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Cancer development is driven by an accumulation of a small number of driver genetic mutations that confer the selective growth advantage to the cell, while most passenger mutations do not contribute to tumor progression. The identification of these driver genes responsible for tumorigenesis is a crucial step in designing effective cancer treatments. Although many computational methods have been developed with this purpose, the majority of existing methods solely provided a single driver gene list for the entire cohort of patients, ignoring the high heterogeneity of driver events across patients. It remains challenging to identify the personalized driver genes. Here, we propose a novel method (PDRWH), which aims to prioritize the mutated genes of a single patient based on their impact on the abnormal expression of downstream genes across a group of patients who share the co-mutation genes and similar gene expression profiles. The wide experimental results on 16 cancer datasets from TCGA showed that PDRWH excels in identifying known general driver genes and tumor-specific drivers. In the comparative testing across five cancer types, PDRWH outperformed existing individual-level methods as well as cohort-level methods. Our results also demonstrated that PDRWH could identify both common and rare drivers. The personalized driver profiles could improve tumor stratification, providing new insights into understanding tumor heterogeneity and taking a further step toward personalized treatment. We also validated one of our predicted novel personalized driver genes on tumor cell proliferation by vitro cell-based assays, the promoting effect of the high expression of Low-density lipoprotein receptor-related protein 1 (LRP1) on tumor cell proliferation.
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Biología Computacional , Mutación , Neoplasias , Medicina de Precisión , Humanos , Neoplasias/genética , Biología Computacional/métodos , Medicina de Precisión/métodos , Perfilación de la Expresión Génica/métodos , Regulación Neoplásica de la Expresión Génica/genética , Modelos Genéticos , Bases de Datos GenéticasRESUMEN
Spent selective catalytic reduction (SCR) catalysts are environmentally hazardous and resource-enriching. In this work, V, W, and As in a spent SCR catalyst was extracted by alkali pressure leaching. Results showed that the V, W, and As were loaded on the anatase TiO2 crystal grains as amorphous oxides. The optimum pressure leaching conditions were NaOH concentration of 20 wt%, reaction temperature of 180 °C, reaction time of 120 min, L/S of 10 mL/g, and stirring speed of 300 rpm. The leaching efficiency of W, V, and As reached 98.83%, 100%, and 100%, respectively. The experiment revealed the preferential leaching of V and As rather than W, and the leaching mechanisms of V, W, and As were studied through experiment and density functional theory (DFT). The leaching kinetics of W conformed to a variant of the shrinking core model and the leaching process of W is controlled by both chemical reactions and diffusion processes. During the leaching process, Na2Ti2O4(OH)2 product powder layer was generated, which affects the mass transfer of W. The destruction of the TiO2 skeleton in the spent SCR catalyst is essential for adequate W extraction, especially for the extraction of W embedded in the TiO2 lattice. The DFT simulation result indicated that the V and As loaded onto the TiO2 support are easier to absorb hydroxide ions rather than W, and the leaching reaction energy of V and As was lower than W, As, and V has leaching priority over the leaching of W. Furthermore, an anatase TiO2 photocatalyst with the {001} crystal surface exposed was successfully prepared from the alkali pressure leaching residue. This work provides theoretical support for the metal leaching and utilization of spent SCR catalysts via alkali pressure leaching.
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Álcalis , Titanio , Álcalis/química , Titanio/química , Metales , Óxidos/química , CatálisisRESUMEN
Objective: Polycystic ovarian syndrome (PCOS) is a prevalent gynecologic disorder, often associated with abnormal follicular development. Cangfu Daotan decoction (CFD) is a traditional Chinese medicine formula that is effective in alleviating PCOS clinically, but the specific mechanism remains unclear. Forkhead box K1 (FOXK1) is associated with cellular function. This study aimed to explore the effects of CFD and FOXK1 on PCOS.Methods: High-fat diet and letrozole were combined to establish PCOS rat models. Next, primary GCs were extracted from those PCOS rats. Then, GC cells were transfected with si-FOXK1 or oe-FOXK1. CFD-contain serum was prepared, and experiments were conducted to investigate the regulation of FOXK1 by CFD.Results: FOXK1 was highly expressed in GCs of PCOS rats. Further investigation revealed that FOXK1 overexpression resulted in inhibition of proliferation and DNA synthesis, along with promotion of apoptosis and autophagy in GCs. Additionally, it was found that FOXK1 promoted the expressions of the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway-related proteins. Interestingly, treatment with CFD reversed all the effects of FOXK1 overexpression in GCs. Conclusion: This study demonstrated that CFD exerted a protective role in PCOS by inhibiting FOXK1, which provided a research basis for the application of CFD in PCOS, and suggested that FOXK1 is a novel therapeutic target in PCOS treatment.
