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BACKGROUND: Acute mountain sickness (AMS) is the most prevalent condition resulting from hypobaric hypoxia (HH) at high altitudes. Although evidence suggests the involvement of inflammatory cytokines in AMS development, there is currently a lack of reports on variations in cytokine levels between individuals susceptible to AMS and those resistant to AMS prior to ascending to high altitude. Thus our current study aims to assess the predictive capability for AMS occurrence by evaluating differences in cytokine levels at low altitudes. METHODS: The present study recruited 48 participants, who ascended from low altitude to middle high-altitude (3700 m) and further to extreme high-altitude (5000 m). Based on Lake Louise Score (LLS) at the two high altitudes, participants were categorized into severe AMS-susceptible (sAMS), moderate AMS-susceptible (mAMS), and non-AMS groups. The Bio-Plex MAGPIX System was employed to measure plasma levels of 11 inflammatory cytokines. Cytokines at low altitude and middle high-altitude were analyzed through receiver operating characteristic (ROC) analysis to obtain area under the ROC curve (AUROC), sensitivity, and specificity. RESULTS: Based on LLS at 3700 m, we initially categorized the study subjects into the sAMS group (n = 8) and the Non-AMS group (n = 40). Among individuals in the non-AMS group (n = 40) at the altitude of 3700 m, those who developed AMS at the altitude of 5000 m were assigned to the mAMS group (n = 17), whereas those who did not experience AMS were included into the non-AMS group (n = 23). The concentration of TNF-α at low altitude exhibited robust predictive performance for predicting AMS occurrence at the altitude of 3700 m. Among the non-AMS group at the altitude of 3700 m, we identified that the concentration of IL-2 and IL-17A demonstrated high efficacy in predicting the onset of AMS following ascent to 5000 m. In addition, differentially expressed cytokines including IL-17A, TNF-α and IL-2 at low altitude possessed discriminatory potential among the three groups at 5000 m.. CONCLUSION: We posited that the levels of TNF-α, IL-2, IL-17A in serum of low altitude could be considered as potential biomarkers to predict the occurrence of AMS at high altitude. NEW & NOTEWORTHY: Through the two comparisons at different two altitudes (baseline level and 3700 m), we provided a model to progressively screen individuals who are susceptible and resistant to different high altitudes (3700 m and 5000 m). TNF-α could firstly screen out the AMS susceptible individuals at the altitude of 3700 m. And through its combination with IL-2 and IL-17A, we could further screen out AMS susceptible individuals at the altitude of 5000 m.
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Doença da Altitude , Altitude , Biomarcadores , Interleucina-17 , Interleucina-2 , Fator de Necrose Tumoral alfa , Humanos , Doença da Altitude/sangue , Masculino , Biomarcadores/sangue , Interleucina-17/sangue , Adulto , Fator de Necrose Tumoral alfa/sangue , Feminino , Interleucina-2/sangue , Doença Aguda , Curva ROC , Pessoa de Meia-IdadeRESUMO
Perfluorooctanoic acid (PFOA), a typical perfluoroalkyl group compound, has received worldwide attention due to its significant environmental toxicity. Following regulatory bans on the production and emission of PFOA, concerns have been raised about the potential health risks and the safety of novel perfluoroalkyl analogues. HFPO-DA (trade name Gen-X) and HFPO-TA are two perfluoroalkyl analogues known to be bioaccumulative, whose level of toxicity and whether they are safe alternatives to PFOA remain unclear. In the following study, the physiological and metabolic effects of exposure to PFOA and its novel analogues were explored in zebrafish using 1/3 LC50 (PFOA 100 µM, Gen-X 200 µM, HFPO-TA 30 µM). At the same LC50 toxicological effect, exposure to PFOA and HFPO-TA resulted in abnormal phenotypes such as spinal curvature, pericardial edema and aberrant body length, while Gen-X was little changed. Metabolically, PFOA, HFPO-TA and Gen-X all significantly increased total cholesterol in exposed zebrafish with PFOA and HFPO-TA also increasing total triglyceride levels. Transcriptome analysis showed that the number of differentially expressed genes in PFOA, Gen-X, and HFPO-TA treated conditions compared to control groups were 527, 572, and 3, 933, respectively. KEGG and GO analysis of differentially expressed genes revealed pathways and functions related to lipid metabolism as well as significant activation of the peroxisome proliferators-activated receptor (PPARs) pathway. Furthermore, RT-qPCR analysis identified significant dysregulation in the downstream target genes of PPARα, which is responsible for lipid oxidative catabolism, and the SREBP pathway, which is responsible for lipid synthesis. In conclusion, both perfluoroalkyl analogues HFPO-TA and Gen-X exhibit significant physiological and metabolic toxicity to aquatic organisms and their environmental accumulation should be closely regulated.
