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Due to their anisotropy, 1D semiconductor nanorod-based materials have attracted much attention in the process of hydrogen production by solar energy. Nevertheless, the rational design of 1D heterojunction materials and the modulation of photo-generated electron-hole transfer paths remain a challenge. Herein, a ZnxCd1-xS@ZnS/MoS2 core-shell nanorod heterojunction is precisely constructed via in situ growth of discontinuous ZnS shell and MoS2 NCs on the ZnâCdâS nanorods. Among them, the Zn vacancy in the ZnS shell builds the defect level, and the nanoroelded MoS2 builds the electron transport site. The optimized photocatalyst shows significant photocatalytic activity without Platinum as an auxiliary catalyst, mainly due to the new interfacial charge transfer channel constructed by the shell vacancy level, the vertical separation and the de-accumulation process of photo-generated electrons and photo-generated holes. At the same time, spectral analysis, and density functional theory (DFT) calculations fully prove that shortening difference of speed between the photogenerated electron and hole movement process is another key factor to enhance the photocatalytic performance. This study provides a new path for the kinetic design of enhanced carrier density by shortening the carrier retention time of 1D heterojunction photocatalysts with improved photocatalytic performance.
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The increasing presence of fluoroquinolone (FQ) antibiotics in aquatic environments is a growing concern due to their widespread use, negatively impacting aquatic organisms. This paper provides an overview of the environmental distribution, sources, fate, and both single and mixed toxicity of FQ antibiotics in aquatic environments. It also examines the accumulation of FQ antibiotics in aquatic organisms and their transfer into the human body through the food chain. The study identifies critical factors such as metabolism characteristics, physiochemical characteristics, light, temperature, dissolved oxygen, and environmental compatibility that influence the presence of FQ antibiotics in aquatic environments. Mixed pollutants of FQ antibiotics pose significant risks to the ecological environment. Additionally, the paper critically discusses advanced treatment technologies designed to remove FQ antibiotics from wastewater, focusing on advanced oxidation processes (AOPs) and electrochemical advanced oxidation processes (EAOPs). The discussion also includes the benefits and limitations of these technologies in degrading FQ antibiotics in wastewater treatment plants. The paper concludes by proposing new approaches for regulating and controlling FQ antibiotics to aid in the development of ecological protection measures.
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Ethanol (EtOH) exerts its effects through various protein targets, including transient receptor potential melastatin 7 (TRPM7) channels, which play an essential role in cellular homeostasis. We demonstrated that TRPM7 is expressed in rat brain microvascular endothelial cells (rBMVECs), the major cellular component of the blood-brain barrier (BBB). Heavy alcohol drinking is often associated with HIV infection, however mechanisms underlying alcohol-induced BBB damage and HIV proteins, are not fully understood. We utilized the HIV-1 transgenic (HIV-1Tg) rat to mimic HIV-1 patients on combination anti-retroviral therapy (cART) and demonstrated TRPM7 expression in rBMVECs wass lower in adolescent HIV-1Tg rats compared to control animals, however control and HIV-1Tg rats expressed similar levels at 9 weeks, indicating persistent presence of HIV-1 proteins delayed TRPM7 expression. Binge exposure to EtOH (binge EtOH) decreased TRPM7 expression in control rBMVECs in a concentration-dependent manner, and abolished TRPM7 expression in HIV-1Tg rats. In human BMVECs (hBMVECs), TRPM7 expression was downregulated after treatment with EtOH, HIV-1 proteins, and in combination. Next, we constructed in vitro BBB models using BMVECs and found TRPM7 antagonists enhanced EtOH-mediated BBB integrity changes. Our study demonstrated alcohol decreased TRPM7 expression, whereby TRPM7 could be involved in the mechanisms underlying BBB alcohol-induced damage in HIV-1 patients on cART.
