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1.
Health Qual Life Outcomes ; 19(1): 6, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407538

RESUMO

BACKGROUND: Disability is an increasingly important health-related outcome to consider as more individuals are now aging with Human Immunodeficiency Virus (HIV) and multimorbidity. The HIV Disability Questionnaire (HDQ) is a patient-reported outcome measure (PROM), developed to measure the presence, severity and episodic nature of disability among adults living with HIV. The 69-item HDQ includes six domains: physical, cognitive, mental-emotional symptoms and impairments, uncertainty and worrying about the future, difficulties with day-to-day activities, and challenges to social inclusion. Our aim was to develop a short-form version of the HIV Disability Questionnaire (SF-HDQ) to facilitate use in clinical and community-based practice among adults living with HIV. METHODS: We used Rasch analysis to inform item reduction using an existing dataset of adults living with HIV in Canada (n = 941) and Ireland (n = 96) who completed the HDQ (n = 1037). We evaluated overall model fit with Cronbach's alpha and Person Separation Indices (PSIs) (≥ 0.70 acceptable). Individual items were evaluated for item threshold ordering, fit residuals, differential item functioning (DIF) and unidimensionality. For item threshold ordering, we examined item characteristic curves and threshold maps merging response options of items with disordered thresholds to obtain order. Items with fit residuals > 2.5 or less than - 2.5 and statistically significant after Bonferroni-adjustment were considered for removal. For DIF, we considered removing items with response patterns that varied according to country, age group (≥ 50 years versus < 50 years), and gender. Subscales were considered unidimensional if ≤ 5% of t-tests comparing possible patterns in residuals were significant. RESULTS: We removed 34 items, resulting in a 35-item SF-HDQ with domain structure: physical (10 items); cognitive (3 items); mental-emotional (5 items); uncertainty (5 items); difficulties with day-to-day activities (5 items) and challenges to social inclusion (7 items). Overall models' fit: Cronbach's alphas ranged from 0.78 (cognitive) to 0.85 (physical and mental-emotional) and PSIs from 0.69 (day-to-day activities) to 0.79 (physical and mental-emotional). Three items were rescored to achieve ordered thresholds. All domains demonstrated unidimensionality. Three items with DIF were retained because of their clinical importance. CONCLUSION: The 35-item SF-HDQ offers a brief, comprehensive disability PROM for use in clinical and community-based practice with adults living with HIV.

3.
Int J Biol Macromol ; 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33460654

RESUMO

Herein, the synthetic mechanism of octenyl succinic anhydride (OSA) modified corn starch (OSCS) and granule shells (OSCs) based on shells separation pretreatment (SSP) was investigated. High intensity peaks around 1720 and 1570 cm-1 were observed for OSCs in Fourier transform infrared (FTIR) spectra after SSP. OSCs showed higher degree of substitution (DS) values (ranging from 0.128 to 0.170) than OSCS (0.121) determined by 1H NMR. The average molecular weight (Mw) of OSA modified CS decreased, due to the introduction of OS groups. X-ray diffraction (XRD) indicated that esterification mainly took place in the amorphous regions of starch granules. X-ray photoelectron spectroscopy (XPS) revealed that a new peak corresponding to 1s orbital electrons of Na was obtained due to the introduction of OSA molecules. Meanwhile, lower surface DS and higher fluorescence intensity were noticed for OSCs. Conclusively, SSP would significantly increase the reaction efficiency of OSA modification process of CS.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33465290

RESUMO

Crustacyanin has the function of binding astaxanthin which is the best antioxidant, and plays an important role in the body color variation of crustaceans. To investigate the causes of body color variation of the ridgetail white prawn, Exopalaemon carinicauda, the present study obtained four subtypes of crustacyanin gene: C1, C2, A1, and A2. Based on fluorescence quantitative polymerase chain reaction, lipocalin-C1 is mainly expressed in the eyestalk, lipocalin-C2 is in the ventral nerve cord, and lipocalin-A1 and lipocalin-A2 are in subcutaneous adipose tissues. Under the inhibiting effect of Cd2+ stress, the expression of four subtypes first increases and then decreases within 24 h, and reaches the maximum at 6 or 12 h. RNA interference experiments showed a decrease in the expression of lipocalin genes in subcutaneous adipose tissue for each subtype, with the body color changing from transparent to red, and the dark red spots on the epidermis changing to bright red. Moreover, the blue protein in the subcutaneous adipose tissue largely disappeared, based on the light micrographs. In view of these findings, the crustacyanin gene appears to fulfill some function in the resistance to heavy metal stress and body color formation of E. carinicauda.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33444649

