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In this work, the acylated anthocyanin (Ca-An) was prepared by enzymatic modification of black rice anthocyanin with caffeic acid, and the binding mechanism of Ca-An to soybean protein isolate (SPI) was investigated by experiments and computer simulation to expand the potential application of anthocyanin in food industry. Multi-spectroscopic studies revealed that the stable binding of Ca-An to SPI induced the folding of protein polypeptide chain, which transformed the secondary structure of SPI trended to be flexible. The microenvironment of protein was transformed from hydrophobic to hydrophilic, while tyrosine played dominant role in quenching process. The binding sites and forces of the complexes were determined by computer simulation for further explored. The protein conformation of the 7S and 11S binding regions to Ca-An changed, and the amino acid microenvironment shifted to hydrophilic after binding. The results showed that more non-polar amino acids existed in the binding sites, while in binding process van der Waals forces and hydrogen bonding played a major role hydrophobicity played a minor role. Based on MM-PBSA analysis, the binding constants of 7S-Ca-An and 11S-Ca-An were 0.518 × 106 mol-1 and 5.437 × 10-3 mol-1, respectively. This information provides theoretical guidance for further studying the interaction between modified anthocyanins and biomacromolecules.
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Antocianinas , Interações Hidrofóbicas e Hidrofílicas , Simulação de Dinâmica Molecular , Ligação Proteica , Proteínas de Soja , Antocianinas/química , Antocianinas/metabolismo , Proteínas de Soja/química , Proteínas de Soja/metabolismo , Sítios de Ligação , Solubilidade , Ligação de HidrogênioRESUMO
Transient receptor potential vanilloid family member 1 (TRPV1) has been revealed as a therapeutic target of osteoarthritis (OA), the most common deteriorating whole joint disease, by impeding macrophagic inflammation and chondrocytes ferroptosis. However, the clinical application for capsaicin as the TRPV1 agonist is largely limited by its chronic toxicity. To address this issue, we developed a bifunctional controllable magnetothermal switch targeting TRPV1 for the alleviation of OA progression by coupling of magnetic nanoparticles (MNPs) to TRPV1 monoclonal antibodies (MNPs-TRPV1). Under the alternating magnetic field (AMF) stimulation, MNPs-TRPV1 locally dissipated heat, which was sufficient to trigger the opening and activation of TRPV1, and effectively impeded macrophagic inflammation and chondrocyte ferroptosis. This magnetothermal modulation of TRPV1 simultaneously attenuated synovitis and cartilage degeneration in mice incurred by destabilization of medial meniscus surgery, indicating the delayed OA progression. Furthermore, MNPs-TRPV1 with AMF exposure remarkably reduced knee pain sensitivity, alleviated the crippled gait, and improved spontaneous ambulatory activity performance in the mice OA model. Overall, this work provides a potential pathogenesis-based precise OA therapy with temporally and spatially magnetothermal modulation of TRPV1 in a controllable manner.
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Microplastics (MPs) as an emerging air pollutant have received widespread attention, but research on airborne MPs at occupational sites is still limited, especially in the rubber industry. Hence, indoor air samples were collected from three production workshops and an office of a rubber factory producing automotive parts to analyze the characteristics of airborne MPs in different workplaces of this industry. We found MP contamination in all air samples from the rubber industry, and the airborne MPs at all sites mainly showed small-sized (< 100 µm) and fragmented characteristics. The abundance and source of MPs at various locations is primarily related to the manufacturing process and raw materials of the workshop. The abundance of MPs in the air was higher in workplaces where production activities are involved than in office (360 ± 61 n/m3), of which the highest abundance of airborne MPs was in the post-processing workshop (559 ± 184 n/m3). In terms of types, a total of 40 polymer types were identified. The post-processing workshop has the largest proportion of injection-molded plastic ABS, the extrusion workshop has a greater proportion of EPDM rubber than the other locations, and the refining workshop has more MPs used as adhesives, such as aromatic hydrocarbon resin (AHCR).
