but then disintegrated. Comparatively, reactors treating organic carbon-based wastewater obtained regular and dense OPGs with better settleability, lower effluent turbidity, excellent structural stability, and higher carbon assimilation rate. Sufficient amounts of organic carbon were crucial for the formation and stability of OPGs as they promoted the secretion of extracellular polymeric substances (EPS) and the growth of filamentous cyanobacteria. This study provides a basis for the startup of OPGs process and facilitates its large-scale application.


Assuntos
Carbono , Hidrodinâmica , Compostos Orgânicos , Oxigênio , Águas Residuárias , Carbono/química , Águas Residuárias/química , Reatores Biológicos , Purificação da Água/métodos , Cianobactérias/metabolismo
8.
Anal Chim Acta ; 1303: 342523, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38609265

RESUMO

BACKGROUND: l-lactate detection is important for not only assessing exercise intensity, optimizing training regimens, and identifying the lactate threshold in athletes, but also for diagnosing conditions like L-lactateosis, monitoring tissue hypoxia, and guiding critical care decisions. Moreover, l-lactate has been utilized as a biomarker to represent the state of human health. However, the sensitivity of the present l-lactate detection technique is inadequate. RESULTS: Here, we reported a sensitive ratiometric fluorescent probe for l-lactate detection based on platinum octaethylporphyrin (PtOEP) doped semiconducting polymer dots (Pdots-Pt) with enzymatic cascade reaction. With the help of an enzyme cascade reaction, the l-lactate was continuously oxidized to pyruvic and then reduced back to l-lactate for the next cycle. During this process, oxygen and NADH were continuously consumed, which increased the red fluorescence of Pdots-Pt that responded to the changes of oxygen concentration and decreased the blue fluorescence of NADH at the same time. By comparing the fluorescence intensities at these two different wavelengths, the concentration of l-lactate was accurately measured. With the optimal conditions, the probes showed two linear detection ranges from 0.5 nM to 5.0 µM and 5.0 µM-50.0 µM for l-lactate detection. The limit of detection was calculated to be 0.18 nM by 3σ/slope method. Finally, the method shows good detection performance of l-lactate in both bovine serum and artificial serum samples, indicating its potential usage for the selective analysis of l-lactate for health monitoring and disease diagnosis. SIGNIFICANCE: The successful application of the sensing system in the complex biological sample (bovine serum and artificial serum samples) demonstrated that this method could be used for sensitive l-lactate detection in practical clinical applications. This detection system provided an extremely low detection limit, which was several orders of magnitude lower than methods proposed in other literatures.


Assuntos
Ácido Láctico , NAD , Humanos , Atletas , Compostos Orgânicos , Oxigênio , Polímeros
9.
Sci Total Environ ; 929: 172415, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38631647

RESUMO

Establishing reliable predictive models for plant uptake of organic pollutants is crucial for environmental risk assessment and guiding phytoremediation efforts. This study compiled an expanded dataset of plant cuticle-water partition coefficients (Kcw), a useful indicator for plant uptake, for 371 data points of 148 unique compounds and various plant species. Quantum/computational chemistry software and tools were utilized to compute various molecular descriptors, aiming to comprehensively characterize the properties and structures of each compound. Three types of models were developed to predict Kcw: a mechanism-driven pp-LFER model, a data-driven machine learning model, and an integrated mechanism-data-driven model. The mechanism-data-driven GBRT-ppLFER model exhibited superior performance, achieving RMSEtrain = 0.133 and RMSEtest = 0.301 while maintaining interpretability. The Shapley Additive Explanation analysis indicated that pp-LFER parameters, ESPI, FwRadicalmax, ExtFP607, and RDF70s are the key factors influencing plant uptake in the GBRT-ppLFER model. Overall, pp-LFER parameter, ESPI, and ExtFP607 show positive effects, while the remaining factors exhibit negative effects. Partial dependency analysis further indicated that plant uptake is not solely determined by individual factors but rather by the combined interactions of multiple factors. Specifically, compounds with ppLFER parameter >4, ESPI > -25.5, 0.098 < FwRadicalmax <0.132, and 2 < RFD70s < 3, are generally more readily taken up by plants. Besides, the predicted Kcw values from the GBRT-ppLFER model were effectively employed to estimate the plant-water partition coefficients and bioconcentration factors across different plant species and growth media (water, sand, and soil), achieving an outstanding performance with an RMSE of 0.497. This study provides effective tools for assessing plant uptake of organic pollutants and deepens our understanding of plant-environment-compound interactions.