RESUMO

BACKGROUND: The endocannabinoid system has been suggested to modulate energy metabolism and stress response and could be an important factor in the pathophysiology of anorexia nervosa (AN). In the context of AN, excessive physical activity may influence endocannabinoid concentrations. The objective of this study was to investigate hair endocannabinoid concentrations at different stages of the disorder. Measurement in hair allows for a cumulative assessment of endocannabinoid concentrations independent of circadian rhythms. METHODS: In a combined cross-sectional and longitudinal design, we measured hair concentrations of the endocannabinoids anandamide and 2-arachidonoylglycerol and the endocannabinoid-related compounds palmitoylethanolamide, oleoylethanolamide, and stearoylethanolamide in female underweight patients with acute AN (n = 67, reassessment of n = 47 after short-term weight restoration with a body mass index increase of at least 14%), individuals long-term recovered from AN (n = 27), and healthy control participants (n = 84). RESULTS: Hair concentrations of anandamide and all endocannabinoid-related compounds were elevated in acute AN and decreased over the course of short-term weight restoration. Anandamide concentrations remained elevated in long-term recovered AN patients. In long-term recovered patients, physical activity correlated positively with the concentrations of all endocannabinoid-related compounds. CONCLUSION: The current study provides evidence for a significant alteration of the endocannabinoid system in acute AN, which may partly persist into long-term recovery. The endocannabinoid system may be a possible target for pharmaceutical interventions in AN, which should be explored in further preclinical and subsequently clinical randomized controlled trials.

6.
Sci Rep ; 11(1): 1456, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446871

RESUMO

In this study, sediments were collected from two different sites in the deep-sea hydrothermal region of the South Atlantic Ocean. Two microbial enrichment cultures (H7S and H11S), which were enriched from the sediments collected at two sample sites, could effectively degrade petroleum hydrocarbons. The bacterial diversity was analyzed by high-throughput sequencing method. The petroleum degradation ability were evaluated by gas chromatography-mass spectrometry and gravimetric analysis. We found that the dominant oil-degrading bacteria of enrichment cultures from the deep-sea hydrothermal area belonged to the genera Pseudomonas, Nitratireductor, Acinetobacter, and Brevundimonas. After a 14-day degradation experiment, the enrichment culture H11S, which was obtained near a hydrothermal vent, exhibited a higher degradation efficiency for alkanes (95%) and polycyclic aromatic hydrocarbons (88%) than the enrichment culture H7S. Interestingly, pristane and phytane as biomarkers were degraded up to 90% and 91% respectively by the enrichment culture H11S, and six culturable oil-degrading bacterial strains were isolated. Acinetobacter junii strain H11S-25, Nitratireductor sp. strain H11S-31 and Pseudomonas sp. strain H11S-28 were used at a density ratio of 95:4:1 to construct high-efficiency oil-degrading consortium H. After a three-day biodegradation experiment, consortium H showed high degradation efficiencies of 74.2% and 65.7% for total alkanes and PAHs, respectively. The degradation efficiency of biomarkers such as pristane and high-molecular-weight polycyclic aromatic hydrocarbons (such as CHR) reached 84.5% and 80.48%, respectively. The findings of this study indicate that the microorganisms in the deep-sea hydrothermal area are potential resources for degrading petroleum hydrocarbons. Consortium H, which was artificially constructed, showed a highly efficient oil-degrading capacity and has significant application prospects in oil pollution bioremediation.