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Medicamentos Herbarios Chinos , Síndrome del Ovario Poliquístico , Humanos , Femenino , Ratas , Animales , Células de la Granulosa/metabolismo , Síndrome del Ovario Poliquístico/metabolismo , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Apoptosis , Mamíferos , Factores de Transcripción Forkhead/genéticaRESUMEN
Although the combined effect of organic ligands and heavy metals in the environment on plants have been frequently reported, their complexed interaction in plants and the physiological effects remain to be revealed. Metal complexing agent benzotriazole (BTR) has extensive environmental pollution. In this study, root-splitting experiments were designed to identify the in vivo and in vitro effects of BTR on the accumulation and translocation of Cu in rice (Oryza sativa L.), and the concentrations and translocation factor (TF) of Cu and BTR in different parts of rice were measured. In the in vitro interaction treatments, low BTR concentrations enhanced Cu uptake and lateral transport in rice, while higher levels of BTR's exposure (i.e., ≥ 100 µM) resulted in opposite effects. Differently, significant increase in the lateral transport of Cu and vertical translocation of BTR in rice presented in the in vivo interaction treatments. TF of Cu from root A to root B (TFRA-RB) increased from 0.05 to 0.272 with the BTR concentration increasing from 0 to 100 µM, and higher TF of BTR from root to shoot (TFR-S), ranging from 1.00 to 1.75, compared with single BTR exposure treatments was observed. The phytotoxicity of BTR expressed by the catalase activity was significantly alleviated by the in vivo accumulated Cu in rice.
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Oryza , Transporte Biológico , Contaminación Ambiental , ExcipientesRESUMEN
A simple paper-based microfluidic device was fabricated to simultaneously detect multiple targets. Microfluidic paper-based analytical devices (µPAD) comprise a single-layer moving sliding PAD (SPAD) to control the flow channel switch together with a folding origami PAD (OPAD) to test the target analytes. The facile assembly without any splicing materials avoids cross-contamination and non-specific adsorption of joining materials that may be caused by multi-target detection. The concentration of Fe(III), Ni(II), Cr(VI), and nitrite in standard solutions and actual aqueous solutions was successfully determined using the designed µPAD. The µPAD was able to achieve LOD of 3.3 mg/L, 1.3 mg/L, 0.35 mg/L, 0.28 mg/L for Fe (III), Ni (II), Cr (VI), and nitrite, respectively. The designed SOPAD exhibits improved stability, with a deviation of less than 7% compared to conventional analytical methods (ICP-OES and UV). Our work demonstrates that this 3D PAD holds great promise and a wide scope in environmental monitoring, biochemical analysis, food testing and other testing industries.
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Maximum likelihood sequence estimation (MLSE) is the optimal signal sequence detection that can remove the inter-symbol interference (ISI). However, we find that the MLSE causes burst consecutive errors alternating between +2 and -2 in M-ary pulse amplitude modulation (PAM-M) IM/DD systems with large ISI. In this paper, we propose to use precoding to suppress the burst consecutive errors resulted from MLSE. A 2 M modulo operation is employed to guarantee that the probability distribution as well as the peak-to-average power ratio (PAPR) of encoded signal remain unchanged. After the receiver-side MLSE, the decoding process that involves adding the current MLSE output to the previous one and applying a 2 M modulo is implemented to break the burst consecutive errors. We conduct experiments to transmit 112/150-Gb/s PAM-4 or beyond 200-Gb/s PAM-8 signals at C-band to investigate the performance of the proposed MLSE integrated with precoding. The results show that the precoding can break burst errors effectively. For 201-Gb/s PAM-8 signal transmission, the precoding MLSE can achieve 1.4-dB receiver sensitivity gain and reduce the maximum length of burst consecutive errors from 16 to 3.
