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1.
Heliyon ; 10(5): e27096, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38486720

RESUMEN

Small and micro enterprises are pivotal in national economic and social development. To foster their growth, managing their credit risks scientifically is crucial. This study starts by examining the credit information of these enterprises. We use imbalanced sample processing algorithms to ensure a balanced representation of minority-class samples. Then, a machine learning classifier is employed to identify key factors contributing to these enterprises' low credibility. Based on these factors, an XGBoost scoring card model is developed. The study reveals: firstly, the integration of the SMOTE algorithm with the XGBoost model exhibits certain performance advantages in handling imbalanced datasets; secondly, trustworthy financial information remains at the heart of crucial risk determinants; thirdly, the XGBoost scoring card model based on significant features effectively enhances the accuracy of credit risk assessment. These insights provide both theoretical references and practical tools for enhancing the robustness of small and micro enterprises, facilitating early warnings on credit risks, and refining financing efficiency.

2.
Clin Lung Cancer ; 25(3): 274-279, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38310035

RESUMEN

INTRODUCTION: Dual inhibition with a T-cell immunoreceptor with immunoglobulin and ITIM domains plus programmed death (ligand)-1 (PD[L]-1) inhibitors, with or without chemotherapy, is an emerging therapeutic strategy in metastatic non-small cell lung cancer (mNSCLC). The STAR-121 (NCT05502237) phase III, global, randomized, open-label study will investigate first-line domvanalimab (anti-TIGIT) and zimberelimab (anti-PD-1) plus chemotherapy versus pembrolizumab plus chemotherapy in mNSCLC with no actionable gene alterations. PARTICIPANTS AND METHODS: Approximately 720 participants (≥18 years old) with untreated mNSCLC and no EGFR and ALK mutations will be randomized into 3 groups (A, B, or C) in a 4:4:1 ratio and stratified by baseline PD-L1 expression (tumor cells <50% vs. ≥50%), histology (squamous vs. nonsquamous), and geographic region (East Asia vs. non-East Asia). Group A will receive domvanalimab 1200 mg plus zimberelimab 360 mg plus platinum-doublet chemotherapy (PT), group B will receive pembrolizumab 200 mg plus PT, and group C will receive zimberelimab 360 mg plus PT, every 3 weeks. Treatment will be administered until disease progression or intolerable toxicity. Dual primary endpoints are progression-free survival (by blinded independent central review [BICR]) and overall survival for group A versus B. Key secondary endpoints comprise overall response rate (by BICR), safety, and quality of life. Exploratory endpoints include efficacy and safety between groups A and C, pharmacokinetics, patient-reported outcomes, and biomarkers. CONCLUSION: Enrollment in the STAR-121 study commenced on October 12, 2022, and is currently ongoing with completion planned by September 2024. The study completion is expected by December 2027.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano
3.
Int J Mol Sci ; 25(4)2024 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-38396711

RESUMEN

Apple latent spherical virus (ALSV) is widely used as a virus-induced gene silencing (VIGS) vector for function genome study. However, the application of ALSV to soybeans is limited by the resistance of many varieties. In this study, the genetic locus linked to the resistance of a resistant soybean variety Heinong 84 was mapped by high-throughput sequencing-based bulk segregation analysis (HTS-BSA) using a hybrid population crossed from Heinong 84 and a susceptible variety, Zhonghuang 13. The results showed that the resistance of Heinong 84 to ALSV is controlled by two genetic loci located on chromosomes 2 and 11, respectively. Cleaved amplified polymorphic sequence (CAPS) markers were developed for identification and genotyping. Inheritance and biochemical analyses suggest that the resistance locus on chromosome 2 plays a dominant dose-dependent role, while the other locus contributes a secondary role in resisting ALSV. The resistance locus on chromosome 2 might encode a protein that can directly inhibit viral proliferation, while the secondary resistance locus on chromosome 11 may encode a host factor required for viral proliferation. Together, these data reveal novel insights on the resistance mechanism of Heinong 84 to ALSV, which will benefit the application of ALSV as a VIGS vector.


