Injectable Peptide Hydrogels Loaded with Murine Embryonic Stem Cells Relieve Ischemia In Vivo after Myocardial Infarction.

Myocardial infarction (MI) is a major cause of morbidity and mortality worldwide, especially in aging and metabolically unhealthy populations. A major target of regenerative tissue engineering is the restoration of viable cardiomyocytes to preserve cardiac function and circumvent the progression to heart failure post-MI. Amelioration of ischemia is a crucial component of such restorative strategies. Angiogenic ß-sheet peptides can self-assemble into thixotropic nanofibrous hydrogels. These syringe aspiratable cytocompatible gels were loaded with stem cells and showed excellent cytocompatibility and minimal impact on the storage and loss moduli of hydrogels. Gels with and without cells were delivered into the myocardium of a mouse MI model (LAD ligation). Cardiac function and tissue remodeling were evaluated up to 4 weeks in vivo. Injectable peptide hydrogels synergized with loaded murine embryonic stem cells to demonstrate enhanced survival after intracardiac delivery during the acute phase post-MI, especially at 7 days. This approach shows promise for post-MI treatment and potentially functional cardiac tissue regeneration and warrants large-scale animal testing prior to clinical translation.

Suppression of myeloid YAP antagonizes adverse cardiac remodeling during pressure overload stress.

Inflammation is an integral component of cardiovascular disease and is thought to contribute to cardiac dysfunction and heart failure. While ischemia-induced inflammation has been extensively studied in the heart, relatively less is known regarding cardiac inflammation during non-ischemic stress. Recent work has implicated a role for Yes-associated protein (YAP) in modulating inflammation in response to ischemic injury; however, whether YAP influences inflammation in the heart during non-ischemic stress is not described. We hypothesized that YAP mediates a pro-inflammatory response during pressure overload (PO)-induced non-ischemic injury, and that targeted YAP inhibition in the myeloid compartment is cardioprotective. In mice, PO elicited myeloid YAP activation, and myeloid-specific YAP knockout mice (YAPF/F;LysMCre) subjected to PO stress had better systolic function, and attenuated pathological remodeling compared to control mice. Inflammatory indicators were also significantly attenuated, while pro-resolving genes including Vegfa were enhanced, in the myocardium, and in isolated macrophages, of myeloid YAP KO mice after PO. Experiments using bone marrow-derived macrophages (BMDMs) from YAP KO and control mice demonstrated that YAP suppression shifted polarization toward a resolving phenotype. We also observed attenuated NLRP3 inflammasome priming and function in YAP deficient BMDMs, as well as in myeloid YAP KO hearts following PO, indicating disruption of inflammasome induction. Finally, we leveraged nanoparticle-mediated delivery of the YAP inhibitor verteporfin and observed attenuated PO-induced pathological remodeling compared to DMSO nanoparticle control treatment. These data implicate myeloid YAP as an important molecular nodal point that facilitates cardiac inflammation and fibrosis during PO stress and suggest that selective inhibition of YAP may prove a novel therapeutic target in non-ischemic heart disease.

The Effects of Drug Exposure and Single Nucleotide Polymorphisms on Aaptinib-Induced Severe Toxicities in Solid Tumors.

