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Serum alkaline phosphatase (ALP) and the enhanced liver fibrosis (ELF) score are used as endpoints in trials of patients with primary sclerosing cholangitis (PSC). We aimed to quantify inter- and intra-individual variation in levels of ALP and the ELF score over time, and evaluated their association with fibrosis progression. We analyzed data from 234 patients with large-duct PSC enrolled in a 2-year, phase 2b placebo-controlled trial of simtuzumab. Participants were assessed by laboratory tests every 4 weeks, and liver biopsies collected at time of screening, week 48, and week 96. Serum levels of ALP and ELF scores did not differ significantly between simtuzumab and placebo groups, so the data were pooled. Median per-patient variations in ALP between clinic visits were approximately 12% over 12 weeks, 20% over 48 weeks, and 20% over 96 weeks. Reductions, unrelated to study intervention, of more than 40% in ALP were observed in 10.9% of patients with baseline activity greater than 2-fold the upper limit of normal (ULN) and 12.5% of patients with more than 3-fold the ULN at 1 year. At 2 years, reductions of more than 40% in ALP were observed in 15.8% of patients with baseline activity greater than 2-fold the ULN and 17.9% of patients with more than 3-fold the ULN. Among the 209 patients with Ishak fibrosis stage 0–4 at baseline, serum ALP activity did not associate with development of cirrhosis or with a 2-point increase in fibrosis stage at 2 years. In contrast, the median per-patient variation in ELF scores between clinic visits was approximately 3% over 12 weeks, 4% over 48 weeks, and 4% over 96 weeks. Elevated ELF scores at baseline and at weeks 12, 24 and 48, each associated with development of cirrhosis at 2 years (odds ratio >2.75; P <.01 for all timepoints). ELF scores at baseline and weeks 12, 24 and 48, also associated with a 2-point increase in fibrosis stage at 2 years (odds ratios all greater than 2; P <.01 for all timepoints). In an analysis of data from patients with large-duct PSC enrolled in a prospective trial, we found large interindividual and intraindividual variations in serum ALP activity. Serum ALP activity did not associate with disease progression over a 2-year period. Variations in ELF score were smaller, and scores determined at multiple timepoints associated with fibrosis progression and development of cirrhosis. [Display omitted] [ABSTRACT FROM AUTHOR]

Purpose: To examine the relationship between lung radiation dose and survival outcomes in children undergoing total body irradiation (TBI)-based hematopoietic stem cell transplantation (HSCT) for acute lymphoblastic leukemia on the Children's Oncology Group trial.Methods and Materials: TBI (1200 or 1320 cGy given twice daily in 6 or 8 fractions) was used as part of 3 HSCT preparative regimens, allowing institutional flexibility regarding TBI techniques, including lung shielding. Lung doses as reported by each participating institution were calculated for different patient setups, with and without shielding, with a variety of dose calculation techniques. The association between lung dose and transplant-related mortality, relapse-free survival, and overall survival (OS) was examined using the Cox proportional hazards regression model controlling for the following variables: TBI dose rate, TBI fields, patient position during TBI, donor type, and pre-HSCT minimal residual disease level.Results: Of a total of 143 eligible patients, 127 had lung doses available for this analysis. The TBI techniques were heterogeneous. The mean lung dose was reported as 904.5 cGy (standard deviation, ±232.3). Patients treated with lateral fields were more likely to receive lung doses ≥800 cGy (P < .001). The influence of lung dose ≥800 cGy on transplant-related mortality was not significant (hazard ratio [HR], 1.78; P = .21). On univariate analysis, lung dose ≥800 cGy was associated with inferior relapse-free survival (HR, 1.76; P = .04) and OS (HR, 1.85; P = .03). In the multivariate analysis, OS maintained statistical significance (HR, 1.85; P = .04).Conclusions: The variability in TBI techniques resulted in uncertainty with reported lung doses. Lateral fields were associated with higher lung dose, and thus they should be avoided. Patients treated with lung dose <800 cGy in this study had better outcomes. This approach is currently being investigated in the Children's Oncology Group AALL1331 study. Additionally, the Imaging and Radiation Oncology Core Group is evaluating effects of TBI techniques on lung doses using a phantom. [ABSTRACT FROM AUTHOR]

