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1.
J Am Chem Soc ; 146(10): 6962-6973, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38426449

RESUMO

The adsorption-type molecular switch exhibits bistable states with an equivalently long lifetime at the organic/inorganic interface, promising reliable switching behavior and superior assembly ability in the electronic circuits at the molecular scale. However, the number of reported adsorption-type molecular switches is currently less than 10, and exploring these molecular switches poses a formidable challenge due to the intricate interplay occurring at the interface. To address this challenge, we have developed a model enabling the identification of diverse molecular switches on metal surfaces based on easily accessible physical characteristics. These characteristics primarily include the metal valency electron concentration, the work function of metal surfaces, and the electronegativity difference of molecules. Using this model, we identified 56 new molecular switches. Employing the gradient descent algorithm and statistical linear discriminant analysis, we constructed an explicit descriptor that establishes a relationship between the interfacial structure and chemical environment and the stability of molecular switches. The model's accuracy was validated through density functional theory calculations, achieving a 90% accuracy for aromatic molecular switches. The conductive switching behaviors were further confirmed by nonequilibrium Green's function transport calculations.

2.
J Hazard Mater ; 465: 133459, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38219581

RESUMO

Non-antibiotic chemicals in farmlands, including microplastics (MPs) and pesticides, have the potential to influence the soil microbiome and the dissemination of antibiotic resistance genes (ARGs). Despite this, there is limited understanding of the combined effects of MPs and pesticides on microbial communities and ARGs transmission in soil ecosystems. In this study, we observed that low-density polyethylene (LDPE) microplastic enhance the accumulation of pyraclostrobin in earthworms, resulting in reduced weight and causing severe oxidative damage. Analysis of 16 S rRNA amplification revealed that exposure to pyraclostrobin and/or LDPE disrupts the microbial community structure at the phylum and genus levels, leading to reduced alpha diversity in both the soil and earthworm gut. Furthermore, co-exposure to LDPE and pyraclostrobin increased the relative abundance of ARGs in the soil and earthworm gut by 2.15 and 1.34 times, respectively, compared to exposure to pyraclostrobin alone. It correlated well with the increasing relative abundance of genera carrying ARGs. Our findings contribute novel insights into the impact of co-exposure to MPs and pesticides on soil and earthworm microbiomes, highlighting their role in promoting the transfer of ARGs. This knowledge is crucial for managing the risk associated with the dissemination of ARGs in soil ecosystems.


Assuntos
Microbiota , Oligoquetos , Praguicidas , Estrobilurinas , Animais , Antibacterianos/farmacologia , Polietileno/farmacologia , Genes Bacterianos , Plásticos , Solo , Resistência Microbiana a Medicamentos , Microplásticos/farmacologia , Praguicidas/análise , Microbiologia do Solo
3.
Plants (Basel) ; 12(22)2023 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-38005797

RESUMO

Highly nutritious traditional plants which are rich in bioactive substances are attracting increasing attention. In this study, the nutritional value, chemical composition, biological activities, and feed indices of different parts of Millettia speciosa were comprehensively evaluated. In terms of its nutritional value, this study demonstrated that the leaves, flowers and seeds of M. speciosa were rich in elements and amino acids; the biological values (BVs) of these ingredients ranged from 85% to 100%, showing the extremely high nutritional value of this plant. GC-MS analysis suggested that the main chemical components of the flower volatile oil were n-hexadecanoic acid (21.73%), tetracosane (19.96%), and pentacosane (5.86%). The antibacterial activities of the flower and seed extracts were significantly stronger than those of the leaves and branches. The leaf extract displayed the strongest antifungal activities (EC50 values: 18.28 ± 0.54 µg/mL for Pseudocryphonectria elaeocarpicola and 568.21 ± 33.60 µg/mL for Colletotrichum gloeosporioides) and were the least toxic to mouse fibroblasts (L929) (IC50 value: 0.71 ± 0.04 mg/mL), while flowers were the most toxic (IC50 value: 0.27 ± 0.03 mg/mL). In addition, the abundance of fiber, protein, mineral elements, and functional metabolite contents indicated the potential applicability of M. speciosa as an animal feed. In conclusion, as a traditional herbal plant used for medicinal and food purposes, M. speciosa shows potential for safe and multifunctional development.

