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For environmental applications, it is crucial to rationally design and synthesize photocatalysts with positive exciton splitting and interfacial charge transfer. Here, a novel Ag-bridged dual Z-scheme Ag/g-C3N4/CoNi-LDH plasmonic heterojunction was successfully synthesized using a simple method, with the goal of overcoming the common drawbacks of traditional photocatalysts such as weak photoresponsivity, rapid combination of photo-generated carriers, and unstable structure. These materials were characterized by XRD, FT-IR, SEM, TEM UV-Vis/DRS, and XPS to verify the structure and stability of the heterostructure. The pristine LDH, g-C3N4, and Ag/g-C3N4/CoNi-LDH composite were investigated as photocatalysts for water remediation, an environmentally motivated process. Specifically, the photocatalytic degradation of tetracycline was studied as a model reaction. The performance of the supports and composite catalyst were determined by evaluating both the degradation and adsorption phenomenon. The influence of several experimental parameters such as catalyst loading, pH, and tetracycline concentration were evaluated. The current study provides important data for water treatment and similar environmental protection applications.
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Nanocompostos , Fotólise , Prata , Poluentes Químicos da Água , Purificação da Água , Nanocompostos/química , Poluentes Químicos da Água/química , Purificação da Água/métodos , Prata/química , Catálise , Nitrilas/química , Compostos de Nitrogênio/química , Adsorção , GrafiteRESUMO
Woodchip bioreactors are an eco-friendly technology for removing nitrogen (N) pollution. However, there needs to be more clarity regarding the dissolved organic matter (DOM) characteristics and bacterial community succession mechanisms and their association with the N removal performance of bioreactors. The laboratory woodchip bioreactors were continuously operated for 360 days under three influent N level treatments, and the results showed that the average removal rate of TN was 45.80 g N/(m3·day) when the influent N level was 100 mg N/L, which was better than 10 mg N/L and 50 mg N/L. Dynamic succession of bacterial communities in response to influent N levels and DOM characteristics was an important driver of TN removal rates. Medium to high N levels enriched a copiotroph bacterial module (Module 1) detected by network analysis, including Phenylobacterium, Xanthobacteraceae, Burkholderiaceae, Pseudomonas, and Magnetospirillaceae, carrying N-cycle related genes for denitrification and ammonia assimilation by the rapid consumption of DOM. Such a process can increase carbon limitation to stimulate local organic carbon decomposition to enrich oligotrophs with fewer N-cycle potentials (Module 2). Together, this study reveals that the compositional change of DOM and bacterial community succession are closely related to N removal performance, providing an ecological basis for developing techniques for N-rich effluent treatment.
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Bactérias , Reatores Biológicos , Nitrogênio , Eliminação de Resíduos Líquidos , Reatores Biológicos/microbiologia , Nitrogênio/análise , Bactérias/metabolismo , Eliminação de Resíduos Líquidos/métodos , MicrobiotaRESUMO
Mining and tailings deposition can cause serious heavy metal(loids) pollution to the surrounding soil environment. Soil microorganisms adapt their metabolism to such conditions, driving alterations in soil function. This study aims to elucidate the response patterns of nitrogen-cycling microorganisms under long-term heavy metal(loids) exposure. The results showed that the diversity and abundance of nitrogen-cycling microorganisms showed negative feedback to heavy metal(loids) concentrations. Denitrifying microorganisms were shown to be the dominant microorganisms with over 60% of relative abundance and a complex community structure including 27 phyla. Further, the key bacterial species in the denitrification process were calculated using a random forest model, where the top three key species (Pseudomonas stutzei, Sphingobium japonicum and Leifsonia rubra) were found to play a prominent role in nitrite reduction. Functional gene analysis and qPCR revealed that nirK, which is involved in nitrite reduction, significantly accumulated in the most metal-rich soil with the increase of absolute abundance of 63.86%. The experimental results confirmed that the activity of nitrite reductase (Nir) encoded by nirK in the soil was increased at high concentrations of heavy metal(loids). Partial least squares-path model identified three potential modes of nitrite reduction processes being stimulated by heavy metal(loids), the most prominent of which contributed to enhanced nirK abundance and soil Nir activity through positive stimulation of key species. The results provide new insights and preliminary evidence on the stimulation of nitrite reduction processes by heavy metal(loids).
