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Antihypertensive agents are frequently prescribed in kidney transplant recipients (KTRs). However, the frequency and patterns of prescribing antihypertensive agents remain uncharacterized in KTRs in China. Therefore, this investigation was carried out.Retrospective prescription data dated 2011 to 2018 from KTRs in China were accessed using the Hospital Prescription Analysis Program database. Information about sex, birth date, and identification number of the patient; city, date, and department of the medical visit; major diagnoses; and the generic names, specifications, quantities, and usage of prescribed drugs were collected. Antihypertensive agents were grouped into 5 classes: angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), β-blockers (BBs), calcium channel blockers (CCBs), and diuretics. The frequency and patterns of prescribing these antihypertensive agents were analyzed.Prescriptions from 174,749 KTRs (67.2% male; mean age, 42.5 [9.4] years) were obtained, and 58.2% of the patients were prescribed antihypertensive agents. The percentage of patients who received antihypertensive treatment increased from 52.9% in 2011 to 61.6% in 2018 and varied by city. Cyclosporine was associated with higher prescription frequency of antihypertensive agents than was tacrolimus (71.7% vs 63.4%; P 0.0001). During the 8-year study period, CCBs were most frequently prescribed (39.0%), followed by ARBs (31.9%), BBs (14.3%), ACEIs (11.6%), and diuretics (3.2%). The mean (SD) number of antihypertensive drugs prescribed per KTR was 1.7 (0.8). Almost half of KTRs (51.2%) received just 1 antihypertensive drug. Co-administration of 2 or more antihypertensive drugs presented an obviously upward trend. The most commonly prescribed 2-drug combination was CCB + ARB (44.8%), followed by CCB + BB (20.1%) and CCB + ACEI (13.0%). In the patients who received 3 antihypertensive drugs, the 2 most frequently prescribed combinations were CCB + ARB + BB (37.5%) and CCB + ARB + ACEI (32.7%). Specific data varied by both year and city.The prescribing patterns of antihypertensive agents in KTRs varied by city even within same country. Hence, more high-quality research studies on the use of antihypertensive agents in KTRs are needed.

The 232Th(n,γ)233Th neutron capture reaction cross-sections at the neutron energies of 4.36 ± 0.06 MeV, 3.52 ± 0.41 MeV and 2.06 ± 0.34 MeV have been measured using the activation method and off-line gamma-ray spectrometric technique. The neutrons were generated by T(p,n)3He reaction and the 197Au(n, γ)198Au was used as a monitor reaction to determine neutron flux. The effects of multiple scattering, flux attenuation, gamma-ray self-absorption and neutron flux fluctuation have been corrected in the experiment. The excitation function of the 232Th(n,γ)233Th reaction was also theoretically calculated using the TALYS-1.9 code. The experimental results were compared with the evaluated data, the calculated data and the previous experimental data.

Background and aims Hyperuricemia is independently associated with cardiovascular disease (CVD) and is considered to be one of the major risk factors for CVD. However, the impact of inter-visit uric acid (UA) variability on cardiovascular risk remains undetermined. Methods We enrolled 3202 patients with coronary artery disease (CAD), who received successful coronary intervention, in a cohort from Taipei Veterans General Hospital from 2006 to 2015. All post-baseline visits UA measurements using standard deviation (SD) were analyzed to correlate with long-term outcome. The primary outcome was the composite of cardiac death, nonfatal MI, nonfatal stroke (MACE). The secondary event was MACE and hospitalization for heart failure. Results During an average 65.06 ± 32.1-month follow-up, there were 66 cardiovascular deaths, 175 nonfatal myocardial infarctions, 64 nonfatal strokes, 287 hospitalizations for heart failure, and 683 revascularization procedures. There was a linear association between high UA SD and future adverse events. Compared to the lowest quartile SD, subjects in the highest quartile SD had a higher risk of MACE (HR: 2.53, 95% CI: 1.78–3.59), myocardial infarction (HR: 2.43, 95% CI: 1.53–3.86), cardiovascular death (HR: 6.45, 95% CI: 2.52–16.55), heart failure-related hospitalization (HR: 3.43, 95% CI: 2.32–5.05), and total major CV events (HR: 2.72, 95% CI: 2.09–3.56). Furthermore, compared to the average achieved on-treatment UA value, increasing UA SD had a stronger association of higher risk of developing MACE (HR: 1.51, 95% CI: 1.36–1.68), myocardial infarction (HR: 1.37, 95% CI: 1.38–1.68), ischemic stroke (HR: 1.43, 95% CI: 1.13–1.82), CV death (HR: 1.77, 95% CI: 1.50–2.11), HF (HR: 1.43, 95% CI: 1.29–1.58), and total major CV events (HR: 1.46, 95% CI: 1.34–1.58). Conclusions High UA variability is associated with a higher risk of developing future cardiovascular events, suggesting the importance of maintaining stable serum UA levels and avoiding large fluctuations in CAD patients after percutaneous coronary intervention (PCI).