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Plásticos , Borracha , Microplásticos , Polietileno , Monitoramento Ambiental , Polienos , Local de Trabalho , EtilenosRESUMO
Fusobacterium nucleatum is a lesion-associated obligate anaerobic pathogen of destructive periodontal disease; it is also implicated in the progression and severity of colorectal cancer. Four genes (FN0625, FN1055, FN1220, and FN1419) of F. nucleatum are involved in producing hydrogen sulfide (H2S), which plays an essential role against oxidative stress. The molecular functions of Fn1419 are known, but their mechanisms remain unclear. We determined the crystal structure of Fn1419 at 2.5 Å, showing the unique conformation of the PLP-binding site when compared with L-methionine γ-lyase (MGL) proteins. Inhibitor screening for Fn1419 with L-cysteine showed that two natural compounds, gallic acid and dihydromyricetin, selectively inhibit the H2S production of Fn1419. The chemicals of gallic acid, dihydromyricetin, and its analogs containing trihydroxybenzene, were potentially responsible for the enzyme-inhibiting activity on Fn1419. Molecular docking and mutational analyses suggested that Gly112, Pro159, Val337, and Arg373 are involved in gallic acid binding and positioned close to the substrate and pyridoxal-5'-phosphate-binding site. Gallic acid has little effect on the other H2S-producing enzymes (Fn1220 and Fn1055). Overall, we proposed a molecular mechanism underlying the action of Fn1419 from F. nucleatum and found a new lead compound for inhibitor development.
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Fusobacterium nucleatum , Sulfeto de Hidrogênio , Fusobacterium nucleatum/metabolismo , Simulação de Acoplamento Molecular , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/metabolismo , Liases de Carbono-Enxofre/genética , Liases de Carbono-Enxofre/metabolismoRESUMO
Depression is a serious public health problem today, especially in middle-aged and older adults. Although the etiology of the disease has not been fully elucidated, environmental factors are increasingly not negligible. Cadmium is widely used in industrial production. The general population may be chronically exposed to low doses of cadmium. This study aimed to investigate the association between blood cadmium and depression and to explore the mediating role of aging indicators in this process. We conducted a cross-sectional study on blood cadmium (N = 7195, age ≥ 20 years) using data from the 2007-2010 National Health and Nutrition Examination Survey (NHANES). Aging indicators (biological and phenotypic age) are calculated by combining multiple biochemical and/or functional indicators. To determine the relationship between blood cadmium concentrations and depressive symptoms, we used weighted multivariate logistic regression and restricted cubic spline functions and employed mediation analysis to explore the possible mediating effects of aging indicators in the process. We found a significant positive association between blood cadmium and depression with an odds ratio (OR) and 95% confidence interval (CI): 1.22 (1.04,1.43). Restricted cubic spline analysis found a linear positive association between blood cadmium and depression. In the fully covariate-adjusted model, we found a positive association between blood cadmium and biological age and phenotypic age with ß and 95% CI: 1.02 (0.65, 1.39) and 2.35 (1.70, 3.01), respectively. In the mediation analysis, we found that phenotypic age mediated 21.32% of the association between blood cadmium and depression. These results suggest that even exposure to low doses of cadmium can increase the risk of depression and that this process may be mediated by phenotypic aging.