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Ouro , Metais Pesados , Mineração , Nitritos , Microbiologia do Solo , Poluentes do Solo , Metais Pesados/toxicidade , Ciclo do Nitrogênio , Desnitrificação , Nitrogênio , Solo/químicaRESUMO
Histone lysine N-methyltransferase 2C (KMT2C) is involved in transcriptional regulation and DNA damage repair. Mutations in KMT2C have been implicated in the progression, metastasis, and drug resistance of multiple cancer types. However, the roles of KMT2C in the regulation of tumor prognosis, immune cell infiltration and the immune microenvironment in these multiple cancer types remain unclear. Therefore, in the present study, data from The Cancer Genome Atlas and Genotype-Tissue Expression databases were used for KMT2C expression analyses. Kaplan-Meier and univariate Cox regression analyses were also performed to investigate the prognostic role of KMT2C. In addition, Gene Set Enrichment Analysis (GSEA) was conducted to study the KMT2C-related signaling pathways. Tumor immune estimation resource 2 and single-sample GSEA were conducted to investigate the correlation between KMT2C expression and immune cell infiltrations, and Spearman's analysis was conducted to study the correlations among KMT2C, tumor mutational burden, microsatellite instability, immune regulators, chemokines and immune receptors. Immunohistochemistry of patient kidney tumor samples was performed to verify the correlation between KMT2C and programmed death-ligand 1 (PD-L1) expression. Finally, RNA interference, wound healing and colony formation assays were conducted to evaluate the effects of KMT2C expression on cell proliferation and metastasis. The results of the present study demonstrated that KMT2C was highly expressed in multiple cancer types, was a protective factor in kidney renal clear cell carcinoma and ovarian serous cystadenocarcinoma, and a risk factor for lung squamous cell carcinoma and uveal melanoma. In addition, KMT2C levels were negatively correlated with immune-activated pathways and the infiltration of immune cells, and positively correlated with inhibitory immune factors and tumor angiogenesis. Patients with low KMT2C expression had higher objective response rates to immunotherapy, and drug sensitivity analysis indicated that topoisomerase, histone deacetylase, DOT1-like histone H3K79 methyltransferase and G9A nuclear histone lysine methyltransferase inhibitors could potentially be used to treat tumors with high KMT2C expression levels. Finally, the KMT2C and PD-L1 expression levels were shown to be positively correlated, and KMT2C knockdown markedly promoted the proliferation and invasion capacities of A549 cells. In conclusion, the present study revealed that low KMT2C expression may be a promising biomarker for predicting the response of patients with cancer to immunotherapy. Conversely, high KMT2C expression was shown to promote tumor angiogenesis, which may contribute to the formation of the immunosuppressive tumor microenvironment.
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Objective: To investigate the effects of basic nursing combined with psychological intervention on treatment compliance, self-care ability, clinical efficacy, lung function and nursing satisfaction of patients with Influenza-A(H1N1). Method: This was application research. Eighty patients with influenza-A (H1N1) admitted to The First Affiliated Hospital of Hebei North University from January 2020 to December 2022 were included as subjects and randomly divided into the observation group(n=40) and the control group(n=40). Patients in the control group were given routine basic nursing intervention, while those in the observation group were treated with combined psychological intervention in addition to basic nursing. The differences in treatment compliance, self-care ability, clinical efficacy, lung function and nursing satisfaction were compared between the two groups. Results: After the intervention, the treatment compliance score and the total self-care ability score of the observation group were higher than those of the control group, with statistically significant differences(P<0.05). After treatment, the clinical efficacy of the observation group was significantly higher than that of the control group(P<0.05). Before treatment, no significant difference was observed between the two groups in terms of various indexes of lung function, which were better in the observation group than in the control group after treatment(P<0.05). Conclusion: Basic nursing combined with psychological intervention results in a variety of benefits in the treatment of patients with Influenza-A(H1N1), such as improved treatment compliance and self-care ability, ameliorated lung function, as well as enhanced treatment outcomes and nursing satisfaction, which needs to be promoted in clinical practice.