4.
Philos Trans R Soc Lond B Biol Sci ; 378(1890): 20220248, 2023 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-37778388

RESUMO

Citrullination is a post-translational modification catalysed by peptidyl arginine deiminase (PAD) enzymes, and dysregulation of protein citrullination is involved in various pathological disorders. During the past decade, a panel of citrullination inhibitors has been developed, while small molecules activating citrullination have rarely been reported so far. In this study, we screened citrullination activator using an antibody against citrullinated histone H3 (cit-H3), and a natural compound demethoxycurcumin (DMC) significantly activated citrullination. The requirement of PAD2 for DMC-activated citrullination was confirmed by a loss of function assay. Notably, DMC directly engaged with PAD2, and showed binding selectivity among PAD family enzymes. Point mutation assay indicated that residue E352 is essential for DMC targeting PAD2. Consistently, DMC induced typical phenotypes of cells with dysregulation of PAD2 activity, including citrullination-associated cell apoptosis and DNA damage. Overall, our study not only presents a strategy for rationally screening citrullination activators, but also provides a chemical approach for activating protein citrullination. This article is part of the Theo Murphy meeting issue 'The virtues and vices of protein citrullination'.


Assuntos
Citrulinação , Histonas , Desiminases de Arginina em Proteínas/genética , Desiminases de Arginina em Proteínas/metabolismo , Histonas/metabolismo , Processamento de Proteína Pós-Traducional , Espaço Extracelular , Hidrolases/genética , Hidrolases/metabolismo
5.
Pest Manag Sci ; 79(12): 5283-5291, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37615248

RESUMO

BACKGROUND: Fertilizers and pesticides are commonly used simultaneously in agriculture. However, the effects of common fertilizers on the dissipation, enantioselectivity, and metabolites of the chiral insecticide fipronil in soil are yet to be reported. RESULT: An enantioselective method for detecting fipronil enantiomers and their metabolites in different soil matrices was developed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The results showed that organic and compound fertilizers significantly decreased the degradation of S- and R-fipronil, whereas phosphate and microbial fertilizers slightly reduced fipronil dissipation. The half-life values for S- and R-fipronil were 43.3 and 28.9 days, 99.0 and 63.0 days, 69.3 and 43.3 days, 46.2 and 30.1 days, and 43.3 and 31.5 days, respectively, in the control and the four fertilizer treatments, respectively. The enantioselectivity of fipronil enantiomers occurred and R-fipronil exhibited preferential degradation with an enantiomeric fraction (EF) of 0.4900-0.6238 in all treatments; but the four tested fertilizers decreased enantioselectivity with EF values changed from 0.4970 to 0.6238 in the control to 0.4900-0.6171 in fertilizer treatments. Two metabolites, fipronil sulfone and sulfide, were produced, and their amounts increased with culture time in all treatments. Fertilization reduced the content of fipronil sulfide and sulfone but hardly reduced the total amount of fipronil and its metabolites. CONCLUSION: Fertilizers affect the environmental behavior of fipronil in the soil. Fertilization alters the soil bacterial community, which may be an important factor. This influence is relatively complicated and should be comprehensively considered in the environmental risk assessment of pesticides. © 2023 Society of Chemical Industry.


Assuntos
Praguicidas , Pirazóis , Solo , Solo/química , Fertilizantes , Cromatografia Líquida , Espectrometria de Massas em Tandem , Sulfetos , Fertilização
6.
Sci Total Environ ; 897: 165381, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37422227

RESUMO

Tebuconazole, consisting of two enantiomers, has a high detectable rate in the soil. The residue of tebuconazole in the soil may cause risk to microbiota community. Antibiotic resistance genes (ARGs) are considered as emerging environmental contaminants, and they can be transferred vertically and horizontally between microbiota community in the soil. Until now, the enantioselective effect of tebuconazole on the microbiota community and ARGs in the soil and earthworm gut has remained largely unknown. Tebuconazole enantiomers showed different bioconcentration behaviors in earthworms. The relative abundances of bacteria belonging to Actinobacteriota, Crenarchaeota and Chloroflexi in R-(-)-tebuconazole-treated soil were higher than those in S-(+)-tebuconazole-treated soil at same concentrations. In the earthworm gut, bacteria belonging to Proteobacteria and Bacteroidota exhibited different relative abundances between the S-(+)-tebuconazole and R-(-)-tebuconazole treatments. The numbers and abundances of ARGs in the soil treated with fungicides were higher than those in the control. In earthworm gut, the diversities of ARGs in all treatments were higher than that in the control, and the relative abundances of Aminoglycoside, Chloramphenicol, Multidrug resistance genes and mobile genetic elements (MGEs) in R-(-)-tebuconazole-treated earthworm gut were higher than those in S-(+)-tebuconazole-treated earthworm gut. Most of ARGs showed a significantly positive correlation with MGEs. Based on network analysis, many ARGs may be carried by bacteria belonging to Bacteroidota and Proteobacteria. These results provide valuable information for understanding the enantioselective effect of tebuconazole on the microbiota community and ARGs.