Primary sclerosing cholangitis (PSC) is a major unmet medical need in clinical hepatology. Cilofexor is a nonsteroidal farnesoid X receptor agonist being evaluated for the treatment of PSC. Here, we describe the safety and preliminary efficacy of cilofexor in a 96-week, open-label extension (OLE) of a phase II trial. Noncirrhotic subjects with large-duct PSC who completed the 12-week, blinded phase of a phase II study (NCT02943460) were eligible, after a 4-week washout period, for a 96-week OLE with cilofexor 100 mg daily. Safety, liver biochemistry, and serum markers of fibrosis, cellular injury, and pharmacodynamic effects of cilofexor (fibroblast growth factor 19, C4, and bile acids [BAs]) were evaluated. Among 52 subjects enrolled in the phase II study, 47 (90%) continued in the OLE phase (median age, 44 years; 60% male patients, 60% with inflammatory bowel disease, and 45% on ursodeoxycholic acid [UDCA]). At OLE baseline (BL), the median serum alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) were 368 U/L (interquartile range [IQR], 277–468 U/L) and 417 U/L (IQR, 196–801 U/L), respectively. Of the 47 subjects enrolled, 15 (32%) discontinued treatment prematurely (pruritus [n = 5], other adverse events [n = 5], subject decision/investigator discretion [n = 5]). At week 96, reductions in liver biochemistry parameters occurred, including serum ALP (median, −8.3% [IQR, −25.9% to 11.0%]; P =.066), GGT (−29.8% [IQR, −42.3% to −13.9%]; P <.001), alanine aminotransaminase (ALT) (−29.8% [IQR, −43.7% to −6.6%]; P =.002), and aspartate aminotransaminase (AST) (−16.7% [IQR, −35.3% to 1.0%]; P =.010), and rebounded after 4 weeks of untreated follow-up. ALP response (≥20% reduction from BL to week 96) was similar in the presence or absence of UDCA therapy (29% vs 39%; P =.71). At week 96, cilofexor treatment was associated with a significant reduction in serum 7α-hydroxy-4-cholesten-3-one (C4) (−29.8% [IQR, −64.3% to −8.5%]; P =.001). In subjects with detectable serum BAs at BL (n = 40), BAs decreased −23.9% (IQR, −44.4% to −0.6%; P =.006) at week 48 (n = 28) and −25.7% (IQR, −35.9% to 53.7%; P =.91) at week 96 (n = 26). Serum cytokeratin 18 (CK18) M30 and M65 were reduced throughout the OLE; significant reductions were observed at week 72 (CK18 M30, −17.3% [IQR, −39.3% to 8.8%]; P =.018; CK18 M65, −43.5% [IQR, −54.9% to 15.3%]; P =.096). At week 96, a small, but statistically significant absolute increase of 0.15 units in Enhanced Liver Fibrosis score was observed compared with BL (median, 9.34 vs 9.53; P =.028). In this 96-week OLE of a phase II study of PSC, cilofexor was safe and improved liver biochemistry and biomarkers of cholestasis and cellular injury. ClinicalTrials.gov identifier: NCT02943460 [ABSTRACT FROM AUTHOR]

Abstract: Objective: To assess the relationship between exercise tolerance test (ETT) performance at 6 weeks poststroke and subsequent performance in a treadmill and overground locomotor training program (LTP). Design: Prospective cohort study. Setting: Exercise testing laboratory in either a primary care hospital or outpatient clinic. Participants: Community-dwelling individuals (N=469), 54.9±19.0 days poststroke, enrolled in the Locomotor Experience Applied Post-Stroke randomized controlled trial. Interventions: Not applicable. Main Outcome Measures: For participants randomly assigned to LTP, the number of sessions needed to attain the training goal of 20 minutes of treadmill stepping was determined. Regression analyses determined the contribution of ETT performance (cycling duration), age, and 6-minute walk test (6MWT) distance to attainment of the stepping duration goal. Results: Age, 6MWT, and ETT performance individually accounted for 10.74%, 10.82%, and 10.76%, respectively, of the variance in the number of sessions needed to attain 20 minutes of stepping. When age and 6MWT were included in the model, the additional contribution of ETT performance was rendered nonsignificant (P=.150). Conclusions: To the extent that ETT performance can be viewed as a measure of cardiovascular fitness rather than neurologic impairment, cardiovascular fitness at the time of the ETT did not make a significant unique contribution to the number of sessions needed to achieve 20 minutes of stepping. The 6MWT, which involves less intensive exercise than the ETT and therefore is likely to be predominantly affected by neurologic impairment and muscular condition, appeared to account for as much variance as the ETT. [Copyright &y& Elsevier]