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Fluorocarbonos , Peixe-Zebra , Animais , Peixe-Zebra/genética , Metabolismo dos Lipídeos , Fluorocarbonos/toxicidade , Caprilatos/toxicidadeRESUMO
OBJECTIVE: This meta-analysis aimed to compare the efficacy and safety of antibiotic treatment and appendectomy for acute uncomplicated appendicitis. METHODS: We searched the randomized controlled studies (RCTs) comparing appendectomy with antibiotic treatment for uncomplicated acute appendicitis in the electronic database including Pubmed, Embase, Cochrane, Web of Science, CNKI, VIP, and WanFang. The primary outcomes included complication-free treatment success at 1 year, complications, surgical complications, and the complicated appendicitis rates. Secondary outcomes included negative appendicitis, length of hospital stay, the quality of life at 1 month, and the impact of an appendicolith on antibiotic therapy. RESULTS: Twelve randomized controlled studies were included. Compared with surgery group, the antibiotic group decreased the complication-free treatment success at 1 year (RR 0.81; 95% CI 0.73-0.91; z = 3.65; p = 0.000). Statistically significance was existed between antibiotic group and surgical group with both surgical types(open and laparoscopic) (RR 0.43; 95% CI 0.31-0.58; z = 5.36; p = 0.000), while no between the antibiotic treatment and laparoscopic surgery (RR 0.72; 95% CI 0.41-1.24; z = 1.19; p = 0.236). There was no statistically significant differences between two groups of surgical complications (RR 1.38; 95% CI 0.70-2.73; z = 0.93; p = 0.353), the complicated appendicitis rate (RR 0.71; 95% CI 0.36-1.42; z = 0.96; p = 0.338), negative appendectomy rate (RR 1.11; 95% CI 0.69-1.79; z = 0.43; p = 0.670), duration of hospital stay (SMD 0.08; 95%CI -0.11-0.27; z = 0.80; p = 0.422), and quality of life at 1 month (SMD 0.09; 95%CI -0.03-0.20; z = 1.53; p = 0.127). However, in the antibiotic treatment group, appendicolith rates were statistically higher in those whose symptoms did not improve (RR 2.94; 95% CI 1.28-6.74; z = 2.55; p = 0.011). CONCLUSIONS: Although the cure rate of antibiotics is lower than surgery, antibiotic treatment is still a reasonable option for patients with uncomplicated acute appendicitis who do not want surgery without having to worry about complications or complicating the original illness.
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Apendicectomia , Apendicite , Humanos , Apendicite/tratamento farmacológico , Apendicite/cirurgia , Antibacterianos/uso terapêutico , Resultado do Tratamento , Doença Aguda , Tempo de InternaçãoRESUMO
OBJECTIVE: To investigate the effect of perfluorooctanoic acid on rat hepatocytes BRL-3 A cell viability and the expression of transcription factor nuclear factor erythroid 2-related factor 2(Nrf2) and arginosuccinate synthase(Ass1). METHODS: Rat hepatocytes BRL-3 A were cultured and divided into control group(0 µmol/L PFOA), low-dose group(6.25 µmol/L PFOA), and medium-dose group(25 µmol/L PFOA), high-dose group(100 µmol/L PFOA). After 48 hours, cell viability was detected by MTT, ROS content was detected by free radical indicator H_2DCFDA, enzyme activity related to oxidative stress was detected by the kit, Nrf2 and Ass1 protein expression level was detected by Western blot and immunocytochemistry(ICC). RESULTS: Compared with the control group, with the increase of the PFOA concentration, the cell viability of the middle and high dose groups had a downward trend, but there was no statistical significance(P>0.05). The intracellular ROS content increased, among which in the middle and high dose groups significantly increased(P<0.05), and the average fluorescence intensity was(5417.66±161.09) and(5725.50±166.83), respectively. Compared with the control group, the content of intracellular TG, TC and MDA in the low and medium dose groups did not change significantly, and the content of TG, TC and MDA in the high dose group was significantly increased(P<0.05), which was(0.21±0.05) mmol/L, (14.5±6.07) mmol/L and(1.23±0.33) nmol/mL, respectively. According to the ICC and Western blot result, the expression level of Nrf2 protein increased significantly in the high-dose group(P<0.05), and the expression level of Ass1 protein increased significantly in the low-dose group(P<0.05). CONCLUSION: Exposure to a certain dose of PFOA can lead to the accumulation of ROS in BRL-3 A cells. Nrf2 and Ass1 can play a certain role in eliminating ROS and ammonia detoxification by increasing their expression under the oxidative damage of rat liver cells caused by PFOA.
