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A widespread concern had been there regarding soil ecological and environmental problems caused by microplastic pollution in agricultural soils. A controlled laboratory incubation experiment was performed to examine the effects of different types of microplastics on soil properties, N2O emissions, and nitrogen ï¼Nï¼ transformations in tropical arable soils from a pepper-corn cropping system in Hainan Province. Three treatments were doneï¼ soil without microplastics ï¼CKï¼ and soil amended with 5% of polyethylene ï¼PEï¼ or with 5% of polybutylene adipate co-terephthalate ï¼PBATï¼. The results showed that both types of microplastic addition increased soil pH, soil organic carbon ï¼SOCï¼, and dissolved organic carbon ï¼DOCï¼ contents, with stronger treatment effects observed for PBAT than those for the PE treatment. In addition, the PE and PBAT treatments increased soil ammonium nitrogen ï¼NH4+-Nï¼ contents by 66.07% and 119.65% and decreased nitrate nitrogen ï¼NO3--Nï¼ contents by 8.56% and 29.68%, respectively. Compared to those in the CK treatment, the addition of PBAT significantly increased soil N2O emissions by 254.92% ï¼P < 0.05ï¼, whereas that of PE produced no significant effects. Furthermore, both the PE and PBAT treatments increased soil net nitrogen mineralization rate ï¼NMRï¼ and decreased soil net nitrification rate ï¼NNRï¼, with more obvious treatment effects observed in PBAT than in the PE treatment. PBAT addition increased the abundance of ureC, while PE had no significant effects. Microplastic addition reduced the abundance of nitrifying gene abundances ï¼AOA-amoA, AOB-amoA, and nxrAï¼, with more obvious treatment effects found in the PBAT treatment. Further, PBAT addition significantly increased the gene abundances of nirK, nirS, nosZ, and fungal nirK ï¼P < 0.05ï¼, whereas the addition of PE had no significant effect on those gene abundances. Soil N2O emissions had positive relationships with NH4+-N intensity, pH, DOC, SOC, and nirS abundance. In conclusion, biodegradable microplastics addition produced stronger influences on soil properties and N transformations than the non-biodegradable one in tropical arable soils and aggravated soil N2O emissions mainly by promoting denitrification.
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An efficient [3 + 2] cycloaddition reaction between in situ generated nitrile imines from hydrazonoyl halides and vinylsulfonium salts is developed. The nitrile imines are demonstrated to be a new class of reaction partner for vinylsulfonium salts to conduct the [3 + 2] cycloaddition reaction. The process provides a concise and efficient method for the construction of pyrazole derivatives under mild reaction conditions with broad substrate scope, good product yields, and high regioselectivity.
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A concise and efficient method for the construction of fully substituted difluoromethylpyrazoles is achieved by a cyclization reaction between difluoroacetohydrazonoyl bromides and 2-acylacetonitrile or malononitrile. The method features advantages such as mild reaction conditions, broad substrate scope, good product yields, and high regioselectivity.
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This study aims to investigate the effect and mechanism of the EtO Ac extract of Draconis Sanguis(DSE) on improving athero sclerosis in ApoE gene knockout(ApoE~(-/-)) mice. The ApoE~(-/-) mice were randomly divided into five groups: control group, mo delgroup, positive group treated with ezetimibe of 5 mg·kg~(-1)(EG), and low(100 mg·kg~(-1)) and high dose(200 mg·kg~(-1)) groups ofDSE. xcept for the control group, all other groups were fed a high-fat diet and administered drugs for 16 successive weeks. After 16 weeks of Eadministration, the body weight, liver, and epididymal fat mass of the mice were measured; the level of blood lipid and the plaquearea of the aortic outflow tract were detected to evaluate the efficacy of DSE in vivo. In addition, in vitro cultures of human umbilical v ein endothelial cell(HUVEC) were conducted. Oxidative stress of endothelial cells was induced by oxidized low-density lipoprot ein(ox-LDL), and the effects of DSE on oxidative stress-related proteins in endothelial cells were examined. The results sho wedthat both doses of DSE significantly improved the epididymal fat mass and index of ApoE~(-/-) mice with atherosclerosis, lowered thelevels of plasma cholesterol, triglyceride, and non-high density lipoprotein cholesterol, and reduced the plaque area of the aortic ou tflow tract. totIn alvitro experiments confirmed that ox-LDL significantly increased the level of lipid peroxidation marker 4-HNE in HUVECcells, confirming that DSE improved the degree of atherosclerotic lesions in ApoE~(-/-) mice by inhibiting ox-LDL-induced oxidative stress in vascular endothelial cells.