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OBJECTIVE: Polycystic ovarian syndrome (PCOS) is a common disorder that leads to infertility in reproductive-aged females. HOTAIR is highly expressed in various gynecological diseases and is associated with a poor prognosis. We aimed to explore the role of HOTAIR in PCOS. METHODS: First, PCOS rats were induced using dehydroepiandrosterone and then treated with si-HOTAIR. Next, HOTAIR mRNA expression and serum hormone levels were detected. HE staining was applied to observe estrus cycle, ovarian morphology and count the number of follicles. Apoptosis in the ovary was detected by TUNEL. Thereafter, ovarian granulosa cells (GCs) were isolated from PCOS rats, transfected with si-HOTAIR and treated with LY294002 (Akt inhibitor) or IGF-1. CCK-8 and flow cytometry assays were used to evaluate cell viability and apoptosis. IGF-1, apoptosis- and PI3K/Akt pathway-associated protein expressions in ovary and GCs were also detected. RESULTS: In in vivo experiments, si-HOTAIR decreased serum T, E2 and LH levels but increased FSH level, restored estrus cycle, ovarian morphology and inhibited apoptosis of ovary in PCOS rats. Meanwhile, in vitro assays showed that si-HOTAIR upregulated the viability but inhibited the apoptosis of PCOS GCs. Furthermore, both in vivo and in vitro assays revealed that si-HOTAIR increased Bcl-2 expression but suppressed Bax, Bad, IGF-1 expressions and PI3K, AKT phosphorylation. However, the aforementioned effects of si-HOTAIR in vitro were further enhanced by LY294002 and partially reversed by IGF-1. CONCLUSIONS: HOTAIR knockdown improved PCOS, and the mechanism may relate to IGF-1-mediated PI3K/Akt pathway, indicating HOTAIR may be a novel therapeutic target for PCOS.
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Síndrome del Ovario Poliquístico , ARN Largo no Codificante , Humanos , Femenino , Ratas , Animales , Síndrome del Ovario Poliquístico/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , ARN Largo no Codificante/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Células de la Granulosa/metabolismoRESUMEN
Microvascular reconstruction is essential for peripheral nerve repair. S-Propargyl-cysteine (SPRC), the endogenous hydrogen sulfide (H2S) donor, has been reported to promote angiogenesis. The aim of this study is to utilize the pro-angiogenic ability of SPRC to support peripheral nerve repair and to explore the potential mechanisms. The effects and mechanisms of SPRC on angiogenesis and peripheral nerve repair were examined under hypoxic condition by establishing a sciatic nerve crushed injury model in mice and rats, and a hypoxia model in human umbilical vascular endothelial cells (HUVECs) in vitro. We found that SPRC accelerated the function recovery of the injured sciatic nerve and alleviated atrophy of the gastrocnemius muscle in mice. It facilitated the viability of Schwann cells (SCs), the outgrowth and myelination of regenerated axons, and angiogenesis in rats. It enhanced the viability, proliferation, adhesion, migration, and tube formation of HUVECs under hypoxic condition. SPRC activated sirtuin1 (SIRT1) expression by promoting the production of endogenous H2S, and SIRT1 negatively regulated Notch signaling in endothelial cells (ECs), thereby promoting angiogenesis. Collectively, our study has provided important evidence that SPRC has an effective role in peripheral nerve repair through microvascular reconstruction, which could be a potentially effective medical therapy for peripheral nerve injury.
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The widespread use of selective catalytic reduction (SCR) catalysts has resulted in a large accumulation of spent SCR catalysts. These spent catalysts present a significant risk of environmental hazards and potential for resource recovery. This paper presents a feasible process, which works using atmospheric pressure leaching, of tungsten and titanium recovery from spent SCR catalysts. In this new method, titanium and tungsten are simultaneously leached with sulfuric acid as the leaching agent. After hydrolysis and calcination, titanium-tungsten powder with low impurity and reconstructed pore properties was obtained. The optimal conditions for the leaching of Ti and W were as follows: temperature, 150 °C; reaction time, 60 min; H2SO4 concentration, 80 %; mass ratio of H2SO4/TiO2, 3:1; and diluted H2SO4 concentration, 20 % after reaction. With these optimum conditions, the leaching efficiency of Ti and W were found to be 95.92 % and 93.83 %, respectively. The ion speciation and reaction mechanism of W were studied by Raman spectroscopy, FTIR, and UV-vis. The formation of heteropolytungstate with a Keggin structure is essential for the synergistic leaching of Ti and W, as the heteropolytungstate can be stably dissolved in the acid solution. During the hydrolysis process, heteropolytungstate gradually decomposed into Ti4+ and WO42- due to the formation of insoluble Ti(OH)4 from Ti4+ in the solution. This study demonstrated an effective method for synergistic recovery of titanium and tungsten from the spent SCR catalyst.