Assuntos
Fungicidas Industriais , Microbiota , Oligoquetos , Animais , Antibacterianos/análise , Fungicidas Industriais/toxicidade , Fungicidas Industriais/análise , Solo , Estereoisomerismo , Resistência Microbiana a Medicamentos/genética , Bactérias/genética , Genes Bacterianos , Proteobactérias/genética , Microbiologia do Solo
7.
Microbiol Spectr ; 11(3): e0008023, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37162357

RESUMO

The composition and structure of fungal communities on healthy and diseased fruits of Cinnamomum burmannii (Nees and Nees) Blume were characterized, with evaluation of the antibacterial activity of secondary metabolites from culturable fungi following the first identification of secondary metabolites in the fungus Medicopsis romeroi (Esf-14; GenBank accession number OK242756). These results are significant for understanding the functional variation in bioactivity in fungal communities and developing a broader range of bioactive resources. High-throughput sequencing results indicated that the fungal community in diseased fruit differed from that in healthy fruit at the phylum, class, order, or genus level, with significant differences in the species and relative abundance of the dominant flora. A total of 49 (healthy fruit) and 122 (diseased fruit) artificially cultivable endophytic fungi were isolated, and 41 different strains (11 from healthy fruit and 30 from diseased fruit) were successfully identified by morphological and molecular biological analyses, which were classified into 8 groups and 23 genera by phylogenetic tree analysis, with Pleosporales, Glomerellales, and Hypocreales being the dominant groups at the order level and Colletotrichum being the dominant group at the genus level. The results of the antibacterial assay demonstrated that the secondary metabolites of all strains had different degrees of antibacterial activity, while the secondary metabolites of endophytic fungi from diseased fruit were generally stronger than those of fungi from healthy fruit, with the active secondary metabolites dominated by small and moderately polar compounds. Combined analysis of fungal communities, phylogenetic tree analysis, and bioactivity analysis of culturable strains revealed strong antibacterial activity of both upregulated and downregulated flora in diseased fruit. Five compounds, including two new (5,6-dimethoxy-[1',1:4,1″-terphenyl]-2-ol [compound 1] and 5-(methoxycarbonyl)-2-methylbenzo[d][1,3]dioxole-2-carboxylic acid [compound 2]) and three known compounds (3,7-dihydroxy-1,9-dimethyldibenzofuran [compound 3], methyl 3-hydroxybenzoate [compound 4], and uracil [compound 5]), were isolated and identified for the first time from the endophytic fungus Medicopsis romeroi. In general, the diversity of fungal communities on diseased fruit was lower than that on healthy fruits, while the antibacterial activity of artificially cultured endophytic fungi on diseased fruits was generally stronger than that on healthy fruits, suggesting excellent promise for the development of secondary metabolites from active strains on diseased fruit as antibacterial agents. IMPORTANCE Powdery fruit disease is a notorious disease of Cinnamomum burmannii that causes severe loss in fruit production. Studies on the function of endophytic fungal communities in healthy plant tissues are not new, while little is known about the functional changes of fungal communities in disease-causing plant tissues. Our results demonstrate that fungal communities in diseased fruits differ from those in healthy fruits at the level of phylum, class, order, or genus, with significant differences in the species and relative abundance of dominant groups. Endophytic fungi in diseased fruits appeared to produce secondary metabolites with stronger antibacterial properties, although the community diversity was not as varied as that in healthy fruits. In addition, secondary metabolites of the Medicopsis romeroi strain from diseased fruits were identified for the first time. These results have important implications for understanding the functional variation of bioactivity in fungal communities and for developing a broader resource of bioactivity.


Assuntos
Ascomicetos , Micobioma , Frutas , Filogenia , Endófitos , Fungos/genética , Antibacterianos/farmacologia , Antibacterianos/metabolismo
8.
Ecotoxicol Environ Saf ; 259: 115022, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37207576

