Efficacy and safety of dual renin-angiotensin system (RAS) blockade for non-elderly diabetic kidney disease patients with preserved eGFR.

AIM: Although sodium glucose cotransporter2 inhibitor (SGLT-2I) is widely used in clinical practice, sufficient renin-angiotensin system (RAS) inhibition remains the cornerstone of diabetic kidney disease (DKD) treatment. The aim of this single-center study was to evaluate the efficacy and safety of dual RAS blockade compared with angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor blocker (ARB) monotherapy in non-elderly DKD patients with preserved eGFR (WHO Standard, < 60y). METHODS: This single-center study was registered in Chinese Clinical Trial Registry (ChiCTR1900024752), and approved by the ethical committee (KY201994). In this study, we recruited non-elderly type 2 diabetes volunteers with initial diagnosis of DKD to receive dual RAS blockade or monotherapy. 150 non-elderly DKD patients with preserved eGFR were recruited. The patients were randomly divided into dual RAS blockade group and monotherapy group. The dual RAS blockade group treatment regimen was an 80 mg valsartan plus a 4 mg perindopril tert-butylamine per day. At the same time, monotherapy group patients who received the 8 mg perindopril tert-butylamine or 160 mg valsartan monotherapy. The clinical data of the three groups were compared at baseline and collected during the follow-up period of 12 months. RESULTS: The baseline of patients who received dual RAS blockade was similar to that of monotherapy group. After 12 months of treatment, the median level of proteinuria in the dual RAS blockade group was significantly lower than that in the monotherapy group. There was no significant difference in the estimated glomerular filtration rate (eGFR) level, potassium, blood pressure and no serious adverse reactions. CONCLUSIONS: In non-elderly DKD patients with preserved eGFR, dual RAS blockade is superior to control proteinuria, and does not increase the probability of adverse reactions such as hyperkalemia, hypotension and acute kidney injury in 12 months.

A single-center, open label, randomized, controlled study of hydroxychloroquine sulfate in the treatment of low risk PLA2R-associated membranous nephropathy.

OBJECTIVE: To evaluate the efficacy and safety of hydroxychloroquine sulfate (HCQ) in the treatment of low risk phospholipase A2 receptor (PLA2R)-associated membranous nephropathy (MN). METHODS: A total of 110 patients with low risk PLA2R-associated MN were included in the study. Patients who met the inclusion and exclusion criteria were assigned randomly to two groups: the HCQ treatment group and the control group. The control group received standard supportive treatment according to the guidelines, while the HCQ treatment group received HCQ in addition to the supportive treatment. The clinical data of the patients were analyzed, with comparisons made at baseline and during the six-month follow-up period. Any adverse reactions were recorded. RESULTS: The baseline data were comparable between the HCQ treatment group and the control group. At the end of the six-month follow-up period, the reductions in urine protein excretion and serum PLA2R antibody titer were more notable in the HCQ treatment group than those in the control group, with these differences being statistically significant (p < 0.05). Compared to the control group, the HCQ treatment group had fewer patients who were converted from low risk to moderate-to-high risk (p = 0.084). There were also no severe adverse reactions in the HCQ treatment group. CONCLUSION: In patients with low risk PLA2R-associated MN, adequate supportive therapy combined with HCQ is superior to supportive therapy alone in controlling proteinuria and reducing serum PLA2R antibody titers. Additionally, our study demonstrated that the incidence of adverse reactions did not increase. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry (Registration No.: ChiCTR1900021757, Date of registration: 2019-03-08).

Desalination Performance of MoS2 Membranes with Different Single-Pore Sizes: A Molecular Dynamics Simulation Study.

Utilizing molecular dynamics simulations, we examined how varying pore sizes affect the desalination capabilities of MoS2 membranes while keeping the total pore area constant. The total pore area within a MoS2 nanosheet was maintained at 200 Å2, and the single-pore areas were varied, approximately 20, 30, 40, 50, and 60 Å2. By comparing the water flux and ion rejection rates, we identified the optimal single-pore area for MoS2 membrane desalination. Our simulation results revealed that as the single-pore area expanded, the water flux increased, the velocity of water molecules passing the pores accelerated, the energy barrier decreased, and the number of water molecules within the pores rose, particularly between 30 and 40 Å2. Balancing water flux and rejection rates, we found that a MoS2 membrane with a single-pore area of 40 Å2 offered the most effective water treatment performance. Furthermore, the ion rejection rate of MoS2 membranes was lower for ions with lower valences. This was attributed to the fact that higher-valence ions possess greater masses and radii, leading to slower transmembrane rates and higher transmembrane energy barriers. These insights may serve as theoretical guidance for future applications of MoS2 membranes in water treatment.