7.
Langmuir ; 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33448224

RESUMO

Developments in spinning systems have triggered revolutions ranging from bioengineering tissue scaffolds to emerging smart wearable fabrics, but the structures of the spinning fibers are usually limited by intrinsic channel configurations and the "dead" nozzle's geometry. In contrast, natural living systems, such as a spider spinning apparatus, use a "live" gate to coordinate microstructures via shearing and expanding at both axial and radial directions. Herein, for the first time, we introduce a dynamic liquid gating effect in artificial systems to mimic the spinning in biological organisms. Theoretical modeling and experimental regime diagram demonstrate that the topographies and microstructures of the fibers self-evolve after passing through the liquid gate and they could be tuned over a wide range, which successfully exceeds the limits of current "dead" spinning channels. In particular, fibers with a periodic spindle-knot structure self-evolve from a water gate and show fast directional water collecting and intelligent sensing ability. The liquid gating design not only sheds new light on fiber structure control in multiple spatiotemporal dimensions but also contributes to the development of high-performance fibers with sophisticated functions.

8.
Int J Med Sci ; 18(2): 555-563, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33390825

RESUMO

Farfarae Flos is a traditional Chinese medicine that has long been used to treat allergies. In this study, we aimed to investigate the effect of a petroleum extract of Farfarae Flos (PEFF) in a mouse model of allergic rhinitis (AR) and to explore the underlying molecular mechanisms of action. An animal model of AR was established by sensitization and challenge of BALB/c mice with ovalbumin (OVA). PEFF was administered intranasally and AR nasal symptoms were assessed on a semi-quantitative scale according to the frequencies of nose rubbing and sneezing and the degree of rhinorrhea. The mechanism of action of PEFF was evaluated by histological analysis of nasal mucosa architecture and inflammatory status; ELISA-based quantification of serum OVA-specific IgE, interferon-γ (IFN-γ), and interleukin-4 (IL-4) concentrations; and immunohistochemical and western blot analysis of T-bet and GATA3 protein expression in nasal mucosa and spleen tissues. The results showed intranasal administration of PEFF alleviated AR symptom scores and reduced both the infiltration of inflammatory cells and tissue damage in the nasal mucosa. PEFF significantly decreased serum concentrations of OVA-specific IgE (P<0.01) and IL-4 (P<0.05) and significantly increased IFN-γ (P<0.01). PEFF also upregulated the expression of T-bet protein (P<0.05) but downregulated GATA3 protein (P<0.05) in nasal mucosa and spleen tissues. In conclusion, PEFF effectively reduces AR nasal symptoms and serum IgE levels in a mouse model and may act by correcting the imbalance between Th1 and Th2 responses.

9.
Theranostics ; 11(2): 878-892, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391510

RESUMO

Purpose: To identify extracellular vesicle (EV)-delivered microRNAs in the patient's serum as indicators for bone-metastatic prostate cancer. Methods: First, the profiling change of serum EV-delivered miRNAs in patients with either benign prostatic hyperplasia (BPH), non-bone metastatic prostate cancer or bone-metastatic prostate cancer was detected by microRNA deep sequencing assay and microRNA-chip array assay, respectively. Second, the candidates were further confirmed using TaqMan microRNA assay in two independent validation cohorts of total 176 patients with either BPH, non-bone metastatic prostate cancer or bone metastatic prostate cancer to seek the most valuable microRNA(s). Results: Through microRNA deep sequencing and microRNA-chip array, we found 4 prospective EV-delivered miRNAs including miR-181a-5p with significantly upregulated expression in bone metastatic groups than in non-bone metastatic prostate cancer groups (p < 0.05). In the validation cohorts, logistic regression analysis was performed to evaluate the diagnostic association of candidates with bone metastasis, which indicated that miR-181a-5p was significantly associated with bone metastatic prostate cancer. Furthermore, accuracy estimate of each candidate for the diagnosis of bone metastatic prostate cancer was quantified using the area under the receiver-operating characteristic curve (AUC), which identified miR-181a-5p as the best biomarker with the AUCs of 85.6% for diagnosis of prostate cancer and 73.8% for diagnosis of bone metastatic prostate cancer. Conclusion: EV-delivered miR-181a-5p from patient's serum is a promising diagnostic biomarker for bone metastatic prostate cancer.