RESUMO

Pesticides and heavy metals commonly coexist in soil. In this study, the influence of Cd and Cu on the toxicity of rac-dinotefuran and the enantioselective behavior of dinotefuran enantiomers in soil-earthworm microcosms were investigated. The acute toxic tests showed that S-dinotefuran has higher toxic than that of R-dinotefuran. The rac-dinotefuran and Cd has an antagonistic effect on earthworms, and the Cu and rac-dinotefuran has a synergistic effect. Earthworms maybe promoted the enantioselective behavior of dinotefuran in soil. Co-exposure to Cd or Cu inhibited the dissipation of dinotefuran enantiomers (S-dinotefuran and R-enantiomers), and slightly reduced the enantioselectivity in soil. The earthworms were found to be preferentially enriched with S-dinotefuran. However, Cd or Cu attenuated the accumulation of dinotefuran enantiomers in earthworms and decreased the enantioselectivity. The effect of Cd and Cu on the environmental behaviors of dinotefuran enantiomers were correlated positively with the dose of Cd/Cu. These results showed that Cd and Cu alter the environmental behaviors and the toxicity of dinotefuran enantiomers in soil-earthworm microcosms. Thus, the influence of coexistent heavy metals on the ecological risk assessment of chiral pesticides should be considered.


Assuntos
Metais Pesados , Oligoquetos , Praguicidas , Poluentes do Solo , Animais , Cádmio/toxicidade , Poluentes do Solo/análise , Metais Pesados/análise , Praguicidas/farmacologia , Solo , Estereoisomerismo
9.
Membranes (Basel) ; 13(4)2023 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-37103803

RESUMO

The level of hydrogen ions in sweat is one of the most important physiological indexes for the health state of the human body. As a type of two-dimensional (2D) material, MXene has the advantages of superior electrical conductivity, a large surface area, and rich functional groups on the surface. Herein, we report a type of Ti3C2Tx-based potentiometric pH sensor for wearable sweat pH analysis. The Ti3C2Tx was prepared by two etching methods, including a mild LiF/HCl mixture and HF solution, which was directly used as the pH-sensitive materials. Both etched Ti3C2Tx showed a typical lamellar structure and exhibited enhanced potentiometric pH responses compared with a pristine precursor of Ti3AlC2. The HF-Ti3C2Tx disclosed the sensitivities of -43.51 ± 0.53 mV pH-1 (pH 1-11) and -42.73 ± 0.61 mV pH-1 (pH 11-1). A series of electrochemical tests demonstrated that HF-Ti3C2Tx exhibited better analytical performances, including sensitivity, selectivity, and reversibility, owing to deep etching. The HF-Ti3C2Tx was thus further fabricated as a flexible potentiometric pH sensor by virtue of its 2D characteristic. Upon integrating with a solid-contact Ag/AgCl reference electrode, the flexible sensor realized real-time monitoring of pH level in human sweat. The result disclosed a relatively stable pH value of ~6.5 after perspiration, which was consistent with the ex situ sweat pH test. This work offers a type of MXene-based potentiometric pH sensor for wearable sweat pH monitoring.

10.
Ann Transl Med ; 11(5): 207, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-37007585

RESUMO

Background: Endothelial-to-mesenchymal transition (EndMT) is the process by which endothelial cells lose their specific markers and acquire mesenchymal or myofibroblastic phenotypes. Studies have demonstrated the importance of endothelial-derived vascular smooth muscle cells (VSMCs) through EndMT in neointimal hyperplasia. Histone deacetylases (HDACs) are epigenetic modification enzymes involved in the epigenetic control of important cellular functions. Recent studies found that HDAC3, a class I HDAC, causes posttranslational modifications, including deacetylation and decrotonylation. However, the effect of HDAC3 on EndMT in neointimal hyperplasia via posttranslational modifications remains to be seen. Therefore, we investigated the effects of HDAC3 on EndMT in carotid artery-ligated mice and human umbilical vein endothelial cells (HUVECs) and the underlying posttranslational modifications. Methods: HUVECs were treated with transforming growth factor (TGF)-ß1 or the inflammatory cytokine tumor necrosis factor (TNF)-α at different concentrations and durations. In HUVECs, HDAC3 expression, the expression of endothelial and mesenchymal markers, and posttranslational modifications were analyzed with Western blotting, quantitative real-time polymerase chain reaction (PCR), and immunofluorescence. C57BL/6 mice underwent left carotid artery ligation. Mice were treated with the HDAC3-selective inhibitor RGFP966 (10 mg/kg, i.p.) from 1 day before to 14 days after ligation. Then, the sections of the carotid arteries were examined histologically using hematoxylin and eosin (HE) and immunofluorescence staining. The carotid arteries from other mice were examined for the expression of EndMT markers and inflammatory cytokines. Furthermore, the acetylation and crotonylation of carotid arteries were immunostained in mice. Results: In HUVECs, TGF-ß1 and TNF-α induced EndMT by decreasing CD31 expression and increasing α-smooth muscle actin expression. TGF-ß1 and TNF-α also upregulated HDAC3 expression in HUVECs. The in vivo study in mice indicated that RGFP966 significantly alleviated neointimal hyperplasia of the carotid artery compared with vehicle treatment. Furthermore, RGFP966 suppressed EndMT and the inflammatory response in carotid artery-ligated mice. Further investigation revealed that HDAC3 regulated EndMT by posttranslational modifications of deacetylation and decrotonylation. Conclusions: These results suggest that HDAC3 regulates EndMT in neointimal hyperplasia through posttranslational modifications.