Asunto(s)
Glycine max , Secoviridae , Glycine max/genética , Vectores Genéticos , Enfermedades de las Plantas/genética
4.
IEEE Trans Biomed Circuits Syst ; 17(5): 1062-1073, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37549077

RESUMEN

This article presents a low-noise high-power-efficiency analog front-end (AFE) for capacitive-micromachined-ultrasonic transducers (CMUT). Implemented in 28-nm CMOS technology, the proposed AFE features three-stage continuous time-gain compensation (TGC) embedded in both trans-impedance amplifiers (TIAs) and an analog beamformer to provide a large compensation range with no extra power-consumption cost. The use of noise cancellation and capacitive feedback optimizes the noise performance of TIAs. The first stage of the TGC is built in the TIA by adjusting the positive and negative resistance loads, which are composed of voltage-controlled transistor arrays. An all-pass passive network is used as the delay unit of the analog beamformer, meanwhile achieving the second TGC stage. Phase shift for all frequency components in the ultrasound pass-band is manifested as a delay to the echoes. The third stage of the TGC is merged with a summing unit, which is a closed-loop amplifier with variable resistance feedback. The design takes into account the ability to handle large signals and power consumption, with TIA and beamforming operating at voltages of 2.5 V and 0.9 V, respectively. Experimental results show that the proposed AFE achieves a 2.11 pA/√Hz input-referred noise (IRN) at the 5 MHz center frequency of the echoes while consuming only 1.02 mW/channel. A total exponential TGC range of 60 dB with continuous ranges of 12 dB, 24 dB, and 24 dB assigned to three stages has been verified for this work.


Asunto(s)
Amplificadores Electrónicos , Transductores , Diseño de Equipo , Ultrasonografía/métodos , Ruido
5.
Mar Environ Res ; 190: 106057, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37422993

RESUMEN

Here, we studied the shipyard impacts on the distribution of PAHs and PCBs in the semi-enclosed Xiangshan Bay, an important mariculture zone in China. The results showed that the shipyard caused a pollution plume for PAHs but not for PCBs. As characteristic pollutants of oil leakage, the PAHs had concentrations of up to 55.82 ng L-1 in the water, 2235.04 ng g-1 in suspended particulate matter (SPM), and 1489.60 ng g-1 in sediment. The PAHs in water and SPM were dominated by phenanthrene and pyrene that were mostly derived from lubricant and diesel, while those in sediments were dominated by the high-molecular-weight PAHs, such as indeno[1,2,3-c,d]pyrene. In contrast, the PCBs concentrations reached up to 10.17 ng L-1, 79.72 ng g-1, and 124.33 ng g-1 in the seawater, SPM, and sediment samples, respectively, and they did not show spatial patterns affected by the shipyard. Moreover, the health risk assessment indicated that the shipyard discharge caused a substantial PAHs ecological risk to the adjacent and downstream water environment. Therefore, point source discharge in semi-enclosed bays should be paid close attention to due to the strong pollutant transport effect.


Asunto(s)
Bifenilos Policlorados , Hidrocarburos Policíclicos Aromáticos , Contaminantes Químicos del Agua , Bahías , Sedimentos Geológicos , Contaminantes Químicos del Agua/análisis , Hidrocarburos Policíclicos Aromáticos/análisis , Pirenos/análisis , Agua , Material Particulado , China , Monitoreo del Ambiente/métodos
6.
Environ Sci Technol ; 57(23): 8588-8597, 2023 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-37236912