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Background: Gut microbiota has significant impact on the cardio-metabolism and inflammation, and is implicated in the pathogenesis and progression of atherosclerosis. However, the long-term prospective association between trimethylamine N-oxide (TMAO) level and major adverse clinical events (MACEs) in patients with coronary artery disease (CAD) with or without diabetes mellitus (DM) habitus remains to be investigated. Methods: This prospective, single-center cohort study enrolled 2090 hospitalized CAD patients confirmed by angiography at Beijing Hospital from 2017-2020. TMAO levels were performed using liquid chromatography-tandem mass spectrometry. The composite outcome of MACEs was identified by clinic visits or interviews annually. Multivariate Cox regression analysis, Kaplan-Meier analysis, and restricted cubic splines were mainly used to explore the relationship between TMAO levels and MACEs based on diabetes mellitus (DM) habitus. Results: During the median follow-up period of 54 (41, 68) months, 266 (12.7%) developed MACEs. Higher TMAO levels, using the tertile cut-off value of 318.28 ng/mL, were significantly found to be positive dose-independent for developing MACEs, especially in patients with DM (HR 1.744, 95%CI 1.084-2.808, p = 0.022). Conclusions: Higher levels of TMAO are significantly associated with long-term MACEs among CAD patients with DM. The combination of TMAO in patients with CAD and DM is beneficial for risk stratification and prognosis.
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Doença da Artéria Coronariana , Diabetes Mellitus , Metilaminas , Humanos , Metilaminas/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/epidemiologia , Feminino , Masculino , Estudos Prospectivos , Pessoa de Meia-Idade , Idoso , Diabetes Mellitus/epidemiologia , Prognóstico , Biomarcadores/sangue , Seguimentos , Fatores de Risco , Estudos de CoortesRESUMO
Wastewater treatment plants (WWTPs) can benefit from utilizing digital technologies to reduce greenhouse gas (GHG) emissions and to comply with effluent quality standards. In this study, the GHG emissions and electricity consumption of a WWTP were evaluated via computer simulation by varying the dissolved oxygen (DO), mixed liquor recirculation (MLR), and return activated sludge (RAS) parameters. Three different measures, namely, effluent water quality, GHG emissions, and energy consumption, were combined as water-energy-carbon coupling index (WECCI) to compare the effects of the parameters on WWTPs, and the optimal operating condition was determined. The initial conditions of the A2O process were set to 4.0â¯mg/L of DO, 100â¯% MLR, and 90.7â¯% RAS. Eighty scenarios with various DO, MLR, and RAS were simulated under steady-state condition to optimize the biological treatment process. The optimal operating conditions were found to be 1.5â¯mg/L of DO, 190â¯% MLR, and 90.9â¯% RAS, which had the highest WECCI of 2.40 when compared to the WECCI of the initial condition (1.07). This optimal condition simultaneously reduced GHG emissions by 1348â¯kg CO2-eq/d and energy consumption by 11.64 MWh/d. This implies that controlling DO, MLR, and RAS through sensors, valves, and pumps offers a promising approach to operating WWTPs with reduced electricity consumption and GHG emissions while attaining effluent quality standards. Additionally, the nitrous oxide stripping rate exhibited linear relationships with the effluent total ammonia and nitrite concentrations in the aerobic reactor, suggesting that monitoring dissolved nitrogen compounds in the effluent and reactor could be a viable strategy to control MLR and DO in the biological reactor. The digital-based assessment and optimization tools developed in this study are expected to hold promise for application in broader environmental management efforts.