To investigate the value of drug exposure and host germline genetic factors in predicting apatinib (APA)-related toxicities. METHOD: In this prospective study, plasma APA concentrations were quantified using liquid chromatography with tandem mass spectrometry, and 57 germline mutations were genotyped in 126 advanced solid tumor patients receiving 250 mg daily APA, a vascular endothelial growth factor receptor II inhibitor. The correlation between drug exposure, genetic factors, and the toxicity profile was analyzed. RESULTS: Non-small cell lung cancer (NSCLC) was more prone to APA-related toxicities and plasma concentrations of APA, and its main metabolite M1-1 could be associated with high-grade adverse events (AEs) (P < 0.01; M1-1, P < 0.01) and high-grade antiangiogenetic toxicities (APA, P = 0.034; P < 0.05), including hypertension, proteinuria, and hand-foot syndrome, in the subgroup of NSCLC. Besides, CYP2C9 rs34532201 TT carriers tended to have higher levels of APA (P < 0.001) and M1-1 (P < 0.01), whereas CYP2C9 rs1936968 GG carriers were predisposed to higher levels of M1-1 (P < 0.01). CONCLUSION: Plasma APA and M1-1 exposures were able to predict severe AEs in NSCLC patients. Dose optimization and drug exposure monitoring might need consideration in NSCLC patients with CYP2C9 rs34532201 TT and rs1936968 GG. SIGNIFICANCE STATEMENT: Apatinib is an anti-VEGFR2 inhibitor for the treatment of multiple cancers. Though substantial in response, apatinib-induced toxicity has been a critical issue that is worth clinical surveillance. Few data on the role of drug exposure and genetic factors in apatinib-induced toxicity are available. Our study demonstrated a distinct drug-exposure relationship in NSCLC but not other tumors and provided invaluable evidence of drug exposure levels and single nucleotide polymorphisms as predictive biomarkers in apatinib-induced severe toxicities.

Preparation of ß-cyclodextrin covalent organic framework-immobilized poly(glycidyl methacrylate) nanoparticle-coated open tubular capillary electrochromatography column for chiral separation.

A new enantioselective open-tubular capillary electrochromatography was developed employing poly(glycidyl methacrylate) nanoparticles/ß-cyclodextrin covalent organic frameworks chemically immobilized on the inner wall of the capillary as a stationary phase. A pretreated silica-fused capillary reacted with 3-aminopropyl-trimethoxysilane followed by poly(glycidyl methacrylate) nanoparticles and ß-cyclodextrin covalent organic frameworks through a ring-opening reaction. The resulting coating layer on the capillary was characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. The electroosmotic flow was studied to evaluate the variation of the immobilized columns. The chiral separation performance of the fabricated capillary columns was validated by the analysis of the four racemic proton pump inhibitors including lansoprazole, pantoprazole, tenatoprazole, and omeprazole. The influences of bonding concentration, bonding time, bonding temperature, buffer type and concentration, buffer pH, and applied voltage on the enantioseparation of four proton pump inhibitors were investigated. Good enantioseparation efficiencies were achieved for all enantiomers. In the optimum conditions, the enantiomers of four proton pump inhibitors were fully resolved within 10 min with high resolutions of 9.5-13.9. The column-to-column and inter- to intra-day repeatability of the fabricated capillary columns through relative standard deviation were found better than 9.54%, exhibiting satisfactory stability and repeatability of the fabricated capillary columns.

Efficacy and safety of granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies in COVID-19 patients: a meta-analysis.

OBJECTIVE: This study aims to determine the efficacy and safety of granulocyte-macrophage colony-stimulating factor (GM-CSF) antibodies in COVID-19 patients. METHODS: We searched Cochrane Library, PubMed, Embase, and ClinicalTrials.gov databases until July 27, 2022. Both randomized control trials (RCTs) and cohort studies were included and analyzed separately. The outcomes included mortality, incidence of invasive mechanical ventilation (IMV), ventilation improvement rate (need oxygen therapy to without oxygen therapy), secondary infection, and adverse events (AEs). The odds ratio (OR) with a 95% confidence interval (CI) was calculated by a random-effects meta-analysis model. RESULTS: Five RCTs and 2 cohort studies with 1726 COVID-19 patients were recruited (n = 866 in the GM-CSF antibody group and n = 891 in the control group). GM-CSF antibodies treatment reduced the incidence of IMV, which was supported by two cohort studies (OR 0.16; 95% CI 0.03, 0.74) and three RCTs (OR 0.62; 95% CI 0.41, 0.94). GM-CSF antibodies resulted in slight but not significant reductions in mortality (based on two cohort studies and five RCTs) and ventilation improvement (based on one cohort study and two RCTs). The sensitive analysis further showed the results of mortality and ventilation improvement rate became statistically significant when one included study was removed. Besides, GM-CSF antibodies did not increase the risks of the second infection (based on one cohort study and five RCTs) and AEs (based on five RCTs). CONCLUSION: GM-CSF antibody treatments may be an efficacious and well-tolerant way for the treatment of COVID-19. Further clinical evidence is still warranted.