Excessive daytime sleepiness is associated with increased residual cardiovascular risks among coronary artery disease patients with obstructive sleep apnea.

OBJECTIVE: Excessive daytime sleepiness (EDS) frequently accompanies obstructive sleep apnea (OSA) and may increase cardiovascular risks. The majority of coronary artery disease (CAD) patients receive understandard treatments, it is not clear whether EDS is associated with increased residual cardiovascular risks in CAD patients with OSA. METHOD: This study is a prospective cohort study that included 1215 consecutive CAD patients underwent overnight sleep study with a 3.7 year follow-up. Sleepiness was is determined by the Epworth Sleepiness Scale questionnaire. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), including cardiovascular death, myocardial infarction, stroke, and heart failure. Kaplan-Meier model and Cox proportional hazards models were used to explore the relationship between residual cardiovascular risks and EDS. RESULT: 1027 cases were eventually enrolled, and a total of 129 patients experienced cardiovascular and cerebrovascular events. Participants with EDS had a higher risk of MACCE compared to those without EDS (17.02% vs. 9.58%, P = 0.005). The presence of EDS is associated with higher incidence of MACCE compared to non-EDS patients (HR 2.833; 95%CI:1.394-5.762; P < 0.001). EDS was significantly associated with increased incidence of MACCE in OSA patients (HR 1.765; 95%CI:1.276-2.543; P = 0.193), while there was no significant association between EDS and cardiovascular risks in non-OSA patients (HR 1.233; 95%CI: 0.893-2.755; P = 0.127). CONCLUSIONS: The existence of EDS may lead to increased cardiovascular risks, EDS is associated with increased cardiovascular risks in CAD patients, especially in patients with OSA.

Phytoferritin functions in two interface-loading of natural pigment betanin and caffeic acid with enhanced color stability and the sustained release of betanin.

Betanin, a natural red pigment, is sensitive and prone to fading and discoloration, affecting its stability and bioavailability. Phytoferritin is a nano-diameter protein with unique interior-/exterior-interfaces. By the unique interfaces and pH-induced self-assembly of ferritin, a ferritin-betanin complex (FB) with an encapsulation efficiency of 17.66 ± 1.24% was prepared. The caffeic acid-FB (CFB) was further fabricated by attaching ferritin with caffeic acid, and the binding number n of caffeic acid was 88.47 ± 9.49, with a binding constant K of (1.63 ± 0.33) × 104 M-1. Fluorescence and Fourier transform infrared analysis indicated that the encapsulation of betanin and the binding of caffeic acid influenced the ferritin structure. The interaction between caffeic acid and ferritin was mainly through van der Waals forces and hydrogen bonds. TEM and DLS showed that the globular structure and diameter (12 nm) remained in CFB. Furthermore, the ferritin and caffeic acid exhibited a synergistic effect in enhancing thermal, light, and ferric ion stabilities, and controlled the betanin release in a more sustained manner in the simulated gastrointestinal tract. In addition, the antioxidant capacity of CFB was enhanced compared with free betanin. This study promotes the bioavailability of betanin by two interface-loading of ferritin, and guides the use of ferritin nanoparticles as a nanocarrier for pigment stabilization.

The Hydrolysis of Pigment-Protein Phycoerythrin by Bromelain Enhances the Color Stability.

Phycoerythrin (PE) is a natural protein-pigment complex with a strong pink color, but it is sensitive to thermal and light variations. In this study, PE was extracted from Porphyra haitanensis in a yield of 0.2% (w/w). The phycoerythrin hydrolysates (PEH) (3-10 kDa) were prepared by enzymatic hydrolysis of PE with bromelain (8000 U/g) at 47 °C for 30 min, with a degree of hydrolysis (DH) of 11.57 ± 0.39% and a color degradation rate of 7.98 ± 0.39%. The physicochemical properties of PEH were evaluated. The UV and fluorescence spectra indicated that bromelain changed the microenvironment around phycoerythrobilin (PEB). The infrared spectrum revealed that the bromelain hydrolysis increased the α-helix content of PEH. The scanning electron microscope showed that bromelain destroyed the dense and smooth structure of PE, resulting in irregular porous structures. The radical scavenging activities of DPPH and ABTS of PEH were increased relative to that of PE (p < 0.05). The thermal (50-80 °C)-, UV (0.5-3 h)-, visible light irradiation (2-8 h)-, and metal ion exposing stabilities of PEH were significantly improved (p < 0.05). This study provides a potential scheme for overcoming the sensitivity of PE to thermal and light variations and facilitates PEH as a natural colorant ingredient in food and pigment applications.

