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Boric acid-functionalized magnetic covalent organic frameworks (Fe3O4-TpBD-B) with large surface area and high porosity were prepared and applied for magnetic solid-phase extraction adsorbent of gentamicin from milk before UPLC-MS/MS detection. By utilizing a new HILIC chromatographic column with zwitterionic sulfoalkyl betaine stationary phase based on ethyl bridged hybrid particles (BEH), isomers of gentamicin (C1, C1a, and C2+C2a components). The developed methods demonstrated good linearity (R2 > 0.99), acceptable accuracy and good precision (<10 %), and low limit of quantitation (1.59 ng mLâ»1 for C1, 1.52 ng mLâ»1 for C1a and 2.72 ng mLâ»1 for C2+C2a). In addition, this method has been effectively applied to the analysis of real milk samples.
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Anti-partial epithelial-mesenchymal transition (pEMT) treatment of renal tubular epithelial cells (TECs) represents a promising therapeutic approach. Hyperuricemia nephropathy (HN) arises as a consequence of hyperuricemia (HUA)-induced tubulointerstitial fibrosis (TIF). Studies have suggested that the Ras homolog member A (RhoA)/Rho-associated kinase (ROCK) pathway is a crucial signaling transduction system in renal fibrosis. Fasudil, a RhoA/ROCK inhibitor, has exhibited the potential to prevent fibrosis progress. However, its impact on the pEMT of TECs in HN remains unclear. Here, an HN rat model and an uric acid (UA)-stimulated human kidney 2 (HK2) cell model were established and treated with Fasudil to explore its effects. Furthermore, the underlying mechanism of action involved in the attenuation of pEMT in TECs by Fasudil during HN was probed by using multiple molecular approaches. The HN rat model exhibited significant renal dysfunction and histopathological damage, whereas in vitro and in vivo experiments further confirmed the pEMT status accompanied by RhoA/ROCK pathway activation and oxidative stress in tubular cells exposed to UA. Notably, Fasudil ameliorated these pathological changes, and this was consistent with the trend of ROCK silencing in vitro. Mechanistically, we identified the Neh2 domain of nuclear factor erythroid 2-related factor 2 (Nrf2) as a target of Fasudil for the first time. Fasudil targets Nrf2 activation and antagonizes oxidative stress to attenuate the pEMT of TECs in HN. Our findings suggest that Fasudil attenuates oxidative stress-induced pEMT of TECs in HN by targeting Nrf2 activation. Thus, Fasudil is a potential therapeutic agent for the treatment of HN.
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1-(5-Isoquinolinasulfonil)-2-Metilpiperazina , Células Epiteliais , Transição Epitelial-Mesenquimal , Hiperuricemia , Nefropatias , Túbulos Renais , Fator 2 Relacionado a NF-E2 , Estresse Oxidativo , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Transição Epitelial-Mesenquimal/efeitos dos fármacos , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Hiperuricemia/tratamento farmacológico , Hiperuricemia/metabolismo , Humanos , Ratos , Masculino , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/patologia , Túbulos Renais/metabolismo , Linhagem Celular , Nefropatias/tratamento farmacológico , Nefropatias/patologia , Nefropatias/metabolismo , Quinases Associadas a rho/metabolismo , Quinases Associadas a rho/antagonistas & inibidores , Ratos Sprague-Dawley , Modelos Animais de Doenças , Transdução de Sinais/efeitos dos fármacosRESUMO
Mixed community microalgal wastewater treatment technologies have the potential to advance the limits of technology for biological nutrient recovery while producing a renewable carbon feedstock, but a deeper understanding of their performance is required for system optimization and control. In this study, we characterized the performance of a 568 m3·day-1 Clearas EcoRecover system for tertiary phosphorus removal (and recovery as biomass) at an operating water resource recovery facility (WRRF). The process consists of a (dark) mix tank, photobioreactors (PBRs), and a membrane tank with ultrafiltration membranes for the separation of hydraulic and solids residence times. Through continuous online monitoring, long-term on-site monitoring, and on-site batch experiments, we demonstrate (i) the importance of carbohydrate storage in PBRs to support phosphorus uptake under dark conditions in the mix tank and (ii) the potential for polyphosphate accumulation in the mixed algal communities. Over a 3-month winter period with limited outside influences (e.g., no major upstream process changes), the effluent total phosphorus (TP) concentration was 0.03 ± 0.03 mg-P·L-1 (0.01 ± 0.02 mg-P·L-1 orthophosphate). Core microbial community taxa included Chlorella spp., Scenedesmus spp., and Monoraphidium spp., and key indicators of stable performance included near-neutral pH, sufficient alkalinity, and a diel rhythm in dissolved oxygen.