Single-molecule long-read sequencing analysis improves genome annotation and sheds new light on the transcripts and splice isoforms of Zoysia japonica.

BACKGROUND: Zoysia japonica is an important warm-season turfgrass used worldwide. Although the draft genome sequence and a vast amount of next-generation sequencing data have been published, the current genome annotation and complete mRNA structure remain incomplete. Therefore, to analyze the full-length transcriptome of Z. japonica, we used the PacBio single-molecule long-read sequencing method in this study. RESULTS: First, we generated 37,056 high-confidence non-redundant transcripts from 16,005 gene loci. Next, 32,948 novel transcripts, 913 novel gene loci, 8035 transcription factors, 89 long non-coding RNAs, and 254 fusion transcripts were identified. Furthermore, 15,675 alternative splicing events and 5325 alternative polyadenylation sites were detected. In addition, using bioinformatics analysis, the underlying transcriptional mechanism of senescence was explored based on the revised reference transcriptome. CONCLUSION: This study provides a full-length reference transcriptome of Z. japonica using PacBio single-molecule long-read sequencing for the first time. These results contribute to our knowledge of the transcriptome and improve the knowledge of the reference genome of Z. japonica. This will also facilitate genetic engineering projects using Z. japonica.

ß-Cyclodextrin covalent organic framework supported by polydopamine as stationary phases for electrochromatographic enantioseparation.

In this work, a new open-tubular capillary electrochromatography (OT-CEC) column was prepared using ß-cyclodextrin covalent organic framework (ß-CD COF) as a stationary phase. Polydopamine was used to assist fabrication of ß-CD COF on an inner wall of a fused-silica capillary. The coating layer on the capillary was characterized by scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Electroosmotic flow (EOF) was also studied to evaluate the variation of the inner wall of immobilized columns. Furthermore, the chiral separation effectiveness of the fabricated capillary column was evaluated by CEC using enantiomers of several related proton pump inhibitors as model analytes, including omeprazole, lansoprazole, pantoprazole and tenatoprazole. The effects of bonding time and concentration of ß-CD COF, the type, concentration and pH of buffer, applied voltage were investigated to obtain satisfactory enantioselectivity. In the optimum conditions, the enantiomers of four analytes were resolved within 15 min with resolutions of 1.63-2.62. The relative standard deviation values for migration times and resolutions of the analytes representing intraday and interday were less than 6.75% and 4.24%, respectively. The results reveal that ß-CD COF has great potential as chiral-stationary phases for enantioseparation in CEC.

An Efficient IAKF Approach for Indoor Positioning Drift Correction.

In this study, an indoor positioning shift correction architecture was developed with an improved adaptive Kalman filter (IAKF) algorithm for the people interference condition. Indoor positioning systems (IPSs) use ultra-wideband (UWB) communication technology. Triangulation positioning algorithms are generally employed for determining the position of a target. However, environmental communication factors and different network topologies produce localization drift errors in IPSs. Therefore, the drift error of real-time positioning points under various environmental factors and the correction of the localization drift error are discussed. For localization drift error, four algorithms were simulated and analyzed: movement average (MA), least square (LS), Kalman filter (KF), and IAKF. Finally, the IAKF algorithm was implemented and verified on the UWB indoor positioning system. The measurement results showed that the drift errors improved by 60% and 74.15% in environments with and without surrounding crowds, respectively. Thus, the coordinates of real-time positioning points are closer to those of actual targets.