Metabolic systems approaches update molecular insights of clinical phenotypes and cardiovascular risk in patients with homozygous familial hypercholesterolemia.

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is an orphan metabolic disease characterized by extremely elevated low-density lipoprotein cholesterol (LDL-C), xanthomas, aortic stenosis, and premature atherosclerotic cardiovascular disease (ASCVD). In addition to LDL-C, studies in experimental models and small clinical populations have suggested that other types of metabolic molecules might also be risk factors responsible for cardiovascular complications in HoFH, but definitive evidence from large-scale human studies is still lacking. Herein, we aimed to comprehensively characterize the metabolic features and risk factors of human HoFH by using metabolic systems strategies. METHODS: Two independent multi-center cohorts with a total of 868 individuals were included in the cross-sectional study. First, comprehensive serum metabolome/lipidome-wide analyses were employed to identify the metabolomic patterns for differentiating HoFH patients (n = 184) from heterozygous FH (HeFH, n = 376) and non-FH (n = 100) subjects in the discovery cohort. Then, the metabolomic patterns were verified in the validation cohort with 48 HoFH patients, 110 HeFH patients, and 50 non-FH individuals. Subsequently, correlation/regression analyses were performed to investigate the associations of clinical/metabolic alterations with typical phenotypes of HoFH. In the prospective study, a total of 84 HoFH patients with available follow-up were enrolled from the discovery cohort. Targeted metabolomics, deep proteomics, and random forest approaches were performed to investigate the ASCVD-associated biomarkers in HoFH patients. RESULTS: Beyond LDL-C, various bioactive metabolites in multiple pathways were discovered and validated for differentiating HoFH from HoFH and non-FH. Our results demonstrated that the inflammation and oxidative stress-related metabolites in the pathways of arachidonic acid and lipoprotein(a) metabolism were independently associated with the prevalence of corneal arcus, xanthomas, and supravalvular/valvular aortic stenosis in HoFH patients. Our results also identified a small marker panel consisting of high-density lipoprotein cholesterol, lipoprotein(a), apolipoprotein A1, and eight proinflammatory and proatherogenic metabolites in the pathways of arachidonic acid, phospholipid, carnitine, and sphingolipid metabolism that exhibited significant performances on predicting first ASCVD events in HoFH patients. CONCLUSIONS: Our findings demonstrate that human HoFH is associated with a variety of metabolic abnormalities and is more complex than previously known. Furthermore, this study provides additional metabolic alterations that hold promise as residual risk factors in HoFH population.

Which model is better in predicting the survival of laryngeal squamous cell carcinoma?: Comparison of the random survival forest based on machine learning algorithms to Cox regression: analyses based on SEER database.

Prediction of postoperative survival for laryngeal carcinoma patients is very important. This study attempts to demonstrate the utilization of the random survival forest (RSF) and Cox regression model to predict overall survival of laryngeal squamous cell carcinoma (LSCC) and compare their performance. A total of 8677 patients diagnosed with LSCC from 2004 to 2015 were obtained from surveillance, epidemiology, and end results database. Multivariate imputation by chained equations was applied to filling the missing data. Lasso regression algorithm was conducted to find potential predictors. RSF and Cox regression were used to develop the survival prediction models. Harrell's concordance index (C-index), area under the curve (AUC), Brier score, and calibration plot were used to evaluate the predictive performance of the 2 models. For 3-year survival prediction, the C-index in training set were 0.74 (0.011) and 0.84 (0.013) for Cox and RSF respectively. For 5-year survival prediction, the C-index in training set were 0.75 (0.022) and 0.80 (0.011) for Cox and RSF respectively. Similar results were found in validation set. The AUC were 0.795 for RSF and 0.715 for Cox in the training set while the AUC were 0.765 for RSF and 0.705 for Cox in the validation set. The prediction error curves for each model based on Brier score showed the RSF model had lower prediction errors both in training group and validation group. What's more, the calibration curve displayed similar results of 2 models both in training set and validation set. The performance of RSF model were better than Cox regression model. The RSF algorithms provide a relatively better alternatives to be of clinical use for estimating the survival probability of LSCC patients.