Assuntos
Biodegradação Ambiental , Plantas , Plantas/metabolismo , Poluentes do Solo/metabolismo , Poluentes Ambientais/metabolismo , Compostos Orgânicos/metabolismo , Aprendizado de Máquina
10.
Chemosphere ; 356: 141946, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38604518

RESUMO

End-of-life electric and electronic devices stand as one of the fastest growing wastes in the world and, therefore, a rapidly escalating global concern. A relevant fraction of these wastes corresponds to polymeric materials containing a plethora of chemical additives. Some of those additives fall within the category of hazardous organic compounds (HOCs). Despite the significant advances in the capabilities of analytical methods, the comprehensive characterization of WEEE plastic remains as a challenge. This research strives to identify the primary additives within WEEE polymers by implementing a non-target and suspect screening approach. Gas chromatography coupled to time-of-flight mass spectrometry (GC-QTOF-MS), using electron ionization (EI), was applied for the detection and identification of more than 300 substances in this matrix. A preliminary comparison was carried out with nominal resolution EI-MS spectra contained in the NIST17 library. BPA, flame retardants, UV-filters, PAHs, and preservatives were among the compounds detected. Fifty-one out of 300 compounds were confirmed by comparison with authentic standards. The study establishes a comprehensive database containing m/z ratios and accurate mass spectra of characteristic compounds, encompassing HOCs. Semi-quantification of the predominant additives was conducted across 48 WEEE samples collected from handling and dismantling facilities in Galicia. ABS plastic demonstrated the highest median concentrations, ranging from 0.154 to 4456 µg g-1, being brominated flame retardants and UV filters, the families presenting the highest concentrations. Internet router devices revealed the highest concentrations, containing a myriad of HOCs, such as tetrabromobisphenol A (TBBPA), tribromophenol (TBrP), triphenylphosphate (TPhP), tinuvin P and bisphenol A (BPA), most of which are restricted in Europe.


Assuntos
Resíduo Eletrônico , Cromatografia Gasosa-Espectrometria de Massas , Plásticos , Resíduo Eletrônico/análise , Plásticos/análise , Plásticos/química , Retardadores de Chama/análise , Substâncias Perigosas/análise , Compostos Orgânicos/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Fenóis/análise , Compostos Benzidrílicos/análise , Monitoramento Ambiental/métodos , Polímeros/química , Polímeros/análise
11.
Sci Total Environ ; 929: 172656, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38653420

RESUMO

There has been increasing concern regarding the adverse environmental and health effects of organic pollutants. A list of priority control organic pollutants (PCOPs) can provide regulatory frameworks for the use and monitoring of organic compounds in the environment. In this study, 20,010 groundwater samples were collected from 15 "first level" groundwater resource zones in China. Fifty (50) organic compounds were analyzed based on their prevalence, occurrence, and physicochemical properties (persistence, bioaccumulation, and toxicity). Results showed that 16 PCOPs, including 12 pesticides, 3 aromatic hydrocarbons (AHs), and 1 phthalate ester, were recognized. Pesticides and AHs accounted for 75 % and 18.75 % of the high-priority pollutants, respectively. There were significant differences in PCOPs between confined and phreatic groundwater. Higher concentrations of pesticides were mainly detected in phreatic groundwater. PCOPs detected in samples from the 15 groundwater resource zones were mainly pesticides and AHs. The groundwater data indicate that the organic compounds detected in the Yellow River Basin (YRB), Yangtze River Basin (YZB), Liaohe River Basin (LRB), and Songhua River Basin (SRB) are mainly categorized as Q1 (high priority) and Q2 (medium priority) pollutants based on the contaminants ranking system in China. The findings from this study offer a snapshot of the wide distribution of PCOPs in the surveyed regions, and are expected to establishing treatment and prevention measures at both the regional and national levels in China.