Preparation of a polydopamine/ß-cyclodextrin coated open tubular capillary electrochromatography column and application for enantioseparation of five proton pump inhibitors.

An open tubular capillary electrochromatography column was prepared by immobilizing ß-cyclodextrin on the inner wall of pretreated capillary via noncovalent adsorption of polydopamine. The resulting coating layer on the capillary was characterized by scanning electron microscopy and Fourier transform infrared spectroscopy. Electroosmotic flow was studied to evaluate the variation of the immobilized columns. The prepared columns showed good chiral separation performance toward five proton pump inhibitors including lansoprazole, pantoprazole, tenatoprazole, rabeprazole, and omeprazole. The influences of ß-cyclodextrin concentration, coating time, buffer pH, buffer concentration, and applied voltage on separation were investigated. In the optimum conditions, the enantiomers of five analytes were fully resolved within 15 min with high resolutions of 4.57 to 8.13. The method was extensively validated in terms of accuracy, precision, and linearity and proved to be robust. The relative standard deviation values for migration times and peak areas of the analytes representing intraday and interday were less than 1.9 and 3.6%, respectively. Further, the polydopamine/ß-cyclodextrin coated capillary column could be successively used over 100 runs without showing significant decrease in the separation efficiency.

Highly sensitive and selective determination of p-nitrophenol at an interpenetrating networks structure of self-assembled rod-like lanthanum hydroxide-oxidized multi-walled carbon nanotubes nanocomposite.

In this study, a novel electrochemical sensor based on self-assembled rod-like lanthanum hydroxide-oxidized multi-walled carbon nanotubes (La(OH)3-OxMWCNTs) nanocomposite was developed for sensitive determination of p-nitrophenol (p-NP). The La(OH)3-OxMWCNTs nanocomposite with an interpenetrating networks structure was characterized by field emission electron microscope (FE-SEM), Fourier transform infrared (FT-IR) spectroscopy, Raman spectra and X-ray photoelectron spectroscopy (XPS). The cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) measurements were performed to study the electrochemical behaviors of La(OH)3-OxMWCNTs modified glassy carbon electrode (La(OH)3-OxMWCNTs/GCE). The La(OH)3-OxMWCNTs/GCE was used for sensitive determination of p-NP by CV and linear sweep voltammetry (LSV). Under the optimum conditions, the peak currents of LSV versus the concentrations of p-NP in the range 1.0-30.0 µmol L-1 showed a good linear relationship (R2=0.9971), and the limit of detection (LOD) was calculated to be 0.27 µmol L-1 (signal-to-noise ratio of 3, S/N=3). The recoveries of p-NP in real samples of industrial wastewater and Xiangjiang water at La(OH)3-OxMWCNTs/GCE were in the range of 95.62-110.75% with relative standard deviation (RSD) in the range of 1.65-3.85%. The intra-day and inter-day precisions were estimated to be less than 2.76% (n= 5), indicating that La(OH)3-OxMWCNTs/GCE possessed highly stability. In addition, La(OH)3-OxMWCNTs/GCE sensor showed good anti-interference ability for determination of p-NP in aqueous mixtures containing high concentrations of inorganic and organic interferents, and a decrease of oxidation peak currents by less than 3.57% relative to the initial levels indicated it possessed excellent selectivity. Therefore, La(OH)3-OxMWCNTs/GCE could be used as a fast, selective and sensitive electrochemical sensor platform for the selective determination and quantification of aqueous p-NP.

Hybrid carbon nanotubes modified glassy carbon electrode for selective, sensitive and simultaneous detection of dopamine and uric acid.