The effect of head rotation on OSA is associated with disease severity: a cross-sectional study.

PURPOSE: Head rotation is an effective positional therapy for obstructive sleep apnea (OSA). However, not all OSA patients benefit from head rotation. This study aimed to explore the clinical phenotype of OSA patients who can benefit from head rotation. METHODS: We performed a retrospective review of 184 consecutive OSA patients who underwent polysomnography. Head rotation in supine position was determined by high-quality video recording. According to the changes in apnea-hypopnea index (AHI) after head rotation, OSA patients were divided into two groups: patients with response to head rotation(HR) and patients without response to head rotation(NHR). Demographic factors and overnight polysomnography were analyzed. RESULTS: Compared with NHR group, HR group showed significantly lower AHI (51.8 vs 31.5, p < 0.01), time spent with oxygen saturation below 90%(5.3% vs 0.51%, p < 0.01), and higher lowest oxygen saturation(80% vs 86%, p < 0.05). Logistic regression showed that AHI was an independent factor to predict the decrease of AHI in head rotation (OR 0.985, 95% CI 0.970-0.979, p < 0.05). Among mild to moderate group (AHI < 30/h), severe group (30/h ≤ AHI < 60/h), and extremely severe group (AHI ≥ 60/h), the percentage decrease of AHI in head rotation was 18.5%, 9.5%, and 2.6%, respectively. Surprisingly, the percentage decrease of AHI of 6 responders in mild to moderate group was more than 50%. CONCLUSION: OSA patients who respond well to head rotation have less severe disease, and patients with mild to moderate OSA are more likely to improve and benefit from this position. Our research provides potential strategies and insights into the individual treatment of OSA patients.

Metabolomic Approach to Screening Homozygotes in Chinese Patients with Severe Familial Hypercholesterolemia.

Homozygous familial hypercholesterolemia (HoFH) is a rare inborn-errors-of-metabolism disorder characterized by devastatingly elevated low-density lipoprotein cholesterol (LDL-C) and premature cardiovascular disease. The gold standard for screening and diagnosing HoFH is genetic testing. In China, it is expensive and is always recommended for the most likely HoFH subjects with aggressive LDL-C phenotype. However, the LDL-C levels of HoFH patients and a substantial proportion of heterozygous FH (HeFH) patients overlapped considerably. Here, we performed a cost-effective metabolomic profiling on genetically diagnosed HoFH (n = 69) and HeFH patients (n = 101) with overlapping LDL-C levels, aiming to discovery a unique metabolic pattern for screening homozygotes in patients with severe FH. We demonstrated a differential serum metabolome profile in HoFH patients compared to HeFH patients. Twenty-one metabolomic alterations showed independent capability in differentiating HoFH from severe HeFH. The combined model based on seven identified metabolites yielded a corrected diagnosis in 91.3% of HoFH cases with an area under the curve value of 0.939. Collectively, this study demonstrated that metabolomic profiling serves as a useful and economical approach to preselecting homozygotes in FH patients with severe hypercholesterolemia and may help clinicians to conduct selective genetic confirmation testing and familial cascade screening.

Arachidonic acid is associated with dyslipidemia and cholesterol-related lipoprotein metabolism signatures.

Introduction: Abnormal lipoprotein metabolism is associated with a variety of diseases, cardiovascular disease in particular. Free fatty acids (FAs) and triglycerides (TGs) are the principal lipid species in adipocytes and are the major components of lipoproteins. However, in routine clinical laboratory testing, only the total plasma concentrations of FAs and TGs are typically measured. Methods: We collected 965 individuals with hyperlipidemia plasma and clinical characteristics; high-throughput metabolomics permits the accurate qualitative and quantitative assessment of a variety of specific FAs and TGs and their association with lipoproteins; through regression analysis, the correlation between multiple metabolites and routine measured lipid parameters was found. Mice were fed a diet containing AA, and the concentrations of TC and TG in the plasma of mice were detected by enzyme method, western blot and qRT-PCR detected the protein and mRNA levels of cholesterol synthesis and metabolism in mice. Result: Using LC-MS/MS identified eight free FA and 27 TG species in plasma samples, the plasma concentrations of free arachidonic acid (AA) and AA-enriched TG species were significantly associated with the plasma low-density lipoprotein-cholesterol, apolipoprotein B (ApoB), and total cholesterol (TC) concentrations after adjustment for age, sex, the use of lipid-lowering therapy, and body mass index. AA-rich diet significantly increased the plasma concentrations of TC and ApoB and the liver expression of ApoB protein and reduced the protein expression of ATP binding cassette subfamily G members 5 and 8 in mice. Discussion: In this study, it was clarified that the plasma concentrations of free AA- and AA-enriched TG species were significantly associated with the plasma low-density lipoprotein-cholesterol, ApoB, and TC concentrations in individuals with hyperlipidemia, and it was verified that AA could increase the plasma TC level in mice. Taken together, these findings suggest a potential role of AA in the regulation of plasma cholesterol and lipoprotein concentrations.