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Cádmio , Exposição Ambiental , Pessoa de Meia-Idade , Humanos , Idoso , Adulto Jovem , Adulto , Exposição Ambiental/análise , Cádmio/análise , Inquéritos Nutricionais , Estudos Transversais , Depressão , EnvelhecimentoRESUMO
BACKGROUND: Epidemiological evidence reported that particulate matter (PM) was associated with increased schizophrenia (SCZ) risk. Disturbance of gut microbiome was involved in SCZ. However, it remains unclear whether PM induces SCZ-like symptoms and how gut microbiome regulates them. Therefore, a multi-omics animal experiment was conducted to verify how urban PM induces SCZ-like behavior and altered gut microbiota and metabolic pathways. METHODS: Using a completely random design, mice were divided into three groups: PM group, control group and MK801 group, which received daily tracheal instillation of PM solution, sterile PBS solution and intraperitoneal injection of MK801 (establish SCZ model), respectively. After a 14-day intervention, feces were collected for multi-omics testing (shotgun metagenomic sequencing and untargeted metabolomic profiling), followed by open field test, tail suspension test, and passive avoidance test. Besides, fecal microbiome of PM group and control group were transplanted into "pseudo-sterile" mice, then behavioral tests were conducted. RESULTS: Similar to MK801 group, mice in PM group showed SCZ-like symptoms, including increased spontaneous activity, excitability, anxiety and decreased learning and spatial memory. PM exposure significantly increased the relative abundance of Verrucomicrobia and decreased that of Fibrobacteres et al. The metabolism pathways of estrogen signaling (estriol, 16-glucuronide-estriol and 21-desoxycortisol) and choline metabolism (phosphocholine) were significantly altered by PM exposure. Verrucomicrobia was negatively correlated with the level of estriol, which was correlated with decreased learning and spatial memory. Fibrobacteres and Deinococcus-Thermus were positively correlated with the level of phosphocholine, which was correlated with increased spontaneous activity, excitability and anxiety. Fecal microbiome transplantation from PM group mice reproduced excitability and anxiety symptoms. CONCLUSIONS: Exposure to PM may affect composition of gut microbiome and alterations of estrogen signaling pathway and choline metabolism pathway, which were associated with partial SCZ-like behaviors. But whether gut microbiome regulates these metabolic pathways and behaviors remains to be determined.
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Microbioma Gastrointestinal , Esquizofrenia , Animais , Camundongos , Material Particulado/toxicidade , Maleato de Dizocilpina/farmacologia , Fosforilcolina/farmacologia , Fezes , Estriol , Estrogênios , RNA Ribossômico 16SRESUMO
ABSTRACT Introduction: Modern exercise physiology theory states that abdominal core muscle strength plays a very important role in the completion of athletes' motor skills; the specific performance is to stabilize the athlete's center of gravity, the source of explosion and power transmission beyond his center of control. Objective: Verify the effect of an experimental training methods on the muscular strength of the abdominal core in volleyball athletes. Methods: 24 athletes were divided into an experimental group and a control group, in order to ensure that the baseline indicators of the two groups before the experiment did not show significant comparison, using independent sample t-test and paired sample t-test. Results: The average number of sit-ups of the two groups of students was 58.15 and 70.52n, respectively, the five baseline indicators of stability of the two groups were all significant, and the strength training methods in the experimental group were better than those in the control group. Conclusion: The presented experimental method helps to improve the success rate in athlete's jump. The core strength training methods used in the experimental group in jumping were superior to the traditional training methods used in the control group. Level of Evidence II; Therapeutic studies - investigation of treatment outcomes.
RESUMO Introdução: A moderna teoria da fisiologia do exercício afirma que a força muscular do core desempenha um papel muito importante na conclusão das habilidades motoras dos atletas; o desempenho específico é estabilizar o centro de gravidade do atleta, a fonte de explosão e transmissão de potência além do seu centro de controle. Objetivo: Verificar o efeito dos métodos de um treinamento experimental sobre a força muscular do core em atletas de voleibol. Métodos: 24 atletas foram divididos em grupo experimental e grupo de controle, a fim de garantir que os indicadores basais dos dois grupos antes do experimento não apresentassem comparação significativa, usando teste t de amostra independente e teste t de amostra pareada. Resultados: O número médio de sit-ups dos dois grupos de estudantes foi de 58,15 e 70,52n, respectivamente, os cinco indicadores básicos de estabilidade dos dois grupos foram todos significativos, e os métodos de treinamento da força no grupo experimental foram melhores do que os do grupo controle. Conclusão: O método experimental apresentada ajuda a melhorar a taxa de sucesso no salto do atleta. Os métodos de treinamento da força do core usados no grupo experimental em salto foram superiores aos métodos tradicionais de treinamento usados no grupo de controle. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.