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Microalgas , Fósforo , Águas Residuárias , Microalgas/metabolismo , Águas Residuárias/química , Eliminação de Resíduos Líquidos/métodos , Biomassa , Purificação da Água/métodosAssuntos
Neoplasias Renais , Veia Cava Inferior , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/epidemiologia , Neoplasias Renais/patologia , Neoplasias Renais/complicações , Fatores de Risco , Estudos Retrospectivos , Estudos de Casos e Controles , Feminino , Masculino , Incidência , Trombose Venosa/etiologiaRESUMO
Illustrating the biodegradation processes of multi-component volatile organic compounds (VOCs) will expedite the implication of biotechnology in purifying industrial exhaust. Here, performance shifts of microbial fuel cell and biotrickling filter combined system (MFC-BTF) are investigated for removing single and dual components of toluene and benzene. Synchronous removal of toluene (95 %) and benzene (97 %) are achieved by MFC-BTF accompanied with the output current of 0.41 mA. Elevated content of extracellular polymeric substance facilitates the mass transfer of benzene with the presence of toluene. Strains of Bacteroidota, Proteobacteria and Chloroflexi contribute to the removal of dual components VOCs. Empty bed reaction time and the VOCs concentration are the important factors influencing their dissolution in the system. The biodegradation of toluene and benzene proceeds with 2-hydroxymuconic semialdehyde and o-hydroxybenzoic acid as the main intermediates. These results provide a comprehensive understanding of multi-component VOCs removal by MFC-BTF and guide the system design, optimization, and scale-up.
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Benzeno , Biodegradação Ambiental , Fontes de Energia Bioelétrica , Tolueno , Tolueno/metabolismo , Benzeno/metabolismo , Filtração/métodos , Compostos Orgânicos Voláteis/metabolismo , Gases/metabolismoRESUMO
Designing modified therapeutic antibodies with enhanced FcRn-binding affinity holds promise in the extension of circulation half-lives and potential refinement of pharmacokinetics. During the development of these new-generation therapeutic antibodies, FcRn binding affinity of IgGs is emphasized and monitored as a critical quality attribute (CQA), alongside other critical assessments including titer and aggregation level. However, the traditional workflow for assessing the overall quality of expressed IgGs in harvested cell culture fluid (HCCF) is blamed to be cumbersome and time-consuming. This study presents an integrated methodology for the rapid quality assessment of IgGs in HCCF by selectively extracting IgGs with favorable high FcRn affinity for subsequent analysis using size exclusion chromatography (SEC). The approach utilizes innovative adsorbents known as FcRn immobilized hydrophilic magnetic graphene (MG@PDA@PAMAM-FcRn) in a magnetic solid-phase extraction (MSPE) process. To simulate the in vivo binding dynamics, MSPE binding and dissociation was performed at pH 6.0 and 7.4, respectively. The composite have demonstrated enhanced extraction efficiency and impurity removal ability in comparison to commercially available magnetic beads. The SEC monomer peak area value provides the output of this method, the ranking of which enabled the facile identification of superior HCCF samples with high overall quality of IgG. Optimization of MSPE parameters was performed, and the method was validated for specificity, precision, sensitivity, and accuracy. The proposed method exhibited an analytical time of 0.6 h, which is 7-22 times shortened in comparison to the conventional workflow.