Comprehensive Metabolomics and Machine Learning Identify Profound Oxidative Stress and Inflammation Signatures in Hypertensive Patients with Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) can aggravate blood pressure and increase the risk of cardiovascular diseases in hypertensive individuals, yet the underlying pathophysiological process is still incompletely understood. More importantly, OSA remains a significantly undiagnosed condition. In this study, a total of 559 hypertensive patients with and without OSA were included. Metabolome and lipidome-wide analyses were performed to explore the pathophysiological processes of hypertension comorbid OSA and derive potential biomarkers for diagnosing OSA in hypertensive subjects. Compared to non-OSA hypertensive patients (discovery set = 120; validation set = 116), patients with OSA (discovery set = 165; validation set = 158) demonstrated a unique sera metabolic phenotype dominated by abnormalities in biological processes of oxidative stress and inflammation. By integrating three machine learning algorithms, six discriminatory metabolites (including 5-hydroxyeicosatetraenoic acid, taurine, histidine, lysophosphatidic acid 16:0, lysophosphatidylcholine 18:0, and dihydrosphingosine) were selected for constructing diagnostic and classified model. Notably, the established multivariate-model could accurately identify OSA subjects. The corresponding area under the curve values and the correct classification rates were 0.995 and 96.8% for discovery sets, 0.997 and 99.1% for validation sets. This work updates the molecular insights of hypertension comorbid OSA and paves the way for the use of metabolomics for the diagnosis of OSA in hypertensive individuals.

[Preparation and application of graphene oxide functionalized melamine-formaldehyde aerogel coated solid-phase microextraction tube].