Wide applications of smart wearable electronics have triggered tremendous needs for energy storage devices featuring lightweight, transparency, foldability and breathability. However, conventional supercapacitor electrodes are always substrate-supported with a compact film structure, which strongly limits their air permeability, flexibility and transparency. In this report, we demonstrate the use of a freestanding, ultrathin (∼ 6 μm), highly conductive (4 × 105 S/m), highly transparent (> 91%), air permeable (2600 mm/s at 10 Pa) and foldable metallic mesh electrode, decorated with active MnO2 microstructures, as a breathable, transparent and foldable supercapacitor electrode. By introducing Au nanoparticles as the “nanoglue” between Ni and MnO2, excellent electrochemical performances including large areal capacitance (268 mF/cm2) and high cycling stability (90.1% capacitance retention after 10000 cycles) are obtained in the MnO2-Au-Ni mesh electrode. Furthermore, the assembled all-solid-state supercapacitor device delivers high optical transparency (∼83.6%), high air permeability (45.4 mm/s at 100 Pa), superior electrochemical performances and can withstand various deformations including bending, folding, and crumpling. The present freestanding mesh structure electrode could be further explored and applied in more potential applications, such as ion batteries, wearable sensors, and conformal healthcare devices.

Cellulose acetate (CA) membranes have shortages of low permeability and membrane fouling. A novel polymer additive (denoted as PA) has both hydrophilic and oleophobic groups was synthesized from CA via a one-step reaction. Blend membrane fabricated from mixing CA and PA in 4:1 showed improved membrane properties. By adding 1 wt% of PVPk30, the pure water flux of blend CA membrane was increased from 0 to 34.0 L/m2·h·bar. The filtration experiments indicated the membranes exhibited good antifouling property, excellent anti-oil performance that 92.5% of oil rejections and 90% relative flux recovery were obtained.

Engineered particle-doped light diffuser is realized by a simple, low-cost soft lithographic method. A flexible photopolymerizable mold is employed as an intermediate transferring template directly from the developed photoresist texture to fabricate engineered particle-doped light diffuser. The well-designed surface microstructure can directionally scatter the incident light, while the doped ultra-violet curable resin with low concentration of the 2 μm-diameter organosilicone particles can homogenize the scattering light without decreasing transmittance. Experimental results show that the measured transmittance can be as high as 96.9% with little backscattering effect over the whole visible regime. Meanwhile, the haze raises from 30% to 75% with increased dopant concentration from 1 wt% to 7 wt% and thickness of the residual layer from 10 μm to 40 μm remained in the imprinting process. The proposed engineered particle-doped light diffuser can manage scattering angle, luminance uniformity and haze, thus it has the capability of homogenizing light and eliminating striations to create more visually pleasing structured lighting in commercial and residential environments. We anticipate that the approach appears to be a strong candidate for future development because of its scalable nature, environmentally-friendly process and relatively low cost.