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Arsenic is a widespread carcinogen and an important etiological factor for lung cancer. Dysregulated miRNAs have been implicated in arsenic carcinogenesis and the mechanisms of arsenic-induced dysregulated miRNAs have not been fully elucidated. N6-methyladenosine (m6A) modification is known to modulate pri-miRNA processing. However, whether m6A-mediated pri-miRNA processing is involved in arsenic carcinogenesis is poorly understood. Here, we found that m6A modification was significantly increased in arsenite-transformed human bronchial epithelial BEAS-2B cells (0.5⯵M arsenite, 16 weeks). Meanwhile, METTL3 was significantly upregulated at week 12 and 16 during cell transformation. The proliferation, migration, invasion, and anchorage-independent growth of arsenite-transformed cells were inhibited by the reduction of m6A levels through METTL3 knockdown. Further experiments suggest that the oncogene miR-106b-5p is a potentially essential m6A target mediating arsenic-induced lung cancer. miR-106b-5p was observed to be upregulated after exposure to arsenite for 12 and 16 weeks, and the reduction of m6A levels caused by METTL3 knockdown inhibited miR-106b-5p maturation in arsenite-transformed cells. What's more, miR-106b-5p overexpression successfully rescued METTL3 knockdown-induced inhibition of the neoplastic phenotypes of transformed cells. Additionally, Basonuclin 2 (BNC2) was uncovered as a potential target of miR-106b-5p and downregulated by METTL3 via enhancing miR-106b-5p maturation. Additionally, the METTL3 inhibitor STM2457 suppressed neoplastic phenotypes of arsenite-transformed BEAS-2B cells by blocking pri-miR-106b methylation. These results demonstrate that m6A modification promotes the neoplastic phenotypes of arsenite-transformed BEAS-2B cells through METTL3/miR-106b-5p/BNC2 pathway, providing a new prospective for understanding arsenic carcinogenesis.
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In recent years, several ERP studies have investigated whether the early computation of agreement is permeable to the emotional content of words. Some studies have reported interactive effects of grammaticality and emotionality in the left anterior negativity (LAN) component, while others have failed to replicate these results. Furthermore, novel findings suggest that grammatical processing can elicit different neural patterns across individuals. In this study, we aim to investigate whether the interaction between grammaticality and emotionality is restricted to participants with a specific neural profile. Sixty-one female native speakers of Spanish performed an agreement judgment task in noun phrases composed of a determiner, a noun, and an unpleasant or neutral adjective that could agree or disagree in gender with the preceding noun. Our results support the existence of two different brain profiles: negative and positive dominance (individuals showing either larger LAN or larger P600 amplitudes in ungrammatical stimuli than in grammatical ones, respectively). Interestingly, the neural pattern of these two groups diverged at different points along the time course. Thus, the negative dominance group showed grammaticality effects as early as 200 ms, along with parallel and autonomous processing of grammaticality and emotionality at the LAN/N400 time window. Instead, for the positive dominance group an early interaction was found at around 200 ms, evidencing a grammaticality effect that emerged only for unpleasant words. Our findings confirm the role of individual differences in the interplay between grammar and emotion at the neural level and call for the inclusion of this perspective in studies on syntactic processing.
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All contemporary psychotherapies agree that (failing) emotion regulation is central to psychological disorders and that psychotherapy is about improving emotion regulation. In his research on the "emotion-laden" complex Jung put an emphasis on the role of failing emotion regulation in contributing to psychological disorders as well as to change in the process of psychotherapy, but he left this field of research and took a very different direction in favour of his archetype concept. Psychodynamic approaches generally argue that changes in emotion regulation are accomplished through corrective emotional experiences in the therapeutic relationship. Insights from affective neurosciences and attachment research have had a major influence on how the therapeutic relationship is constructed in contemporary psychodynamic approaches. There is a lack of similar developments in analytical psychology, which leads to substantial differences between the models of Jungian psychotherapy in contrast to other contemporary psychodynamic approaches. The implications of these differences for the practice of psychotherapy and especially the role of the therapeutic relationship are pointed out.
Toutes les psychothérapies actuelles s'accordent sur le fait que la régulation (défaillante) de l'émotion est au centre des désordres psychologiques et que la psychothérapie vise à améliorer la régulation de l'émotion. Dans sa recherche sur le « complexe à haute charge émotionnelle ¼, Jung a mis l'accent sur le rôle de la régulation défaillante de l'émotion comme participant aux désordres psychologiques ainsi qu'au changement dans le processus de psychothérapie. Mais il a abandonné ce champ de recherche et pris une direction très différente, y préférant son concept de l'archétype. Les approches psychodynamiques plaident généralement en faveur de l'idée que les changements dans la régulation de l'émotion sont atteints par les expériences émotionnelles corrective dans la relation thérapeutique. Des apports venant des neurosciences affectives et des recherches sur l'attachement ont eu une influence majeure sur comment la relation thérapeutique est construite dans les approches psychodynamiques actuelles. De tels développements font défaut dans la psychologie analytique, ce qui conduit à des différences considérables entre les modèles de psychothérapie jungienne en contraste avec les autres approches psychodynamiques actuelles. L'article souligne les conséquences de ces différences dans la pratique de la psychothérapie, tout particulièrement en ce qui concerne le rôle de la relation thérapeutique.