Based on a hybrid carbon nanotube composite, a novel electrochemical sensor with high sensitivity and selectivity was designed for the simultaneous determination of dopamine (DA) and uric acid (UA). The hybrid carbon nanotube composite was prepared by ultrasonic assembly of carboxylated multi-walled carbon nanotube (MWCNT-COOH) and hydroxylated single-walled carbon nanotube (SWCNT-OH). And the hybrid (MWCNT-COOH/SWCNT-OH) composite was characterized by field emission scanning electron microscopy (FE-SEM) and Fourier transform infrared (FT-IR) spectroscopy. The electrochemical performances of MWCNT-COOH/SWCNT-OH composite modified glassy carbon electrode (MWCNT-COOH/SWCNT-OH/GCE) were analyzed by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and differential pulse voltammetry (DPV). Under the optimum experimental conditions, the as-prepared sensor showed high sensitivity and selectivity for DA and UA. The calibration curves obtained were linear for the currents versus DA and UA concentrations in the range 2-150 µM, and limits of detection (LODs) were calculated to be 0.37 µM and 0.61 µM (signal-to-noise ratio of 3, S/N = 3), respectively. The recoveries of DA and UA in bovine serum samples at MWCNT-COOH/SWCNT-OH/GCE were in the range 96.18-105.02%, and relative standard deviations (RSDs) were 3.34-7.27%. The proposed electrochemical sensor showed good anti-interference ability, excellent reproducibility and stability, as well as high selectivity, which might provide a promising platform for determination of DA and UA.

A sensitive non-enzymatic electrochemical sensor based on acicular manganese dioxide modified graphene nanosheets composite for hydrogen peroxide detection.

In this work, a novel manganese dioxide-graphene nanosheets (MnO2-GNSs) composite was synthesized by a facile one-step hydrothermal method, in which manganese dioxide (MnO2) was fabricated by hydrothermal reduction of KMnO4 with GNSs. The structure and morphology of MnO2-GNSs composite were characterized by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS), X-ray diffraction (XRD) analysis and X-ray photoelectron spectroscopy (XPS). A sensitive non-enzymatic electrochemical sensor based on MnO2-GNSs composite for the detection of low concentration hydrogen peroxide (H2O2) was fabricated. The electrochemical properties of MnO2-GNSs composite modified glassy carbon electrode (MnO2-GNSs/GCE) were investigated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS) and amperometry. The observations confirmed that the fabricated sensor exhibited high electrocatalytic activity for oxidation of H2O2 owing to the catalytic ability of MnO2 particles and the conductivity of GNSs. Under the optimum conditions, the calibration curve was linear for the amperometric response versus H2O2 concentration over the range 0.5-350 µM with a low detection limit of 0.19 µM (S/N = 3) and high sensitivity of 422.10 µA mM-1 cm-2. The determination and quantitative analysis of H2O2 in antiseptic solution on MnO2-GNSs/GCE exhibited percent recovery of 96.50%-101.22% with relative standard deviation (RSD) of 1.48%-4.47%. The developed MnO2-GNSs/GCE might be a promising platform for the practical detection of H2O2 due to its prominent properties including excellent reproducibility, good anti-interference and repeatability.

[Effects of Acupuncture at Zusanli on Plasma Dopamine and Lung Function of Rats with COPD].