Many solid-phase microextraction (SPME) sorbents have been developed from aerogels because of their low densities, large surface areas, and high porosities. Melamine-formaldehyde (MF) aerogel, made from melamine and formaldehyde by a sol-gel reaction, is one of the typical organic aerogels. MF aerogel has better mechanical strength, chemical stability and extraction performance than inorganic aerogels. The performance of the aerogel is limited in some fields, while composite aerogels can meet different requirements such as good mechanical strength and strong adsorption performance. Graphene oxide (GO) is a two-dimensional nanomaterial composed of a single layer of carbon atoms and provides π-π interaction by a large π-electron. In addition, the oxygen-containing groups at the edge of the lamellar structure improve the hydrophilicity of the material and can interact with various compounds. To improve the extraction performance of MF aerogel for polycyclic aromatic hydrocarbons (PAHs), GO/MF aerogels were prepared by functionalizing MF aerogel with GO. In this study, 1.2612 g of melamine and 80 mg of sodium carbonate were dissolved in 30 mL of water, and the mixture was heated to 80 ℃ under stirring. Then, 2.8 mL formaldehyde solution (37%) was slowly added, and a clear solution was obtained gradually. Next, 50 mg of GO powder was ultrasonically dispersed in 10.0 mL of water and evenly mixed with the above solution. After adjusting the pH to 1.5, the sol-gel process was performed for 48 h, then the gel was aged at room temperature for 24 h. The gel was then soaked in ethanol, acetone, and cyclohexane in turn to replace the solvent. Finally, the GO/MF aerogel was obtained by freeze-drying for 24 h. The GO/MF aerogel was characterized by scanning electron microscopy (SEM) and X-ray photoelectric spectroscopy (XPS), confirming that GO was successfully introduced into MF aerogel, while retaining its three-dimensional network and porous structure. GO/MF aerogel was coated onto the surface of a stainless steel wire to be used as sorbent. Four such wires were placed into a polyetheretherketone (PEEK) tube (0.75 mm i. d., 30 cm length) for in-tube (IT) SPME. The tube was combined with a high-performance liquid chromatography (HPLC) unit to construct an IT-SPME-HPLC online system. When the six-way valve was in the Load state, sample solution achieved online enrichment with analytes while it flowed through the extraction tube. After extraction, the valve was turned to the Inject state, and the analytes were eluted into the chromatographic column by the mobile phase at a flow rate of 1.0 mL/min for separation and detection with the detector. Under the same extraction conditions (sampling volume=30 mL, sampling rate=1.00 mL/min, and concentration of polycyclic aromatic hydrocarbons (PAHs, viz. naphthalene (Nap), acenaphthylene (Acy), acenaphthene (Ace), fluorine (Flu), phenanthrene (Phe), anthracene (Ant), fluoranthene (Fla) and pyrene (Pyr))=5.00 µg/L), GO/MF aerogel-based tube was compared with that of MF aerogel-based tube. GO enhanced the enrichment efficiency of MF aerogel towards PAHs from 1.1 to 2.5 times, due to the increased number of adsorption sites and enhanced π-π interaction with PAHs. IT-SPME was affected by the sampling volume, sampling rate, concentration of organic solvent in sample, desorption solvent, desorption rate, and desorption time. To obtain accurate results, the main extraction and desorption conditions (sampling volume, sampling rate, organic solvent concentration, desorption time) were investigated carefully. As the sampling volume in the extraction tube was increased, the extraction efficiency was found to increase gradually until saturation. In this study, the extraction efficiency was investigated for sampling volumes ranging from 30 to 80 mL, and 70 mL was selected as a suitable sampling volume to achieve satisfactory extraction efficiency. The sampling rate affects not only the extraction efficiency, but also the extraction time. When the sample flows through the extraction tube at a low rate, it requires a long test time. Although the increase in sampling rate reduces the extraction time, it often decreases extraction efficiency. In addition, large sampling rate leads to high pressure in the tube, which in turn reduces the service life of the tube. Therefore, the effect of sampling rate (1.25-2.50 mL/min) on extraction efficiency was investigated, and good extraction efficiency and short test time were achieved when the sampling rate was 2 mL/min. High hydrophobic PAHs have poor solubility in water. An appropriate amount of organic solvent in the sample solution can improve the solubility of PAHs to obtain accurate analytical results. However, the extraction efficiency was affected by the added organic solvent. Thus, the effect of volume fraction of methanol (0, 0.5%, 1%, 2%, 3%, and 5%, v/v) on the extraction efficiency was investigated. The sample solution without methanol afforded better extraction efficiency and satisfactory repeatability. After online extraction, the desorption directly affects the desorption efficiency. The peak areas of the eight PAHs were investigated with different desorption times (0.2, 0.4, 0.6, 0.8, 1.0, and 2.0 min), and a desorption time of 2.0 min was required to fully desorb all analytes and reduce their residuals. The IT-SPME-HPLC-DAD method was established under the optimized conditions, and the limits of detection (LODs), linear equations, linear ranges, and correlation coefficients were obtained. The LODs of the eight PAHs were in the range of 0.001-0.005 µg/L, the quantitative ranges of the analytes were 0.003-15.0 µg/L for Fla and Pyr, 0.010-20.0 µg/L for Phe and Ant, and 0.017-20.0 µg/L for Nap, Acy, Ace and Flu, the enrichment factors were in the range of 2029-2875, and the analytical precision was satisfactory (intra-day RSD%≤4.8%, and inter-day RSD≤8.6%). Compared with some reported methods, the method reported herein provided higher sensitivity, wider linear range, and shorter test time. This method was applied to the detection of PAHs in common drinking water, including bottled mineral water and water from drinking fountain. The satisfactory recovery (76.3%-132.8%) obtained proves that the method is suitable for the determination of trace PAHs in real water samples, with high sensitivity, rapid testing, online detection, and good accuracy. The extraction tube also exhibited satisfactory durability and chemical stability.

Carbonized metal-organic framework-74/carbon aerogel composites for the efficient extraction of triazole fungicides from fruits and vegetables.