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Full-component pyrolysis has been proven to be a prospective method for the disposal of organic matters and the cathode material reduction of spent LiNixCoyMnzO2 (NCM) lithium-ion batteries (LIBs). However, the kinetics of the full-component pyrolysis of spent NCM LIBs is still unclear. This work represents the first attempt to study the kinetics of different stages of full-component pyrolysis of NCM LIBs based on isoconversional method to guide the recycling of spent LIBs. Pyrolysis process was divided into four stages in accordance to the main weight loss temperature ranges and the classical Kissinger-Akahira-Sunose and Flynn-Wall-Ozawa kinetics models were employed to calculate the activation energy (E) in each stage. The main physicochemical reactions were clarified though in situ analysis, and the average E in the four stages was determined: (I) The volatilization of electrolytes occurred in the temperature range of 100-200 °C with the E of 98.6 kJ/mol. (II) The decomposition of organic matters and the preliminary reduction of cathode material transpired in the temperature range of 400-500 °C with the E of 227.2 kJ/mol. (III) The further reduction of NiO and CoO occurred from 650 to 800 °C with the E of 258.8 kJ/mol. (â £) The reduction of MnO took place from 850 to 1000 °C with the E of 334.9 kJ/mol. The recycling strategies based on full-component pyrolysis of spent NCM LIBs was accordingly proposed. During pyrolysis, the cathode material was gradually reduced and the pyrolytic products can be controlled through temperature regulation.
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BACKGROUND: Recent advances in next-generation sequencing technologies have helped investigators generate massive amounts of cancer genomic data. A critical challenge in cancer genomics is identification of a few cancer driver genes whose mutations cause tumor growth. However, the majority of existing computational approaches underuse the co-occurrence mutation information of the individuals, which are deemed to be important in tumorigenesis and tumor progression, resulting in high rate of false positive. RESULTS: To make full use of co-mutation information, we present a random walk algorithm referred to as DriverRWH on a weighted gene mutation hypergraph model, using somatic mutation data and molecular interaction network data to prioritize candidate driver genes. Applied to tumor samples of different cancer types from The Cancer Genome Atlas, DriverRWH shows significantly better performance than state-of-art prioritization methods in terms of the area under the curve scores and the cumulative number of known driver genes recovered in top-ranked candidate genes. Besides, DriverRWH discovers several potential drivers, which are enriched in cancer-related pathways. DriverRWH recovers approximately 50% known driver genes in the top 30 ranked candidate genes for more than half of the cancer types. In addition, DriverRWH is also highly robust to perturbations in the mutation data and gene functional network data. CONCLUSION: DriverRWH is effective among various cancer types in prioritizes cancer driver genes and provides considerable improvement over other tools with a better balance of precision and sensitivity. It can be a useful tool for detecting potential driver genes and facilitate targeted cancer therapies.
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Neoplasias , Oncogenes , Genómica/métodos , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Mutación , Neoplasias/genéticaRESUMEN
Polycystic ovary syndrome (PCOS) is an endocrine disease associated with reproduction. The Cuscuta-Salvia formula has been widely used to treat for PCOS in clinic. However, its chemical and pharmacological properties remain unclear. We identified the active components and related targets of Cuscuta-Salvia using UHPLC-ESI-Q-TOF-MS and TCMSP database. Disease targets were obtained from the DisGeNET and GeneCards databases. Subsequently, common targets between Cuscuta-Salvia and PCOS were identified using a Venn diagram. PPI network was established. Core genes were selected using a Cytoscape software plugin. GO and KEGG enrichment analyses were performed for common targets using the "pathview" package in R. Several core targets were verified using molecular and Immunological methods. By combining UHPLC-ESI-Q-TOF-MS with a network pharmacology study, 14 active components and a total of 80 common targets were obtained. Ten core genes were regulated by Cuscuta-Salvia in PCOS, including IL6, AKT1, VEGFA, TP53, TNF, MAPK1, JUN, EGF, CASP3, and EGFR. GO results showed that cellular response to drugs, response to oxygen levels, response lipopolysaccharides, and response to molecule of bacterial origin in BP category; membrane, transcription regulator complex, nuclear chromatin, postsynaptic membrane, and vesicle lumen in CC category; DNA-binding transcription factor binding, RNA polymerase II-specific DNA-binding transcription factor binding, DNA-binding transcription activator activity, RNA polymerase II-specific, DNA-binding transcription activator activity, and cytokine receptor binding in MF terms. The KEGG enrichment pathway was mainly involved in the PI3K - Akt, MAPK, TNF, IL-17 signalling pathways, and in cellular senescence. Furthermore, the results of the experimental study showed that Cuscuta-Salvia ameliorated the pathological changes in the ovaries, liver and adipose tissue. And it improved the expressions of the genes or proteins. Our results demonstrate that Cuscuta-Salvia may provide a novel pharmacological basis in an experimental model of PCOS by regulating gene expression. This study provides a basis for future research and clinical applications.