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Infecções por HIV , Canais de Cátion TRPM , Canais de Potencial de Receptor Transitório , Ratos , Animais , Humanos , Adolescente , Barreira Hematoencefálica/metabolismo , Canais de Cátion TRPM/metabolismo , Infecções por HIV/complicações , Infecções por HIV/metabolismo , Células Endoteliais/metabolismo , Etanol/toxicidade , Etanol/metabolismo , Ratos Transgênicos , Proteínas do Vírus da Imunodeficiência Humana/metabolismo , Canais de Potencial de Receptor Transitório/metabolismo , Proteínas Serina-Treonina Quinases/metabolismoRESUMO
Artificially performing chemical reactions in living biosystems to attain various physiological aims remains an intriguing but very challenging task. In this study, the Schiff base reaction was conducted in cells using Sc(OTf)3 as a catalyst, enabling the in situ synthesis of a hollow covalent organic polymer (HCOP) without external stimuli. The reversible Schiff base reaction mediated intracellular Oswald ripening endows the HCOP with a spherical, hollow porous structure and a large specific surface area. The intracellularly generated HCOP reduced cellular motility by restraining actin polymerization, which consequently induced mitochondrial deactivation, apoptosis, and necroptosis. The presented intracellular synthesis system inspired by the Schiff base reaction has strong potential to regulate cell fate and biological functions, opening up a new strategic possibility for intervening in cellular behavior.
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Polímeros , Bases de Schiff , Bases de Schiff/químicaRESUMO
The redox homeostasis in living cells is greatly crucial for maintaining the redox biological function, whereas accurate and dynamic detection of intracellular redox states still remains challenging. Herein, a reversible surface-enhanced Raman scattering (SERS) nanosensor based on covalent organic frameworks (COFs) was prepared to dynamically monitor the redox processes in living cells. The nanosensor was fabricated by modifying the redox-responsive Raman reporter molecule, 2-Mercaptobenzoquione (2-MBQ), on the surface of gold nanoparticles (AuNPs), followed by the in situ coating of COFs shell. 2-MBQ molecules can repeatedly and quickly undergo reduction and oxidation when successively treated with ascorbic acid (AA) and hypochlorite (ClO-) (as models of reductive and oxidative species, respectively), which resulted in the reciprocating changes of SERS spectra at 900 cm-1. The construction of the COFs shell provided the nanosensor with great stability and anti-interference capability, thus reliably visualizing the dynamics of intracellular redox species like AA and ClO- by SERS nanosensor. Taken together, the proposed SERS strategy opens up the prospects to investigate the signal transduction pathways and pathological processes related with redox dynamics.
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Nanopartículas Metálicas , Estruturas Metalorgânicas , Ácido Ascórbico , Ouro , Ácido Hipocloroso , Oxirredução , Análise Espectral Raman/métodosRESUMO
BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is a worldwide crisis caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Many COVID-19 patients present with fever in the early phase, with some progressing to a hyperinflammatory phase. Ethanol (EtOH) exposure may lead to systemic inflammation. Network meta-analysis was conducted to examine possible relationships between EtOH consumption and COVID-19 pathologies. METHODS: Molecules affected by EtOH exposure were identified by analysis with QIAGEN Knowledge Base. Molecules affected by COVID-19 were identified from studies in MEDLINE, bioRxiv, and medRxiv reporting gene expression profiles in COVID-19 patients, QIAGEN Coronavirus Network Explorer, and analysis of the RNA-sequencing data of autopsied lungs of COVID-19 patients retrieved from the GEO database. Network meta-analysis was then conducted on these molecules using QIAGEN Ingenuity Pathway Analysis (IPA). RESULTS: Twenty-eight studies reporting significant gene expression changes in COVID-19 patients were identified. One RNA-sequencing dataset on autopsied lungs of COVID-19 patients was retrieved from GEO. Our network meta-analysis suggests that EtOH exposure may augment the effects of SARS-CoV-2 infection on hepatic fibrosis signaling pathway, cellular metabolism and homeostasis, inflammation, and neuroinflammation. EtOH may also enhance the activity of key mediators including cytokines, such as IL-1ß, IL-6, and TNF, and transcription factors, such as JUN and STAT, while inhibiting the activity of anti-inflammatory mediators including glucocorticoid receptor. Furthermore, IL-1ß, IL-6, TNF, JUN, and STAT were mapped to 10 pathways predicted to associate with SARS-CoV-2 proteins, including HMGB1, IL-1, and IL-6 signaling pathways. CONCLUSIONS: Our meta-analyses demonstrate that EtOH exposure may augment SARS-CoV-2-induced inflammation by altering the activity of key inflammatory mediators. Our findings suggest that it is important for clinicians to caution patients about the risk of alcohol consumption, which has increased during the COVID-19 pandemic. The findings also call for further investigation into how alcohol exposure affects viral infections.