RESUMEN

Edible seaweed consumption is an essential route of human exposure to complex organoarsenicals, including arsenosugars and arsenosugar phospholipids. However, the effects of gut microbiota on the metabolism and bioavailability of arsenosugars in vivo are unknown. Herein, two nori and two kelp samples with phosphate arsenosugar and sulfonate arsenosugar, respectively, as the predominant arsenic species, were administered to normal mice and gut microbiota-disrupted mice treated with the broad-spectrum antibiotic cefoperazone for 4 weeks. Following exposure, the community structures of the gut microbiota, total arsenic concentrations, and arsenic species in excreta and tissues were analyzed. Total arsenic excreted in feces and urine did not differ significantly between normal and antibiotic-treated mice fed with kelp samples. However, the total urinary arsenic of normal mice fed with nori samples was significantly higher (p < 0.05) (urinary arsenic excretion factor, 34-38 vs 5-7%), and the fecal total arsenic was significantly lower than in antibiotic-treated mice. Arsenic speciation analysis revealed that most phosphate arsenosugars in nori were converted to arsenobetaine (53.5-74.5%) when passing through the gastrointestinal tract, whereas a large portion of sulfonate arsenosugar in kelp was resistant to speciation changes and was excreted in feces intact (64.1-64.5%). Normal mice exhibited greater oral bioavailability of phosphate arsenosugar from nori than sulfonate arsenosugar from kelp (34-38 vs 6-9%). Our work provides insights into organoarsenical metabolism and their bioavailability in the mammalian gut.


Asunto(s)
Arsénico , Arsenicales , Microbioma Gastrointestinal , Algas Marinas , Humanos , Animales , Ratones , Disponibilidad Biológica , Arsenicales/orina , Algas Marinas/química , Ingestión de Alimentos , Mamíferos
7.
Sci Total Environ ; 867: 161493, 2023 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-36634779

RESUMEN

Antibiotics ubiquitously occur in soils and pose a potential threat to ecosystem health. Concurrently, urbanization and land-use intensification have transformed soil ecosystems, but how they affect antibiotic contamination remain largely unknown. Therefore, we profiled a broad-scale pattern of antibiotics in soil from agricultural lands and green spaces across urbanization gradients, and explored the hypothetical models to verify the effects of urbanization and land-use intensity on antibiotic contamination. The results showed that antibiotic concentrations and seasonality were higher in agricultural soil than in green spaces, which respectively showed linear or hump-shaped declines along with the increasing distance to urban centers. However, the response of antibiotic pollution to land-use intensity depended strongly on the urbanization level. More importantly, interactions between urbanization and land-use explained, on average, 59.6 % of the variation in antibiotic concentrations in soil across urbanization gradients. The proposed interactions can predict the non-linear changes in soil vulnerability to antibiotic contamination. Our study revealed that the urbanization can modulate the effects of land-use intensity on antibiotic concentration and seasonality in the soil environment, and that there is high stress on peri-urban soil ecosystems due to ongoing land-use changes arising from rapid urbanization processes.


Asunto(s)
Suelo , Urbanización , Humanos , Ecosistema , Antibacterianos , Agricultura , China
8.
Environ Monit Assess ; 195(2): 290, 2023 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-36629982

RESUMEN

Buildings are the main component of urban, and their three-dimensional spatial patterns affect meteorological conditions and consequently, the spatial distribution of gaseous pollutants (CO, NO, NO2, and SO2). This study uses the Jinan Central District as the study area and constructs a building spatial distribution index system based on DEM, urban road network, and building big data. ANOVA and spatial regression models were used to study the effects of building spatial distribution indicators on the distribution of gaseous pollutants along with their spatial heterogeneity. The results showed that (1) the effects of most of spatial distribution indexes of building on the concentration distribution of the four gaseous pollutants were significant, with one-way ANOVA outcomes reaching a significance level of 0.01 or more. The DEM mean, building altitude, and their interaction with other building spatial distribution indicators are important factors affecting the distribution of gaseous pollutants; The interaction of other three-factor indicators did not have a significant effect on the distribution of gaseous pollutant concentrations. (2) The spatial distribution of CO and NO2 is mainly influenced by the indicators of the spatial distribution of buildings in this study unit, and the effects of CO and NO2 concentrations in adjacent study units are the result of the action of stochastic factors. The NO and SO2 concentrations are influenced by the spatial distribution index of buildings in this study unit, the neighborhood homogeneity index, and NO and SO2 concentrations. (3) Spatial heterogeneity was observed in the effects of building spatial distribution indicators on the concentrations of different pollutants. The GWR models constructed using CO and NO concentrations and building spatial distribution indicators were well fitted globally and locally. The CO and NO concentrations were negatively correlated with the mean topographic elevation and NO concentrations were correlated with building density.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Ambientales , Contaminación del Aire/análisis , Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente/métodos , Gases , Dióxido de Nitrógeno , Material Particulado/análisis
9.
Environ Toxicol ; 38(3): 694-700, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36454668