To improve the extraction efficiency, availability, and stability of metal-organic framework (MOF) for pipette-tip solid-phase extraction (PT-SPE), a carbonized MOF-74/carbon aerogel composite (CMOF-74/CA) was developed. A carbon aerogel with a surface area of 547.7 m2 g-1 was prepared by carbonizing a watermelon peel. After that, via a hydrothermal reaction, the MOF-74 was in situ grown on the surface. After the pyrolysis at 700 °C for 2 h, the CMOF-74/CA composite was obtained. Through regulating the concentration of reactants, a series of MOF-74/CA and CMOF-74/CA materials were prepared. These materials were used to extract hexaconazole and diniconazole in fruits and vegetables before gas chromatography-flame ionization detection (GC-FID). The adsorbent type and amount, sample pH, and the desorption solvent type and volume were optimized factor by factor. Under the optimized conditions, a PT-SPE-GC-FID method was established. Moreover, good linearity in the concentration ranges of 0.098-200.0 mg kg-1 and 0.196-200.0 mg kg-1, and detection limits ranging between 0.033 and 0.065 mg kg-1 were achieved for two triazole fungicides (TFs). The relative standard deviations (n = 3) for intra-day and inter-day tests were in the ranges of 3.1-3.2% and 3.0-3.4%, respectively. The method showed satisfactory analytical performance in different samples with good relative recoveries in the range of 72.6-116%. Compared with some methods, it displayed wider linearity, better or comparable sensitivity, and enhanced analytical precision.

Efficient degradation of hydroquinone by a metabolically engineered Pseudarthrobacter sulfonivorans strain.

Pseudarthrobacter sulfonivorans strain Ar51 can degrade crude oil and multi-substituted benzene compounds efficiently at low temperatures. However, it cannot degrade hydroquinone, which is a key intermediate in the degradation of several other compounds of environmental importance, such as 4-nitrophenol, g-hexachlorocyclohexane, 4-hydroxyacetophenone and 4-aminophenol. Here we co-expressed the two subunits of hydroquinone dioxygenase from Sphingomonas sp. strain TTNP3 with different promoters in the strain Ar51. The strain with 2 hdnO promoters exhibited the strongest hydroquinone catabolic activity. However, in the absence of antibiotic selection this ability to degrade hydroquinone was lost due to plasmid instability. Consequently, we constructed a hisD knockout strain, which was unable to synthesise histidine. By introducing the hisD gene onto the plasmid, the ability to degrade hydroquinone in the absence of antibiotic selection was stabilised. In addition, to make the strain more stable for industrial applications, we knocked out the recA gene and integrated the hydroquinone dioxygenase genes at this chromosomal locus. This strain exhibited the strongest activity in catabolizing hydroquinone, up to 470 mg/L in 16 h without antibiotic selection. In addition, this activity was shown to be stable when the strain has cultured in medium without antibiotic selection after 20 passages.

ANGPTL3 and Cardiovascular Outcomes in Patients With Acute Coronary Syndrome and Obstructive Sleep Apnea.

Background The aim of this prospective study was to determine the impact of elevated ANGPTL3 (angiopoietin-like protein 3) on cardiovascular events (CVEs) following acute coronary syndrome (ACS) in patients with or without obstructive sleep apnea (OSA). Methods and Results A total of 1174 patients with ACS underwent successful percutaneous coronary intervention were included in this prospective cohort study (NCT03362385). Patients were categorized according to the apnea-hypopnea index (≥15 events/h, OSA) and further classified by ANGPTL3 levels. We analyzed the incidence of CVEs in patients with ACS according to the status of OSA and ANGPTL3. During a median of 3.1 years of follow-up, 217 (18.48%) CVEs occurred. The patients with ACS with OSA had higher ANGPTL3 levels than those without OSA (30.4 [20.9-43.2] versus 27.80 [19.1-41.5] ng/mL; P<0.001). In all patients with ACS, 29≤ANGPTL3<42 mg/dL and ANGPTL3≥42 mg/dL were associated with an increased risk of CVEs with hazard ratios (HRs) of 1.555 (95% CI, 1.010-2.498) and 2.489 (95% CI 1.613-3.840), respectively. When the status of OSA or not was incorporated in stratifying factors, 29≤ANGPTL3<42 mg/dL and ANGPTL3≥42 mg/dL were associated with a significantly higher risk of CVEs in patients with ACS with OSA (HR, 1.916 [95% CI, 1.019-3.601] and HR, 2.692 [95% CI, 1.379-4.503]) but not without OSA. Moreover, adding ANGPTL3 to the Cox model increased C-statistic values by 0.035 and 0.029 in the OSA group and all patients with ACS, respectively, but was not statistically improved in patients with ACS without OSA. Conclusions In conclusion, our study demonstrates a predictive impact of plasma ANGPTL3 on cardiovascular risk in patients with ACS, especially in patients with ACS with OSA. It might be of clinical value in refining risk stratification and tailoring treatment of patients with ACS and OSA. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03362385.