RESUMEN Introducción: La teoría moderna de la fisiología del ejercicio afirma que la fuerza muscular del core desempeña un papel muy importante en la realización de las habilidades motrices de los atletas; la actuación específica consiste en estabilizar el centro de gravedad del atleta, la fuente de explosión y la transmisión de potencia más allá de su centro de control. Objetivo: Verificar el efecto de los métodos de un entrenamiento experimental sobre la fuerza muscular del core en atletas de voleibol. Métodos: 24 atletas fueron divididos en un grupo experimental y un grupo de control, con el fin de garantizar que los indicadores basales de los dos grupos antes del experimento no mostraran una comparación significativa, utilizando la prueba t de muestras independientes y la prueba t de muestras emparejadas. Resultados: El número medio de sentadillas de los dos grupos de estudiantes fue de 58,15 y 70,52n, respectivamente, los cinco indicadores de estabilidad de referencia de los dos grupos fueron todos significativos, y los métodos de entrenamiento de fuerza del grupo experimental fueron mejores que los del grupo de control. Conclusión: El método experimental presentado ayuda a mejorar la tasa de éxito en el salto del atleta. Los métodos de entrenamiento del core utilizados en el grupo experimental en los saltos fueron superiores a los métodos de entrenamiento tradicionales utilizados en el grupo de control. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.
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Laccase is a potential target for novel agricultural fungicide discovery. PMDD-5Y was the first agent reported with high activity against laccase to control phytopathogenic fungi. Thirty-two novel agents containing cinnamaldehyde thiosemicarbazide were synthesized with PMDD-5Y as the lead compound, with most of the target compounds exhibiting excellent activity in vitro. Compound a2 (EC50 = 9.71 µg/mL) exhibited greater potency against Magnaporthe oryzae than the commercial fungicide isoprothiolane (EC50 = 18.62 µg/mL). The curative and protective effects of a2 against M. oryzae on rice were more than those of PMDD-5Y. Scanning electron microscopy indicated that a2 could cause mycelial growth atrophy and malformation. Furthermore, a2 (IC50 = 0.18 mmol/L) showed higher activity against laccase than PMDD-5Y (IC50 = 0.33 mmol/L) and cysteine (IC50 = 0.30 mmol/L). Molecular docking analysis revealed the nature of interaction between these compounds and laccase. This research identified a novel laccase inhibitor a2 as a fungicide candidate to control rice blast in agriculture.
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Fungicidas Industriais , Fungicidas Industriais/farmacologia , Lacase , Doenças das Plantas/microbiologia , Simulação de Acoplamento Molecular , Relação Estrutura-AtividadeRESUMO
A label-free and ultrasensitive electrochemical biosensor for oral cancer overexpressed 1 (ORAOV1) gene was constructed via exonuclease III-assisted target recycling and dual enzyme-assisted signal amplification strategies. Capture DNA with a sulfhydryl group at its 3' terminus was modified onto the surface of a bare gold electrode via an Au-S bond. Assisted DNA hybridized with basal DNA to form hybrid DNA in advance, and ORAOV1 gene hybridized continuously with such a hybrid DNA from the other terminus to construct intact double-stranded DNA. Exonuclease III digested basal DNA in such intact double-stranded DNA specifically, and both ORAOV1 gene and assisted DNA were released into solution. ORAOV1 gene induced another intact double-stranded DNA digestion for target recycling, while assisted DNA hybridized with the capture DNA to form double-stranded DNA on the modified electrode surface. Unhybridized capture DNA on the modified electrode surface was hydrolyzed by RecJf exonuclease to reduce the background electrochemical signal. The 3' terminus of double-stranded DNA on the modified electrode surface was prolongated to be guanine-rich oligonucleotides under the catalysis of terminal deoxynucleotidyl transferase. In the presence of K+ ions, hemin adsorbed onto guanine-rich oligonucleotides to construct a G-quadruplex/hemin complex with a large steric hindrance effect to efficiently avoid the charge transfer of the [Fe(CN)6]3-/4- probe toward the electrode surface. The electrochemical impedance value was increased significantly after the addition of ORAOV1 gene via exonuclease III-assisted target recycling and dual enzyme-assisted signal amplification strategies. The electrochemical impedance value was linearly related to the logarithmic concentration of ORAOV1 gene in the range from 0.05 fM to 20 pM, and the detection limit of ORAOV1 gene was low to 0.019 fM. This biosensor was used to detect ORAOV1 gene in complicated human saliva samples with satisfactory results.