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Caprilatos , Fluorocarbonos , Animais , Caprilatos/toxicidade , Fluorocarbonos/toxicidade , Hepatócitos , Fígado , RatosRESUMO
OBJECTIVES: Perfluorooctanoic acid (PFOA) can cause lipid metabolism disorders in animal body and affect the lipolysis and synthesis of fatty acids. Peroxisome proliferators-activated receptor (PPAR) plays an extremely important role in this process. This study aims to explore the effects of PFOA on liver lipid metabolism disorders in Sprague Dewley (SD) rats and the expression of PPAR. METHODS: A total of 40 male SD rats were randomly divided into 4 groups (n=10 in each group): a control group (ddH2O), a low-dose PFOA group [PFOA 1.25 mg/(kg·d)], a middle-dose PFOA group [PFOA 5.00 mg/(kg·d)], and a high-dose PFOA group [PFOA 20.00 mg/(kg·d)]. The rats were fed with normal diet, and PFOA exposure were performed by oral gavage for 14 days, and the rats were observed, weighted and recorded every day during the exposure. After the exposure, the blood was collected, and the livers were quickly stripped after the rats were killed. Part of the liver tissues were fixed in 4% paraformaldehyde for periodic acid-schiff (PAS) staining; the contents of HDLC, LDLC, TG, TC in serum and liver tissues, as well as the activities of their related enzymes were assayed; The expression levels of cyclic adenosine monophosphate-response element binding protein (Cbp), general control of amino acid synthesis 5-like 2 (Gcn5L2), peroxidation peroxisome proliferation factor activated receptor γ (PPAR), silent information regulator 1 (Sirt1) and human retinoid X receptor alpha 2 (Rxrα2) ) were detected by Western blotting. RESULTS: After 14 days of PFOA exposure, the PAS staining positive particles in the cytoplasm and nucleus of SD rats in the medium and high dose groups were significantly reduced compared with the control group. The serum levels of LDLC and TC in the low-dose and middle-dose groups were significantly reduced compared with the control group (all P<0.05), while the high-dose group showed an increasing tendency, without siginificant difference (P>0.05), there was no significant difference in HDLC and TG (both P>0.05). The activities of alkaline phosphatase (AKP) and alanine aminotransferase (ALT) were increased significantly (both P<0.05) compared with control group; the ratio of ALT/aspartate aminotransferase (AST) in the high-dose group was increased significantly (P<0.05), there was no significant difference in LDH and TG (both P>0.05); the HDLC content in the liver tissues in the high-dose group was significantly reduced, compared with the control group (P<0.05); the TC contents in the liver tissues in the low, medium and high-dose groups were significantly increased (all P<0.05), there was no significant difference in LDLC and TG (both P>0.05); the AKP activity in the livers in the medium and high-dose groups was significantly increased (both P<0.05), there was no siginificant difference in LDH, ALT, and the ratio of ALT/AST (all P>0.05); the protein expression levels of Ppar γ, Cbp and Rxrα2 in the liver in the high dose groups were significantly down-regulated compared with the control group (all P<0.05), while the protein expression levels of Sirt1 were significantly up-regulated (all P<0.05). CONCLUSIONS: PFOA exposure can cause lipid metabolism disorder and glycogen reduction in SD rat livers, which may be related to the activation of Sirt1 and inhibition of Ppar γ expression, leading to affecting the normal metabolism of fatty acids and promoting glycolysis.