RESUMEN

2,6-dichloro-1,4-benzoquinone (2,6-DCBQ), as an emerging disinfection by-product, has been frequently detected in waters, posing potential health risk on public health. Although some studies have pointed out that 2,6-DCBQ exposure can induce cytotoxicity, limited information is available for underlying mechanism for 2,6-DCBQ-induced cytotoxicity. To explore this mechanism, we assessed the levels of reactive oxygen species (ROS), acridine orange (AO) staining, and the mRNA transcriptions of genes (Chk2, Cdk2, Ccna, Ccnb and Ccne) involved in cell-cycle and genes (p53, bax, bcl-2 and caspase 3) involved in apoptosis in zebrafish embryo, after exposed to different concentrations (10, 30, 60, 90 and 120 µg/L) of 2,6-DCBQ for 72 h. Our results indicated that 2,6-DCBQ exposure induced ROS generation and cell apoptosis, and disturbed the mRNA transcription of genes related to cell cycle and apoptosis in zebrafish embryo. Moreover, we also found that 30 ~ 60 µg/L 2,6-DCBQ is the important transition from cell-cycle arrest to cell apoptosis. These results provided novel insight into 2,6-DCBQ-induced cytotoxicity.


Asunto(s)
Apoptosis , Pez Cebra , Animales , Especies Reactivas de Oxígeno/metabolismo , Pez Cebra/metabolismo , Apoptosis/genética , Puntos de Control del Ciclo Celular , ARN Mensajero/metabolismo
10.
Artículo en Inglés | MEDLINE | ID: mdl-36360680

RESUMEN

2,6-Dichlorobenzoquinone (2,6-DCBQ), as an emerging disinfection by-production, was frequently detected and identified in the drinking water; however, limited information is available for the toxic effect of 2,6-DCBQ on mice. In the present study, adult mice were used to assess the impact of 2,6-DCBQ via measuring the responses of antioxidant enzymes (superoxide dismutase (SOD) and catalase (CAT)), the key genes (Heme oxygenase-1 (HO-1), NADPH quinone oxidoreductase 1 (NQO1) and glutamate-L-cysteine ligase catalytic subunit (GCLC)) in the Nrf2-keap1 pathway, and lipid peroxidation (malonaldehyde, MDA). Our results clearly indicated that 2,6-DCBQ decreased the activities of SOD and CAT, repressed the transcriptional levels of key genes in Nrf2-keap1 pathway, further caused oxidative damage on mice. These results provided evidence for assessing the threat of 2,6-DCBQ on human.


Asunto(s)
Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Ratones , Humanos , Animales , Proteína 1 Asociada A ECH Tipo Kelch/genética , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/genética , Antioxidantes/metabolismo , Superóxido Dismutasa/metabolismo , Transcripción Genética
11.
Sci Rep ; 12(1): 14317, 2022 08 22.
Artículo en Inglés | MEDLINE | ID: mdl-35995949