Assuntos
Apolipoproteínas E , Aterosclerose , Camundongos Knockout , Animais , Aterosclerose/tratamento farmacológico , Aterosclerose/genética , Aterosclerose/metabolismo , Camundongos , Apolipoproteínas E/genética , Masculino , Humanos , Estresse Oxidativo/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/administração & dosagem , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Camundongos Endogâmicos C57BLRESUMO
BACKGROUND: Baoyuan decoction (BYD) has been widely utilized as a traditional prescription for the treatment of various conditions such as coronary heart disease, aplastic anemia, and chronic renal failure. However, its potential efficacy in improving atherosclerosis has not yet been investigated. PURPOSE: Our research aimed to assess the potential of BYD as an inhibitor of atherosclerosis and uncover the underlying mechanism by which it acts on foam cell formation. STUDY DESIGN AND METHODS: High-fat diet-induced ApoE-/- mice were employed to explore the effect of BYD on atherosclerosis. The differential metabolites in feces were identified and analyzed by LC-Qtrap-MS. In addition, we utilized pharmacological inhibition of BYD on foam cell formation induced by oxLDL in THP-1 cells to elucidate the underlying mechanisms specifically in macrophages. RESULTS: The atherosclerotic plaque burden in the aortic sinus of ApoE-/- mice was notably reduced with BYD treatment, despite no significant alterations in plasma lipids. Metabolomic analysis revealed that BYD suppressed the increased levels of peroxidized fatty acids, specifically 9/13-hydroxyoctadecadienoic acid (9/13-HODE), in the feces of mice. As a prominent peroxidized fatty acid found in oxLDL, we confirmed that 9/13-HODE induced the overexpression of CD36 in THP-1 macrophages by upregulating PPARγ. In subsequent experiments, the decreased levels of CD36 triggered by oxLDL were observed after BYD treatment. This decrease occurred through the regulation of the Src/MMK4/JNK pathway, resulting in the suppression of lipid deposition in THP-1 macrophages. CONCLUSIONS: These results illustrate that BYD exhibits potential anti-atherosclerotic effects by inhibiting CD36 expression to prevent foam cell formation.
Assuntos
Aterosclerose , Antígenos CD36 , Medicamentos de Ervas Chinesas , Células Espumosas , Lipoproteínas LDL , Animais , Aterosclerose/tratamento farmacológico , Antígenos CD36/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Masculino , Camundongos , Células Espumosas/efeitos dos fármacos , Células Espumosas/metabolismo , Lipoproteínas LDL/metabolismo , Dieta Hiperlipídica , Ácidos Graxos , Camundongos Endogâmicos C57BL , Células THP-1 , Placa Aterosclerótica/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Apolipoproteínas ERESUMO
An effective [3 + 2] cycloaddition reaction of difluoromethyl or trifluoromethyl hydrazonoyl bromides with alkylidene pyrazolones was disclosed. This method provides an efficient approach for accessing a variety of highly functionalized fluoroalkyl spiropyrazolones in good yields. This protocol also features some advantages such as easily available and stable substrates, simple operation procedures, and atom and step economy. The formation of (cis)- and (trans)-products was discussed.