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Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/metabolismo , COVID-19/epidemiologia , COVID-19/metabolismo , Etanol/efeitos adversos , Consumo de Bebidas Alcoólicas/genética , COVID-19/genética , Citocinas/genética , Citocinas/metabolismo , Etanol/administração & dosagem , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes/fisiologia , Humanos , Mediadores da Inflamação/metabolismo , Metanálise em RedeRESUMO
Targeted cell ablation is a powerful approach for studying the role of specific cell populations in a variety of organotypic functions, including cell differentiation, and organ generation and regeneration. Emerging tools for permanently or conditionally ablating targeted cell populations and transiently inhibiting neuronal activities exhibit a diversity of application and utility. Each tool has distinct features, and none can be universally applied to study different cell types in various tissue compartments. Although these tools have been developed for over 30 years, they require additional improvement. Currently, there is no consensus on how to select the tools to answer the specific scientific questions of interest. Selecting the appropriate cell ablation technique to study the function of a targeted cell population is less straightforward than selecting the method to study a gene's functions. In this review, we discuss the features of the various tools for targeted cell ablation and provide recommendations for optimal application of specific approaches.
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Bacteriocinas/metabolismo , Ácido Clodrônico/química , Toxina Diftérica/genética , Optogenética/métodos , Simplexvirus/fisiologia , Animais , Ácido Clodrônico/toxicidade , Toxina Diftérica/metabolismo , Humanos , Intoxicação por MPTP/metabolismo , Intoxicação por MPTP/patologia , Neurônios/fisiologia , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Simplexvirus/enzimologiaRESUMO
Binge drinking affects the onset and progression of human immunodeficiency virus (HIV)-associated neurological disorders. The HIV-1 transgenic (HIV-1Tg) rat was created with a gag- and pol-deleted HIV-1 viral genome to mimic HIV-infected patients receiving combination anti-retroviral therapy (cART). Docosahexaenoic acid (DHA) is a marine compound that modulates inflammatory responses. Using HIV-1Tg rats subjected to binge exposure to ethanol (EtOH), this study examined whether DHA could reduce the detrimental neurological effects of EtOH and HIV proteins. Young adult male HIV-1Tg and F344 control rats received 4 mL/kg/day saline as a control (Saline group), 20 mg/kg/day DHA (DHA group), 4.8 g/kg/day 52% w/v EtOH (EtOH group), or 4.8 g/kg/day 52% w/v EtOH and 20 mg/kg/d DHA (DHA + EtOH group) by gavage for 5 weeks (n = 6 per group). EtOH was administrated on days 5, 6, and 7 of each week. Locomotor activity (LMA) was assessed using open field tests before and 45, 90, 135, and 180 min after each treatment. Repeated binge EtOH exposure gradually decreased LMA measured before daily treatments in HIV-1Tg and F344 rats, an effect that was reversed by DHA only in the HIV-1Tg rats. Decreased LMA of rats after treatment and under the influence of EtOH was less pronounced, and the reversal effect of DHA did not reach statistical significance. The plasma endotoxin level was significantly higher in HIV-1Tg rats than in F344 rats. IL-6 and IL-18 expression in the striatum was significantly higher in the HIV-1Tg EtOH group than in the F344 EtOH group. DHA significantly decreased the high levels of IL-6, IL-18, and NF-κB expression observed in the HIV-1Tg EtOH group. DHA appears to ameliorate inflammation and consequently lessen the reductions in LMA produced by the combination of EtOH and HIV-1 viral proteins.