RESUMEN

Based on nighttime light data and statistical data, this study calculated the level of urban-rural integration (URI) of Shandong province, researched spatial heterogeneity of URI levels by local spatial autocorrelation analysis, Geodetector, and geographically weighted regression, and analyzed its influencing factors and spatial heterogeneity. The results concluded that: (1) The spatial pattern of urban-rural integrated level is consistent with the level of regional economic development in Shandong province. The level of URI is higher along the Qingdao-Jinan railway and along the coast, whereas the level is lower in southwest Shandong and northwest Shandong. (2) The cities of Yantai and Weifang are High-High cluster areas of urban integration, and Jining is a Low-Low cluster area. The spatial agglomeration characteristics are not significant in other cities. (3) Among the main factors affecting URI, the explanatory power of the rural population with high school or technical secondary school education or above, the area of urban construction land, and the secondary and tertiary industry GDP to the spatial pattern of URI in Shandong province are 73.58%, 62.08%, and 58.66%, respectively. As the key factors, spatial heterogeneity, such as north-south differences, southwest-to-northeast differences, and east-west differences, is evident.


Asunto(s)
Población Rural , Regresión Espacial , China/epidemiología , Ciudades , Humanos , Análisis Espacial
12.
Biomed Chromatogr ; 36(11): e5473, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35916265

RESUMEN

Soyasaponin Bb is one of the bioactive oleanolic acid-type triterpenoid saponins mainly isolated from soybean. It possesses significant antithrombosis, hypolipidemic, anticancer, and antioxidant activities. However, the metabolic profiles of soyasaponin Bb are still unknown. The present study investigated the metabolites of soyasaponin Bb in plasma, bile, urine, and feces samples after intragastric administration using ultra-performance liquid chromatography coupled with quadrupole-time-of-flight-mass spectrometry, and its possible metabolic pathways were subsequently proposed. Using the metabolite profiling strategy, 11 metabolites were first identified from urine, plasma, bile, and feces of rats after intragastric administration of soyasaponin Bb. Hydroxylation and hydrolysis were the major metabolic pathways of soyasaponin Bb in rat. The results expand our knowledge of the metabolism of soyasaponin Bb, which could provide valuable information for better comprehension of future pharmacological research.


Asunto(s)
Ácido Oleanólico , Saponinas , Administración Oral , Animales , Antioxidantes/análisis , Bilis/química , Cromatografía Líquida de Alta Presión/métodos , Heces/química , Ácido Oleanólico/análisis , Ratas , Saponinas/análisis
13.
J Ethnopharmacol ; 297: 115535, 2022 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-35840059

RESUMEN

ETHNOPHARMACOLOGICAL REVELVANCE: Astragaloside IV, a glycoside derived from Astragalus membranaceus, has anti-renal fibrosis effects. However, its mechanism of action has not yet been fully elucidated. AIM OF THE STUDY: The purpose of this study was to investigate the anti-fibrotic effect of AS-IV and to clarify its underlying mechanism. MATERIALS AND METHODS: The network pharmacology method, molecular docking and surface plasmon resonance (SPR) was used to identify potential targets and pathways of AS-IV. A unilateral ischemia-reperfusion injury (UIRI) animal model, as well as TGF-ß1-induced rat renal tubular epithelial cells (NRK-52E) and renal fibroblasts (NRK-49F) were used to investigate and validate the anti-fibrotic activity and pharmacological mechanism of AS-IV. Network pharmacology was performed to construct a drug-target-pathway network. The anti-fibrosis effect of AS-IV was determined using hematoxylin-eosin (H&E) and MASSON staining, as well as immunostaining methods. qRT-PCR and western blotting were used to elucidate and validate the mechanism of AS-IV. RESULTS: Network pharmacology revealed that the PI3K/AKT pathway is an important pathway in AS-IV. AS-IV inhibited the expression of α-SMA, collagen I, and fibronectin in NRK-52E, NRK-49F, and UIRI rats, and reduced serum creatinine and blood urea nitrogen levels in UIRI rats. AS-IV inhibited AKT phosphorylation, blocked GSK-3ß phosphorylation, and restored GSK-3ß activity, which contributed to the degradation of ß-catenin, thereby preventing epithelial-mesenchymal transition (EMT). CONCLUSION: Astragaloside IV alleviated renal fibrosis through the AKT1/GSK-3ß pathway. In addition, our findings indicate that the network pharmacology method is a powerful tool for exploring the pharmacological mechanisms of drugs.