Assuntos
Monitoramento Ambiental , Água Subterrânea , Poluentes Químicos da Água , China , Poluentes Químicos da Água/análise , Água Subterrânea/química , Bioacumulação , Praguicidas/análise , Compostos Orgânicos/análise
12.
Environ Geochem Health ; 46(5): 151, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578445

RESUMO

Nitrate attenuation during river bank infiltration is the key process for reducing nitrogen pollution. Temperature is considered to be an important factor affecting nitrate attenuation. However, the magnitude and mechanism of its impact have not been clear for a long time. In this study, the effects of temperature and temperature gradient on the nitrate denitrification rate were investigated via static batch and dynamic soil column simulation experiments. The results showed that temperature had a significant effect on the denitrification rate. Temperature effects were first observed in denitrifying bacteria. At low temperatures, the microorganism diversity was low, resulting in a lower denitrification rate constant. The static experimental results showed that the denitrification rate at 19 °C was approximately 2.4 times that at 10 °C. The dynamic soil column experiment established an exponential positive correlation between the nitrate denitrification decay kinetic constant and temperature. The affinity of denitrifying enzymes for nitrate in the reaction substrate was ordered as follows: decreasing temperature gradient (30 °C → 10 °C) > zero temperature gradient (10 °C) > increasing temperature gradient condition (0 °C → 10 °C). This study provides a theoretical basis for the biogeochemical processes underlying river bank infiltration, which will help aid in the development and utilization of groundwater resources.


Assuntos
Nitratos , Rios , Nitratos/análise , Temperatura , Desnitrificação , Compostos Orgânicos , Nitrogênio/análise , Solo/química
13.
Appl Microbiol Biotechnol ; 108(1): 297, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607564

RESUMO

Glycosidic osmolytes are widespread natural compounds that protect microorganisms and their macromolecules from the deleterious effects of various environmental stresses. Their protective properties have attracted considerable interest for industrial applications, especially as active ingredients in cosmetics and healthcare products. In that regard, the osmolyte glucosylglycerate is somewhat overlooked. Glucosylglycerate is typically accumulated by certain organisms when they are exposed to high salinity and nitrogen starvation, and its potent stabilizing effects have been demonstrated in vitro. However, the applications of this osmolyte have not been thoroughly explored due to the lack of a cost-efficient production process. Here, we present an overview of the progress that has been made in developing promising strategies for the synthesis of glucosylglycerate and its precursor glycerate, and discuss the remaining challenges. KEY POINTS: • Bacterial milking could be explored for fermentative production of glucosylglycerate • Glycoside phosphorylases of GH13_18 represent attractive alternatives for biocatalytic production • Conversion of glycerol with alditol oxidase is a promising strategy for generating the precursor glycerate.


Assuntos
Glicosídeos , Compostos Orgânicos , Biocatálise , Fermentação , Glicerol
14.
Front Immunol ; 15: 1355380, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38633262