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Transtornos do Metabolismo dos Lipídeos , Metabolismo dos Lipídeos , Animais , Caprilatos , Ácidos Graxos/metabolismo , Ácidos Graxos/farmacologia , Fluorocarbonos , Transtornos do Metabolismo dos Lipídeos/induzido quimicamente , Transtornos do Metabolismo dos Lipídeos/metabolismo , Fígado/metabolismo , Masculino , PPAR gama , Ratos , Ratos Sprague-Dawley , Sirtuína 1/metabolismoRESUMO
Hydrogenation of alkenes is one of the most fundamental transformations in organic synthesis, and widely used in the petrochemical, pharmaceutical, and food industries. Although numerous hydrogenation methods have been developed, novel types of catalysis with new mechanisms and new hydrogen sources are still desirable. Thioxanthone (TX) is widely used in energy-transfer photoreactions, but rarely in photoredox processes. Herein we show that a catalytic amount of TfOH as a co-catalyst can tune the properties of TX to make it a photoredox catalyst with highly enhanced oxidative capability in the hydrogenation of carbonylated alkenes with the cheap petroleum industrial product p-xylene serving as the hydrogen source. Deuterium can also be introduced by this method by using D2 O as the D source. To the best of our knowledge, this is the first example of using p-xylene as a hydrogen source.
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Alcenos , Hidrogênio , Hidrogenação , Alcenos/química , Hidrogênio/química , Elétrons , CatáliseRESUMO
BACKGROUND: The human leukocyte antigen (HLA) gene family plays a key role in the immune response and thus is crucial in many biomedical and clinical settings. Utilizing Sanger sequencing, the golden standard technology for HLA typing enables accurate identification of HLA alleles in high-resolution. However, only the commercial software, such as uTYPE, SBT-Assign, and SBTEngine, and very few open-source tools could be applied to perform HLA typing based on Sanger sequencing. RESULTS: We developed a user-friendly, cross-platform and open-source desktop application, known as SOAPTyping, for Sanger-based typing in HLA class I and II alleles. SOAPTyping can produce accurate results with a comprehensible protocol and featured functions. Moreover, SOAPTyping supports a more advanced group-specific sequencing primers (GSSP) module to solve the ambiguous typing results. We used SOAPTyping to analyze 36 samples with known HLA typing from the University of California Los Angeles (UCLA) International HLA DNA Exchange platform and 100 anonymous clinical samples, and the HLA typing results from SOAPTyping are identical to the golden results and 5.5 times faster than commercial software uTYPE, which shows the usability of SOAPTyping. CONCLUSIONS: We introduce the SOAPTyping as the first open-source and cross-platform HLA typing software with the capability of producing high-resolution HLA typing predictions from Sanger sequence data.
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Antígenos HLA/genética , Teste de Histocompatibilidade/métodos , Análise de Sequência de DNA , Software , Alelos , Primers do DNA , Antígenos de Histocompatibilidade Classe I , Antígenos de Histocompatibilidade Classe II , HumanosRESUMO
Submicrometer dual-stripe temperature sensors made from a single piece of metal thin film (e.g., Pd) are developed. With the narrowest sensor being 900 nm in width, they show sensitivity of 1-2 µV/K for the full range of 10-300 K. The results confirm the size effect in Seebeck coefficient previously observed in microstripe sensors of the same device configuration.