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Técnicas Biossensoriais , Exodesoxirribonucleases , Neoplasias Bucais , Proteínas de Neoplasias , Técnicas Biossensoriais/métodos , DNA/genética , Técnicas Eletroquímicas/métodos , Exodesoxirribonucleases/química , Exodesoxirribonucleases/metabolismo , Guanina/química , Hemina/química , Humanos , Limite de Detecção , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/genética , Proteínas de Neoplasias/química , Oligonucleotídeos/químicaRESUMO
Sulfonamides (SAs) have been of ecotoxicological concern for ambient ecosystems due to their widespread application in the veterinary industry. Herein, we developed a powerful advanced oxidation peracetic acid (PAA) activation process for the remediation of SAs by Co3O4 with double-layered hollow structures (Co3O4 DLHSs). Systematic characterization results revealed that the polyporous hollow hierarchical structure endows Co3O4 DLHSs with abundant active reaction sites and enhanced mass transfer rate, which were conducive for improving the PAA activation efficiency. Laser flash photolysis experiment and mechanism studies indicated that organic radical species were dominant reactive species for SAs removal. The present system is also highly effective under natural water matrices and trace SAs concentration (20 µg/L) condition. More importantly, the chlorella acute toxicity of the SAs solution was eliminated during mineralization process, supporting this catalytic system may be efficaciously applied for the remediation of SAs contamination in ambient waterways.
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Chlorella , Ácido Peracético , Cobalto , Ecossistema , Cinética , Óxidos , Sulfanilamida , SulfonamidasRESUMO
Background: Sepsis-induced liver dysfunction is believed to be an independent risk factor for multiple organ dysfunction and death. Idebenone (IDE), a synthetic analog of coenzyme Q10 (CoQ10), possesses an antioxidizing property. The present study aimed to investigate the efficacy of IDE on sepsis-induced liver injury and discuss its reaction mechanism in vivo and in vitro. Methods: To establish an in vivo model of sepsis-induced liver injury, rats were treated with high-grade cecal ligation and puncture (CLP). Hematoxylin-eosin staining was applied to observe the liver pathological changes, and liver function was examined using alanine aminotransferase (ALT) and aspartate aminotransferase (AST) assay kits. Enzyme-linked immunosorbent assay (ELISA) kits were employed to assess the levels of inflammatory cytokines in serum and tissues. The activities of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were analyzed using MDA, SOD, and GSH-Px assay kits, respectively. The apoptosis of liver tissues was measured by terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) staining, and western blot was employed to estimate apoptosis-related proteins. In vitro, 0.5 µg/mL lipopolysaccharide (LPS) was adopted to administrate primary hepatocytes. The expressions of receptor for advanced glycation end products (RAGE)/p38-related proteins were evaluated by western blot. Cell counting kit-8 (CCK-8) and dichloro-dihydro-fluorescein diacetate (DCFH-DA) assays were utilized to estimate cell viability and reactive oxygen species (ROS) content. Moreover, the transfection efficacy of overexpression (Ov)-RAGE in primary hepatocytes was tested by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. Results: IDE could improve liver function and reduce sepsis-induced pathological damage. The levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) in the serum and liver tissue of sepsis rats were suppressed by IDE. Additionally, IDE repressed the oxidative stress and apoptosis of liver tissues in sepsis-induced rats. IDE also inhibited RAGE/p38 signaling. Furthermore, IDE revived the decreased viability in LPS-induced hepatocytes concentration-dependently. After overexpressing RAGE, RAGE expression in hepatocytes was significantly elevated. Further functional experiments revealed that IDE attenuated cell viability injury, apoptosis, oxidative stress, and inflammatory damage in LPS-induced hepatocytes via RAGE/p38 signaling. Conclusions: IDE helped to protect against sepsis-induced liver injury via the regulation of RAGE/p38 signaling.