OBJECTIVE: To explore the mechanism of acupuncture in regulating chronic inflammation through dopamine in rats with chronic obstructive pulmonary disease (COPD). METHODS: 32 SD rats were randomly divided into control, model, sham acupuncture and acupuncture groups (n=8) . COPD condition was induced by eight-week exposure to cigarette smoking and lipopolysaccharides (LPS) of the rats, except for those in the control group. From the beginning of the 7th week, the acupuncture group received bilateral electroacupuncture on the Zusanli (ST-36), while the sham acupuncture group received bilateral electroacupuncture on the non-points, 30 min/time, 1/day, for 2 weeks prior to exposure to cigarette smoking. Post treatment changes in plasma dopamine and inflammatory factors [tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8)], lung function [total lung capacity (TLC), functional residual capacity (FRC), the 50 µs forced expiratory volume (FEV) vs. forced vital capacity (FVC)( FEV50/FVC), the 100 µs FEV vs. FVC (FEV100/FVC), total airway resistance (RL), lung dynamic compliance (Cdyn)], and the ratio of total alveolus area to tissue area (A/t) and cell counts in the alveolar lavage fluid (BALF) were measured. Pearson correlations between plasma dopamine and the above indicators were calculated. RESULTS: Acupuncture increased plasma dopamine and improved the inflammatory factors, lung function, A/t and BALF cell counts. Compared with the model rats, the rats that received acupuncture had higher levels of TNF-α and IL-1ß, A/t and BALF cell counts, and lung function (FEV50/FVC, FEV100/FVC, RL, Cdyn) (P<0.05). The effects of acupuncture were superior on the ST-36 points compared with the non-points. Significant correlations between lung function (FRC, RL, Cdyn) and inflammatory factors (TNF-α, IL-1ß, IL-6, IL-8) were found (P<0.001) . TLC was correlated with IL-8, IL-1ß and A/t (P<0.05). Plasma dopamine was correlated with FRC, TLC, FEV50/FVC, FEV100/FVC (P<0.05). CONCLUSION: Acupuncture can alleviate inflammation, improve lung function and raise plasma dopamine level in COPD rats, and the effect of acupuncture on lung function may be related to reducing inflammatory factors and increasing dopamine level.

Serum adipocyte fatty acid-binding protein level is associated with arterial stiffness quantified with cardio-ankle vascular index in kidney transplant patients.

BACKGROUND: Arterial stiffness is an established marker of cardiovascular risk and an independent predictor of cardiovascular disease (CVD) events and mortality in kidney transplant (KT) patients. Adipocyte fatty acid-binding protein (A-FABP), a novel adipokine, is positively associated with atherosclerosis. The present study evaluated the relationship between fasting circulating A-FABP and peripheral arterial stiffness using the cardio-ankle vascular index (CAVI) in KT patients. METHODS: Fasting blood samples were collected from 74 KT patients, and serum A-FABP levels were measured using an enzyme immunoassay. CAVI was calculated using a waveform device (CAVI-VaSera VS-1000). The cutoff values for high and low levels of arterial stiffness were defined by the CAVI values of ≥9 and <9, respectively. RESULTS: Thirty-four patients (45.9%) were classified into the high arterial stiffness group. Compared with the low arterial stiffness group, the high arterial stiffness group had higher values for age (p = 0.015), systolic blood pressure (p < 0.001), pulse pressure (p < 0.001), duration of kidney transplantation (p = 0.005), serum total cholesterol and triglyceride levels (p = 0.033 and 0.047, respectively), glomerular filtration rate (p = 0.019), fasting glucose levels (p = 0.012), and serum A-FABP levels (p < 0.001). Multivariate forward stepwise linear regression analysis showed that age (p = 0.004), systolic blood pressure (p = 0.001), and serum A-FABP levels (p = 0.003) were independent predictors of CAVI value in KT patients. CONCLUSION: Serum fasting A-FABP level is positively associated with peripheral arterial stiffness in KT patients.

Plant functional traits and canopy structure control the relationship between photosynthetic CO2 uptake and far-red sun-induced fluorescence in a Mediterranean grassland under different nutrient availability.

Sun-induced fluorescence (SIF) in the far-red region provides a new noninvasive measurement approach that has the potential to quantify dynamic changes in light-use efficiency and gross primary production (GPP). However, the mechanistic link between GPP and SIF is not completely understood. We analyzed the structural and functional factors controlling the emission of SIF at 760 nm (F760 ) in a Mediterranean grassland manipulated with nutrient addition of nitrogen (N), phosphorous (P) or nitrogen-phosphorous (NP). Using the soil-canopy observation of photosynthesis and energy (SCOPE) model, we investigated how nutrient-induced changes in canopy structure (i.e. changes in plant forms abundance that influence leaf inclination distribution function, LIDF) and functional traits (e.g. N content in dry mass of leaves, N%, Chlorophyll a+b concentration (Cab) and maximum carboxylation capacity (Vcmax )) affected the observed linear relationship between F760 and GPP. We conclude that the addition of nutrients imposed a change in the abundance of different plant forms and biochemistry of the canopy that controls F760 . Changes in canopy structure mainly control the GPP-F760 relationship, with a secondary effect of Cab and Vcmax . In order to exploit F760 data to model GPP at the global/regional scale, canopy structural variability, biodiversity and functional traits are important factors that have to be considered.