Todas las psicoterapias contemporáneas coinciden en que la regulación (fallida) de las emociones es central a los trastornos psicológicos y que la psicoterapia consiste en mejorar la regulación de las emociones. En su investigación sobre el complejo "de tonalidad afectiva", Jung hizo hincapié en el rol de una fallida regulación emocional en el desarrollo de los trastornos psicológicos, así como al cambio en el proceso de psicoterapia, pero abandonó este campo de investigación y tomó una dirección muy diferente en favor de su concepto de arquetipo. En general, los enfoques Psicodinámicos sostienen que los cambios en la regulación de las emociones se logran a través de experiencias emocionales correctivas en la relación terapéutica. Los conocimientos de las neurociencias afectivas y la investigación sobre el apego han tenido una gran influencia en cómo comprender la conformación de la relación terapéutica en los abordajes psicodinámicos contemporáneos. Faltan desarrollos similares en la psicología analítica, lo que conduce a diferencias sustanciales entre los modelos de la psicoterapia Junguiana en contraste con otros enfoques psicodinámicos contemporáneos. Se señalan las implicaciones de estas diferencias para la práctica de la psicoterapia y se destaca especialmente el rol de la relación terapéutica.
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Volatile N-nitrosamines (VNAs) are probably and possibly carcinogenic compounds to humans and widely found in processed meat products. In this study, the dietary exposure distribution and probabilistic cancer risk for main VNAs (N-nitrosodimethylamine, N-nitrosodiethylamine, N-nitrosomethylethylamine, N-nitrosopiperidine, N-nitrosodibutylamine, and N-nitrosodi-n-propylamine) were calculated by Monte Carlo simulation (MCS). The lowest and highest mean concentrations of these six NAs were related to NDBA and NDEA as 0.350 and 2.655 µg/kg, respectively. In the 95th percentile, chronic daily intake of total VNAs for children (3-14 years) and adults (15-70 years) were calculated to be 2.83 × 10-4 and 5.90 × 10-5 mg/kg bw/day, respectively. The cancer risk caused by the consumption of chicken sausages was less than 10-4, indicating low concern for the Iranian population. According to principal component analysis and heat map results, NDEA, NPIP and frying showed a positive correlation, highlighting that the variables follow a similar trend.
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In this work, we used photoinert anhydrous cerium(III) chloride, to form a transient charge-transfer (CT) complex with NXS (N-bromosuccinimide or NBS and N-iodosuccinimide or NIS) in acetonitrile. These transient CT complexes acted as a semi-heterogeneous photocatalyst. These complexes allowed the Ce(III) ions to absorb light, turning them into strong electron donors that transferred electrons to NXS. This created halide radicals from NXS radical anions, helping to turn N-propargylamides into oxazole aldehydes. Experiments with DMPO and spin-trapping showed that a radical-based mechanism followed a single electron transfer (SET) pathway. Notably, CeCl3 was reused after the reaction without much decomposition, as it was regenerated and separated through simple filtration.