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Técnicas Biossensoriais , Nanopartículas/química , Nanotecnologia , Calibragem , Criopreservação , Luz , Metais/química , Microscopia Eletrônica de Varredura , Óptica e Fotônica , Fotoquímica , Temperatura , Termodinâmica , Raios UltravioletaRESUMO
Perfluorooctanoic acid (PFOA) exposure is associated with kidney dysfunction, however the exact mechanisms by which PFOA induces nephrotoxicity and the specific involvement of aquaporins (AQPs) in kidney tissue remains unclear. In this study, adult male Sprague-Dawley (SD) rats were exposed to PFOA by oral gavage for 28 days and compared with controls. Body weight, water intake and urine volume were recorded daily. At the end of the experiment, blood and kidney samples were collected, and serum urea, creatine and uric acid levels were assessed. The renal expression levels of water channel proteins AQP1, AQP3, AQP2 and p-AQP2 (Ser256) were observed by immunohistochemical staining, and the corresponding transcription levels were detected by Western blot and qRT-PCR. The results showed that PFOA exposure inhibited weight gain and increased water intake, urine volume, kidney weight and renal visceral index. PASM staining and transmission electron microscopy revealed pathological thickening of the glomerular capsule and basement membrane. Serum urea levels were increased, while serum creatine levels were decreased compared to controls. Additionally, the expression levels of AQP1, AQP3, AQP2 and p-AQP2 in kidney tissues were decreased, and the phosphorylation of AQP2 at Ser256 was inhibited. In conclusion, we demonstrate that PFOA exposure can damage the renal filtration barrier and reduce the expression level of AQPs in renal tissues, leading to renal filtration and reabsorption disorders.
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Aquaporina 2 , Caprilatos , Creatina , Fluorocarbonos , Ratos , Animais , Masculino , Aquaporina 2/genética , Aquaporina 2/metabolismo , Regulação para Baixo , Creatina/metabolismo , Ratos Sprague-Dawley , Rim/metabolismo , Ureia/metabolismoRESUMO
The assessment of the concentration and distribution of l6N, derived from 16O in the cooling water exposed to neutron irradiation, is essential for ensuring radiation safety during nuclear reactor operation. The imaging method allows for the visualization of the intensity distribution of these l6N by capturing gamma-rays emitted during their decay process. However, the existing gamma camera is exclusively compatible with gamma-rays below 2 MeV. In this paper, a novel gamma camera featuring a thick double-conical penumbra aperture, a pixelated Lu1.8Y0.2SiO5:Ce scintillator array, and a position-sensitive photomultiplier tube is proposed to address this limitation. This innovative design offers a large field of view (FOV) and is suitable for high energy extended gamma source imaging. The optimization of key parameters of the camera was conducted, and a FOV of 60° and an angular resolution of up to 4.57° were achieved. Imaging simulations, including a simplified model of the primary loop of the pressurized-water reactor by GEANT4 code and image reconstruction using the expectation maximum algorithm, demonstrated that the proposed gamma camera could obtain a satisfactory spatial resolution for diagnosing the distribution of 16N in the primary loop of a nuclear reactor.
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We propose a novel Optical Network Units (ONU) migration mechanism within the Time and Wavelength Division Multiplexed PON (TWDM-PON) framework by rearranging the working ONUs to a minimum number of wavelengths and turning off the rest to save power. We show through simulation that the number of working wavelengths can be minimized up to a theoretical lower bound, e.g. 23%, under the typical ONU online profiles. We further investigate how the migration interval and delay influence the user Service Level Agreement (SLA). We find that under the example ONU online profiles, 99.99% ONU SLA can be realized with the migration delay of 1000 milli-seconds. However to realize 99.999% ONU SLA, the migration delay must be 100 milli-seconds or lower.
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Perfluorooctanoic acid (PFOA) is the most prominent member of a widely utilized family of compounds named Perfluoroalkyl substances (PFASs). Initially produced for use in both industrial and consumer applications, it has since been recognized that PFASs are extremely persistent in the environment where they have been characterized as persistent organic pollutants (POPs). While previous studies have demonstrated that PFOA may induce disorders of lipid and carbohydrate metabolism, the precise mechanisms by which PFOA produces this phenotype and the involvement of downstream AMPK/mTOR pathways remains unclear. In this study, male rats were exposed to 1.25, 5 and 20 mg PFOA/kg body weight/day for 28 days by oral gavage. After 28 days, blood was collected and tested for serum biochemical indicators and livers were removed and weighed. To investigate aberrant metabolism in rats exposed to PFOA, livers were analyzed by performing LC-MS/MS untargeted metabolomics, quantitative real-time PCR, western blotting, immunohistochemical staining was also performed on exposed tissues. Our results showed that exposure to PFOA induced liver damage, increased the expression of glucose and lipid related biochemical indexes in liver and serum, and altered the expression levels of AMPK/mTOR pathway related genes and proteins. In summary, this study clarifies the mechanisms responsible for PFOA toxicity in the liver of exposed animals.