Simultaneous determination of 12 pharmaceuticals in water samples by ultrasound-assisted dispersive liquid-liquid microextraction coupled with ultra-high performance liquid chromatography with tandem mass spectrometry.

A new analytical method was developed for simultaneous determination of 12 pharmaceuticals using ultrasound-assisted dispersive liquid-liquid microextraction (DLLME) followed by ultra-high performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS). Six nonsteroidal anti-inflammatory drugs (NSAIDs, ketoprofen, mefenamic acid, tolfenamic acid, naproxen, sulindac, and piroxicam) and six antibiotics (tinidazole, cefuroxime axetil, ciprofloxacin, sulfamethoxazole, sulfadiazine, and chloramphenicol) were extracted by ultrasound-assisted DLLME using dichloromethane (800 µL) and methanol/acetonitrile (1:1, v/v, 1200 µL) as the extraction and dispersive solvents, respectively. The factors affecting the extraction efficiency, such as the type and volume of extraction and dispersive solvent, vortex and ultrasonic time, sample pH, and ionic strength, were optimized. The ultrasound-assisted process was applied to accelerate the formation of the fine cloudy solution by using a small volume of dispersive solvent, which increased the extraction efficiency and reduced the equilibrium time. Under the optimal conditions, the calibration curves showed good linearity in the range of 0.04-20 ng mL-1 (ciprofloxacin and sulfadiazine), 0.2-100 ng mL-1 (ketoprofen, tinidazole, cefuroxime axetil, naproxen, sulfamethoxazole, and sulindac), and 1-200 ng mL-1 (mefenamic acid, tolfenamic acid, piroxicam, and chloramphenicol). The LODs and LOQs of the method were in the range of 0.006-0.091 and 0.018-0.281 ng mL-1, respectively. The relative recoveries of the target analytes were in the range from 76.77 to 99.97 % with RSDs between 1.6 and 8.8 %. The developed method was successfully applied to the extraction and analysis of 12 pharmaceuticals in five kinds of water samples (drinking water, running water, river water, influent and effluent wastewater) with satisfactory results. Graphical Abstract Twelve pharmaceuticals in water samples analyted by UHPLC-MS/MS using ultrasound-assisted DLLME.

Efficient synthesis and antioxidant activities of N-heterocyclyl substituted Coenzyme Q analogues.

A new strategy for the efficient synthesis of C-5 heterocyclyl substituted Coenzyme Q analogues was developed by N-alkylation of bromomethylated quinone 11 with a series of amines 12 under metal-free conditions. In vitro antioxidant activities of these Coenzyme Q analogues were evaluated and compared with commercial antioxidant Coenzyme Q10 by employing DPPH assay. All these N-heterocyclyl substituted Coenzyme Q analogues are found to be exhibiting good antioxidant properties and may be used as potent antioxidants for combating oxidative stress.

Serum adiponectin is a negative predictor of central arterial stiffness in kidney transplant patients.