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BACKGROUND: Melatonin, one of the most versatile hormones in the body, is well appreciated in managing circadian rhythm and for antioxidant properties. Produced in the pineal gland and within mitochondria, melatonin influences many physiologic processes through receptor mediated and direct effects. OBJECTIVE: The present investigation explores the evolving pharmacologic properties of melatonin, as well as current therapeutic uses in areas where mitigating oxidative stress, inflammation, and cellular senescence. This review also delves into novel therapeutic potential of melatonin and how current research is revealing a wide array of therapeutic promise in pain medicine. STUDY DESIGN: A systematic review of randomized controlled trials (RCTs) and observational studies was performed using various search engines focused on melatonin and its role in pain medicine. METHODS: The available literature on melatonin and pain medicine was reviewed. A comprehensive literature search of multiple databases from 1966 to July 2024, including manual searches of the bibliography of known review articles was performed. Quality assessment of the included studies and best evidence synthesis were incorporated into qualitative and quantitative evidence synthesis. OUTCOME MEASURES: The primary outcome measure was the proportion of patients receiving melatonin with significant relief and functional improvement of greater than 50% of at least 3 months. Duration of relief was categorized as short-term (less than 6 months) and long-term (greater than 6 months). RESULTS: Melatonin can affect intervertebral disc (IVD) health through the enhancement of survival and function of nucleus pulposus cells, primarily through activation of the ERK1/2 signaling pathway. Melatonin also influences the biochemical environment of the IVD by modulating inflammation and oxidative stress, crucial factors in the pathogenesis of disc degeneration. Melatonin has been shown to reduce senescence and promote autophagy within disc cells, vital for clearing out damaged cellular components, preserving cellular function and preventing deterioration associated with aging and degenerative diseases. LIMITATIONS: Despite the availability of multiple studies, the paucity of clinical pain related literature is considered as the major drawback. CONCLUSION: Based on the present systematic review, melatonin plays a critical role in sleep, but evolving studies have demonstrated substantive roles in mitigating degenerative conditions in various tissues, including IVD degeneration. Ongoing studies will better clarify the role of melatonin as a potential therapeutic agent, including the targeted delivery to various body regions.
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Degeneração do Disco Intervertebral , Melatonina , Melatonina/uso terapêutico , Humanos , Degeneração do Disco Intervertebral/tratamento farmacológico , Antioxidantes/uso terapêutico , Antioxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Manejo da Dor/métodosRESUMO
The electrocatalytic C-N coupling from CO2 and nitrate emerges as one of the solutions for waste upgrading and urea synthesis. In this work, we constructed electron-deficient Cu sites by the strong metal-polymer semiconductor interaction, to boost efficient and durable urea synthesis. In situ Raman spectroscopy identified the existence of electron-deficient Cu sites and was able to withstand electrochemical reduction conditions. Operando synchrotron-radiation Fourier transform infrared spectroscopy and theoretical calculations disclosed the vital role of electron-deficient Cu in adsorption and C-N coupling of oxygen-containing species. The electron-deficient Cu displayed a high urea yield rate of 255.0 mmol h-1 g-1 at -1.4 V versus the reversible hydrogen electrode and excellent electrochemical durability, superior than that of non-electron-deficient counterpart with conductive carbon material as the support. It can be concluded that the regulation of site electronic structure is more important than the optimization of catalyst conductive properties in the C-N coupling reactions.
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BACKGROUND/AIMS: Individual resistance to hypoxia is an important feature of the physiological profile of an organism, particularly in relation to lead-induced toxicity. METHODS: Our study focused on evaluating parameters of mitochondrial oxygen consumption, microsomal oxidation, intensity of lipoperoxidation processes and antioxidant defences in the liver of rats with low (LR) and high (HR) resistance to hypoxia to elucidate the mechanisms of action of L-arginine and the NO synthase inhibitor L-NNA before or after exposure to lead nitrate. RESULTS: Our study suggests that the redistribution of oxygen-dependent processes towards mitochondrial processes under the influence of the nitric oxide precursor amino acid L-arginine is an important mechanism for maintaining mitochondrial respiratory chain function during per os lead nitrate exposure (3.6 mg lead nitrate/kg bw per day for 30 days). Animals were given L-arginine at a dose of 600 mg/kg bw (i.p., 30 min) before and after exposure to lead nitrate or the NO synthase inhibitor Nω-nitro-L-arginine (L-NNA) at a dose of 35 mg/kg bw (i.p., 30 min) before and after exposure to lead nitrate. Our experiments demonstrated the efficacy of using lead nitrate to simulate lead-related toxic processes via Pb levels in liver tissue; we demonstrated significantly reduced levels of nitrites and nitrates, i.e. stable metabolites of the nitric oxide system, in both LR and HR animals. The effect of the amino acid L-arginine stabilised the negative effects of lead nitrate exposure in both groups of LR and HR rats. We observed the efficiency of mitochondrial energy supply processes and showed a greater vulnerability of NADH-dependent oxidation during lead nitrate exposure in the liver of HR rats. CONCLUSION: L-arginine initiated the processes of oxidation of NADH-dependent substrates in the LR group, whereas in the HR group this directionality of processes was more effective when the role of the nitric oxide system was reduced (use of L-NNA). Our study of key antioxidant enzyme activities in rat liver tissue during lead nitrate exposure revealed changes in the catalase-peroxidase activity ratio. We found different activities of antioxidant enzymes in the liver tissue of rats treated with lead nitrate and L-arginine or L-NNA, with a significant increase in GPx activity in the LR group when L-arginine was administered both before and after exposure to lead nitrate.