11.
Fish Shellfish Immunol ; 136: 108703, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36948366

RESUMO

NK-lysin (NKL) is a positively charged antimicrobial peptide with broad-spectrum bactericidal activities. In this study, the cDNA sequence of NKL (TmNKL) from black scraper (Thamnaconus modestus) was cloned, which encodes a predicted polypeptide of 150 amino acids that contains a surfactant protein B domain with three disulfide bonds. Phylogenetically, TmNKL was most closely related to its teleost counterpart from tiger puffer (Takifugu rubripes). Expression analysis demonstrated that TmNKL transcripts were constitutively expressed in all tested tissues, with the highest expression levels in the gills. Its expression was significantly upregulated in the gills, head kidney, and spleen after infection with Vibrio parahaemolyticus. A linear peptide (TmNKLP40L) and a disulfide-type peptide (TmNKLP40O) were further synthesized and results showed that disulfide bonds are not essential for bactericidal activities of TmNKL, and that both forms of TmNKL exhibited potent bactericidal activities against 4 gram- negative bacteria, including V. parahaemolyticus, V. alginolyticus, Edwardsiella tarda, and V. harveyi. Observed antimicrobial activities are likely due to the effects of TmNKLP40L and TmNKLP40O treatment on disrupting the integrity of both inner and outer membrane of V. parahaemolyticus, resulting in hydrolysis of bacterial genomic DNA. Damaged cell membranes and leakage of intracellular contents were further confirmed using scanning and transmission microscopy. Moreover, administration of 1.0 µg/g TmNKLP40L or TmNKLP40O significantly decreased bacterial load in tissues and thus, pronouncedly enhanced the survival of V. parahaemolyticus-infected fish. Overall, our results demonstrated that TmNKL is a potent innate effector and provides protective effects against bacterial infection.


Assuntos
Anti-Infecciosos , Doenças dos Peixes , Tetraodontiformes , Animais , Proteínas de Peixes/química , Peptídeos , Bactérias Gram-Negativas , Anti-Infecciosos/farmacologia , Doenças dos Peixes/microbiologia
12.
Drug Deliv ; 30(1): 2183834, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36843571

RESUMO

In present, there was no detailed report on the formulation optimization and quality evaluation of aprepitant (APT) injectable lipid emulsion (APT-IE). The aim of the present investigation was to prepare and evaluate its properties of APT-IE loaded with an APT phospholipid complex (APT-PC) in vitro and in vivo. APT-PC was obtained by solvent evaporation with APT and phospholipids, then analyzed by X-ray diffraction, Fourier transform infrared spectroscopy and differential scanning calorimetry. Lipid emulsions are a new formulation that can reduce side effects and improve drug loading.APT-IE prepared by High-pressure homogenization and optimized by response surface methodology (RSM). The proportion of sodium oleate, poloxamer 188 and soybean oil were selected as variables for the optimization. The optimal formulation of ATP-IE had the following characteristics: particle size, 82.83 ± 1.89 nm; polydispersity index, 0.243 ± 0.008; zeta potential, -59.0 ± 2.54 mV; encapsulation efficiency, 98.84%±1.43%; drug loading, 7.08 ± 0.16 mg/mL; and osmotic pressure, 301 ± 2.15 mOsmol/kg. Transmission electron microscopy images indicated that the particle diameter of APT-IE was approximately 100 nm, with a morphology of spheroidal or spherical. APT-IE exhibited sufficient stability after storage at 4 ± 2 °C for more than 6 months. The results of the pharmacokinetic study demonstrated that APT-IE had the advantages of better safety, higher bioavailability, and obvious liver targeting than APT solution (APT-SL). The area under the curve (AUC) of APT-IE was 3-fold enhanced compared with APT-SL. The targeted enhancement multiple of APT-IE to liver tissue was greater than that of APT-SL. These results suggested that APT-IE has broad clinical application and industrial production potential.