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Fluorocarbonos , Metabolismo dos Lipídeos , Masculino , Ratos , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Glucose/metabolismo , Cromatografia Líquida , Espectrometria de Massas em Tandem , Caprilatos/toxicidade , Fígado/metabolismo , Fluorocarbonos/toxicidade , Fluorocarbonos/metabolismo , Serina-Treonina Quinases TOR/metabolismoRESUMO
Fluorinated molecules are widely used in pharmaceutical and agrochemical industries. Herein we report the synthesis of 2-(3,3-difluoro-4-(silyloxy)but-1-en-1-yl)benzamides from the unprecedented rhodium(III)-catalyzed alkenylation of various benzamides with difluorohomoallylic silyl ethers. The practicability of this protocol is demonstrated by its broad substrate compatibility, good functional group tolerance, ready scalability and high regioselectivity. The oxygen in difluorohomoallylic silyl ethers makes ß-H elimination feasible, which suppresses both the ß-F elimination and dialkenylation of benzamides. This redox-neutral reaction proceeds efficiently via N-O bond cleavage without external oxidants and thus provides new opportunities for the synthesis of elaborate difluorinated compounds from readily available fluorinated synthons.
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This paper reports a practical and versatile oxidative cyclization of 2-arylethynylanilines towards 2-hydroxy-2-substituted indol-3-ones via a copper-catalyzed radical approach in the presence of O2. The transformation of 2-hydroxy-2-arylindol-3-ones to 3-hydroxy-3-arylindol-2-ones proceeds well with good yields and highlights the practicability and utility of this catalytic system. Mechanistic investigations showed that the acetyl substituent on 2-arylaethynylanilines played an important role in the formation of the cyclic products and the reaction proceeded via an N-center radical-based 5-endo-dig aza-cyclization pathway.
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Cobre , Indóis , Estrutura Molecular , Ciclização , Catálise , Estresse OxidativoRESUMO
Background: Ascending to high altitude can induce a range of physiological and molecular alterations, rendering a proportion of lowlanders unacclimatized. The prediction of acute mountain sickness (AMS) prior to ascent to high altitude remains elusive. Methods: A total of 40 participants were enrolled for our study in the discovery cohort, and plasma samples were collected from all individuals. The subjects were divided into severe AMS-susceptible (sAMS) group, moderate AMS-susceptible (mAMS) group and non-AMS group based on the Lake Louise Score (LLS) at both 5000m and 3700m. Proteomic analysis was conducted on a cohort of 40 individuals to elucidate differentially expressed proteins (DEPs) and associated pathways between AMS-susceptible group and AMS-resistant group at low altitude (1400m) and middle high-altitude (3700m). Subsequently, a validation cohort consisting of 118 individuals was enrolled. The plasma concentration of selected DEPs were quantified using ELISA. Comparative analyses of DEPs among different groups in validation cohort were performed, followed by Receiver Operating Characteristic (ROC) analysis to evaluate the predictive efficiency of DEPs for the occurrence of AMS. Results: The occurrence of the AMS symptoms and LLS differed significantly among the three groups in the discovery cohort (p<0.05), as well as in the validation cohort. Comparison of plasma protein profiles using GO analysis revealed that DEPs were primarily enriched in granulocyte activation, neutrophil mediated immunity, and humoral immune response. The comparison of potential biomarkers between the sAMS group and non-AMS group at low altitude revealed statistically higher levels of AAT, SAP and LTF in sAMS group (p=0.01), with a combined area under the curve(AUC) of 0.965. Compared to the mAMS group at low altitude, both SAP and LTF were found to be significantly elevated in the sAMS group, with a combined AUC of 0.887. HSP90-α and SAP exhibited statistically higher levels in the mAMS group compared to the non-AMS group at low altitude, with a combined AUC of 0.874. Conclusion: Inflammatory and immune related biological processes were significantly different between AMS-susceptible and AMS-resistant groups at low altitude and middle high-altitude. SAP, AAT, LTF and HSP90-α were considered as potential biomarkers at low altitude for the prediction of AMS.