RESUMO

Objectives: To identify age-related plasma extracellular vehicle (EVs) phenotypes in healthy adults. Methods: EV proteomics by high-resolution mass spectrometry to evaluate EV protein stability and discover age-associated EV proteins (n=4 with 4 serial freeze-thaws each); validation by high-resolution flow cytometry and EV cytokine quantification by multiplex ELISA (n=28 healthy donors, aged 18-83 years); quantification of WI-38 fibroblast cell proliferation response to co-culture with PKH67-labeled young and old plasma EVs. The EV samples from these plasma specimens were previously characterized for bilayer structure, intra-vesicle mitochondria and cytokines, and hematopoietic cell-related surface markers. Results: Compared with matched exo-EVs (EV-depleted supernatants), endo-EVs (EV-associated) had higher mean TNF-α and IL-27, lower mean IL-6, IL-11, IFN-γ, and IL-17A/F, and similar mean IL-1ß, IL-21, and IL-22 concentrations. Some endo-EV and exo-EV cytokine concentrations were correlated, including TNF-α, IL-27, IL-6, IL-1ß, and IFN-γ, but not IL-11, IL-17A/F, IL-21 or IL-22. Endo-EV IFN-γ and exo-EV IL-17A/F and IL-21 declined with age. By proteomics and confirmed by flow cytometry, we identified age-associated decline of fibrinogen (FGA, FGB and FGG) in EVs. Age-related EV proteins indicated predominant origins in the liver and innate immune system. WI-38 cells (>95%) internalized similar amounts of young and old plasma EVs, but cells that internalized PKH67-EVs, particularly young EVs, underwent significantly greater cell proliferation. Conclusion: Endo-EV and exo-EV cytokines function as different biomarkers. The observed healthy aging EV phenotype reflected a downregulation of EV fibrinogen subpopulations consistent with the absence of a pro-coagulant and pro-inflammatory condition common with age-related disease.


Assuntos
Vesículas Extracelulares , Envelhecimento Saudável , Interleucina-27 , Adulto , Humanos , Interleucina-17/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-27/metabolismo , Interleucina-6/metabolismo , Vesículas Extracelulares/metabolismo , Citocinas/metabolismo , Sistema Imunitário/metabolismo , Fibrinogênio/metabolismo , Compostos Orgânicos
15.
Microb Biotechnol ; 17(4): e14460, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38635191

RESUMO

Aromatic compounds are used in pharmaceutical, food, textile and other industries. Increased demand has sparked interest in exploring biotechnological approaches for their sustainable production as an alternative to chemical synthesis from petrochemicals or plant extraction. These aromatic products may be toxic to microorganisms, which complicates their production in cell factories. In this study, we analysed the toxicity of multiple aromatic compounds in common production hosts. Next, we screened a subset of toxic aromatics, namely 2-phenylethanol, 4-tyrosol, benzyl alcohol, berberine and vanillin, against transporter deletion libraries in Escherichia coli and Saccharomyces cerevisiae. We identified multiple transporter deletions that modulate the tolerance of the cells towards these compounds. Lastly, we engineered transporters responsible for 2-phenylethanol tolerance in yeast and showed improved 2-phenylethanol bioconversion from L-phenylalanine, with deletions of YIA6, PTR2 or MCH4 genes improving titre by 8-12% and specific yield by 38-57%. Our findings provide insights into transporters as targets for improving the production of aromatic compounds in microbial cell factories.


Assuntos
Álcool Feniletílico , Saccharomyces cerevisiae , Álcool Benzílico , Biotecnologia , Escherichia coli , Proteínas de Membrana Transportadoras , Compostos Orgânicos
16.
Environ Microbiol ; 26(4): e16625, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38653479

RESUMO

Diatoms can survive long periods in dark, anoxic sediments by forming resting spores or resting cells. These have been considered dormant until recently when resting cells of Skeletonema marinoi were shown to assimilate nitrate and ammonium from the ambient environment in dark, anoxic conditions. Here, we show that resting cells of S. marinoi can also perform dissimilatory nitrate reduction to ammonium (DNRA), in dark, anoxic conditions. Transmission electron microscope analyses showed that chloroplasts were compacted, and few large mitochondria had visible cristae within resting cells. Using secondary ion mass spectrometry and isotope ratio mass spectrometry combined with stable isotopic tracers, we measured assimilatory and dissimilatory processes carried out by resting cells of S. marinoi under dark, anoxic conditions. Nitrate was both respired by DNRA and assimilated into biomass by resting cells. Cells assimilated nitrogen from urea and carbon from acetate, both of which are sources of dissolved organic matter produced in sediments. Carbon and nitrogen assimilation rates corresponded to turnover rates of cellular carbon and nitrogen content ranging between 469 and 10,000 years. Hence, diatom resting cells can sustain their cells in dark, anoxic sediments by slowly assimilating and respiring substrates from the ambient environment.