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Consumo Excessivo de Bebidas Alcoólicas/tratamento farmacológico , Corpo Estriado/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/farmacologia , Infecções por HIV/tratamento farmacológico , Locomoção/efeitos dos fármacos , Animais , Consumo Excessivo de Bebidas Alcoólicas/fisiopatologia , Consumo Excessivo de Bebidas Alcoólicas/virologia , Corpo Estriado/química , Corpo Estriado/metabolismo , Corpo Estriado/virologia , Modelos Animais de Doenças , Endotoxinas/sangue , Expressão Gênica , Infecções por HIV/fisiopatologia , Infecções por HIV/virologia , HIV-1/genética , Interleucina-18/sangue , Interleucina-18/genética , Interleucina-18/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Locomoção/fisiologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , NF-kappa B/sangue , NF-kappa B/genética , NF-kappa B/metabolismo , Ratos , Ratos Endogâmicos F344 , Ratos TransgênicosRESUMO
A fluorogenic assay for SIRT5 has been developed to screen their small molecule modulators based on the recent discovery that SIRT5 is a demalonylase and desuccinylase. However, this assay uses a fluorogenic peptide containing 7-amino-4-methylcoumarin (AMC), which becomes the cause of false positive hits from the screening. To overcome this, we have developed an alternative method called a FRET-based assay, which will be reliable and useful for screening SIRT5 modulators in a high-throughput format since no AMC group present in this assay.
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Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes/química , Sirtuínas/metabolismo , Sequência de Aminoácidos , Cumarínicos/química , Ensaios Enzimáticos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Cinética , Dados de Sequência Molecular , Peptídeos/química , Peptídeos/metabolismo , Sirtuínas/antagonistas & inibidores , Especificidade por Substrato , p-Dimetilaminoazobenzeno/análogos & derivados , p-Dimetilaminoazobenzeno/químicaRESUMO
BACKGROUND: Thymic atrophy is characterized by loss of thymocytes, destruction of thymic architecture, and a subsequent decrease in naïve T cells with compromised immunity. Thymic atrophy occurs during aging. Environmental factors including alcohol misuse also induce thymic atrophy. Despite the link between alcohol misuse and thymic atrophy, the underlying mechanism is understudied. We aimed to identify molecules and signaling pathways that underly alcohol-induced thymic atrophy during aging. METHODS: F344 rats were given 3-day binge-ethanol (4.8 g/kg/day; 52% w/v; i.g.) and the thymus was collected and weighed. Molecular mechanisms underlying ethanol-induced thymic atrophy were investigated by network meta-analysis using the QIAGEN Ingenuity Pathway Analysis (IPA). The molecules associated with ethanol were identified from the QIAGEN Knowledge Base (QKB) and those associated with thymic atrophy were identified from QKB and Mouse Genome Informatics (MGI). Aging-mediated Differential Expression Genes (DEGs) from mouse thymocytes were obtained from the Gene Expression Omnibus (GEO) database (GSE132136). The relationship between the molecules and associated signaling pathways were studied using IPA. RESULTS: Binge-ethanol decreased thymic weight in F344 rats. Our meta-analysis using IPA identified molecules commonly shared by ethanol and thymic atrophy through which simulation with ethanol increased thymic atrophy. We then obtained aging-mediated DEGs from the atrophied thymocytes. We found that ethanol contributed to thymic atrophy through modulation of the aging-mediated DEGs. Our network meta-analysis suggests that ethanol may augment thymic atrophy through increased expression of cytokines (e.g., IL-6, IL-17A and IL-33) along with their regulators (e.g., STAT1 and STAT3). CONCLUSIONS: Exposure to alcohol may augment thymic atrophy by altering the activity of key inflammatory mediators, such as STAT family members and inflammatory cytokines. These findings provide insights into the signaling pathways and upstream regulators that underly alcohol-induced thymic atrophy during aging, suggesting that alcohol consumption could prepone thymic atrophy.