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Arginina , Hipóxia , Chumbo , Nitratos , Nitroarginina , Ratos Wistar , Animais , Arginina/metabolismo , Arginina/farmacologia , Nitratos/metabolismo , Masculino , Ratos , Nitroarginina/farmacologia , Hipóxia/metabolismo , Chumbo/toxicidade , Fígado/metabolismo , Fígado/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Mitocôndrias Hepáticas/metabolismo , Mitocôndrias Hepáticas/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Catalase/metabolismoRESUMO
INTRODUCTION: Aspirin is known for its therapeutic benefits in preventing strokes and relieving pain. However, it is toxic to some individuals, and the biological mechanisms causing toxicity are unknown. Limited literature is available on the role of glycine conjugation as the principal pathway in aspirin detoxification. Previous studies have quantified this two-step enzyme reaction as a singular enzymatic process. Consequently, the individual contributions of these enzymes to the kinetics remain unclear. AREAS COVERED: This review summarized the available information on the pharmacokinetics and detoxification of aspirin by the glycine conjugation pathway. Literature searches were conducted using Google Scholar and the academic journal databases accessible through the North-West University Library. Furthermore, the factors affecting interindividual variation in aspirin metabolism and what is known regarding aspirin toxicity were discussed. EXPERT OPINION: The greatest drawback in understanding the pharmacokinetics of aspirin is the limited information available on the substrate preference of the xenobiotic ligase (ACSM) responsible for activating salicylate to salicyl-CoA. Furthermore, previous pharmacokinetic studies did not consider the contribution of other substrates from the diet or genetic variants, to the detoxification rate of glycine conjugation. Impaired glycine conjugation might contribute to adverse health effects seen in Reye's syndrome and cancer.
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Context: The postacute heart failure (AHF) rehospitalization rate is attributed to persistent hemodynamic congestion despite clinical improvement. Peak atrial longitudinal strain (PALS), utilizing speckle tracking echocardiography technology, shows potential in post-AHF prognosis. Meanwhile, N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) remains a known biomarker of intracardiac congestion. Aims: This study aimed to determine the relationship between predischarge PALS and NT-proBNP as predictors of major adverse cardiac event (MACE) in patients after AHF hospitalization. Settings and Design: This study is a prospective cohort study, conducted in Prof. Dr. I G.N.G Ngoerah Hospital, Bali, Indonesia. Subjects and Methods: The study included hospitalized AHF patients, collecting demographic data, comorbidities, therapies, and echocardiographic measures before discharge. Predischarge PALS and NT-proBNP were taken within 24 h before discharge. The main outcome was MACE, defined as rehospitalization and cardiovascular mortality within 90 days. Statistical Analysis Used: Comparative statistical analyses was done using independent t-test for continuous variables (Mann-Whitney U test for variables with abnormal distribution) and Chi-squared tests. Receiver operating characteristic (ROC) used in determining optimal threshold values of predischarge PALS and NT-proBNP as a predictor of MACE. Kaplan-Meier curves were employed to gauge event-free survival differences between these cohorts. Then, independent Cox regression was used to identify the predictors of MACE. Results: The study enrolled 67 patients with varying ejection fraction (EF) (16 - heart failure with preserved ejection fraction, 10 - heart failure with mildly reduced ejection fraction, and 41 - heart failure with reduced ejection fraction; mean age: 56.88 ± 14.57 years). Over the 90-day follow-up, 21 patients (31.3%) encountered MACE. Both PALS (area under the curve [AUC] 0.816) and NT-proBNP (AUC 0.856) before discharge served as predictors of MACE. There was no significant AUC difference between ROC curves (area difference: 0.039, P = 0.553). The regression model highlighted that PALS and NT-proBNP level before discharge acted as independent predictors of MACE, irrespective of EF, average E/e', or estimated predischarge pulmonary capillary wedge pressure. Conclusions: Predischarge PALS is comparable to NT-proBNP levels as independent predictors of short-term MACE after AHF hospitalization.