Asunto(s)
Enfermedades Renales , Fosfatidilinositol 3-Quinasas , Animales , Transición Epitelial-Mesenquimal , Fibrosis , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Enfermedades Renales/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Farmacología en Red , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Saponinas , Transducción de Señal , Factor de Crecimiento Transformador beta1/metabolismo , Triterpenos
14.
J Hazard Mater ; 437: 129350, 2022 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-35749896

RESUMEN

Antibiotics accumulate in soils via various agricultural activities, endangering soil biota that play fundamental roles in maintaining agroecosystem function. However, the effects of land-use heterogeneity on soil biota tolerance to antibiotic stresses are not well understood. In this study, we explored the relationships between antibiotic residues, bacterial communities, and earthworm populations in areas with different land-use types (forest, maize, and peanut fields). The results showed that antibiotic levels were generally higher in maize and peanut fields than in forests. Furthermore, land use modulated the effects of antibiotics on soil bacterial communities and earthworm populations. Cumulative antibiotic concentrations in peanut fields were negatively correlated with bacterial diversity and earthworm abundance, whereas no significant correlations were detected in maize fields. In contrast, antibiotics improved bacterial diversity and richness in forest soils. Generally, earthworm populations showed stronger tolerance to antibiotics than did soil bacterial communities. Agricultural land use differentially modified the responses of the soil bacterial community and earthworm population to antibiotic contamination, and earthworms might provide an alternative for controlling antibiotic contamination.


Asunto(s)
Oligoquetos , Suelo , Agricultura/métodos , Animales , Antibacterianos/farmacología , Bacterias , Biota , Oligoquetos/fisiología , Suelo/química , Microbiología del Suelo
15.
Phytomedicine ; 102: 154147, 2022 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-35567992

RESUMEN

BACKGROUND: Rhein, an anthraquinone compound, displays extensive antifibrotic effects; however, its potential mechanisms are not fully understood. In this study, we explored the underlying molecular mechanism of action of rhein. METHOD: An integrated network pharmacology and cell metabolomics approach was developed based on network pharmacology and bioinformatics method, and then successfully applied to speculate the potential targets of rhein and construct a rhein-target-metabolic enzyme-metabolite network. Thereafter, the antifibrotic mechanism of rhein was validated in TGF-ß- and oleic acid- induced HK-2 and NRK-52E cells in vitro as well as a unilateral ischemia-reperfusion injury Sprague-Dawley rat model. RESULTS: Based on the construction of the rhein-target-metabolic enzyme-metabolite network, we found that rhein played an antifibrotic role through the PPAR-α-CPT1A-l-palmitoyl-carnitine axis. In vitro experiments demonstrated that rhein effectively activated the expression of PPARα and its downstream proteins (CPT1A and ACOX1) to alleviate lipid accumulation and fibrosis development. In vivo experiments indicated that rhein attenuated renal fibrosis mainly by activating the fatty acid oxidation pathway and improving lipid metabolism. CONCLUSION: Taken together, our findings reveal that rhein is a novel agonist of PPARα, which contributes to its renoprotection through the regulation of the PPARα-CPT1A axis. Moreover, our study provides a novel insight into an integrated network pharmacology-metabolomics strategy for uncovering the pharmacological mechanisms of drugs from the system perspective.