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As novel difluoromethyl building blocks, difluoromethylated N-acylhydrazones react with allyltrimethylsilanes and the halogen source via a tandem addition/cyclization/halogenation strategy, which produces various difluoromethylpyrazoline compounds in good yields. The method features mild reaction conditions, broad substrate scopes, and a transition metal-free process with easy operation. It also proves that difluoromethylated N-acylhydrazones are useful difluoromethyl building blocks for the construction of difluoromethylated nitrogen heterocycles.
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A highly efficient and metal-free [3+2] cyclization/rearrangement reaction toward the synthesis of multisubstituted trifluoromethyloxazolines from α-hydroxyketones and trifluoromethyl N-acylhydrazones has been developed. The unprecedented rearrangement of the amide fragment under acidic conditions after cleavage of the N-N bond of acylhydrazones has opened up new avenues for the development of reactions involving trifluoromethyl N-acylhydrazones. DFT calculations show that the mechanism involves multiple proton transfer processes.
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A p-TsOH/halotrimethylsilane facilitated cycloketonization of γ-hydroxyl ynones is detailed. This methodology enables the one-step synthesis of polysubstituted 3(2H)-furanone products. It is remarkable that the reaction exhibits excellent regio- and chemoselectivity by the addition of very small quantities of p-toluenesulfonic acid and water.
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Acquisition of new stem cell fates relies on the dissolution of the prior regulatory network sustaining the existing cell fates. Currently, extensive insights have been revealed for the totipotency regulatory network around the zygotic genome activation (ZGA) period. However, how the dissolution of the totipotency network is triggered to ensure the timely embryonic development following ZGA is largely unknown. In this study, we identify the unexpected role of a highly expressed 2-cell (2C) embryo specific transcription factor, ZFP352, in facilitating the dissolution of the totipotency network. We find that ZFP352 has selective binding towards two different retrotransposon sub-families. ZFP352 coordinates with DUX to bind the 2C specific MT2_Mm sub-family. On the other hand, without DUX, ZFP352 switches affinity to bind extensively onto SINE_B1/Alu sub-family. This leads to the activation of later developmental programs like ubiquitination pathways, to facilitate the dissolution of the 2C state. Correspondingly, depleting ZFP352 in mouse embryos delays the 2C to morula transition process. Thus, through a shift of binding from MT2_Mm to SINE_B1/Alu, ZFP352 can trigger spontaneous dissolution of the totipotency network. Our study highlights the importance of different retrotransposons sub-families in facilitating the timely and programmed cell fates transition during early embryogenesis.
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Retroelementos , Fatores de Transcrição , Animais , Camundongos , Desenvolvimento Embrionário/genética , Regulação da Expressão Gênica no Desenvolvimento , Retroelementos/genética , Solubilidade , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Zigoto/metabolismoRESUMO
A visible-light-induced four-component Ritter-type reaction was developed for the synthesis of ß-trifluoromethyl imides from CF3Br, alkenes, carboxylic acids, and nitriles. This protocol features mild reaction conditions, a broad substrate scope, and excellent functional group compatibility. Furthermore, this method has been proven to be suitable for the late-stage diversification of drug molecules. A mechanism involving a Ritter-type reaction and Mumm rearrangement was proposed on the basis of the control experiments.
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Imidas , Luz , Imidas/química , Alcenos/química , Ácidos Carboxílicos/química , Nitrilas/químicaRESUMO
It has been reported that glycogen in Escherichia coli has two structural states, that is, fragility and stability, which alters dynamically. However, molecular mechanisms behind the structural alterations are not fully understood. In this study, we focused on the potential roles of two important glycogen degradation enzymes, glycogen phosphorylase (glgP) and glycogen debranching enzyme (glgX), in glycogen structural alterations. The fine molecular structure of glycogen particles in Escherichia coli and three mutants (ΔglgP, ΔglgX and ΔglgP/ΔglgX) were examined, which showed that glycogen in E. coli ΔglgP and E. coli ΔglgP/ΔglgX were consistently fragile while being consistently stable in E. coli ΔglgX, indicating the dominant role of GP in glycogen structural stability control. In sum, our study concludes that glycogen phosphorylase is essential in glycogen structural stability, leading to molecular insights into structural assembly of glycogen particles in E. coli.