Abstract: The plant growth, nitrogen absorption, and assimilation in watermelon (Citrullus lanatus [Thunb.] Mansf.) were investigated in self-grafted and grafted seedlings using the salt-tolerant bottle gourd rootstock Chaofeng Kangshengwang (Lagenaria siceraria Standl.) exposed to 100mM NaCl for 3d. The biomass and NO3 − uptake rate were significantly increased by rootstock while these values were remarkably decreased by salt stress. However, compared with self-grafted plants, rootstock-grafted plants showed higher salt tolerance with higher biomass and NO3 − uptake rate under salt stress. Salinity induced strong accumulation of nitrate, ammonium and protein contents and a significant decrease of nitrogen content and the activities of nitrate reductase (NR), nitrite reductase (NiR), glutamine synthetase (GS), and glutamate synthase (GOGAT) in leaves of self-grafted seedlings. In contrast, salt stress caused a remarkable decrease in nitrate content and the activities of GS and GOGAT, and a significant increase of ammonium, protein, and nitrogen contents and NR activity, in leaves of rootstock-grafted seedlings. Compared with that of self-grafted seedlings, the ammonium content in leaves of rootstock-grafted seedlings was much lower under salt stress. Glutamate dehydrogenase (GDH) activity was notably enhanced in leaves of rootstock-grafted seedlings, whereas it was significantly inhibited in leaves of self-grafted seedlings, under salinity stress. Three GDH isozymes were isolated by native gel electrophoresis and their expressions were greatly enhanced in leaves of rootstock-grafted seedlings than those of self-grafted seedlings under both normal and salt-stress conditions. These results indicated that the salt tolerance of rootstock-grafted seedlings might (be enhanced) owing to the higher nitrogen absorption and the higher activities of enzymes for nitrogen assimilation induced by the rootstock. Furthermore, the detoxification of ammonium by GDH when the GS/GOGAT pathway was inhibited under salt stress might play an important role in the release of salt stress in rootstock-grafted seedlings. [Copyright &y& Elsevier]

When a frequency oscillation occurs, effective control measures should be taken to suppress the oscillation as soon as possible to avoid subsequent failures caused by the oscillation. Prime movers, including governors and turbines, with negative damping are the major cause of frequency oscillations, and quitting the primary frequency regulations of these units can increase the damping ratio of the system mode and make the oscillation decay. The dissipation energy flow method is further developed to evaluate the damping of prime movers for emergency control. The dissipation energy flow into the prime movers is computed online using phasor measurement data of 2–3 oscillation periods and is then used to evaluate the damping of the prime movers. The primary frequency regulations of the units with the lowest damping are quit to suppress the oscillation. The procedure of online emergency control is presented. Test results verify the validity of the proposed approach. [ABSTRACT FROM AUTHOR]

Rhizosphere-enriched microbes induced by foliar phytopathogen infection can be assembled into a functional community to enhance plant defense mechanisms. However, the functions of stably-colonizing rhizosphere microbiota are rarely investigated. In this study, Botrytis cinerea infection changed rhizosphere bacterial communities in tomato plants. The phytopathogen-infected plants recruited specific rhizosphere bacterial taxa, while several bacterial taxa stably colonized the rhizosphere, regardless of phytopathogen infection. Through the analysis of the rhizosphere bacterial community, we established a synthetic community harboring 8 phytopathogen-inducible and 30 stably-colonizing bacteria species. Furthermore, the 38-species community was simplified into a three-species community, consisting of one phytopathogen-inducible (Asticcacaulis sp.) and two stably-colonizing species (Arachidicoccus sp. And Phenylobacterium sp.). The simplified community provided a durable protection for the host plants by synergistic effects, with the phytopathogen-inducible species triggering plant defense responses and the stably-colonizing species promoting biofilm formation. The simplified community exhibited similar protective effects as the 38-species community. Moreover, the activation of oxylipin pathways in the phytopathogen-infected leaves was significantly intensified by the simplified community. However, the inhibited biosynthesis of antimicrobial divinyl ethers, including colneleic and colnelenic acid, fully abolished the community-induced plant disease resistance. In contrast, transgenic plants overexpressing SlLOX5 and SlDES1 , with higher levels of divinyl ethers, displayed stronger resistance against B. cinerea compared to wild-type plants. Collectively, these findings provided insights into the utilization of the simplified community for preventing gray mold disease. • Botrytis cinerea -infected tomato reshaped rhizosphere microbiome. • A simplified synthetic community activated plant oxylipin pathways. • Overexpression of SlLOX5 and SlDES1 increased disease resistance in tomato. [ABSTRACT FROM AUTHOR]