Asunto(s)
Enfermedades Renales , PPAR alfa , Animales , Antraquinonas/farmacología , Fibrosis , Enfermedades Renales/tratamiento farmacológico , Metabolómica , Farmacología en Red , PPAR alfa/metabolismo , Ratas , Ratas Sprague-Dawley
16.
Arch Toxicol ; 96(2): 525-533, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35066598

RESUMEN

Gelsenicine, mainly isolated from Gelsemium elegans Benth., is one of the most toxic alkaloids. The lack of information on gelsenicine leads to inaccurate risk and poisoning evaluation. In this study, the metabolic profiling and toxicokinetics of gelsenicine was studied by ultra-high performance liquid chromatography (UPLC) with quadrupole time-of-flight (Q-ToF) and tandem mass spectrometry in rats after intraperitoneal (i.p., 40 µg/kg) and intragastric (i.g., 60 µg/kg) administration. After i.p. administration, the area under the curve (AUC), the apparent volume of distribution (V), and the total body clearance (CL/F) of gelsenicine in plasma were 3.79 µg/L h, 38.47 L/kg, and 11.87 mL/h kg, respectively. After i.g. administration, the corresponding values were slightly increased (5.49 µg/L h; 53.10 mL/kg, and 12.66 mL/h kg). The toxicokinetic results indicated that the hepatic first-pass effect was predominant after i.p. administration. The UPLC-Q-ToF-MS data revealed nine metabolites in plasma, urine, and bile which were largely obtained by demethylation, hydroxylation, acetylation and glycine conjugation. Metabolites were mainly excreted through urine and bile, most of which in urine was basically eliminated in 24 h. Molecular docking and liver microsome experiments further showed that gelsenicine was metabolized by cytochrome P450 3A4 and 3A5. Summarizing, the present study provides metabolic and toxicokinetic information on gelsenicine which in turn may help in future risk assessment and forensic identification after poisonings.


Asunto(s)
Citocromo P-450 CYP3A/metabolismo , Alcaloides Indólicos/farmacocinética , Animales , Área Bajo la Curva , Cromatografía Líquida de Alta Presión/métodos , Humanos , Alcaloides Indólicos/toxicidad , Masculino , Microsomas Hepáticos/metabolismo , Simulación del Acoplamiento Molecular , Ratas , Ratas Sprague-Dawley , Espectrometría de Masas en Tándem/métodos , Distribución Tisular , Toxicocinética
17.
Sci Total Environ ; 808: 152056, 2022 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-34861298

RESUMEN

Veterinary antibiotics are intensively and widely used in animal farming to treat or prevent diseases, as well as improve growth rate and feed efficiency. Animal manure is an important reservoir of veterinary antibiotics due to their high excretion rates, and thus manure application has been a critical source of veterinary antibiotics in agro-ecosystems. However, how veterinary antibiotics affect agroecosystem functions is still unclearly understood. In this study, we evaluated the effects of veterinary antibiotics on soil bacteria and earthworms in agricultural land with long-term manure application. The potential mechanisms of antibiotic-induced changes in crop yields were also revealed. The results showed that the increasing prevalence of veterinary antibiotics in agro-ecosystems inhibited earthworm abundance and bacterial diversity, and then decreased the bioavailability of soil nutrients. Furthermore, high-dose exposure to veterinary antibiotics improved the abundance of plant pathogenic bacteria. Analysis indicated that veterinary antibiotics played an important underlying role in driving the negative effects on peanut grain yields via disturbing microbe- and earthworm-mediated soil available nutrient contents. The direct toxicity effects of antibiotics on peanut relative yields were stronger than their indirect mediating effects. Additionally, the tradeoffs between antibiotics and agroecosystem functions increased at low exposure levels and then decreased at high exposure levels, which indicated the effects of antibiotics on agroecosystem functions were dose-dependent, except for earthworm biomass. Antibiotic contamination which will impose threats to agricultural sustainability was highlighted and should be paid more attention.