Assuntos
Fosfolipídeos , Aprepitanto , Fosfolipídeos/química , Emulsões/química , Disponibilidade Biológica , Administração Intravenosa , Tamanho da Partícula
13.
J Ethnopharmacol ; 303: 115952, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36442759

RESUMO

ETHNOPHARMACOLOGIC RELEVANCE: Licorice is a traditional Chinese medicine that has been used for cardiovascular diseases. Recent studies found that supplementation with licorice extracts attenuated the development of atherosclerosis (AS) in hypercholesterolemic patients. Many studies have shown that licorice flavonoids, the main active components of licorice, have a variety of pharmacological effects, including anti-inflammation, regulation of lipid metabolism, and antioxidation. However, the key active components against AS in licorice flavonoids are still unclear. AIM OF THE STUDY: The aim of this paper is to investigate the active components of licorice flavonoids that exert anti-atherosclerotic effects and the underlying mechanisms. MATERIALS AND METHODS: Network pharmacology was used to screen the active components of licorice flavonoids that have anti-atherosclerotic effects. Combining bioinformatics analysis and in vitro studies, the effects and underlying mechanisms of the active component isoliquiritigenin (ISL) on cell pyroptosis were further investigated in tumor necrosis factor (TNF)-α-treated human umbilical vein endothelial cells (HUVECs). RESULTS: We constructed a compound-target network and screened 3 active components, namely, ISL, glabridin, and naringenin in licorice flavonoids. The half maximal effective concentration values of these 3 components suggested that ISL was the key active component against TNF-α-induced endothelial cell injury. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that ISL could potentially treat AS via the nucleotide-binding and oligomerization domain (NOD)-like receptor signaling pathway. An in vitro study verified that ISL suppressed TNF-α-induced NLRP3 activation and pyroptosis in HUVECs. The molecular docking and cellular thermal shift assay showed good compatibility between ISL and class III histone deacetylase sirtuin 6 (SIRT6). Moreover, we found that ISL upregulated the expression of SIRT6 in TNF-α-treated HUVECs. Further study found that SIRT6 knockdown reduced the inhibitory effect of ISL on pyroptosis, whereas the NLRP3 inhibitor reversed this process in TNF-α-treated HUVECs. CONCLUSIONS: Our results demonstrate that ISL is a key active component of licorice flavonoids. ISL attenuates NLRP3-mediated vascular endothelial cell pyroptosis via SIRT6, and SIRT6 may be a potential target of ISL for the treatment of AS.


Assuntos
Chalconas , Glycyrrhiza , Sirtuínas , Humanos , Fator de Necrose Tumoral alfa/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Flavonoides/farmacologia , Flavonoides/metabolismo , Glycyrrhiza/química , Piroptose , Simulação de Acoplamento Molecular , Chalconas/farmacologia , Células Endoteliais da Veia Umbilical Humana , Sirtuínas/metabolismo
14.
J Integr Plant Biol ; 65(3): 772-790, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36354146

RESUMO

Lateral roots play essential roles in drought tolerance in maize (Zea mays L.). However, the genetic basis for the variation in the number of lateral roots in maize remains elusive. Here, we identified a major quantitative trait locus (QTL), qLRT5-1, controlling lateral root number using a recombinant inbred population from a cross between the maize lines Zong3 (with many lateral roots) and 87-1 (with few lateral roots). Fine-mapping and functional analysis determined that the candidate gene for qLRT5-1, ZmLRT, expresses the primary transcript for the microRNA miR166a. ZmLRT was highly expressed in root tips and lateral root primordia, and knockout and overexpression of ZmLRT increased and decreased lateral root number, respectively. Compared with 87-1, the ZmLRT gene model of Zong3 lacked the second and third exons and contained a 14 bp deletion at the junction between the first exon and intron, which altered the splicing site. In addition, ZmLRT expression was significantly lower in Zong3 than in 87-1, which might be attributed to the insertions of a transposon and over large DNA fragments in the Zong3 ZmLRT promoter region. These mutations decreased the abundance of mature miR166a in Zong3, resulting in increased lateral roots at the seedling stage. Furthermore, miR166a post-transcriptionally repressed five development-related class-III homeodomain-leucine zipper genes. Moreover, knockout of ZmLRT enhanced drought tolerance of maize seedlings. Our study furthers our understanding of the genetic basis of lateral root number variation in maize and highlights ZmLRT as a target for improving drought tolerance in maize.