• Arhgef1 is highly expressed in NSCs. • Arhgef1 deficiency decreased self-renewal and proliferation of NSCs. • Arhgef1 deficiency in NSCs increased the neurogenesis. • Regulator effect of Arhgef1 on NSCs involves cell cycle pathway. The role of the Arhgef1 as a RhoA-specific guanine nucleotide exchange factor has been widely investigated in the immune system. Our previous findings reveal that Arhgef 1 is highly expressed in neural stem cells (NSCs) and controls the process of neurite formation. However, the functional role of Arhgef 1 in NSCs remains poorly understood. In order to investigate the role of Arhgef 1 in NSCs, Arhgef 1 expression in NSCs was reduced by using lentivirus-mediated short hairpin RNA interference. Our results indicate that down-regulated expression of Arhgef 1 reduced the self-renewal, proliferation capacity of NSCs and affect cell fate determination. In addition, the comparative transcriptome analysis from RNA-seq data determines the mechanisms of deficits in Arhgef 1 knockdown NSCs. Altogether, our present studies show that Arhgef 1 down-regulation leads to interruption of the cell cycle procession. The importance of Arhgef 1 for regulating self-renewal, proliferation and differentiation in NSCs is reported for the first time. [ABSTRACT FROM AUTHOR]

• Copigmentation effect of KSA and tannic acid was optimal with a molar ratio of 1:150. • Phenolic acid was stronger copigment than dicarboxylic acid through π-π interaction. • Acylation groups in KSA weakened copigmentation effect due to steric hindrance. • Quantum mechanical calculation proved the binding ability with Fer was MCG > Cy-G > Dp-G. Anthocyanins are attractive alternatives to synthetic colorants, but their low stability impedes practical applications. Intermolecular copigmentation can enhance both color intensity and stability. Herein, the copigmentation interactions of Kyoho grape skin anthocyanins (KSA) or cyanidin-3-O-glucoside (Cy-G) with organic acids were investigated. Color enhancement was evaluated at different acid molar ratios and treatment temperatures. The optimal copigmentation effects were observed for KSA/tannic acid (1:150) and Cy-G/tannic acid (1:100). Based on enthalpy variation, KSA/ferulic acid and Cy-G/ferulic acid exhibited the highest stability. The distinct color differences observed in the presence of different acids were attributed to structural effects. The influence of ferulic acid on various anthocyanins was also evaluated using theoretical approaches. Owing to steric hindrance, the acyl groups in KSA affected the spatial conformation, hydrogen bonding, and van der Waals interactions of the complexes. Further, hydroxyl groups decreased complex stability. These findings contribute to furthering the understanding of copigmentation effects. [ABSTRACT FROM AUTHOR]