Modified asphalt was prepared by mixing coal tar pitch (CTP) and petroleum asphalt (PA), and the effects of blending conditions on the properties of softening point, ductility, penetration, and elastic modulus of CTP-modified asphalt (CTPMA) were discussed. The group compositions of PA and CTPMA were analyzed by Fourier transform infrared spectroscopy (FTIR). Results show that PA properties (i.e., softening point, ductility, and penetration) can be improved by CTP addition because of the formation of large-molecule compounds as polycondensation reaction products from small-molecule materials in the blending process. CTP is compatible to PA, and CTP percent of 15% is proper under the blending conditions. CTP addition can also improve the anti-aging effect and decrease the elastic deformation of asphalt mixture. Experiments verify that the modification of PA by CTP addition is technologically feasible, and modified PA can be used to pave asphalt.

Polymeric micelles are effective drug-loading sites and often used to formulate poorly water-soluble agents. In the present study, the amphiphilic copolymer methoxy-capped poly(ethyleneglycol)-block-poly(ε-caprolactone) (mPEG-b-PCL) was successfully developed for the delivery of 20(R)-dammarane-3β,12β,20,25-tetrol (25-OH-PPD), a natural anticancer product from Panax notoginseng. The 25-OH-PPD-loaded micelles were characterized by morphological observation and thermodynamic stability testing. The concentrations of 25-OH-PPD were determined by HPLC-MS/MS. The optimum MRM transition of 25-OH-PPD was selected at m/z 479.4.0 → 461.4. The chromatographic separation was achieved on a SB-C18 column (1.8 μm, 2.1×50 mm) with an optimized gradient mobile phase system. The extraction recoveries of plasma and various tissue homogenates were within the range of 81.1% to 110.4% and the matrix effects ranged from 81.9% to 106.7%. The intra- and inter-day precision values (RSD%) were less than 12.0%, with accuracies ranging from 85.2% to 114.2%. In addition, 25-OH-PPD was found to be stable in different biological matrix after three freeze-thaw cycles, at room temperature and at −70°C for 4 weeks. The pharmacokinetics of 25-OH-PPD-loaded micelles was evaluated in rats. The micelles appeared as transparent liquid, stable and uniform spheres with an average particle size of 35.4±4.2nm. The maximum concentration of 25-OH-PPD in micelles was much lower than in free drug preparation. However, the drug in the micelles was released steadily, with a t½ of 9.1±4.0 h, significantly longer than in free drug (3.3±1.4 h). However, the drug concentrations in tissues after the micelle administration were lower than the levels after administration of the free drugs. In summary, the micelles were characterized by long circulation and sustained release, with an ability to avoid uptake by the reticuloendothelial system, providing a promising approach to deliver intravenous 25-OH-PPD for therapy.

Objective: This study aimed to evaluate the association between antipsychotic drugs (APs) and the risk of venous thromboembolism (VTE). Methods: We searched Pubmed, Embase, and the Cochrane Library from inception to August 15, 2019 for case-control studies and cohort studies that explored the association between APs and VTE. Two researchers independently screened the literature, extracted the data and evaluated the bias risk included in the study. Meta-analysis was carried out by using STATA 13.0. Results: 1,468 studies were identified through database search, and 22 studies were finally included (14 case-control studies and 8 cohort studies). Overall, the APs usage was associated with increased risk of VTE and pulmonary embolism (PE) with no publication bias. Both the first-generation APs (FGAs) and second-generation APs (SGAs) can increased the risk of VTE. The low-potency FGAs lead to a higher risk of VTE than high-potency FGAs. The risk of PE and VTE in younger patients was about 3-fold higher compared with elderly. Conclusion: This review demonstrates that APs usage can increase the risk of VTE. Young people are at a higher risk of VTE than elderly when taking APs.