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Grafite , Receptores Fc , Receptores Fc/química , Receptores Fc/metabolismo , Imunoglobulina G/química , Meia-Vida , Antígenos de Histocompatibilidade Classe I/química , Antígenos de Histocompatibilidade Classe I/metabolismo , Técnicas de Cultura de Células , Fenômenos MagnéticosRESUMO
Resource recovery from wet organic wastes can support circular economies by creating financial incentives to produce renewable energy and return nutrients to agriculture. In this study, we characterize the potential for hydrothermal liquefaction (HTL)-based resource recovery systems to advance the economic and environmental sustainability of wastewater sludge, FOG (fats, oils, and grease), food waste, green waste, and animal manure management through the production of liquid biofuels (naphtha, diesel), fertilizers (struvite, ammonium sulfate), and power (heat, electricity). From the waste management perspective, median costs range from -193 $·tonne-1 (FOG) to 251 $·tonne-1 (green waste), and median carbon intensities range from 367 kg CO2 eq·tonne-1 (wastewater sludge) to 769 kg CO2 eq·tonne-1 (green waste). From the fuel production perspective, the minimum selling price of renewable diesel blendstocks are within the commercial diesel price range (2.37 to 5.81 $·gal-1) and have a lower carbon intensity than petroleum diesel (101 kg CO2 eq·MMBTU-1). Finally, through uncertainty analysis and Monte Carlo filtering, we set specific targets (i.e., achieve wastewater sludge-to-biocrude yield >0.440) for the future development of hydrothermal waste management system components. Overall, our work demonstrates the potential of HTL-based resource recovery systems to reduce the costs and carbon intensity of resource-rich organic wastes.
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Eliminação de Resíduos , Águas Residuárias , Animais , Esgotos , Dióxido de Carbono/análise , Alimentos , Biocombustíveis/análise , CarbonoRESUMO
Recently, the diffractive deep neural network (D2NN) has demonstrated the advantages to achieve large-scale computational tasks in terms of high speed, low power consumption, parallelism, and scalability. A typical D2NN with cascaded diffractive elements is designed for monochromatic illumination. Here, we propose a framework to achieve the multi-wavelength D2NN (MW-D2NN) based on the method of weight coefficients. In training, each wavelength is assigned a specific weighting and their output planes construct the wavelength weighting loss function. The trained MW-D2NN can implement the classification of images of handwritten digits at multi-wavelength incident beams. The designed 3-layers MW-D2NN achieves a simulation classification accuracy of 83.3%. We designed a 1-layer MW-D2NN. The simulation and experiment classification accuracy are 71.4% and 67.5% at RGB wavelengths. Furthermore, the proposed MW-D2NN can be extended to intelligent machine vision systems for multi-wavelength and incoherent illumination.
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Germacrone, a kind of natural sesquiterpenoid compound, has been reported to exhibit many pharmacological properties, especially the anticancer effect. Many in vitro experiments have been performed on various cancer cell lines, trying to explore their anticancer mechanism. Aiming at investigating the anticancer effect of germacrone, this article reviews the extant information on existing literature about germacrone-related studies. The anticancer mechanisms and clinical usages of germacrone are summarized. Literature databases (such as PubMed and CNKI) are used to search the current studies and experimental research about the anticancer effect information of germacrone. Anticancer mechanism of germacrone includes cell cycle arrest inducing, programmed cell death (apoptosis, autophagy, pyroptosis and ferroptosis) inducing, and estrogen-related genes mediating. Structural modification and analogue design are worthy of further study in the future.