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Doença da Altitude , Humanos , Doença da Altitude/diagnóstico , Doença da Altitude/epidemiologia , Altitude , Proteômica , Doença Aguda , BiomarcadoresRESUMO
Perfluorooctanoic acid (PFOA) is a typical C8 representative compound of perfluoroalkyl and polyfluoroalkyl substances (PFAS) widely used in industrial and domestic products. It is a persistent organic pollutant found in the environment as well as in the tissues of humans and wildlife. Despite emerging scientific and public interest, the precise mechanisms of PFOA toxicity remain unclear. In this study, male rats were exposed to 1.25, 5, and 20 mg PFOA/kg body weight/day for 14 days by gavage; food intake and bodyweight changes were recorded every day. After 14 days, blood was collected for sera biochemistry, livers were quickly stripped and weighed after execution. Part of the liver tissue was frozen by liquid nitrogen for iTRAQ-Based Quantitative Proteomics Analysis; and some was fixed in 4% paraformaldehyde (PFA) for histological section and hematoxylin-eosin (HE) staining. Urine samples were also collected and monitored by raising rats in metabolic cages. Real-time quantitative PCR and western blot was used to validate the proteomics assay after bioinformatics analysis. The results demonstrate that 20 mg/kg/d PFOA exposure cause body weight loss and significant liver swelling and reduced urea metabolism. The sera biochemistry assay shows that ALT, GGT, BILD and UREA levels have significant changes compared with normal control group and reference range of rat sera. The subsequent iTRAQ-based quantitative proteomics analysis of rat livers identified 3,327 non-redundant proteins of which 112 proteins were significantly upregulated and 80 proteins were downregulated. Gene ontology analysis revealed proteins are primarily involved in cellular, metabolic and single-organism processes. Among them, eight proteins (ACOX1, ACOX2, ACOX3, ACSL1, EHHADH, GOT2, MTOR and ACAA1) were related to oxidation of fatty acids and two proteins (ASS1 and CPS1) were found to be associated with urea cycle disorder. The downregulation of urea synthesis proteins ASS1 and CPS1 after exposure to PFOA was then confirmed through qPCR and western blot analysis. Together, these data demonstrate that PFOA exposure directly influences urea metabolism and provides insight into specific mechanisms of hepatotoxicity as a result of PFOA exposure.
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Caprilatos/toxicidade , Fluorocarbonos/toxicidade , Metabolismo dos Lipídeos , Fígado/metabolismo , Proteômica/métodos , Transcriptoma , Ureia/metabolismo , Animais , Poluentes Ambientais/toxicidade , Ácidos Graxos/metabolismo , Expressão Gênica/efeitos dos fármacos , Ontologia Genética , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Polymers have an excellent effect in terms of moderating fast neutrons with rich hydrogen and carbon, which plays an indispensable role in shielding devices. As the shielding of neutrons is typically accompanied by the generation of γ-rays, shielding materials are developed from monomers to multi-component composites, multi-layer structures, and even complex structures. In this paper, based on the typical multilayer structure, the integrated design of the shield component structure and the preparation and performance evaluation of the materials is carried out based on the design sample of the heat-resistant lightweight polymer-based interlayer. Through calculation, the component structure of the polymer-based materials and the three-layer thickness of the shield are obtained. The mass fraction of boron carbide accounts for 11% of the polymer-based material. Since the polymer-based material is the weak link of heat resistance of the multilayer shield, in terms of material selection and modification, the B4C/TiO2/polyimide molded plate was prepared by the hot-pressing method, and characterization analysis was conducted for its structure and properties. The results show that the ball milling method can mix the materials well and realize the uniform dispersion of B4C and TiO2 in the polyimide matrices. Boron carbide particles are evenly distributed in the material. Except for Ti, the other elemental content of the selected areas for mapping is in good agreement with the theoretical values of the elemental content of the system. The prepared B4C/TiO2/polyimide molded plate presents excellent thermal properties, and its glass transition temperature and initial thermal decomposition temperature are as high as 363.6 °C and 572.8 °C, respectively. In addition, the molded plate has good toughness performs well in compression resistance, shock resistance, and thermal aging resistance, which allows it to be used for a long time under 300 °C. Finally, the prepared materials are tested experimentally on an americium beryllium neutron source. The experimental results match the simulation results well.