10.
J Pharmacol Exp Ther ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33414131

RESUMO

Short-chain fatty acids (SCFAs) are metabolites produced almost exclusively by the gut microbiota and are an essential mechanism by which gut microbes influence host physiology. Given that SCFAs induce vasodilation, we hypothesized that they might have additional cardiovascular effects. In this study, novel mechanisms of SCFA action were uncovered by examining the acute effects of SCFAs on cardiovascular physiology in vivo and ex vivo Acute delivery of SCFAs in conscious radiotelemetry implanted mice results in a simultaneous decrease in both mean arterial pressure and heart rate. Inhibition of sympathetic tone by the selective ß-1 adrenergic receptor antagonist atenolol blocks the acute drop in HR seen with acetate administration, yet the decrease in mean arterial pressure persists. Treatment with tyramine, an indirect sympathomimetic, also blocks the acetate-induced acute drop in HR. Langendorff preparations show that acetate lowers HR only after long term exposure and at a smaller magnitude than seen in vivo. Pressure-volume loops after acetate injection show a decrease in load-independent measures of cardiac contractility. Isolated trabecular muscle preparations also show a reduction in force generation upon SCFA treatment, though only at supraphysiological concentrations. These experiments demonstrate a direct cardiac component of the SCFA cardiovascular response. These data show that acetate affects blood pressure and cardiac function through parallel mechanisms and establish a role for SCFAs in modulating sympathetic tone and cardiac contractility. These results further advance our understanding of the role of SCFAs in blood pressure regulation. Significance Statement Acetate, a short-chain fatty acid, acutely lowers HR as well as MAP in vivo in radiotelemetry implanted mice. Acetate is acting in a sympatholytic manner on HR and exerts negative inotropic effects in vivo This work has implications for potential short-chain fatty acid therapeutics as well as gut dysbiosis-related disease states.

11.
Inorg Chem ; 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33417439

RESUMO

It is of great research interest to understand the nanostructures contributing to the activity observed in the reduction of oxygen by non-platinum group metal (PGM) electrocatalysts in acidic media. Iron- and nitrogen-containing carbon networks are often the most studied structures, among which single-atom iron-coordinated nitrogen (FeNx) moieties have often been proposed to be the structures leading to the high activity in these non-PGM electrocatalysts. Iron nanoparticles embedded within a carbon support are also formed under certain conditions as a result of the synthetic processes in making non-PGM electrocatalysts. In this study, we present a study to understand the oxygen reduction reaction (ORR) activity of prepared iron- and nitrogen-containing non-PGM electrocatalysts obtained through the pyrolysis of metal-organic framework (MOF) precursors. We studied the structure-property relationship among nanostructures made from the MOF precursor ZIF-8 under different pyrolysis conditions. Density functional theory calculations were used to explain the effect of structural moieties on the ORR activity. Our results suggest that iron-coordinated C-N structures and iron nanoparticles act synergistically to catalyze the ORR.

12.
Crit Rev Food Sci Nutr ; : 1-11, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33401939

RESUMO

With increasing awareness of environmental protection, petroleum-based raw materials are continuously decreasing, which in turn necessitated the development of eco-friendly sustainable biomaterials, as alternative strategy. Starch could be an ideal substitute. Corn starch has been used as a renewable material for development of biodegradable packaging, owing to great varieties, low cost, large-scale industrial production, and good films forming properties. Unfortunately, its poor mechanical and barrier properties have limited the application of starch-based films. Thence, plasticizers were added to overcome the aforementioned pitfalls and improve the films elongation, distribution, flexibility, elasticity, and rigidity. Addition of plasticizers can change the continuity and therefore would enhance the properties of corn starch-based films. While plasticization can improve the tensile strength and percent elongation, it can reduce the water resistance in prepared films. Herein, we focused on changes of starch granules during gelatinization process, types of biodegradable films, as well as the types of modified starch with plasticizers. Furthermore, the influence of plasticizers on corn starch-based films and the physicochemical properties of various types of corn starch-based films were also addressed.