Increasing circulating ESM-1 and adhesion molecules are associated with earlystage atherosclerosis in OSA patients:A cross-sectional study.

BACKGROUND: There are increasing evidences for a direct relationship between the vascular system and obstructive sleep apnea (OSA). The aim of this study was to investigate the relationship between circulating endothelial cell specific molecule-1 (ESM-1), adhesion molecules and subclinical atherosclerosis in patients with OSA. METHODS: This was a cross-sectional study in which 161 patients with OSA and 56 controls were recruited. Demographic data, biochemical and polysomnography parameters were collected. We used a powerful high-throughput Multiplex Immunobead Assay technique to simultaneously test plasm levels of ESM-1, P-selectin, E-selectin, L-selectin, inter-cellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1). Carotid intima-media thickness (CIMT) were measured as parameters of vascular endothelial dysfunction and early atherosclerosis. RESULTS: Increasing circulating levels of ESM-1, P-selectin, E-selectin, L-selectin, ICAM-1 and VCAM-1 were found increased in patients with OSA (all P < 0.001). Furthermore, OSA patients exhibited increased CIMT than controls (P < 0.05). Multivariate linear analysis indicated that elevated ESM-1, P-Selectin, E-selectin, and L-selectin levels were associated with AHI (all P < 0.05). Moreover, multivariate analysis showed that increasing ESM-1, VCAM-1, P-Selectin, and L-selectin were significantly associated with thick CIMT in OSA patients (all P < 0.05). CONCLUSIONS: Increased circulating ESM-1 and adhesion molecules associated with thick CIMT in OSA, which is a marker of subclinical atherosclerosis. Strict attention to monitor circulating ESM-1 and adhesion molecules is necessary for early detection of subclinical atherosclerosis in OSA patients.

Carbon aerogels derived from waste paper for pipette-tip solid-phase extraction of triazole fungicides in tomato, apple and pear.

In order to develop environmentally friendly, economical and facile preparation method of carbon aerogels (CAs), the waste printing paper as the raw material was combined with graphene oxide and carboxylic multi-walled carbon nanotubes to produce CAs (ρ = 44 mg cm-3). The CAs with different composition were investigated, the addition of graphene oxide led to the reduction of adsorption sites and the reduction of extraction performance. But the carbon nanotubes made CAs have a better pore structure. The CAs as adsorbent were loaded into a pipette-tip for solid-phase extraction of hexaconazole and diniconazole. Coupled with gas chromatography, an analytical method was established under the optimized conditions. The limits of detection were between 0.08 and 0.32 mg kg-1, the linear ranges were 0.96-200.0 mg kg-1 and 0.24-200.0 mg kg-1. The relative recoveries were in the range of 81.0-119%. The results indicated that the method had potential application for the determination of triazole fungicides.

A new bacterial tRNA enhances antibiotic production in Streptomyces by circumventing inefficient wobble base-pairing.

We report the discovery and functional characterization of a new bacterial tRNA species. The tRNA-Asp-AUC, from a fast-growing desert streptomycete, decodes GAU codons. In the absence of queuosine tRNA anticodon modification in streptomycetes, the new tRNA circumvents inefficient wobble base-pairing during translation. The tRNA, which is constitutively expressed, greatly enhances synthesis of 4 different antibiotics in the model mesophilic species Streptomyces coelicolor, including the product of a so-called cryptic pathway, and increases yields of medically-important antibiotics in other species. This can be rationalised due to increased expression of both pleiotropic and pathway-specific transcriptional activators of antibiotic biosynthesis whose genes generally possess one or more GAT codons; the frequency of this codon in these gene sets is significantly higher than the average for streptomycete genes. In addition, the tRNA enhances production of cobalamin, a precursor of S-adenosyl methionine, itself an essential cofactor for synthesis of many antibiotics. The results establish a new paradigm of inefficient wobble base-pairing involving GAU codons as an evolved strategy to regulate gene expression and, in particular, antibiotic biosynthesis. Circumventing this by expression of the new cognate tRNA offers a generic strategy to increase antibiotic yields and to expand the repertoire of much-needed new bioactive metabolites produced by these valuable bacteria.