Purpose This study explores factors that affect behavior in critically ill patients receiving continuous renal replacement therapy (CRRT) with imipenem and provides dosing regimens for these patients. Methods A prospective, open-label study was conducted in a clinical setting. Both blood and effluent samples were collected pairwise at the scheduled time points. Plasma and effluent imipenem concentrations were determined by HPLC-UV. A population pharmacokinetic model was developed using a nonlinear mixed-effects modeling method. The final model was evaluated by a bootstrap and visual predictive check. A population pharmacokinetic and pharmacodynamic analysis using Monte Carlo simulations was performed to explore the effects of empirically used dosing regimens (0.5 g q6h, 0.5 g q8h, 0.5 g q12h, 1 g q6h, 1 g q8h, and 1 g q12h) on the probability of target attainment. Findings Thirty patients were included in the population model analysis. Imipenem concentration data were best described by a 3-compartment model (central, peripheral, and dialysis compartments). The clearance of the dialysis compartment (CLd) was used to characterize drug elimination from the dialyzer. Creatinine clearance (CrCl) was the covariate that influenced the central clearance (CLc), and the effects of dialysate flow (Qd) was significant for CLd. Model validation revealed that the final model had qualified stability and acceptable predictive properties. A pharmacokinetic and pharmacodynamic analysis was conducted by Monte Carlo simulation, and patients were categorized into 12 subgroups based on different CrCl values ( 90 mL/min) and Qd values (300, 500, and 1000 mL/h). Under the same MIC value and administration regimen, probability of target attainment values decreased with an increase of CrCl and Qd. Implications CrCl and Qd had significant effects on CLc and CLd, respectively. The proposed final model may be used to guide practitioners in imipenem dosing in this specific patient population.

A new lithographic approach for the fabrication of an enticing optical diffuser with concave microlens array (MLA) is reported. A flexible photopolymerizable polymer mold is employed as an intermediate transferring template from nickel stamp and directly adopted to fabricate concave MLA diffuser films. The influence of the parameters (such as diameter, fill factor etc.) of concave MLA is analyzed experimentally and theoretically. The results verify that the optical gain can be reached as high as 53%, which has a similar fascinating diffusion effect compared with that of conventional convex MLA diffuser films. Additionally, it is found that diffusion angle could be manipulated by the profile of the concave elliptical MLA, leading to luminance increase in long axis larger than that in short axis. The approach demonstrated here affords the intriguing opportunity to large scale industrial processing for high-quality diffusers with low manufacturing and materials cost.

The assembly of multiple enzymes has received increasing attention due to the promising application in improving biocatalytic process. In this study, supramolecular nanoreactors were engineered by assembly of polyphosphate kinase (PPK) and bifunctional glutathione synthetase (GshF) for adenosine triphosphate (ATP) regeneration in vitro. Tetrameric PPK and dimeric GshF were first self-assembled via peptide-peptide interaction of fused leucine zipper domains to form multienzyme complexes (MECs) with plate-like morphology. Further, under the driving force of polymerization of PPK driven by substrate polyphosphate (polyP), MECs were assembled into multienzyme nanoreactors (MENRs) with branch-like morphology. MENRs were applied to a two-enzyme cascade reaction in vitro. The ATP regeneration efficiency of MENRs system was 57 % higher than that of unassembled enzymes mixture, and the thermal stability was improved by 46 %. When reused for ATP regeneration, the assemblies retained more than 70 % of the initial activity even after seven cycles. This is the first report in which an artificial complex was constructed by substrate-driven assembly of multiple enzymes for cascade reaction. The strategy demonstrated potential application of multienzyme assembly in synthetic biotechnology and nanotechnology.

Carbamoyl phosphate synthetase (CPS) is a key enzyme in both pyrimidine and arginine biosynthesis. However, it is inhibited strongly by uridine monophosphate (UMP), which is an intermediate of the de-novo synthesis of pyrimidine nucleoside. In this study, the native carbamoyl phosphate synthetase, from Escherichia coli, was evolved by site-directed mutation and casting error-prone PCR. Compared with the wild-type, the variant N1015 F had released sensitivity to UMP and exhibited 100% of the initial activity in the presence of UMP. Variant K1006A exhibited 0.14-fold improvement in initial activity and kept above 65% of relative activity under the saturated concentration of inhibitor. Structure analysis of variants demonstrated that the reduced sensitivity to inhibitor was largely attributed to the decreased hydrogen bonds, which could reduce the binding affinity with UMP. Also, Phe with large side chain could narrow the binding pocket and generate more steric hindrance. Based on the results in this study, N1015F was an ideal alternative catalyst for the wild-type CPS for pyrimidine biosynthesis.

The nucleophilic substitution reactions of vinylic bromides with intramolecular thioamide or thiourea moieties proceed to give a series of substituted thiazoles and imidazole-2-thiones.