Abstract: Background: Parvovirus B19 (B19V) is a common pathogenic virus infecting humans. Previous studies have shown evidence of B19V infection in patients with non-Hodgkin's lymphoma (NHL) and Hodgkin's lymphoma using ELISA and PCR on serum specimens. B19V nonstructural protein is known to alter the expression of cellular factors including interleukin-6 (IL-6), which can increase the risk for and worsen the prognosis of lymphomas. Objective: The objective of this study was to detect B19V capsid protein and IL-6 expression in normal and malignant lymphoid tissue, as well as any correlation between the two. Study design: IHCs for B19V capsid protein, IL-6, and B19V co-receptors P-antigen and α5β1 integrin were performed on a tissue array containing 70 duplicated pediatric and adult lymphoma tissues and 5 duplicated benign lymph node sections. Cases were identified as normal, B-cell NHL, diffuse large B-cell NHL, Hodgkin's lymphoma, extranodal NK/T cell lymphoma, anaplastic large cell lymphoma, or mantle cell lymphoma. IL-6 and B19V capsid staining were quantified using a positive pixel count algorithm, and P-antigen and α5β1 staining using a membrane quantification algorithm. Results: B19V capsid protein was detected in both benign and malignant lymphoid tissue. The Spearman rank correlation coefficient analysis was performed to determine the relationship between the level of positivity for B19V and IL-6 staining, yielding an overall correlation coefficient of 0.679 (p-value<0.0001). Conclusions: Our results show a moderate correlation between the levels of positive B19V and IL-6 staining by IHC, indicating a possible role for B19V in the pathogenesis of lymphomas. [Copyright &y& Elsevier]

• van't Hoff analysis was employed to assess ΔH, ΔS and ΔCp. • CBM4 binds to both CNC and CNF but with different modes. • Binding of CBM4 on CNF is mainly enthalpically driven while entropically on CNC. • Negative ΔCp for the CBM4 binding to CNF while positive to CNC. The binding affinity and thermodynamics of family 4 carbohydrate-binding module (CBM4), belonging to type B CBM, on model surfaces of cellulose nanocrystals (CNC) and nanofibrils (CNF) were investigated by quartz crystal microbalance with dissipation monitoring (QCM-D) technology in real-time at different temperatures. The thermodynamic parameters associated with the interaction, such as Gibbs free energy, enthalpy change, entropy change and heat capacity were obtained using the van't Hoff analysis via a nonlinear parameter estimation. The results demonstrated CBM4 binds preferentially to both CNF and CNC, whereas the driving forces behind them were very different. The former was related to the hydrogen bonds formed in the CBM4 clefts, resulting in a favorable enthalpy but compensated by unfavorable entropy change; on the contrary, the latter was mainly driven by favorable entropy but compensated by unfavorable enthalpic change due to water rearrangement. [ABSTRACT FROM AUTHOR]

• A series of CXs with DS ranging from 0.051 to 0.113 were synthesized. • The optimum DS of CXs was down shifted to about 0.05−0.06 in high medium conductivity. • The performance of CXs with a high DS was inferior to that of native xylan. • DS of CXs correlated with the adsorption capacity and conformation of adlayer. Hemicelluloses have been considered as an efficient component to improve the bonding or strength of fiber networks. The degree of substitution (DS) of cationic hemicelluloses and the ionic strength of applied medium are therefore two most important and crucial factors influencing its performance in wet-end of papermaking. Therein, the impact of DS of cationic xylan (CX) derived from corncob on the strength of fiber networks was systematically explored in aqueous media with various ionic strengths. Initially, a series of CXs with DS ranging from 0.051 to 0.113 were synthesized via a microwave-assisted method. The resulting CXs were applied as wet-end additives in the media with conductivity of 500, 2500, and 5000 μs/cm, representing the low, moderate, and high level of electrolytes in closed white water circulation, respectively. Comparing to the control, all CXs improved the tensile and tear strength of paper significantly, while not in burst strength. The medium conductivity had an adverse impact on the performance of CXs, and the optimum DS of CXs was down shifted to about 0.05 ∼ 0.06. To mimic the adsorption of CXs on fiber surface, the adsorption behavior of CXs on negatively charged gold sensor was monitored by SPR in an attempt to reveal the mechanism. It was found that CXs with low DS had a larger adsorption capacity, thicker and softer adlayer, which are beneficial to fiber bonding and paper strength. This study is meaningful to the applications of xylan into value-added products and to the valorization of agricultural and forestry wastes. [ABSTRACT FROM AUTHOR]