BACKGROUND: The role of adiponectin in arterial stiffness and its relationship to cardiovascular disease is not fully demonstrated and needs further elaboration. In this study, the association between adiponectin level and arterial stiffness is studied among kidney transplant patients. MATERIAL AND METHODS: Anthropometric data and biochemical data including fasting glucose, lipid profile, renal function and serum adiponectin were determined in 55 kidney transplant patients. Central arterial stiffness was measured and presented by carotid-femoral pulse wave velocity. RESULTS: Univariate linear analysis showed that body weight, waist circumference, brachial pulse pressure and body mass index were correlated positively with carotid-femoral pulse wave velocity in this patient group. However, logarithmically transformed adiponectin level (log-adiponectin) correlated negatively with carotid-femoral pulse wave velocity. In multivariate regression analysis of factors significantly associated with carotid-femoral pulse wave velocity, it showed that both log-adiponectin (ß = -0.427; R(2) = 0.205, p = 0.001) and body weight (ß = 0.327; R(2 )=( )0.106, p = 0.007) were independently predictive of central arterial stiffness. CONCLUSION: Our study suggests that fasting serum adiponectin is negatively associated with carotid-femoral pulse wave velocity, hence arterial stiffness, in kidney transplant patients.

Hypoadiponectinemia correlates with arterial stiffness in kidney transplantation patients.

BACKGROUND: Adiponectin is a fat-derived hormone produced and secreted exclusively by adipocytes that have anti-atherosclerotic effects. The aim of this study was to evaluate the relationship between fasting serum adiponectin levels and arterial stiffness among kidney transplant (KT) patients. METHODS: Fasting blood samples were obtained from 69 KT patients. Brachial-ankle pulse wave velocity (baPWV) was measured in the right or left brachial artery to the ankle segments using an automatic pulse wave analyzer. Plasma adiponectin levels were measured using a commercial enzyme-linked immunosorbent assay kit. Left or right baPWV values of >14.0 m/s were used to define the high arterial stiffness group. RESULTS: Thirty-five KT patients (35/69; 50.7 %) were defined in high arterial stiffness group. Diabetes (P = 0.013), smoking (P = 0.001), KT duration (P < 0.001), body weight (P = 0.013), waist circumference (P = 0.013), body mass index (P = 0.001), fasting glucose (P = 0.013), systolic blood pressure (P < 0.001), diastolic blood pressure (P = 0.008), and pulse pressure (P = 0.003) were higher, while serum adiponectin level (P = 0.004) was lower in high arterial stiffness group compared with low arterial stiffness group. Multivariate logistic regression analysis showed that adiponectin (odds ratio 0.90, 95 % confidence interval 0.81-0.99, P = 0.034) was still the independent predictors of arterial stiffness among the KT patients. CONCLUSION: Serum fasting adiponectin level was inversely associated with arterial stiffness among KT patients.

High Serum Osteoprotegerin Is Associated with Arterial Stiffness in Kidney Transplant Patients.

Osteoprotegerin (OPG) is a cytokine that regulates bone resorption by inhibiting osteoclastogenesis, and OPG has been implicated in the process that causes vascular stiffness. An increase in serum OPG level has been associated with the development of arterial stiffness. Kidney transplant (KT) patients are susceptible to aortic stiffness, which is considered to be a predictor of cardiovascular events in this patient population. Carotid-femoral pulse wave velocity (cfPWV) has emerged as a gold standard for non-invasive evaluation of aortic stiffness. The aim of this study was to evaluate the relationship between serum OPG concentration and cfPWV among KT patients. Fasting blood samples were obtained from 57 KT patients and their cfPWV was measured using applanation tonometry. The serum OPG levels were measured using an enzyme-linked immunosorbent assay. Univariable linear regression analysis showed that the cfPWV in KT patients was significantly and positively correlated with age, body weight, waist circumference, body mass index, log-creatinine, systolic blood pressure, diastolic blood pressure, pulse pressure, and the log-OPG concentration. KT patients with metabolic syndrome had higher cfPWV values than those without metabolic syndrome (P = 0.036), which indicates a higher incidence of aortic stiffness in this patient population. Multivariable forward stepwise linear regression analysis of the significant variables showed that the log-OPG (P = 0.001), the log-creatinine (P = 0.004), and the SBP (P = 0.005) remained as independent and positive predictors of cfPWV values. These findings indicate that serum OPG levels are positively associated with cfPWV in KT patients.