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A core-shell nanostructure of gold nanoparticles@covalent organic framework (COF) loaded with palladium nanoparticles (AuNPs@COF-PdNPs) was designed for the rapid monitoring of catalytic reactions with surface-enhanced Raman spectroscopy (SERS). The nanostructure was prepared by coating the COF layer on AuNPs and then in situ synthesizing PdNPs within the COF shell. With the respective SERS activity and catalytic performance of the AuNP core and COF-PdNPs shell, the nanostructure can be directly used in the SERS study of the catalytic reaction processes. It was shown that the confinement effect of COF resulted in the high dispersity of PdNPs and outstanding catalytic activity of AuNPs@COF-PdNPs, thus improving the reaction rate constant of the AuNPs@COF-PdNPs-catalyzed hydrogenation reduction by 10 times higher than that obtained with Au/Pd NPs. In addition, the COF layer can serve as a protective shell to make AuNPs@COF-PdNPs possess excellent reusability. Moreover, the loading of PdNPs within the COF layer was found to be in favor of avoiding intermediate products to achieve a high total conversion rate. AuNPs@COF-PdNPs also showed great catalytic activities toward the Suzuki-Miyaura coupling reaction. Taken together, the proposed core-shell nanostructure has great potential in monitoring and exploring catalytic processes and interfacial reactions.
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Ouro , Nanopartículas Metálicas , Paládio , Análise Espectral Raman , Ouro/química , Análise Espectral Raman/métodos , Paládio/química , Nanopartículas Metálicas/química , Catálise , Estruturas Metalorgânicas/química , Propriedades de Superfície , HidrogenaçãoRESUMO
Both microplastics and antibiotics are commonly found contaminants in aquatic ecosystems. Microplastics have the ability to absorb antibiotic pollutants in water, but the specific adsorption behavior and mechanism are not fully understood, particularly in relation to the impact of microplastics on toxicity in aquatic environments. We review the interaction, mechanism, and transport of microplastics and antibiotics in water environments, with a focus on the main physical characteristics and environmental factors affecting adsorption behavior in water. We also analyze the effects of microplastic carriers on antibiotic transport and long-distance transport in the water environment. The toxic effects of microplastics combined with antibiotics on aquatic organisms are systematically explained, as well as the effect of the adsorption behavior of microplastics on the spread of antibiotic resistance genes. Finally, the scientific knowledge gap and future research directions related to the interactions between microplastics and antibiotics in the water environment are summarized to provide basic information for preventing and treating environmental risks. Environ Toxicol Chem 2024;00:1-12. © 2024 SETAC.
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BACKGROUND: We previously reported that binge ethanol induces atrophy of the spleen, a key immune organ, in adolescent male F344 rats. Because there are significant sex effects in immune function, we investigated whether binge ethanol exerts sex-dependent effects on the spleen, including producing splenic atrophy. METHODS: We gave F344 rats ethanol (4.8 g/kg/day; 52% w/v; i.g.) on postnatal days [PND] 36 ~ 38 and sacrificed them on PND 39 for spleen collection. We performed immunophenotyping analysis of splenic cells and examined the expression of 158 genes related to alcohol metabolism, epigenetic modification, and immune regulation in the spleens of adolescent (PND 39) male and female rats. RESULTS: Following a 3-day ethanol exposure, a loss of body weight, and absolute and relative spleen weight, was seen only in male adolescent rats. Ethanol altered the relative proportions of lymphocyte subtypes in both sexes with different patterns. We also found that 3-day ethanol exposure induced sex-dependent gene expression changes in spleen. Among the 158 genes studied, the expression of only three genes was significantly increased in female rats. However, the expression of 30 genes was significantly increased/decreased in male rats. Female rats had greater expression of alcohol metabolizing enzyme genes in the spleen under physiological conditions and when stimulated by binge ethanol. The genes are involved in epigenetic modification were differentially expressed in a sex-dependent manner. CONCLUSION: We found that male adolescent rats were more sensitive to binge ethanol than female rats. Differential expression of the genes related to alcohol metabolism and epigenetic modification (of DNA methyltransferase and histone deacetylases) between the sexes could account for the observed sex-dependent responses to binge ethanol in adolescent rats.