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Scaffolds mimicking the native annulus fibrosus (AF) extracellular matrix (ECM) structure are crucial to guide the seeding cells to regenerate aligned tissue, while fabricating such a scaffold by synthetic material is challengeable. Native acellular scaffolds derived from AF tissue certainly possess the advantages of natural structure and composition. Based on previous studies, we modified decellularization procedure and especially compared two drying methods, including gradient dehydration and freeze-drying. The decellularization process can effectively remove the host cells and antigens such as α-Gal, while maintaining the original ECM including GAG and collagen I. Compared with gradient dehydration, freeze-drying not only rendered the decellularized scaffold in dry state for storage but also gave the scaffold more aligned porous structure and hydrophilicity. And, the acellular porous scaffold manifested better capacity of supporting cell ingrowth when seeded human bone marrow mesenchymal stem cells (hBMSCs) or implanted in vivo. Furthermore, this optimized freeze-dried scaffold showed similar mechanical elastic modulus as native AF and demonstrated rare inflammatory granuloma and immune rejection as observed in HE staining and immunohistochemistry staining (IHC) of CD8 and MAC387 epitopes when implanted subcutaneously in vivo. To sum up, through our decellularization and freeze-drying procedure, an aligned porous three-dimensional scaffold derived from the natural AF ECM was successfully fabricated with good retention of ECM components and benign biocompatibility. It will be a promising scaffold for AF tissue engineering.
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Anel Fibroso , Engenharia Tecidual , Matriz Extracelular/química , Humanos , Porosidade , Engenharia Tecidual/métodos , Alicerces Teciduais/químicaRESUMO
Multidrug and toxic compound extrusion (MATE) transporters contribute to multidrug resistance and play major determinants of aluminum (Al) tolerance in plants. Alfalfa (Medicago sativa L.) is the most extensively cultivated forage crop in the world, yet most alfalfa cultivars are not Al tolerant. The basic knowledge of the MATE transcripts family and the characterisation of specific MATE members involved in alfalfa Al stress remain unclear. In this study, 88 alfalfa MATE (MsMATE) transporters were identified at the whole transcriptome level. Phylogenetic analysis classified them into four subfamilies comprising 11 subgroups. Generally, five kinds of motifs were found in group G1, and most were located at the N-terminus, which might confer these genes with Al detoxification functions. Furthermore, 10 putative Al detoxification-related MsMATE genes were identified and the expression of five genes was significantly increased after Al treatment, indicating that these genes might play important roles in conferring Al tolerance to alfalfa. Considering the limited functional understanding of MATE transcripts in alfalfa, our findings will be valuable for the functional investigation and application of this family in alfalfa.
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An intelligent theranostic nanoplatform based on nanovalve operated metal-organic framework (MOF) core-shell hybrids, incorporating tumorous microenvironment-triggered drug release, magnetic resonance imaging (MRI) guidance, sustained release, and effective chemotherapy in one pot is reported. The core-shell hybrids are constructed by an in situ growth method, in which Fe3 O4 particles with superior abilities of MRI and magnetic separation form the core and UiO-66 MOF with high loading capacity compose the shell, and then are surface-installed with pillararene-based pseudorotaxanes as tightness-adjustable nanovalves. This strategy endows the system with the ability of targeted, multistimuli responsive drug release in response to pH changes, temperature variations, and competitive agents. Water-soluble carboxylatopillar[6]arene system achieved sustained drug release over 7 days due to stronger host-guest binding, suggesting that the nanovalve tightness further reinforces the desirable release of anticancer agent over a prolonged time at the lesion site.