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Antineoplásicos , Curcuma , Humanos , Proliferação de Células , Curcuma/química , Antineoplásicos/farmacologia , Pontos de Checagem do Ciclo Celular , ApoptoseRESUMO
OBJECTIVES: Per- and polyfluoroalkyl substances (PFAS) are man-made chemicals that are widely used in various products. PFAS are characterized by their fluorinated carbon chains that make them hard to degrade and bioaccumulate in human and animals. Toxicological studies have shown PFAS toxic effects: cytotoxicity, immunotoxicity, neurotoxicity, and reproductive toxicity. However, it is still unclear how the structures of PFAS, such as carbon-chain length and functional groups, determine their reproductive toxicity. METHODS AND RESULTS: By using a mouse-oocyte-in-vitro-maturation (IVM) system, we found the toxicity of two major categories of PFAS, perfluoroalkyl carboxylic acid (PFCA) and perfluoroalkyl sulfonic acid (PFSA), is elevated with increasing carbon-chain length and the inclusion of the sulfonate group. Specifically, at 600 µM, perfluorohexanesulfonic acid (PFHxS) and perfluorooctanesulfonic acid (PFOS) reduced the rates of both germinal-vesicle breakdown (GVBD) and polar-body extrusion (PBE) as well as enlarged polar bodies. However, the shorter PFSA, perfluorobutanesulfonic acid (PFBS), and all PFCA did not show similar adverse cytotoxicity. Further, we found that 600 µM PFHxS and PFOS exposure induced excess reactive oxygen species (ROS) and decreased mitochondrial membrane potential (MMP). Cytoskeleton analysis revealed that PFHxS and PFOS exposure induced chromosome misalignment, abnormal F-actin organization, elongated spindle formation, and symmetric division in the treated oocytes. These meiotic defects compromised oocyte developmental competence after parthenogenetic activation. CONCLUSIONS: Our study provides new information on the structure-toxicity relationship of PFAS.
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Fluorocarbonos , Técnicas de Maturação in Vitro de Oócitos , Animais , Humanos , Alcanossulfonatos , Fluorocarbonos/toxicidade , Fluorocarbonos/químicaRESUMO
BACKGROUND: Beta2-microglobulin, a novel marker of kidney function, predicts kidney failure and mortality in the general population. However, few studies have evaluated the association of serum ß2-MG level with clinical outcome in maintenance hemodialysis (MHD) patients. METHODS: This prospective cohort study enrolled 303 MHD patients to investigate the factors related to ß2-MG and its relationship to mortality in MHD patients. Multivariate linear regression analysis was used to examine the factors related to ß2-MG level. Multivariable Cox regression was used to calculate the hazard ratios for ß2-MG on all-cause and cardiovascular mortality. RESULTS: The median value of serum ß2-MG was 44.6 mg/L (interquartile range 37.60-50.40 mg/L). During the follow-up period of 24 months, there were 48 all-cause deaths (23.0%), including 36 cardiovascular causes (75.0% of all deaths). Multiple linear regression showed that dialysis duration, serum creatinine, and alkaline phosphatase were independent predictors of serum ß2-MG level. Kaplan-Meier analysis revealed that mortality in MHD patients was significantly higher in low albumin patients with ß2-MG > 44.6 mg/L. Cox regression analysis showed that ß2-MG was a significant predictor of all-cause mortality (HR = 1.122, 95% CI: 1.058-1.190, ð < 0.001) and cardiovascular mortality (HR = 1.145, 95%CI: 1.065-1.123, P < 0.001) in MHD patients with low albumin level after adjusting for confounding factors. However, our results showed that serum ß2-MG was not associated with mortality in MHD patients with normal albumin level. CONCLUSION: These results are supportive of the potential role of the serum ß2-MG level as a predictor of mortality in MHD patients with low albumin.
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Doenças Cardiovasculares , Falência Renal Crônica , Humanos , Diálise Renal/efeitos adversos , Falência Renal Crônica/complicações , Estudos Prospectivos , Doenças Cardiovasculares/etiologia , AlbuminasRESUMO
The Siberian roe deer (Capreolus pygargus) is a widely distributed ungulate in northeast China. Due to a series of human disturbance activities such as large-scale forest cutting, deforestation and reclamation, road construction in the past, the appearance and internal structure of forest vegetation in the habitat of Siberian roe have changed significantly. At the same time, Siberian roe population had a series of ecological adaptation responses in the face of such habitat changes. Therefore, two typical vegetation types with differences were selected in the Muling Forest, China. We used nutritional ecology and microbial metagenomic analysis techniques to compare the nutritional selection strategy and the structure and functional characteristics of faecal microbiota of Siberian roe groups in two vegetation types. The results showed that the α diversity of dietary and gut microbes of deer in Natural Forest was higher than that in Plantation Forest. However, the gut microbes of the Plantation Forest group contained more unique enzymes in the functional pathways of carbon metabolism and biosynthesis of amino acids. This study suggests that habitat type is associated with plant community composition, and contributes to changes in the intake proportions of major macronutrients by altering the availability, quality, and composition of certain edible plants. Feeding behaviour may be an important regulatory factor of gut microbiota structure and function of deer. The metabolic function of gut microbiota to different nutrients may affect the microbial community structure. Therefore, our results suggest that the gut microbes of Siberian roe may have coevolved with their diets, and reflect the adaptability of deer populations to environmental changes (e.g., vegetation type). Our study provides new insights into how spatial heterogeneity affects nutrition and microecosystems by describing the interactions among the environment, diet, and symbiotic gut microbes in wild ungulates.