13.
Ecotoxicol Environ Saf ; 208: 111655, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396169

RESUMO

An enormous amount of oil-containing drill cuttings have been produced by the marine oil and gas industry. The environmental impacts of discharged drilling waste have been extensively studied. However, there is still an urgent need to develop alternative methods to identify the genotoxicity of untreated and treated drill waste in a timely manner before it is discharged. In this study, we developed a relatively rapid, sensitive, and accurate genotoxicity-detection method using Comet assay and the marine benthic goby Mugilogobius chulae. This goby is sensitive to a standard toxicant mitomycin C (MMC). The optimal exposure period for genotoxicity detection using M. chulae was determined. Three genotoxic indices (tail length (TL), tail DNA content (TD), and tail moment (TM)) were used to assess the effectiveness of high-temperature treatment of oil-contaminated waste. Untreated oil-containing drill cuttings exhibited the highest genotoxicity to goby cells. Genotoxicity was dramatically reduced after thermal treatment of drill cuttings at 350 °C and 500 °C. TD and TM exhibited significant correlation with the concentration of total petroleum hydrocarbons (TPHs)/total polycyclic aromatic hydrocarbons (PAHs) according to Pearson and Mantel correlation analyses (P values were <0.05). Using redundancy analysis (RDA) and variation partition analysis (VPA), the genotoxic effects of the drill cuttings were ascribed to total alkanes and specific groups of PAHs. In conclusion, this newly established biological model has the potential to be widely used to detect the genetic damage of untreated or treated oil-containing drill cuttings discharged into the marine environment.

14.
Metab Brain Dis ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33411215

RESUMO

Cobalamin C (cblC) disease and Kallmann syndrome (KS) are rare hereditary diseases. To date, no report has described the coexistence of those two genetic disorders in the same patient, or an association between them. We report the case of a 23-year-old woman with cblC defect and KS. She first presented mild memory problems in puberty, which worsened in adulthood to progressive memory loss accompanied by slow and unsteady walking, slow response, inattention, cognitive impairment, insomnia, no sense of smell, and the lack of spontaneous puberty. Laboratory tests revealed gonadotropin deficiency, a low estrogen level, and remarkably elevated serum homocysteine and serum and urine organic acid levels. Whole-exome sequencing detected compound heterozygous variants in MMACHC [c.398_399del (p.Gln133Argfs*4) and c.482G > A (p.Arg161Gln)] and heterozygous variants in PROKR2 [c.337T > C (p.Tyr113His)]. Thus, clinical and genetic examinations confirmed the cblC disease and KS diagnoses. This report on coexisting cblC disease and KS caused by different pathogenic genes in a single patient enriches the clinical research on these two rare genetic diseases.

15.
Eur J Anaesthesiol ; Publish Ahead of Print2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33399382

RESUMO

BACKGROUND: The glycocalyx plays an important physiological role and may be damaged during cardiopulmonary bypass. Sevoflurane can protect the glycocalyx; however, its relevance in a clinical setting is unknown. OBJECTIVE: Glycocalyx degradation during cardiopulmonary bypass in patients was investigated. On the basis of the available experimental data, we hypothesised that sevoflurane-based anaesthesia would confer additional protection against cardiopulmonary bypass-induced glycocalyx damage. DESIGN: Randomised controlled study. SETTING: Clinical study at The First Affiliated Hospital of Wenzhou Medical University between June 2018 and March 2019. PATIENTS: Fifty-one patients. INTERVENTIONS: After intubation and mechanical ventilation, patients undergoing elective heart valve surgery were maintained under general anaesthesia with either propofol or sevoflurane during surgery. MAIN OUTCOME MEASURES: Glycocalyx markers (such as syndecan-1, heparan sulphate and hyaluronan), sheddases responsible for the degradation of the endothelial glycocalyx (such as matrix metalloproteinase-9 and cathepsin-B), urine albumin-to-creatinine ratio and levels of lactic acid and myocardial enzymes were all measured. Postoperative mechanical ventilation time and length of stay in the cardiac care unit and hospital were also measured. Morbidity and mortality after 30 days and 1 year were evaluated. RESULTS: The vascular endothelial glycocalyx was damaged during cardiopulmonary bypass. The glycocalyx damage in the sevoflurane group was less extensive than that in the propofol group. The urine albumin-to-creatinine ratio increased in both groups but was lower in the sevoflurane group. Enzymes including matrix metalloproteinase-9 and cathepsin-B were positively correlated with glycocalyx marker concentrations. After operation, the sevoflurane group showed lower levels of lactic acid and myocardial enzyme, as well as shorter duration of postoperative mechanical ventilation than the propofol group. CONCLUSION: Sevoflurane can decrease glycocalyx degradation in patients undergoing heart valve surgery under cardiopulmonary bypass. TRIAL REGISTRATION: Chinese Clinical Trial Registry, chictr.org.cn, identifier: ChiCTR1800016367.