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Sistema da Enzima Desramificadora do Glicogênio , Glicogenólise , Escherichia coli , Citoplasma , GlicogênioRESUMO
Efficient visible-light-induced radical cascade trifluoromethylation/cyclization of inactivated alkenes with CF3Br, which is a nonhygroscopic, noncorrosive, cheap and industrially abundant chemical, was developed in this work, producing trifluoromethyl polycyclic quinazolinones, benzimidazoles and indoles under mild reaction conditions. The method features wide functional group compatibility and a broad substrate scope, offering a facile strategy to pharmaceutically produce valuable CF3-containing polycyclic aza-heterocycles.
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Benzimidazóis , Indóis , Quinazolinonas , Catálise , LuzRESUMO
Currently, more and more studies suggested that reductionism was lack of holistic and integrative view of biological processes, leading to limited understanding of complex systems like microbiota and the associated diseases. In fact, microbes are rarely present in individuals but normally live in complex multispecies communities. With the recent development of a variety of metaomics techniques, microbes could be dissected dynamically in both temporal and spatial scales. Therefore, in-depth understanding of human microbiome from different aspects such as genomes, transcriptomes, proteomes, and metabolomes could provide novel insights into their functional roles, which also holds the potential in making them diagnostic biomarkers in many human diseases, though there is still a huge gap to fill for the purpose. In this mini-review, we went through the frontlines of the metaomics techniques and explored their potential applications in clinical diagnoses of human diseases, e.g., infectious diseases, through which we concluded that novel diagnostic methods based on human microbiomes shall be achieved in the near future, while the limitations of these techniques such as standard procedures and computational challenges for rapid and accurate analysis of metaomics data in clinical settings were also examined.
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An efficient and novel photoinduced trifluoromethylation employing CF3Br as a trifluoromethyl source is described. With commercially accessible fac-Ir(III)(ppy)3 as the catalyst, radical trifluoromethylation between O-silyl enol ether and CF3Br occurs successfully. This method provides various α-CF3-substituted ketones with a broad substrate scope in good yields under mild reaction conditions.
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A tandem addition/cyclization reaction between trifluoromethyl N-acylhydrazones and cyanamide is described, which provides a novel and efficient process for the synthesis of polysubstituted 3-trifluoromethyl-1,2,4-triazolines and their derivatives. The method has the advantages of mild reaction conditions, a broad substrate scope, good product yields, and atom economy.
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Cianamida , Triazóis , Ciclização , EstereoisomerismoRESUMO
Currently, there exist a variety of glycogen extraction methods, which either damage glycogen spatial structure or only partially extract glycogen, leading to the biased characterization of glycogen fine molecular structure. To understand the dynamic changes of glycogen structures and the versatile functions of glycogen particles in bacteria, it is essential to isolate glycogen with minimal degradation. In this study, a mild glycogen isolation method is demonstrated by using cold-water (CW) precipitation via sugar density gradient ultra-centrifugation (SDGU-CW). The traditional trichloroacetic acid (TCA) method and potassium hydroxide (KOH) method were also performed for comparison. A commonly used lab strain, Escherichia coli BL21(DE3), was used as a model organism in this study for demonstration purposes. After extracting glycogen particles using different methods, their structures were analyzed and compared through size exclusion chromatography (SEC) for particle size distribution and fluorophore-assisted capillary electrophoresis (FACE) for linear chain length distributions. The analysis confirmed that glycogen extracted via SDGU-CW had minimal degradation.