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Cuscuta , Síndrome del Ovario Poliquístico , Salvia , Regulación de la Expresión Génica , Farmacología en Red , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/genética , Síndrome del Ovario Poliquístico/metabolismoRESUMEN
[This corrects the article DOI: 10.3389/fphar.2020.592827.].
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BACKGROUND: Ber, a Chinese herbal monomer has been reported to exhibit an array of pharmacological activities related to the lowering of blood glucose and the treatment of polycystic ovarian syndrome (PCOS). In the present study, we aimed to elucidate the effect of berberine (Ber) on a rat model of PCOS mediated via the PI3K/AKT signaling pathway. METHODS: A PCOS animal model was induced with the administration of letrozole, and animals were then randomized into untreated or Ber and metformin hydrochloride treated groups. After administration, fasting blood glucose, HOMA-IR, fasting insulin (FINS) values, and the serum hormone levels were measured in PCOS rats. The ovarian tissues were stained with hematoxylin and eosin and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) for pathological and apoptosis examination. Moreover, the effect of Ber on the proliferation and apoptosis of granulosa cells was detected by CCK-8 assays and flow cytometry. The influence of Ber on granulosa cells was confirmed by blockade of the PI3K/AKT pathway. In addition, the modulatory effect of the blockade of the PI3K/AKT pathway on the expression of related proteins was demonstrated via western blotting. RESULTS: We found that Ber was able to restore the serum hormone levels and improve IR in a PCOS rat model. The morphological lesions and apoptosis of the ovary were also restored by the Ber treatment. Blockade of the PI3K/AKT pathway attenuated the influences of Ber on the proliferation and apoptosis of granulosa cells. CONCLUSION: The beneficial effects of Ber on PCOS included alterations of the serum hormone levels, recovery of morphological lesions in the ovary, improvement of insulin resistance, and cell viability and inhibition of apoptosis, which were all mediated through the PI3K/AKT pathway.
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Berberina , Resistencia a la Insulina , Síndrome del Ovario Poliquístico , Animales , Berberina/farmacología , Femenino , Humanos , Fosfatidilinositol 3-Quinasas , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-akt , RatasRESUMEN
Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder prevalent in females of reproductive age; insulin resistance (IR) is the major pathogenic driver. Pharmacology is a basic option for PCOS therapy; traditional Chinese medicine (TCM), as a significant part of complementary and alternative medicine, has a long history in the clinical management of PCOS. Cangfudaotan decoction (CFD) has been used clinically for gynaecological diseases especially PCOS. In this study, first, chemical components in CFD were clarified using UPLC-Q/TOF-MS analysis. Then, an animal model of PCOS was established, granular cells were also isolated from the rats with PCOS, and CFD was administrated at different dosages in PCOS rats and granular cells, to investigate the therapeutic effect and mechanisms of CFD for PCOS treatment. The result showed that CFD treatment is effective in PCOS rats and granulosa cells. CFD was able to improve IR, restore the serum hormone levels, inhibit the inflammatory cytokines in PCOS rat, and alleviate ovary morphological injury and apoptosis in PCOS rats. In granulosa cells of PCOS, the result showed that the cell viability was improved, and cell apoptosis was inhibited after CFD administration. Further experiments suggested that CDF improves IR, follicular development, cell apoptosis, and inflammatory microenvironment, and this was associated to the regulation of IGF-1-PI3K/Akt-Bax/Bcl-2 pathway-mediated gene expression. Given that CFD sufficiently suppresses insulin resistance and improves follicular development in this study, exploring these mechanisms might help to optimize the therapeutic treatment of CFD in PCOS patients.