Assuntos
Compostos de Amônio , Diatomáceas , Nitratos , Oxirredução , Nitratos/metabolismo , Compostos de Amônio/metabolismo , Diatomáceas/metabolismo , Anaerobiose , Escuridão , Compostos Orgânicos/metabolismo , Espectrometria de Massa de Íon Secundário , Sedimentos Geológicos/microbiologia , Carbono/metabolismo , Nitrogênio/metabolismo
17.
J Neuroinflammation ; 21(1): 103, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643194

RESUMO

BACKGROUND: Colony stimulating factor 1 receptor (CSF1R) signaling is crucial for the maintenance and function of various myeloid subsets. CSF1R antagonism was previously shown to mitigate clinical severity in experimental autoimmune encephalomyelitis (EAE). The associated mechanisms are still not well delineated. METHODS: To assess the effect of CSF1R signaling, we employed the CSF1R antagonist PLX5622 formulated in chow (PLX5622 diet, PD) and its control chow (control diet, CD). We examined the effect of PD in steady state and EAE by analyzing cells isolated from peripheral immune organs and from the CNS via flow cytometry. We determined CNS infiltration sites and assessed the extent of demyelination using immunohistochemistry of cerebella and spinal cords. Transcripts of genes associated with neuroinflammation were also analyzed in these tissues. RESULTS: In addition to microglial depletion, PD treatment reduced dendritic cells and macrophages in peripheral immune organs, both during steady state and during EAE. Furthermore, CSF1R antagonism modulated numbers and relative frequencies of T effector cells both in the periphery and in the CNS during the early stages of the disease. Classical neurological symptoms were milder in PD compared to CD mice. Interestingly, a subset of PD mice developed atypical EAE symptoms. Unlike previous studies, we observed that the CNS of PD mice was infiltrated by increased numbers of peripheral immune cells compared to that of CD mice. Immunohistochemical analysis showed that CNS infiltrates in PD mice were mainly localized in the cerebellum while in CD mice infiltrates were primarily localized in the spinal cords during the onset of neurological deficits. Accordingly, during the same timepoint, cerebella of PD but not of CD mice had extensive demyelinating lesions, while spinal cords of CD but not of PD mice were heavily demyelinated. CONCLUSIONS: Our findings suggest that CSF1R activity modulates the cellular composition of immune cells both in the periphery and within the CNS, and affects lesion localization during the early EAE stages.


Assuntos
Encefalomielite Autoimune Experimental , Camundongos , Animais , Encefalomielite Autoimune Experimental/induzido quimicamente , Encefalomielite Autoimune Experimental/tratamento farmacológico , Compostos Orgânicos/farmacologia , Medula Espinal/patologia , Microglia , Receptores de Fator Estimulador de Colônias , Receptores Proteína Tirosina Quinases , Camundongos Endogâmicos C57BL
18.
J Chem Inf Model ; 64(8): 3021-3033, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38602390

RESUMO

Synthesis planning of new pharmaceutical compounds is a well-known bottleneck in modern drug design. Template-free methods, such as transformers, have recently been proposed as an alternative to template-based methods for single-step retrosynthetic predictions. Here, we trained and evaluated a transformer model, called the Chemformer, for retrosynthesis predictions within drug discovery. The proprietary data set used for training comprised ∼18 M reactions from literature, patents, and electronic lab notebooks. Chemformer was evaluated for the purpose of both single-step and multistep retrosynthesis. We found that the single-step performance of Chemformer was especially good on reaction classes common in drug discovery, with most reaction classes showing a top-10 round-trip accuracy above 0.97. Moreover, Chemformer reached a higher round-trip accuracy compared to that of a template-based model. By analyzing multistep retrosynthesis experiments, we observed that Chemformer found synthetic routes, leading to commercial starting materials for 95% of the target compounds, an increase of more than 20% compared to the template-based model on a proprietary compound data set. In addition to this, we discovered that Chemformer suggested novel disconnections corresponding to reaction templates, which are not included in the template-based model. These findings were further supported by a publicly available ChEMBL compound data set. The conclusions drawn from this work allow for the design of a synthesis planning tool where template-based and template-free models work in harmony to optimize retrosynthetic recommendations.