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A series of Au(I) complexes containing unsymmetrical N-heterocyclic carbene (imidazolylidene and benzimidazolylidene) functionalized with a xyloside group and an alkyl moiety (methyl and mesityl) was prepared using efficient procedures from D-xylose. Their characterization was carried out in solution by multinuclear NMR, HR-MS spectrometry and cyclic voltammetry, as well as in the solid state by means of single crystal X-ray diffraction analysis for two of them. Evaluation of their ability to inhibit bacterial growth showed a preference for a Gram-positive strain, Staphylococcus aureus, over a Gram-negative strain, Pseudomonas aeruginosa.
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BACKGROUND: Abscisic acid (ABA) plays a crucial role in seed dormancy, germination, and growth, as well as in regulating plant responses to environmental stresses during plant growth and development. However, detailed information about the PYL-PP2C-SnRK2s family, a central component of the ABA signaling pathway, is not known in pitaya. RESULTS: In this study, we identified 19 pyrabactin resistance-likes (PYLs), 70 type 2 C protein phosphatases (PP2Cs), and 14 SNF1-related protein kinase 2s (SnRK2s) from pitaya. In pitaya, tandem duplication was the primary mechanism for amplifying the PYL-PP2C-SnRK2s family. Co-linearity analysis revealed more homologous PYL-PP2C-SnRK2s gene pairs located in collinear blocks between pitaya and Beta vulgaris L. than that between pitaya and Arabidopsis. Transcriptome analysis showed that the PYL-PP2C-SnRK2s gene family plays a role in pitaya's response to infection by N. dimidiatum. By spraying ABA on pitaya and subsequently inoculating it with N. dimidiatum, we conducted qRT-PCR experiments to observe the response of the PYL-PP2C-SnRK2s gene family and disease resistance-related genes to ABA. These treatments significantly enhanced pitaya's resistance to pitaya canker. Further protein interaction network analysis helped us identify five key PYLs genes that were upregulated during the interaction between pitaya and N. dimidiatum, and their expression patterns were verified by qRT-PCR. Subcellular localization analysis revealed that the PYL (Hp1879) gene is primarily distributed in the nucleus. CONCLUSION: This study enhances our understanding of the response of PYL-PP2C-SnRK2s to ABA and also offers a new perspective on pitaya disease resistance.
Assuntos
Ácido Abscísico , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Transdução de Sinais , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Estresse Fisiológico/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Perfilação da Expressão Gênica , Filogenia , Fosfoproteínas Fosfatases/genética , Fosfoproteínas Fosfatases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Família Multigênica , Proteína Fosfatase 2C/metabolismo , Proteína Fosfatase 2C/genéticaRESUMO
Despite several screening levels for NDMA reported in water, soil, air, and drugs, the human risk assessment using biomonitoring concentrations has not been performed. In this study, gender-specific exposure guidance values were determined in humans, then biomonitoring measurements in healthy Korean subjects (32 men and 40 women) were compared to the exposure guidance values to evaluate the current exposure level to NDMA. For the human risk assessment of NDMA, the gender-specific physiologically based pharmacokinetic (PBPK) model was developed in humans using proper physiological parameters, partition coefficients, and biochemical parameters. Using the PBPK model, a Monte Carlo simulation was performed to describe the magnitudes of inter-individual variability and uncertainty on the single model predictions. The PBPK modeling and Monte Carlo simulation allowed the estimation of the relationship between external dose and blood concentration for the risk assessment. The procedure for the human risk assessment was summarized as follows: (1) estimating a steady-state blood concentration (Cavg) corresponding to the daily no observed adverse effect level (NOAEL) administration in rats; (2) applying uncertainty factors (UFs) for deriving the human Cavg; (3) determining the exposure guidance values as screening criteria; (4) interpreting the human biomonitoring measurements by forward and reverse dosimetry approaches. Using the biomonitoring concentrations, current daily exposures to NDMA were estimated to be 3.95 µg/day/kg for men and 10.60 µg/day/kg for women, respectively. The result of the study could be used as a basis for implementing further risk management and regulatory decision-making for NDMA.