Background Little is known about the effectiveness of recombinant human bone morphogenetic proteins (rhBMPs) in reducing the demand for opioids after surgery. We investigated the association between rhBMP use and the likelihood of achieving opioid independence and changes in opioid demand in the first postoperative year. Methods Using the Multi-Payer Claims Database from 2007 to 2010, patients aged >20 years who had undergone a degenerative disc disease–indicated lumbar fusion procedure and had had ≥1 opioid prescription in the 3 months before surgery were identified. Propensity score matching (1:1) of rhBMP-exposed and rhBMP-unexposed patients was used to mitigate confounding. The outcomes of interest were opioid independence and decreases in opioid doses in morphine equivalent units, assessed at 3–6 and 9–12 months after the procedure. Logistic regression and analysis of covariance models were used. Results The data from 318 patients were analyzed. Most patients were women (61%) and aged <65 years (68%). Few had achieved opioid independence at 3–6 (n = 71; 22.3%) or 9–12 (n = 115; 36.2%) months postoperatively. During the 3–6-month window, the rhBMP group reduced their opioid use rates (estimated mean difference. −28.4 vs. −19.5; P = 0.69) and achieved opioid independence (21.4% vs. 23.3%; odds ratio, 0.92; 95% confidence interval, 0.54–1.56; P = 0.74) at rates that were statistically comparable to their matched comparators. Similar patterns were observed during the 9–12-month window. Conclusion We found no evidence to suggest that rhBMP use during spinal fusion procedures is associated with either the discontinuation or decrease of opioid analgesic therapy. The continued opioid use after surgery warrants further clinical and research attention. Highlights • Roughly 1 in 5 patients (22.7%) with opioid-managed LDDD was taking >120 mg OMEUs before spinal fusion surgery. • The rate of opioid use remained high even after spinal fusion surgery for LDDD. • rhBMP use was not associated with either the discontinuation of, or decrease in, opioid analgesic therapy after surgery. [ABSTRACT FROM AUTHOR]

The present paper has used a comprehensive approach to study atmosphere pollution sources including the study of vertical distribution characteristics, the epicenters of occurrence and transport of atmospheric aerosol in North-West China under intensive dust storm registered in all cities of the region in April 2014. To achieve this goal, the remote sensing data using Moderate Resolution Imaging Spectroradiometer satellite (MODIS) as well as model-simulated data, were used, which facilitate tracking the sources, routes, and spatial extent of dust storms. The results of the study have shown strong territory pollution with aerosol during sandstorm. According to ground-based air quality monitoring stations data, concentrations of PM 10 and PM 2.5 exceeded 400 μg/m 3 and 150 μg/m 3 , respectively, the ratio PM 2.5 /PM 10 being within the range of 0.123–0.661. According to MODIS/Terra Collection 6 Level-2 aerosol products data and the Deep Blue algorithm data, the aerosol optical depth (AOD) at 550 nm in the pollution epicenter was within 0.75–1. The vertical distribution of aerosols indicates that the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observations (CALIPSO) 532 nm total attenuates backscatter coefficient ranges from 0.01 to 0.0001 km −1  × sr −1 with the distribution of the main types of aerosols in the troposphere of the region within 0–12.5 km, where the most severe aerosol contamination is observed in the lower troposphere (at 3–6 km). According to satellite sounding and model-simulated data, the sources of pollution are the deserted regions of Northern and Northwestern China. [ABSTRACT FROM AUTHOR]

Objective To examine the comparative effectiveness of inhaled long-acting beta-agonist (LABA), inhaled corticosteroid (ICS), and ICS/LABA combinations. Methods We used a retrospective cohort design of patients older than 12 years with asthma diagnosis in the Clinical Practice Research Datalink to evaluate asthma-related morbidity measured by oral corticosteroid (OCS) initiation within 12 months of initiating LABAs, ICSs, or ICSs/LABAs. Asthma severity 12 months before drug initiation (use of OCSs, asthma-related hospital or emergency department visits, and number of short-acting beta-agonist prescriptions) and during follow-up (short-acting beta-agonist prescriptions and total number of asthma drug classes) was adjusted as a time-varying variable via marginal structural models. Results A total of 51,103 patients with asthma were followed for 12 months after receiving first prescription for study drugs from 1993 to 2010. About 92% initiated ICSs, 1% initiated LABAs, and 7% initiated ICSs/LABAs. Compared with ICSs, LABAs were associated with a 10% increased risk of asthma exacerbations requiring short courses of OCSs (hazard ratio [HR] 1.10; 95% confidence interval [CI] 1.07–1.18). ICS/LABA initiators were 62% less likely than ICS initiators (HR 0.38; 95% CI 0.12–0.66) and 50% less likely than LABA initiators to receive OCS prescriptions for asthma exacerbations (HR 0.50; 95% CI 0.14–0.78). Conclusions In concordance with current asthma management guidelines, inhaled LABAs should not be prescribed as monotherapy to patients with asthma. The findings suggest the presence of time-dependent confounding by asthma severity, which was accounted for by the marginal structural model. [ABSTRACT FROM AUTHOR]