Assuntos
Resistência à Seca , MicroRNAs , Zea mays/genética , Raízes de Plantas/genética , Plântula/genética , MicroRNAs/metabolismo , Clonagem Molecular , Secas
15.
Int J Psychophysiol ; 182: 47-56, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36202262

RESUMO

Previous experience often guides people's decision-making. How the corresponding consecutive outcomes in the gain-loss frame modulate feedback evaluation in dynamic situations remains unclear. In this study, we used event-related potentials (ERPs) with a Balloon Analogue Risk Task (BART) to investigate the effect of the consistency with previous feedback on current choices under the gain-loss frame and the neural mechanism by coding ERP signals evoked by consecutive outcomes among adults (N = 42). Results indicated that the framing effect on feedback-related negativity (FRN) amplitudes following current feedback in decision-making was insensitive to prior feedback. In contrast, the P300 amplitudes following two inconsistent consecutive rounds of feedback were greater than that following two consistent consecutive rounds of feedback in the gain frame, while this effect was absent in the loss frame, revealing a more significant valance-framing effect. These findings demonstrate that two inconsistent rounds of feedback enhance the framing effect, and suggest that the framing effect is sensitive to prior feedback in a late cognitive appraisal stage in decision-making under uncertainty, rather than in an early feedback processing stage. The present study provides novel insights into how consecutive outcomes in the gain-loss frame modulate feedback evaluation in dynamic situations.


Assuntos
Tomada de Decisões , Eletroencefalografia , Adulto , Humanos , Retroalimentação , Tomada de Decisões/fisiologia , Potenciais Evocados/fisiologia , Retroalimentação Psicológica/fisiologia , Encéfalo/fisiologia
16.
Nanomaterials (Basel) ; 12(19)2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36234503

RESUMO

Medical applications of nanotechnology are promising in creating efficient and targeted therapies. However, so far, nanodrug design has not taken into consideration possible effects on human microbiota. The beneficial functions of bacteria could be stimulated by nanodrugs while negative effects on beneficial bacteria could cause risks to human health. Here, simulated intestinal fluid (IF) was optimized for culturing a human commensal and probiotic bacterial strain, Lactobacillus casei, to study the effects of medically relevant NPs­Ag and hyaluronic acid-coated Au NPs (HA-Au NPs)­in conditions pertinent to the gastrointestinal tract. When cultivated either aerobically or anaerobically, the specific growth rates of L. casei were ~0.2 h−1 in IF and ~0.4 h−1 in the standard medium of lactobacilli (MRS). Ag NPs inhibited the growth of L. casei in IF at lower concentrations (EC50 ~ 65 and 15 mg/L in aerobic and anaerobic conditions, respectively) than in MRS (EC50 > 100 mg/L), likely caused by differences in the composition of the two media and different intrinsic growth rates of bacteria in IF and MRS. Ag NP dissolution in IF and MRS did not explain the differences in growth inhibition, implying NP-specific effects. HA-Au NPs were not growth-inhibitory to L. casei up to 250 mg/L. Still, both NPs at sub-growth-inhibitory concentrations suppressed the expression of bacteriocin genes in L. casei, suggesting an inhibitory effect of NPs on the probiotic properties of L. casei, i.e., its competitiveness in microbial communities. However, HA-Au NPs did not appear to affect or even stimulated the immunomodulatory properties of L. casei in human intestinal epithelial cells. Thus, medically relevant NPs at low, sub-bacteriostatic levels can affect the metabolism of beneficial human bacteria and potentially induce changes in the microbiota and immune signaling.

17.
Membranes (Basel) ; 12(9)2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36135922

RESUMO

Solid-contact ion-selective electrodes (SC-ISEs) exhibit great potential in the detection of routine and portable ions which rely on solid-contact (SC) materials for the transduction of ions to electron signals. Carbon-based materials are state-of-the-art SC transducers due to their high electrical double-layer (EDL) capacitance and hydrophobicity. However, researchers have long searched for ways to enhance the interfacial capacitance in order to improve the potential stability. Herein, three representative carbon-based SC materials including nitrogen-doped mesoporous carbon (NMC), reduced graphene oxide (RGO), and carbon nanotubes (CNT) were compared. The results disclose that the NMC has the highest EDL capacitance owing to its mesopore structure and N-doping while maintaining high hydrophobicity so that no obvious water-layer effect was observed. The Ca2+-SC-ISEs based on the SC of NMC exhibited high potential stability compared with RGO and CNT. This work offers a guideline for the development of carbon-material-based SC-ISEs through mesoporous and N-doping engineering to improve the interfacial capacitance. The developed NMC-based solid-contact Ca2+-SC-ISE exhibited a Nernstian slope of 26.3 ± 3.1 mV dec-1 ranging from 10 µM to 0.1 M with a detection limit of 3.2 µM. Finally, a practical application using NMC-based SC-ISEs was demonstrated through Ca2+ ion analysis in mineral water and soil leaching solutions.