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Particle-reinforced composites are widely applied as nuclear radiation shielding materials for their excellent comprehensive properties. The work aimed to calculate the influence of the functional reinforced particles spatial arrangement on the neutron shielding performance of composites and attempted to explain the influence mechanism by investigating the neutron flux distribution in the materials. Firstly, four suitable physical models were established based on the Monte Carlo Particle Transport Program (MCNP) and mathematical software MATLAB, namely the RSA (Random Sequential Adsorption) Model with particles random arrangement and FCC Model, BCC Model and Staggered Arrangement Model (SA Model) with particle periodic arrangements. Later, based on these four physical models, the neutron transmittance of two kinds of typical B4C reinforced composites, 316 stainless steel matrix composite and polyethylene matrix composite, were calculated under different energy neutrons sources (0.0253 eV, 50 eV, 50 keV, fission spectrum, 241Am-Be spectrum and 14.1 MeV) and the neutron flux distribution in the 316 stainless steel composite was also analyzed under 0.0253 eV neutron and fission neutron sources. The results indicated that the spatial arrangement of B4C has an impact on the neutrons shielding performance of the composite and the influence changes with neutron energy and B4C content. It can be concluded that the RSA model and the periodic arrangement models can be used in different calculation cases in the future.
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In this research, a high-boron-content composite material with both neutron and γ rays shielding properties was developed by an optimized design and manufacture. It consists of 304 stainless steel as the matrix and spherical boron carbide (B4C) particles as the functional particles. The content of B4C is 24.68 wt%, and the particles' radius is 1.53 mm. The density of the newly designed material is 5.17 g·cm-3, about 68.02% of that of traditional borated stainless steel containing 1.7 wt% boron, while its neutrons shielding performance is much better. Firstly, focusing on shielding properties and material density, the content and the size of B4C were optimized by the Genetic Algorithm (GA) program combined with the MCNP program. Then, some samples of the material were manufactured by the infiltration casting technique according to the optimized results. The actual density of the samples was 5.21 g cm-3. In addition, the neutron and γ rays shielding performance of the samples and borated stainless steel containing 1.7 wt% boron was tested by using an 241Am-Be neutron source and 60Co and 137Cs γ rays sources, respectively, and the results were compared. It can be concluded that the new designed material could be used as a material for nuclear power plants or spent-fuel storage and transportation containers with high requirements for mobility.
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BACKGROUND: Pain on injection is a well-recognized adverse event of propofol administration for the stimulation of general anesthesia. Pre-treatment with lidocaine or flurbiprofen axetil has proven to be effectual in the reduction propofol-induced pain in adults. Nonetheless, only few studies have evaluated the clinical therapeutic effects of lidocaine combination with flurbiprofen axetil to prevent pain on injection of propofol. The current study aims to evaluate the clinical therapeutic effects of lidocaine combination with flurbiprofen axetil to reduce pain on injection of propofol among adult patients. METHODS: The literature search will be conducted from their inception to November 2020 from MEDLINE, EMBASE, Web of Science, and Cochrane Library databases without date or geographical restrictions. However, language will be restricted to publications in English and Chinese. Two authors will independently screen abstracts and titles of all papers to determine whether to include or exclude them. The authors will also study characteristic and outcomes of data extraction and carry out risk of bias assessment. We plan to use either a fixed-effects or random-effects model to estimate the risk ratios (RR) or mean difference (MD) or standardized mean difference (SMD) together with 95% confidence interval (CI). RESULTS: This study will provide high-quality evidence for the clinical therapeutic effects of lidocaine combination with flurbiprofen axetil for reducing pain on injection of propofol in adult patients. CONCLUSION: This study will summarize current evidence for the management of pain on injection of propofol in adult patients and provide guidance for both intervention and future research. ETHICS AND DISSEMINATION: Since no data collection will be involved, there is no need for an ethics approval. REGISTRATION NUMBER: November 17, 2020.osf.io/72tpj/. (https://osf.io/72tpj/).