16.
Lett Appl Microbiol ; 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33386625

RESUMO

Sialic acid (N-acetylneuraminic acid), a 9-carbon monosaccharide, has been widely studied in immunology, oncology, and neurology. However, the effects of sialic acid on organ and intestinal development, liver function and gut microbiota were rarely studied. In this study, we found that oral sialic acid tended to increase the relative weight of liver and decreased the serum aspartate aminotransferase (GPT) activity. In addition, sialic acid treatment markedly reduced gut villus length, depth, the ratio of villus length/depth (L/D), areas, width, and the number of goblet cells. Furthermore, gut microbes were changed in response to oral oral sialic acid, such as Staphylococcus lentus, Corynebacterium stationis, Corynebacterium urealyticum, Jeotgalibaca sp_PTS2502, Ignatzschineria indica, Sporosarcina pasteurii, Sporosarcina sp_HW10C2, Facklamia tabacinasalis, Oblitimonas alkaliphila, Erysipelatoclostridium ramosum, Blautia sp_YL58, Bacteroids thetaiotaomicron, Morganella morganii, Clostridioides difficile, Helicobacter tryphlonius, Clostridium sp_Clone47, Alistipes finegoldii, [pseudomonas]_geniculata and Pseudomonas parafulva at the species level. In conclusion, oral sialic acid altered the intestinal pathological state and microbial compositions, and the effect of sialic acid on host health should be further studied.

17.
Biochem Biophys Res Commun ; 534: 193-198, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33280820

RESUMO

Vaccination evoking immunity in susceptible individuals has become the most effective solution to combat infectious diseases. The surface antigen of hepatitis B virus (HBsAg) is a mandatory vaccine for children in China. Herein, we designed an antimicrobial protein consisting of an antimicrobial peptide Thanatin at the N-terminus fused with the HBsAg at the C-terminus. The expressed Thanatin-GFP-HBsAg (TGH) quantitively bound with the anti-HBsAg antibody by ELISA, and after exposure to TGH, Gram-negative E. coli cells became fluorescencent indicating the binding of TGH with the bacterial cells. We also demonstrated that TGH could intercalated into the lipid bilayer as shown by the quartz crystal microbalance with dissipation (QCM-D) and TEM. Moreover, the TGH bound E. coli cells attracted anti-HBsAg IgG as shown by the experiments that in turn treated the E. coli cells with TGF, anti-HBsAg serum and PE labelled goat anti-mouse IgG antibodies. After supplementation with serum from HBsAg vaccinated individuals, TGH showed improved bactericidal effect in vitro. In vivo experiments showed that the mice receiving TGH vaccination show quicker clearance of MDR E. coli pretreated with TGH and better survive in comparison with groups treated with piperacillin plus subatan. In addition, anti-HBsAg serum supplementation also improved the endocytosis of TGH decorated bacteria by leukocytes. This study reported a novel solution to combat infectious pathogens based on the membrane penetrating effect of antimicrobial peptides.