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Cervos , Microbioma Gastrointestinal , Microbiota , Humanos , Animais , Cervos/fisiologia , Microbioma Gastrointestinal/genética , Florestas , Dieta/veterináriaRESUMO
BACKGROUND: Anemia is a common consequence of chronic kidney disease (CKD). Red cell distribution width (RDW) and mean corpuscular volume (MCV) are principally used for differential diagnosis of anemia. Limited evidence is available for its prognostic value for mortality in hemodialysis (HD) patients. We aimed to definite the relationship between RDW and MCV and mortality in HD patients. METHOD: This cohort study examined all-cause and cardiovascular (CV) mortality with 181 maintenance HD patients from February 2015. Patients were divided into four groups according to the median of RDW and MCV. Pearson analysis was conducted to determine the related factors of RDW and MCV. The independent association of RDW and MCV with mortality was examined with Kaplan-Meier curve and Cox regression analysis. RESULTS: This study included 181 HD patients for a median follow-up of 71 months. We found RDW was positively related to neutrophil count, C-reaction protein, and ferritin, while negatively related to hemoglobin, albumin, and creatinine. Only neutrophil count and ferritin were significantly related to MCV in this study. In the multivariate Cox regression analysis, the high RDW group was associated with higher risk of all-cause mortality (odds ratio, 3.787; 95% confidence interval, 1.037 to 13.834; p = 0.044). The relationship between RDW and MCV and CV mortality was not significant. CONCLUSIONS: RDW could emerge as an additive risk factor for all-cause mortality in maintenance HD patients, independent of other factors. An absolute value of MCV to predict mortality and the underlying pathophysiologic mechanisms should be confirmed in the future.
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Anemia , Índices de Eritrócitos , Humanos , Índices de Eritrócitos/fisiologia , Estudos de Coortes , Prognóstico , Diálise RenalRESUMO
With the successful development in computer vision, building a deep convolutional neural network (CNNs) has been mainstream, considering the character of shared parameters in a convolutional layer. Stacking convolutional layers into a deep structure improves performance, but over-stacking also ramps up the needed resources for GPUs. Seeing another surge of Transformers in computer vision, the issue has aroused severely. A resource-hungry model is hardly implemented for limited hardware or single-customers-based GPU. Therefore, this work focuses on these concerns and proposes an efficient but robust backbone, which equips with channel and spatial direction attentions, so the attentions help to expand receptive fields in shallow convolutional layers and pass the information to every layer. An attention-boosted network based on already efficient CNNs, Universal Pixel Attention Networks (UPANets), is proposed. Through a series of experiments, UPANets fulfil the purposes of learning global information with less needed resources and outshine many existing SOTAs in CIFAR-{10, 100}.
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Hydrogen sulfide (H2S), an endogenous gaseous signaling transmitter, has gained recognition for its physiological effects. In this review, we aim to summarize and discuss existing studies about the roles of H2S in renal functions and renal disease as well as the underlying mechanisms. H2S is mainly produced by four pathways, and the kidneys are major H2S-producing organs. Previous studies have shown that H2S can impact multiple signaling pathways via sulfhydration. In renal physiology, H2S promotes kidney excretion, regulates renin release and increases ATP production as a sensor for oxygen. H2S is also involved in the development of kidney disease. H2S has been implicated in renal ischemia/reperfusion and cisplatin-and sepsis-induced kidney disease. In chronic kidney diseases, especially diabetic nephropathy, hypertensive nephropathy and obstructive kidney disease, H2S attenuates disease progression by regulating oxidative stress, inflammation and the renin-angiotensin-aldosterone system. Despite accumulating evidence from experimental studies suggesting the potential roles of H2S donors in the treatment of kidney disease, these results need further clinical translation. Therefore, expanding the understanding of H2S can not only promote our further understanding of renal physiology but also lay a foundation for transforming H2S into a target for specific kidney diseases.