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Anabolic steroids and ß-agonists are commonly prohibited substances found in doping control studies; therefore, the determination of anabolic substances in biological samples is crucial. To analyze the anabolic compounds in urine, an adsorbent, polyethylene glycol (PEG)-grafted magnetic nanoparticle material (Fe3O4@SiO2-PEG), with low toxicity and strong biocompatibility was prepared in this investigation. Compared to those of Fe3O4 and Fe3O4@SiO2, the grafted PEG chains (approximately 5.4 wt.%) on the magnetic nanoparticles improved the extraction efficiencies by factors of 3.9-17.0 and 2.5-2.9, respectively, likely due to the electrostatic attraction and hydrogen bonding. To achieve maximum extraction efficiency, several extraction parameters were optimized, including the kind and volume of desorption solvent, pH, and the extraction and desorption time. The standard curves were linear within the range of 0.5-20 µg/L for methyltestosterone and trenbolone, and 0.02-5 µg/L for clenbuterol. The limits of detection for the three drugs were 0.01-0.12 µg/L. The limits of quantification were 0.02-0.40 µg/L. The levels of precision of the optimized method were assessed based on the respective intra- and inter-day and batch-to-batch relative standard deviations in the ranges of 3.2-5.2 % (n = 5), 5.9-11.3 % (n = 4), and 6.7-9.2 % (n = 3). The Fe3O4@SiO2-PEG nanoparticles could exclude urine matrix interferences (matrix effect of 91.8-98.1 %) and achieve satisfactory recoveries (75.5-116.1 %), affording sensitive and accurate determination of trace anabolic substances in urine.
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Anabolizantes , Limite de Detecção , Nanopartículas de Magnetita , Polietilenoglicóis , Humanos , Polietilenoglicóis/química , Anabolizantes/urina , Anabolizantes/isolamento & purificação , Nanopartículas de Magnetita/química , Dopagem Esportivo , Adsorção , Reprodutibilidade dos Testes , Extração em Fase Sólida/métodos , Dióxido de Silício/químicaRESUMO
Chiral pesticides exhibit enantioselective differences in processes such as biological absorption, metabolism, and toxic effects. Organisms have different physiological characteristics at different developmental stages. Therefore, conducting enantiomeric toxicity studies at different developmental stages of organisms can help deepen the understanding of the ecological effects of chiral pesticides. This study focused on trans-tetramethrin (Tet) and investigated the enantioselectivity in bioconcentration, developmental toxicity, estrogenic effects, and immunotoxicity of Tet's racemate ((±)-Tet) and its two enantiomers ((+)-Tet and (-)-Tet) in three developmental stages of zebrafish: embryos, yolk sac larvae, and juveniles. The results showed that Tet exhibited different enantioselectivity in lethal, bioconcentration, and teratogenic effects on zebrafish at different developmental stages. The LC50 value was (+)-Tet > (±)-Tet > (-)-Tet, with embryos being the most sensitive, followed by juveniles and yolk sac larvae. The enantioselective bioconcentration was (±)-Tet > (+)-Tet > (-)-Tet, and the bioconcentration effect was greater in embryos than that in yolk sac larvae and juveniles. Developmental toxicity indicated that (+)-Tet and (±)-Tet had higher teratogenic effects on yolk sac larvae than on embryos. Tet exhibited different enantioselective effects on the expression of zebrafish estrogen-related genes and innate immune-related genes at different developmental stages. These results will contribute to a more comprehensive assessment of the aquatic toxicity and environmental risks of chiral pesticides.