Resveratrol has been found to have potent antioxidant, anti-inflammatory, and anticarcinogenic effects. The safety and efficacy of resveratrol supplementation in older adults are currently unknown. We conducted a double-blind, randomized, placebo-controlled trial to examine the safety and metabolic outcomes in 32 overweight, older adults (mean age, 73 ± 7 years). Participants were randomized into one of three treatment groups: (1) placebo, (2) moderate dose resveratrol (300 mg/day), and (3) high dose resveratrol (1000 mg/day). Both resveratrol and placebo were orally ingested in capsule form twice daily for 90 days. Blood chemistry values remained within the normal range, and there were no significant differences in the number of participants reporting adverse events across conditions. Compared to placebo, glucose levels were significantly lower at post-treatment among participants randomized to both resveratrol conditions, with and without adjustment for the corresponding baseline values (ps < 0.05). Glucose values of participants in the treatment groups, however, were not significantly different from baseline levels. These findings suggest that short-term resveratrol supplementation at doses of 300 mg/day and 1000 mg/day does not adversely affect blood chemistries and is well tolerated in overweight, older individuals. These findings support the study of resveratrol for improving cardio-metabolic health in older adults in larger clinical trials. [ABSTRACT FROM AUTHOR]

• Enzymatic digestibility of 76.9% was achieved for DES-pretreated bamboo residues. • Changes of cellulose properties made contribute to the enzymatic digestibility. • Enzymatic digestibility linearly correlated to change of physicochemical property. Deep eutectic solvent (DES) is a promising pretreatment for improving enzymatic digestibility of lignocellulosic material by altering the physicochemical properties. However, few work has been done to quantitatively analysis the physicochemical properties changes of lignocellulosic material with enzymatic digestibility. In this work, DES pretreatment with different molar ratios of choline chloride/lactic acid was carried out on bamboo residues and respective enzymatic digestibility was investigated and linearly fitted with corresponding physicochemical features changes of the pretreated bamboo residues. Results showed that enzymatic digestibility of DES-pretreated bamboo residues was enhanced with the increasing molar ratio of choline chloride/lactic acid, which was due to DES pretreatment's ability to remove lignin and xylan, reduce the degree of polymerization of cellulose, enhance the crystallite size of cellulose, and improve cellulose accessibility. Several compelling linear correlations (R2 = 0.6–0.9) were observable between enzymatic digestibility and these changes of physicochemical properties, demonstrating how DES pretreatment improve the enzymatic digestibility. [ABSTRACT FROM AUTHOR]

Dendritic cells (DCs) are the sentinels of the immune system and play a critical role in initiating adaptive immune responses against pathogens. As the most powerful antigen presenting cells, DCs are also important in maintaining immune homeostasis and participating in the development of autoimmune diseases. How the maturation and function of DCs is regulated in these conditions and what is the function of various transcription factors is still unclear. In this study, we found that the expression of the transcription factor Foxp1 gradually increased during the maturation of DCs. Then, we constructed a recombinant adenovirus carrying Foxp1-interfering RNA (Ad-simFoxp1) and transfected murine bone marrow-derived DCs in vitro. DCs transfected with Ad-simFoxp1 exhibited markedly lower costimulatory molecules, and decreased cytokines. And Ad-simFoxp1 greatly inhibited mature DC-induced T cell responses. Moreover, in vivo infusion with Ad-simFoxp1-modified DCs significantly delayed the onset of experimental autoimmune encephalomyelitis (EAE). Therefore, adoptive transfection of Ad-simFoxp1 in DCs may be a potential treatment strategy against autoimmune diseases. • Foxp1 is upregulated during the maturation of DCs. • Silence of Foxp1 in DCs inhibits the expression of the costimulatory molecules, cytokines, and T cell responses. • Silence of Foxp1 in DCs delays the onset of EAE. [ABSTRACT FROM AUTHOR]