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Nefropatias Diabéticas , Sulfeto de Hidrogênio , Insuficiência Renal Crônica , Nefropatias Diabéticas/tratamento farmacológico , Humanos , Sulfeto de Hidrogênio/metabolismo , Rim , Estresse Oxidativo , Insuficiência Renal Crônica/tratamento farmacológicoRESUMO
FcγRIIIa-binding affinity is one of the key factors to ensure the efficacy of many antitumor therapeutic antibodies, which should be monitored along with the titer, protein aggregation, and other critical quality attributes. The conventional workflow for the quality assessment of therapeutic antibodies in harvested cell culture fluid (HCCF) is time-consuming and costly nevertheless. In this study, a tractable method was established for rapid quality assessment of a HCCF sample through differentially extracting IgG with different FcγRIIIa affinity levels using FcγRIIIa-immobilized magnetic microspheres, followed by size exclusion chromatography (SEC) to determine the amount and monomer percentage of IgGs in the preceding eluate. FcγRIIIa-immobilized magnetic microspheres with polydopamine (PDA) and hydrophilic dendrimer (PAMAM) coating (denoted as Fe3O4@PDA@PAMAM-FcγRIIIa) were synthesized for the first time as magnetic adsorbents. The PDA cladding endowed the composites with good chemical stability in acidic elution buffer, and the PAMAM dendrimer empowered the composites of high ligand immobilization capacity and hydrophilic surface. The labile FcγRIIIa was immobilized under mild conditions. By directly applying a simple magnetic solid phase extraction procedure to treat HCCF, favored IgG species with high FcγRIIIa affinity would be selectively captured by Fe3O4@PDA@PAMAM-FcγRIIIa composites for subsequent SEC analysis. The monomer peak area value in SEC, which was set as the read-out of the proposed method, correlated directly with the theoretical overall quality of standard-spiked HCCF samples.
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Fenômenos Magnéticos , Magnetismo , Técnicas de Cultura de Células , Imunoglobulina G , MicroesferasRESUMO
BACKGROUND: Depression is one of the most important psychiatric disorders in chronic kidney disease patients who undergo maintenance hemodialysis (MHD). Previous studies have shown that low-grade inflammation is involved in the progression of depressive symptoms. The neutrophil-to-lymphocyte ratio (NLR) is an inflammatory marker that is inexpensive and easy to measure. However, the association between NLR and depression symptoms in MHD patients has not been examined. METHODS: In this single-center, cross-sectional study, we included 160 patients undergoing MHD. The Patient Health Questionnaire-9 (PHQ-9) was used to assess depressive symptoms. NLR was calculated as the ratio of neutrophils to lymphocytes. Multinomial logistic regression and multivariate linear regression analyses were used to examine the association between NLR and depressive symptoms in MHD patients. RESULTS: Depressive symptoms were detected in 36.7% of the 160 MHD patients. Multinomial logistic regression showed that NLR was a significant predictor of mild (odds ratio [OR]: 1.383, 95% confidence interval [CI]: 1.015-1.884, p = 0.04) and moderate/moderately severe depressive symptoms (OR: 1.441, 95% CI: 1.017-2.042, p = 0.04) in MHD patients, adjusted for age, sex, Kt/V, dialysis duration, history of kidney transplantation, history of hypertension, and Charlson comorbidity index score. In addition, multivariate linear regression analysis showed that NLR was an independent influencing factor for PHQ-9 score in MHD patients, after adjusting for confounding factors. CONCLUSIONS: These findings suggest that NLR can be used as a biomarker for predicting depressive symptoms in MHD patients.