Asunto(s)
Oligoquetos , Animales , Antibacterianos/toxicidad , Bacterias , Ecosistema , Estiércol , Suelo
18.
Molecules ; 26(24)2021 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-34946723

RESUMEN

A series of carbon-coated LiMn1-xFexPO4 (x = 0, 0.1, 0.2, 0.3, 0.4) materials are successfully constructed using glucose as carbon sources via sol-gel processes. The morphology of the synthesized material particles are more regular and particle sizes are more homogeneous. The carbon-coated LiMn0.8Fe0.2PO4 material obtains the discharge specific capacity of 152.5 mAh·g-1 at 0.1 C rate and its discharge specific capacity reaches 95.7 mAh·g-1 at 5 C rate. Iron doping offers a viable way to improve the electronic conductivity and lattice defects of materials, as well as improving transmission kinetics, thereby improving the rate performance and cycle performance of materials, which is an effective method to promote the electrical properties.

19.
Ecotoxicol Environ Saf ; 227: 112883, 2021 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-34653941

RESUMEN

Arsenic (As) in the aquatic environment is a considerable environmental issue, previous studies have reported the toxic effects of low concentrations (≤ 150 µg/L) of As on fish. However, limited information is available regarding the impact of low levels of As on apoptosis. To evaluate this, zebrafish embryos were exposed to different concentrations (0, 25, 50, 75, and 150 µg/L) of As (arsenite [AsIII] and arsenate [AsV]) for 120 h. Our results indicated that low concentrations of AsIII exposure significantly inhibited the survival of zebrafish larvae, and significantly increased the transcription of Caspase-9 and Caspase-3, the ratio of Bax/Bcl-2 transcription, and protein levels of Caspase-3. In contrast, AsV decreased the ratios of Bax/Bcl-2 transcription and protein levels, as well as protein levels of Caspase-3. Our data demonstrated that AsIII and AsV exert different toxic effects, AsIII induced apoptosis via the mitochondrial pathway and the extrinsic pathway, while AsV induced apoptosis only via the mitochondrial pathway.


Asunto(s)
Arsénico , Animales , Apoptosis , Arseniatos/toxicidad , Arsénico/toxicidad , Larva , Pez Cebra
20.
Environ Sci Pollut Res Int ; 28(47): 66990-66997, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34244935

RESUMEN

Paspalum distichum L. was tested to evaluate their phytoremediation capacity for Hg contaminated soil through analyzing the dissipation of Hg in soil through a greenhouse study by using self-made rhizos box. Original soil samples were collected at Hg mining site with serious Hg contamination and a control site, respectively. Planting of P. distichum. L last for 60 days. Soil and plant samples were collected from four periods (0 d, 20 d, 40 d, and 60 d) and soil samples were collected from five different rhizosphere distance in horizontal direction (0-2 cm, 2-4cm, 4-6cm, 6-8cm, 8-10cm). The results showed that the presence of P. distichum. L significantly accelerated the Hg dissipation in soil compared with control. Hg concentration in the rhizospheric soil was affected by the plant growth period and the distance to the plant roots. The closer of soil to the root of P. distichum. L, the lower mercury concentration in soil. During the 60-day growing period, the concentrations of total Hg (THg) and methylmercury (MeHg) reduced by 45% and 64%, respectively, in the rhizosphere (0-2cm) of Hg contaminated soil. However, MeHg concentration was increased near the roots (0-4 cm) during the initial growing period (0-20 d), which may be attributed to the influence of root exudates. Root is the major part for Hg accumulation in P. distichum. L. The low ratio between Hg concentrations in underground and aboveground tissues indicated that it seemed difficult for Hg translocation from root to shoot. The highest THg (9.71 ± 3.09 µg·g-1) and MeHg (26.97 ± 0.98 ng·g-1) value in root of P. distichum. L were observed at the 20th day when P. distichum. L grown in Hg contaminated soil. The results of chemical fractions analyses showed that elemental Hg and residual Hg were the two major speciations followed by organic bound Hg in the Hg contaminated soil, which indicated the high bioavailability and ecological potential risk of Hg in Hg contaminated soil.


Asunto(s)
Mercurio , Compuestos de Metilmercurio , Paspalum , Contaminantes del Suelo , Monitoreo del Ambiente , Mercurio/análisis , Rizosfera , Suelo , Contaminantes del Suelo/análisis
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