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Medicamentos Herbarios Chinos/farmacología , Resistencia a la Insulina , Folículo Ovárico/efectos de los fármacos , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Animales , Apoptosis , Supervivencia Celular , Citocinas/metabolismo , Femenino , Células de la Granulosa/efectos de los fármacos , Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Medicina Tradicional China , Ovario/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Microambiente Tumoral/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismoRESUMEN
A high-efficient method for determining the total petroleum hydrocarbon (TPH) was established by gas chromatography-flame ionization detection, coupled with an efficient 10 m short chromatographic column; the analyzing period was narrowed to 5 mins. The limits of detection of the method included 1.47, 4.02, and 0.69 mg/kg, and the corresponding limits of quantification reached 4.45, 12.2, and 2.10 mg/kg for the three fractions C10-C16, C17-C34, and C35-C40, respectively. The method was employed to real samples to achieve the routine environmental monitoring of TPH in polluted sites from Fushan oilfield, China. As revealed from the analysis of 30 soil samples in the study area, a wide range of TPH concentrations were achieved: 61.6-7300 mg/kg (average, 1055 mg/kg) for ΣC10-C16, 438-14,280 mg/kg (average, 4544 mg/kg) for ΣC17-C34, 25.4-638 mg/kg (average, 250 mg/kg) for ΣC35-C40, and 617-15,348 (average, 5848 mg/kg) for ΣC10-C40, respectively. According to the Nemerow integrated pollution index, the Fushan oilfield has been slightly polluted by TPH. As suggested from the distribution of TPH concentrations, the main sources of TPH in soil samples of Fushan oilfield included oil spills during temporary storage, transportation, and oil exploitation. Adopting the developed method to delve into oilfield soil samples further verifies the effectiveness of the method, indicating that the method can well meet the growing demand of regulatory guidelines for related risk assessment and environmental monitoring and remediation strategy formulation.
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Contaminación por Petróleo/análisis , Petróleo/análisis , Contaminantes del Suelo/análisis , China , Cromatografía de Gases , Ionización de Llama , Hidrocarburos/análisis , Yacimiento de Petróleo y Gas , Suelo , SolventesRESUMEN
INTRODUCTION: The goal of this study was to review relevant case-control trials in order to determine the association of paraoxonase 1 (PON1) gene polymorphisms (-108C/T, 55L/M, 192Q/R) and polycystic ovarian syndrome (PCOS) susceptibility. METHODS: Using appropriate keywords, we identified relevant studies using PubMed, Cochrane, Embase, CNKI, VANFUN, and VIP. Key pertinent sources in the literature were also reviewed, and all articles published through April 2019 were considered for inclusion. Based on the qualified studies, we performed a meta-analysis of associations between -108C/T, 55L/M and 192Q/R polymorphisms in PON1 and risk of PCOS. RESULTS: We included 13 case-control studies with 3,660 total patients in the PCOS group and 2,835 in the control group. These studies found that the population with -108C/T locus T were associated with lower PCOS susceptibility by heterozygote model (OR 0.442, 95% CI 0.259-0.754); the Caucasian population with -108C/T locus T were associated with higher PCOS susceptibility by regressive model (OR 2.087, 95% CI 1.242-3.504). The population with 55L/M locus M were associated with higher PCOS susceptibility by regressive model (OR 1.518, 95% CI 1.067-2.160); the Asian population with 55L/M locus M were associated with lower PCOS susceptibility by dominant model and heterozygote model. The population with 192Q/R locus R were associated with higher PCOS susceptibility by the 5 gene models. The Asian population with 192Q/R locus R were associated with higher PCOS susceptibility: allelic model (OR 1.271, 95% CI 1.139-1.417); homozygote model (OR 1.575, 95% CI 1.244-1.995); dominant model (OR 1.299, 95% CI 1.069-1.580); regressive model (OR 1.421, 95% CI 1.207-1.673). The Caucasian population with 192Q/R locus R were associated with higher PCOS susceptibility: heterozygote model (OR 2.113, 95% CI 1.266-3.526). CONCLUSION: Our meta-analysis suggested that 192Q/R locus R were associated with higher PCOS susceptibility in both the Asian and Caucasian population.