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Depressão , Neutrófilos , Biomarcadores , Estudos Transversais , Depressão/diagnóstico , Humanos , Linfócitos/citologia , Diálise Renal/psicologiaRESUMO
In mammalian species, females are born with a number of oocytes exceeding what they release via ovulation. In humans, an average girl is born with over a thousand times more oocytes than she will ovulate in her lifetime. The reason for having such an excessive number of oocytes in a neonatal female ovary is currently unknown. However, it is well established that the oocyte number decreases throughout the entire lifetime until the ovary loses them all. In this review, data published in the past 80 years were used to assess the current knowledge regarding the changing number of oocytes in humans and mice, as well as the reported factors that contribute to the decline of oocyte numbers. Briefly, a collective estimation indicates that an average girl is born with approximately 600,000 oocytes, which is 2,000 times more than the number of oocytes that she will ovulate in her lifetime. The oocyte number begins to decrease immediately after birth and is reduced to half of the initial number by puberty and almost zero by age 50 years. Multiple factors that are either intrinsic or extrinsic to the ovary contribute to the decline of the oocyte number. The inflammation caused by the ovulatory luteinizing hormone surge is discussed as a potential contributing factor to the decline of the oocyte pool during the reproductive lifespan.
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Core-shell structured magnetic covalent-organic frameworks (Fe3O4@TaTp) were facilely synthesized based on one-step functionalization at room temperature and applied for magnetic solid-phase extraction of okadaic acid from seawater and shellfish prior to LC-MS/MS detection. Parameters, including adsorbent amount, extraction time, desorption solution, and desorption time which could affect the extraction efficiency, were respectively investigated. The developed methods demonstrated good linearity (R2 > 0.99), acceptable accuracy and good precision (<15%), and low limit of detection (0.5 pg·mL-1 for seawater and 0.04 µg·kg-1 for shellfish). The amount of the material used (1 mg for seawater and 5 mg for shellfish) and the time required (4 min for seawater and 15 min for shellfish) for extracting analyte from 5 mL of seawater and 2 g of shellfish are both greatly shortened compared with the previous reports. In addition, we successfully applied this method to real sample analysis.
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Estruturas Metalorgânicas , Adsorção , Cromatografia Líquida , Limite de Detecção , Fenômenos Magnéticos , Ácido Okadáico/análise , Água do Mar , Frutos do Mar/análise , Extração em Fase Sólida , Espectrometria de Massas em TandemRESUMO
The gasotransmitter hydrogen sulfide (H2S) plays important physiological and pathological roles in the cardiovascular system. However, the involvement of H2S in recovery from uremic cardiomyopathy (UCM) remains unclear. This study aimed to determine the therapeutic efficacy and elucidate the underlying mechanisms of H2S in UCM. A UCM model was established by 5/6 nephrectomy in 10-week-old C57BL/6 mice. Mice were treated with sodium hydrosulfide (NaHS, H2S donor), L-cysteine [L-Cys, cystathionine gamma-lyase (CSE) substrate], and propargylglycine (PPG, CSE inhibitor). Treatment of H9C2 cardiomyocytes utilized different concentrations of uremic serum, NaHS, PPG, and PI3K inhibitors (LY294002). Mouse heart function was assessed by echocardiography. Pathological changes in mouse myocardial tissue were identified using hematoxylin and eosin and Masson's trichrome staining. Cell viability was assessed using the Cell Counting Kit-8. The protein expressions of CSE, p-PI3K, PI3K, p-PKB, PKB, p-mTOR, mTOR, and autophagy-related markers (Beclin-1, P62, and LC3) were detected using Western blotting. We found that NaHS and L-Cys treatment attenuated myocardial disarray, fibrosis, and left ventricular dysfunction in UCM mice. These abnormalities were further aggravated by PPG supplementation. Enhanced autophagy and decreased phosphorylation of PI3K, PKB, and mTOR protein expression by UCM were altered by NaHS and L-Cys treatment. In vitro, uremic serum increased overactive autophagy and decreased the phosphorylation levels of PI3K, PKB, and mTOR in cardiomyocytes, which was substantially exacerbated by endogenous H2S deficiency and attenuated by pre-treatment with 100 µm NaHS. However, the protective effects of NaHS were completely inhibited by LY294002. These findings support a protective effect of H2S exerted against UCM by reducing overactive autophagy through activation of the PI3K/PKB/mTOR pathway.