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Hydrogen sulfide (H2S), an important gas signal molecule, participates in intercellular signal transmission and plays a considerable role in physiology and pathology. However, in-situ monitoring of H2S level during the processes of material transport between cells remains considerably challenging. Herein, a cell membrane-targeted surface-enhanced Raman scattering (SERS) nanoprobe was designed to quantitatively detect H2S secreted from living cells. The nanoprobes were fabricated by assembling cholesterol-functionalized DNA strands and dithiobis(phenylazide) (DTBPA) molecules on core-shell gold nanostars embedded with 4-mercaptoacetonitrile (4-MBN) (AuNPs@4-MBN@Au). Thus, three functions including cell-membrane targeted via cholesterol, internal standard calibration, and responsiveness to H2S through reduction of azide group in DTBPA molecules were integrated into the nanoprobes. In addition, the nanoprobes can quickly respond to H2S within 90 s and sensitively, selectively, and reliably detect H2S with a limit of detection as low as 37 nM due to internal standard-assisted calibration and reaction specificity. Moreover, the nanoprobes can effectively target on cell membrane and realize SERS visualization of dynamic H2S released from HeLa cells. By employing the proposed approach, an intriguing phenomenon was observed: the other two major endogenous gas transmitters, carbon monoxide (CO) and nitric oxide (NO), exhibited opposite effect on H2S production in living cells stimulated by related gas release molecules. In particular, the introduction of CO inhibited the generation of H2S in HeLa cells, while NO promoted its output. Thus, the nanoprobes can provide a robust method for investigating H2S-related extracellular metabolism and intercellular signaling transmission.
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Técnicas Biossensoriais , Sulfeto de Hidrogênio , Nanopartículas Metálicas , Humanos , Sulfeto de Hidrogênio/metabolismo , Células HeLa , Análise Espectral Raman/métodos , Ouro , Óxido Nítrico , Membrana Celular/metabolismo , ColesterolRESUMO
Induced pluripotent stem (iPS) cells, especially those reprogrammed from patient somatic cells, have a great potential usage in regenerative medicine. The expression of p53 has been proven as a key barrier limiting iPS cell generation, but how p53 is regulated during cell reprogramming remains unclear. In this study, we found that the ectopic expression of miR-138 significantly improved the efficiency of iPS cell generation via Oct4, Sox2, and Klf4, with or without c-Myc (named as OSKM or OSK, respectively), without sacrificing the pluripotent characteristics of the generated iPS cells. Exploration of the mechanism showed that miR-138 directly targeted the 3' untranslated region (UTR) of p53, significantly decreasing the expression of p53 and its downstream genes. Furthermore, the ectopic expression of p53 having a mutant 3'-UTR, which cannot be bound by miR-138, seriously impaired the effect of miR-138 on p53 signaling and OSKM-initiated somatic cell reprogramming. Combined with the fact that miR-138 is endogenously expressed in fibroblasts, iPS cells, and embryonic stem cells, our study demonstrated that regulation of the p53 signaling pathway and promotion of iPS cell generation represent an unrevealed important function of miR-138.
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Células-Tronco Pluripotentes Induzidas/metabolismo , MicroRNAs/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Técnicas de Cultura de Células , Diferenciação Celular/fisiologia , Regulação para Baixo , Técnicas de Inativação de Genes , Fator 4 Semelhante a Kruppel , Camundongos , MicroRNAs/genética , Células NIH 3T3 , Transdução de Sinais , Proteína Supressora de Tumor p53/genéticaRESUMO
Bovine enterovirus (BEV) is a highly infectious pathogen that may cause respiratory and gastrointestinal disease outbreaks in cattle. This study aimed to investigate the prevalence and genetic characteristics of BEVs in Guangxi Province, China. A total of 1,168 fecal samples from 97 different bovine farms were collected between October 2021 and July 2022 in Guangxi Province, China. BEV was confirmed using a reverse transcription-PCR (RT-PCR) method targeting the 5' untranslated region (UTR), and isolates were genotyped by sequencing their genomes. The nearly complete genome sequences of eight BEV strains showing cytopathic effects in MDBK cells were determined and analyzed. In total, 125 (10.7%) of 1,168 fecal samples were positive for BEV. BEV infection was significantly associated with farming patterns and clinical symptoms (P < 0.05; odds ratio [OR] > 1). Molecular characterization indicated that five BEV strains from this study belonged to EV-E2 and one strain to EV-E4. Two BEV strains (GXNN2204 and GXGL2215) could not be assigned to a known type. Strain GXGL2215 showed the closest genetic relationship with GX1901 (GenBank accession number MN607030; China) in its VP1 (67.5%) and P1 (74.7%) and with NGR2017 (MH719217; Nigeria) in its polyprotein (72.0%). It was also close to the EV-E4 strain GXYL2213 from this study when the complete genome (81.7%) was compared. Strain GXNN2204 showed the closest genetic relationship with Ho12 (LC150008; Japan) in the VP1 (66.5%), P1 (71.6%), and polyprotein (73.2%). Genome sequence analysis suggested that strains GXNN2204 and GXGL2215 originated from the genomic recombination of EV-E4 and EV-F3 and EV-E2 and EV-E4, respectively. This study reports the cocirculation of multiple BEV types and the identification of two novel BEV strains in Guangxi, China, and it will provide further insights into the epidemiology and evolution of BEV in China. IMPORTANCE Bovine enterovirus (BEV) is a pathogen that causes intestinal, respiratory, and reproductive disease infections in cattle. This study reports on the widespread prevalence and biological characteristics of the different BEV types which currently exist in Guangxi Province, China. It also provides a reference for the study of the prevalence of BEV in China.
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The human digestive tract contains a diverse and abundant microbiota that is important for health. Excessive alcohol use can disrupt the balance of these microbes (known as dysbiosis), leading to elevated blood endotoxin levels and systemic inflammation. Using QIAGEN Ingenuity Pathway Analysis (IPA) bioinformatics tool, we have confirmed that peripheral endotoxin (lipopolysaccharide) mediates various cytokines to enhance the neuroinflammation signaling pathway. The literature has identified alcohol-mediated neuroinflammation as a possible risk factor for the onset and progression of neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), and psychiatric disorders such as addiction to alcohol and other drugs. In this review, we discuss alcohol-use-induced dysbiosis in the gut and other body parts as a causal factor in the progression of Central Nervous System (CNS) diseases including neurodegenerative disease and possibly alcohol use disorder.
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Doenças Neurodegenerativas , Humanos , Doenças Neurodegenerativas/induzido quimicamente , Sistema Nervoso CentralRESUMO
Clinically used opioids, such as morphine, activate the mu opioid receptor (MOR) encoded by Opioid Receptor Mu 1 (OPRM1) gene. Examination of the opioid receptor genes showed that the human OPRM1 pre-mRNA undergoes extensive alternative splicing events and capable of expressing 21 isoforms. However, characterization of OPRM1 signaling is generalized, and only one isoform (MOR-1) has been extensively studied. Compounding this issue is the increasing significance of intravenous drug abuse in HIV neuropathogenesis. Here, we investigated the molecular impact of morphine and HIV-1 on regulation of OPRM1 pre-mRNA splicing in in vitro and in vivo models. Our results suggested that morphine treatment specifically induces the alternative splicing of MOR-1X isoform among the other isoforms analyzed in neuronal cells. Interestingly, alternative splicing and expression of MOR-1X isoform was also induced in postmortem brain tissues obtained from people with HIV (PWH). Additionally, treatment of control rats with morphine induced alternative splicing of MOR-1X in the brain regions involved in the reward pathways. More interestingly, HIV-1 transgenic (HIV-1Tg) rats, showed an additive induction of MOR-1X isoform with the exposure to morphine. To further assess the possible role of HIV secretory proteins in alternative splicing of OPRM1 gene, we analyzed the impact of HIV-1 Tat, gp120 and Nef proteins on alternative splicing of MOR-1X isoform. While the Tat and gp120 had no visible effects, treatment of neurons with Nef induced MOR-1X alternative splicing that was comparable to treatment with morphine. Altogether, our results suggest that HIV-1 may alter MOR isoform expression with Nef protein by amplifying the rate of MOR-1X alternative splicing induced by morphine.