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Arildialquilfosfatasa/genética , Pueblo Asiatico/genética , Predisposición Genética a la Enfermedad/genética , Síndrome del Ovario Poliquístico/genética , Población Blanca/genética , Alelos , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad/etnología , Heterocigoto , Humanos , Síndrome del Ovario Poliquístico/etnología , Polimorfismo GenéticoRESUMEN
The crisis of male infertility is an issue of human reproductive health worldwide. The Wuzi Yanzong pill (WZYZP) is a traditional Chinese medicine prescription that shows efficacy in kidney reinforcement and essence benefit to ameliorate male reproductive dysfunctions. However, the pharmacological mechanisms of the WZYZP on male infertility have not been investigated and clarified clearly. This study was designed to investigate the effects of the WZYZP on spermatogenesis disorder and explore its underlying pharmacological mechanisms. First, based on a network pharmacology study, 39 bioactive compounds and 40 targets of the WZYZP associated with spermatogenesis disorder were obtained, forming a tight compound-target network. Molecular docking tests showed tight docking of these compounds with predicted targeted proteins. The protein-protein interaction (PPI) network identified TP53, TNF, AKT1, Bcl-XL, Bcl-2, and IκBA as hub targets. The Kyoto Encyclopedia of Genes and Genomes pathway network and pathway-target-compound network revealed that the apoptosis pathway was enriched by multiple signaling pathways and multiple targets, including the hub targets. Subsequently, the chemical characterization of WZYZP was analyzed using liquid chromatography to quadrupole/time-of-flight mass spectrometry, and 40 compounds in positive ion mode and 41 compounds in negative ion mode in the WZYZP were identified. Furthermore, based on the prediction of a network pharmacology study, a rat model of spermatogenesis disorder was established to evaluate the curative role and underlying mechanisms of the WZYZP. The results showed that WZYZP treatment improved rat sperm quality and attenuated serum hormone levels, reversed histopathological damage of the testis, reduced cell apoptosis in testis tissues, and ameliorated the expression of the predicted hub targets (TP53, TNF-α, AKT1, NFκB, and IκBA) and the apoptosis related proteins (Bcl-XL, Bcl-2, Bax, Caspase 3, and Caspase 9). These results indicated that the WZYZP has a protective effect on spermatogenesis disorder, suggesting that it could be an alternative choice for male infertility therapy.
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Goethite (α-FeOOH) possesses excellent catalytic activity, high selectivity and good stability as a catalyst for NO oxidation through the catalytic decomposition of gaseous H2O2. as the primary reactive oxygen species is involved in the NO oxidation process together with ·OH, and N2O5 is found for the first time in the products of NO oxidation.
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Objective: Previous genome-wide sequencing revealed that Ras-related protein Rab-5B (RAB5B) is a susceptible target in patients with polycystic ovary syndrome (PCOS).Methods: Direct sequencing was performed to analyze the RAB5B gene rs1045435, rs11550558, rs34962186, rs705700, rs58717357, rs11171718, rs60028217, rs772920 loci genotypes in 300 PCOS patients and 300 healthy controls. The plasma microRNA (miRNA)-24, miR-320 levels were measured by reverse transcription fluorescent quantitative PCR (RT-qPCR).Results: The risk of PCOS in C allele carriers of RAB5B gene rs1045435 locus was 3.91 times higher than that of G allele. The risk of PCOS in rs11550558 locus G allele was 4.09 times higher than A allele. The risk of PCOS in rs705700 locus C allele was 1.66 times greater than T allele. The risk of PCOS in rs11171718 locus A allele carrier was 3.84 times higher than G allele. The rs11550558 SNP was associated with PCOS risk only in those with age ≥ 31.1 years. And RAB5B gene rs11550558, rs1045435, and rs11171718 SNPs were significantly associated with PCOS risk only in subjects with BMI ≥ 23.8 kg/m2 We also found that the RAB5B gene rs1045435 SNP was associated with plasma miR-24 levels. The RAB5B gene rs11550558, rs705700, rs11171718 SNPs were correlated with plasma miR-230 levels.Conclusion: The single nucleotide polymorphisms of the rs1045435, rs11550558, rs705700, and rs11171718 loci of the RAB5B gene are associated with PCOS risk. The rs1045435 locus is likely an miR-24 binding site, while rs11550558, rs705700, and rs11171718 loci may be miR-320 binding sites.