18.
Int J Mol Sci ; 23(15)2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35955415

RESUMO

Sirtuin 3 (SIRT3) deacetylase is a key regulator for chemoresistance in acute myeloid leukemia (AML) cells due to its capability of modulating mitochondrial metabolism and reactive oxygen species (ROS). SIRT3 is de-SUMOylated by SUMO-specific peptidase 1 (SENP1), which enhances its deacetylase activity. Therefore, dysregulation of SIRT3 SUMOylation may lead to fortified chemoresistance in AML. Indeed, SIRT3 de-SUMOylation was induced by chemotherapeutic agents, which in turn, exacerbated resistance against chemotherapies in AML by activating SIRT3 via preventing its proteasome degradation. Furthermore, RNA-seq revealed that expression of a collection of genes was altered by SIRT3 de-SUMOylation including inhibition of transcription factor Hes Family BHLH Transcription Factor 1 (HES1), a downstream substrate of Notch1 signaling pathway, leading to increased fatty acids oxidation (FAO). Moreover, the SENP1 inhibitor momordin-Ic or HES1 overexpression synergized with cytarabine to eradicate AML cells in vitro and in xenograft mouse models. In summary, the current study revealed a novel role of SIRT3 SUMOylation in the regulation of chemoresistance in AML via HES1-dependent FAO and provided a rationale for SIRT3 SUMOylation and FAO targeted interventions to improve chemotherapies in AML.


Assuntos
Leucemia Mieloide Aguda , Sirtuína 3 , Animais , Resistencia a Medicamentos Antineoplásicos/genética , Ácidos Graxos/metabolismo , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Camundongos , Sirtuína 3/genética , Sirtuína 3/metabolismo , Sumoilação , Fatores de Transcrição HES-1/genética , Fatores de Transcrição HES-1/metabolismo
19.
Sensors (Basel) ; 22(12)2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35746273

RESUMO

The PID control algorithm for balancing robot attitude control suffers from the problem of difficult parameter tuning. Previous studies have proposed using metaheuristic algorithms to tune the PID parameters. However, traditional metaheuristic algorithms are subject to the criticism of premature convergence and the possibility of falling into local optimum solutions. Therefore, the present paper proposes a CFHBA-PID algorithm for balancing robot Dual-loop PID attitude control based on Honey Badger Algorithm (HBA) and CF-ITAE. On the one hand, HBA maintains a sufficiently large population diversity throughout the search process and employs a dynamic search strategy for balanced exploration and exploitation, effectively avoiding the problems of classical intelligent optimization algorithms and serving as a global search. On the other hand, a novel complementary factor (CF) is proposed to complement integrated time absolute error (ITAE) with the overshoot amount, resulting in a new rectification indicator CF-ITAE, which balances the overshoot amount and the response time during parameter tuning. Using balancing robot as the experimental object, HBA-PID is compared with AOA-PID, WOA-PID, and PSO-PID, and the results demonstrate that HBA-PID outperforms the other three algorithms in terms of overshoot amount, stabilization time, ITAE, and convergence speed, proving that the algorithm combining HBA with PID is better than the existing mainstream algorithms. The comparative experiments using CF prove that CFHBA-PID is able to effectively control the overshoot amount in attitude control. In conclusion, the CFHBA-PID algorithm has great control and significant results when applied to the balancing robot.


Assuntos
Mel , Mustelidae , Robótica , Algoritmos , Animais , Simulação por Computador
20.
Nanomaterials (Basel) ; 12(8)2022 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-35457992

RESUMO

Recycling biomass waste into functional materials has attracted much attention, and a rational structural design can make more effective use of each component. In our previous work, the fabrication of electrospun cellulose-acetate (CA)/chitosan (CS) adsorbents for humic-acid (HA) removal guided by the intermolecular interaction mechanism was demonstrated. Herein, a core-sheath structure was designed via one-step co-axial electrospinning, where a mixture of CS and CA was employed as the sheath layer to efficiently adsorb HA, and cellulose nanocrystals (CNCs) derived from waste cotton fabrics were incorporated into the CA core as load-bearing components. Compared to the non-layered electrospun CS/CA fibers, all the CS/CA-CNC fibers with a core-sheath structure exhibited smaller diameters, greater homogeneity, and significantly improved mechanical strength. Meanwhile, their maximum adsorption capacities towards HA had no significant differences. Even after the complete hydrolysis of CA into cellulose, the electrospun fibers maintained the fibrous structures and showed a higher tensile strength while exhibiting an acceptable adsorption capacity towards HA. Therefore, this work demonstrates the importance of rational design in the efficient preparation of functional materials and the feasibility of using electrospun core-sheath fibers derived from biomass wastes for the removal of water contaminants.

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