18.
Environ Sci Technol ; 55(1): 230-239, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33307673

RESUMO

The presence of anthropogenically emitted chlorinated paraffins (CPs) has been reported in the pristine regions, providing evidence of their long-range transport. This study comprehensively analyzed the short-chain chlorinated paraffins (SCCPs) and medium-chain chlorinated paraffins (MCCPs) in both gas and particle phases at King George Island, West Antarctica (the Chinese Great Wall Station), from 2014 to 2018. The atmospheric levels of CPs ranged between 71.4 and 4230 pg/m3, with an increasing temporal trend during the sampling time. Three different models (J-P model, H-B model, and L-M-Y model) were built to estimate the progress of gas/particle partitioning of CPs at the measurement site. Furthermore, we compared the measured data of the gas/particle partitioning with the data estimated using three different models. We found that the steady-state model (L-M-Y model) was more suitable for investigating the gas/particle partitioning of CPs instead of equilibrium state models (J-P model and H-B model). The result indicated that steady-state approximation rather than the equilibrium state represents the most predominant contribution to the transport of CPs to the Antarctic region. The steady-state further made it conducive to sustaining the levels of CPs for a more extended period in the atmosphere of West Antarctica.

19.
Biochem Biophys Res Commun ; 534: 34-40, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33310185

RESUMO

Abnormal crosstalk between gut immune and the liver was involved in nonalcoholic steatohepatitis (NASH). Mice with methionine choline-deficient (MCD) diet-induced NASH presented an imbalance of pro-(IL-6 and IFN-γ) and anti-inflammatory cytokines (IL-10) in the intestine. We also clarified that the ratio of CD4+ T cells and found that the NASH mesenteric lymph node (MLN) presents decreased numbers of CD4+Th17 cells but increased numbers of CD4+CD8+FoxP3+ regulatory T cells (Tregs). Furthermore, the intestinal immune imbalance in NASH was attributed to impaired gut chemokine receptor 9 (CCR9)/chemokine ligand 25 (CCL25) signalling, which is a crucial pathway for immune cell homing in the gut. We also demonstrated that CD4+CCR9+ T cell homing was dependent on CCL25 and that the numbers and migration abilities of CD4+CCR9+ T cells were reduced in NASH. Interestingly, the analysis of dendritic cell (DC) subsets showed that the numbers and retinal dehydrogenase (RALDH) activity of CD103+CD11b+ DCs were decreased and that the ability of these cells to upregulate CD4+ T cell CCR9 expression was damaged in NASH. Taken together, impaired intestinal CCR9/CCL25 signalling induced by CD103+CD11b+ DC dysfunction contributes to the gut immune imbalance observed in NASH.

20.
J Clin Pharmacol ; 61(2): 254-268, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32949031

RESUMO

Ceftolozane/tazobactam (C/T) is a combination of a novel cephalosporin with tazobactam, recently approved for the treatment of hospital-acquired and ventilator-associated pneumonia. The plasma pharmacokinetics (PK) of a 3-g dose of C/T (2 g ceftolozane and 1 g tazobactam) administered via a 1-hour infusion every 8 hours in adult patients with nosocomial pneumonia (NP) were evaluated in a phase 3 study (ASPECT-NP; NCT02070757). The present work describes the development of population PK models for ceftolozane and tazobactam in plasma and pulmonary epithelial lining fluid (ELF). The concentration-time profiles of both agents were well characterized by 2-compartment models with zero-order input and first-order elimination. Consistent with the elimination pathway, renal function estimated by creatinine clearance significantly affected the clearance of ceftolozane and tazobactam. The central volumes of distribution for both agents and the peripheral volume of distribution for tazobactam were approximately 2-fold higher in patients with pneumonia compared with healthy participants. A hypothetical link model was developed to describe ceftolozane and tazobactam disposition in ELF in healthy participants and patients with pneumonia. Influx (from plasma to the ELF compartment) and elimination (from the ELF compartment) rate constants were approximately 97% lower for ceftolozane and 52% lower for tazobactam in patients with pneumonia versus healthy participants. These population PK models adequately described the plasma and ELF concentrations of ceftolozane and tazobactam, thus providing a foundation for further modeling and simulation, including the probability of target attainment assessments to support dose recommendations of C/T in adult patients with NP.

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