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Escherichia coli , Glicogênio , Cromatografia em Gel , Escherichia coli/metabolismo , Glicogênio/metabolismo , Estrutura MolecularRESUMO
In clinical settings, rapid and accurate diagnosis of antibiotic resistance is essential for the efficient treatment of bacterial infections. Conventional methods for antibiotic resistance testing are time consuming, while molecular methods such as PCR-based testing might not accurately reflect phenotypic resistance. Thus, fast and accurate methods for the analysis of bacterial antibiotic resistance are in high demand for clinical applications. In this pilot study, we isolated 7 carbapenem-sensitive Klebsiella pneumoniae (CSKP) strains and 8 carbapenem-resistant Klebsiella pneumoniae (CRKP) strains from clinical samples. Surface-enhanced Raman spectroscopy (SERS) as a label-free and noninvasive method was employed for discriminating CSKP strains from CRKP strains through computational analysis. Eight supervised machine learning algorithms were applied for sample analysis. According to the results, all supervised machine learning methods could successfully predict carbapenem sensitivity and resistance in K. pneumoniae, with a convolutional neural network (CNN) algorithm on top of all other methods. Taken together, this pilot study confirmed the application potentials of surface-enhanced Raman spectroscopy in fast and accurate discrimination of Klebsiella pneumoniae strains with different antibiotic resistance profiles. IMPORTANCE With the low-cost, label-free, and nondestructive features, Raman spectroscopy is becoming an attractive technique with great potential to discriminate bacterial infections. In this pilot study, we analyzed surfaced-enhanced Raman spectroscopy (SERS) spectra via supervised machine learning algorithms, through which we confirmed the application potentials of the SERS technique in rapid and accurate discrimination of Klebsiella pneumoniae strains with different antibiotic resistance profiles.
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Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/efeitos dos fármacos , Análise Espectral Raman/métodos , Análise Discriminante , Humanos , Klebsiella pneumoniae/química , Klebsiella pneumoniae/genética , Aprendizado de Máquina , Testes de Sensibilidade Microbiana , Redes Neurais de Computação , Projetos PilotoRESUMO
As novel and efficient difluoromethyl building blocks, difluoroacetohydrazonoyl bromides have been synthesized for the first time. The synthetic utility of this reagent for the construction of difluoromethyl organic compounds is demonstrated by their effective regioselective [3 + 2] cycloaddition reactions with ynones, alkynoates, and ynamides. The reactions provide a novel and efficient protocol to access difluoromethyl-substituted pyrazoles in good to excellent yields.
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According to the sit-and-wait hypothesis, long-term environmental survival is positively correlated with increased bacterial pathogenicity because high durability reduces the dependence of transmission on host mobility. Many indirectly transmitted bacterial pathogens, such as Mycobacterium tuberculosis and Burkhoderia pseudomallei, have high durability in the external environment and are highly virulent. It is possible that abiotic stresses may activate certain pathways or the expressions of certain genes, which might contribute to bacterial durability and virulence, synergistically. Therefore, exploring how bacterial phenotypes change in response to environmental stresses is important for understanding their potentials in host infections. In this study, we investigated the effects of different concentrations of salt (sodium chloride, NaCl), on survival ability, phenotypes associated with virulence, and energy metabolism of the lab strain Escherichia coli BW25113. In particular, we investigated how NaCl concentrations influenced growth patterns, biofilm formation, oxidative stress resistance, and motile ability. In terms of energy metabolism that is central to bacterial survival, glucose consumption, glycogen accumulation, and trehalose content were measured in order to understand their roles in dealing with the fluctuation of osmolarity. According to the results, trehalose is preferred than glycogen at high NaCl concentration. In order to dissect the molecular mechanisms of NaCl effects on trehalose metabolism, we further checked how the impairment of trehalose synthesis pathway (otsBA operon) via single-gene mutants influenced E. coli durability and virulence under salt stress. After that, we compared the transcriptomes of E. coli cultured at different NaCl concentrations, through which differentially expressed genes (DEGs) and differential pathways with statistical significance were identified, which provided molecular insights into E. coli responses to NaCl concentrations. In sum, this study explored the in vitro effects of NaCl concentrations on E. coli from a variety of aspects and aimed to facilitate our understanding of bacterial physiological changes under salt stress, which might help clarify the linkages between bacterial durability and virulence outside hosts under environmental stresses.