Assuntos
Descoberta de Drogas , Descoberta de Drogas/métodos , Compostos Orgânicos/química , Compostos Orgânicos/síntese química , Modelos Químicos
19.
Ying Yong Sheng Tai Xue Bao ; 35(3): 639-647, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38646751

RESUMO

Vegetation restoration can effectively enhance soil quality and soil organic carbon (SOC) sequestration. In this study, the distribution characteristics of soil nutrients and SOC along soil profile (0-100 cm), and their responses to restoration years (16, 28, 38 years) were studied in Caragana korshinskii plantations in the southern mountainous area of Ningxia, compared with cropland and natural grassland. The results showed that: 1) the contents of SOC, soil total nitrogen (TN), total phosphorus (TP), particulate organic carbon (POC), mineral-associated organic carbon (MAOC) and the proportion of particulate organic carbon to total organic carbon (POC/SOC) all decreased with increasing soil depth. The ratio of mineral-associated organic carbon to total organic carbon (MAOC/SOC) exhibited an opposite trend. 2) The contents of SOC, TN, TP, C:P, N:P, POC and MAOC gra-dually decreased as the restoration years increased. However, the C:N ratio showed no significant change. The POC/SOC ratio initially increased and then decreased, while the MAOC/SOC ratio decreased initially and then increased. 3) In three different types of vegetation, POC, MAOC, and SOC showed a highly significant positive linear correlation, with the increase in SOC mainly depended on the increase in MAOC. The SOC, TN, TP, POC and MAOC contents in natural grassland and C. korshinskii plantations were significantly higher than those in cropland. In conclusion, soil nutrients and POC and MAOC contents of C. korshinskii plantations gradually decreased with the increases in restoration years. However, when compared with cropland, natural grassland and C. korshinskii plantations demonstrated a greater capacity to maintain and enhance soil nutrient and carbon storage.


Assuntos
Caragana , Carbono , Florestas , Nitrogênio , Compostos Orgânicos , Fósforo , Solo , China , Solo/química , Carbono/análise , Caragana/crescimento & desenvolvimento , Nitrogênio/análise , Fósforo/análise , Compostos Orgânicos/análise , Nutrientes/análise , Recuperação e Remediação Ambiental/métodos , Sequestro de Carbono , Ecossistema
20.
Environ Sci Technol ; 58(14): 6204-6214, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38557085

RESUMO

Marine permeable sediments are important sites for organic matter turnover in the coastal ocean. However, little is known about their role in trapping dissolved organic matter (DOM). Here, we examined DOM abundance and molecular compositions (9804 formulas identified) in subtidal permeable sediments along a near- to offshore gradient in the German North Sea. With the salinity increasing from 30.1 to 34.6 PSU, the DOM composition in bottom water shifts from relatively higher abundances of aromatic compounds to more highly unsaturated compounds. In the bulk sediment, DOM leached by ultrapure water (UPW) from the solid phase is 54 ± 20 times more abundant than DOM in porewater, with higher H/C ratios and a more terrigenous signature. With 0.5 M HCl, the amount of leached DOM (enriched in aromatic and oxygen-rich compounds) is doubled compared to UPW, mainly due to the dissolution of poorly crystalline Fe phases (e.g., ferrihydrite and Fe monosulfides). This suggests that poorly crystalline Fe phases promote DOM retention in permeable sediments, preferentially terrigenous, and aromatic fractions. Given the intense filtration of seawater through the permeable sediments, we posit that Fe can serve as an important intermediate storage for terrigenous organic matter and potentially accelerate organic matter burial in the coastal ocean.


Assuntos
Matéria Orgânica Dissolvida , Ferro , Ferro/química , Água do Mar/química , Água , Compostos Orgânicos
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