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Aims: To investigate the potential linear relationship between serum concentrations of klotho and frailty., Methods: A retrospective analysis was conducted on the data of 9,597 middle-aged and older adults (aged 40-79 years) from the five cycles of the National Health and Nutrition Examination Survey (NHANES). Frailty was assessed using the Frailty Index, calculated as a percentage of accumulated deficits across 53 health items. Restricted cubic spline curves, subgroup analyses and logistic regression models were employed to evaluate the specific linear trend connection between circulating klotho protein concentration and frailty., Results: When taking Klotho into account as a continuous component in Models 1 and 2, there was a substantial association between the increasing Klotho level and the reduced risk of frailty. Model 3 revealed a strong negative correlation between the Klotho and Frailty, suggesting that high levels of Klotho protein decreases the frailty prevalence [Odd ratio (OR): 0.25; 95% confidence interval (CI): 0.15-0.43]. Furthermore, according to the quartile analyses, after fully adjusting for the covariates, it was observed that, comparing to the lowest quartile of Klotho, the highest quartile of Klotho demonstrated lowest risk of frailty (OR 0.69; 95% CI 0.58-0.81, P trend < 0.001). The restricted cubic spline curves showed a linear relationship and an inverse association between frailty and the Klotho levels (P linearity < 0.001; P non-linearity = 0.736)., Conclusion: Klotho is inversely and linearly associated with physical frailty in the general population (aged 40-79 years), specifically in the population with an age < 65 and body mass index (BMI) ≥ 25 kg/m 2 . More necessary prospective studies should be done to further investigate the mechanisms underlying frailty and aging and to elucidate individual frailty causes., Competing Interests: None., (AJTR Copyright © 2024.)

This report presents liquid metal-based infrared-modulating materials and systems with multiple modes to regulate the infrared reflection. Inspired by the brightness adjustment in chameleon skin, shape-morphing liquid metal droplets in silicone elastomer (Ecoflex) matrix are used to resemble the dispersed "melanophores". In the system, Ecoflex acts as hormone to drive the deformation of liquid metal droplets. Both total and specular reflectance-based infrared camouflage are achieved. Typically, the total and specular reflectances show change of ~44.8% and 61.2%, respectively, which are among the highest values reported for infrared camouflage. Programmable infrared encoding/decoding is explored by adjusting the concentration of liquid metal and applying areal strains. By introducing alloys with different melting points, temperature-dependent infrared painting/writing can be achieved. Furthermore, the multi-layered structure of infrared-modulating system is designed, where the liquid metal-based infrared modulating materials are integrated with an evaporated metallic film for enhanced performance of such system., (© 2024. The Author(s).)

Beta-cypermethrin (β-CY) residues in food are an important threat to human health. Microorganisms can degrade β-CY residues during fermentation of fruits and vegetables, while the mechanism is not clear. In this study, a comprehensively investigate of the degradation mechanism of β-CY in a food microorganism was conducted based on proteomics analysis. The β-CY degradation bacteria Gordonia alkanivorans GH-1 was derived from fermented Pixian Doubanjiang. Its crude enzyme extract could degrade 77.11% of β-CY at a concentration of 45 mg/L within 24 h. Proteomics analysis revealed that the ester bond of β-CY is broken under the action of esterase to produce 3-phenoxy benzoic acid, which was further degraded by oxidoreductase and aromatic degrading enzyme. The up-regulation expression of oxidoreductase and esterase was confirmed by transcriptome and quantitative reverse transcription PCR. Meanwhile, the expression of esterase Est280 in Escherichia coli BL21 (DE3) resulted in a 48.43% enhancement in the degradation efficiency of β-CY, which confirmed that this enzyme was the key enzyme in the process of β-CY degradation. This study reveals the degradation mechanism of β-CY by microorganisms during food fermentation, providing a theoretical basis for the application of food microorganisms in β-CY residues., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

To date, there has been limited research on the interactive effects of yeast and lactic acid bacteria (LAB) on the sensory qualities of navel orange wine. In this study, using Jintang navel orange juice as the raw material, multi-microbial fermentation was conducted with Saccharomyces cerevisiae SC-125 and Angel yeast SY, as well as Lactiplantibacillus plantarum BC114. Single yeast and co-fermentation with Lactiplantibacillus plantarum were used as the control groups. The research aimed to investigate the physicochemical parameters of navel orange wine during fermentation. Additionally, headspace solid-phase microextraction gas chromatography-mass spectrometry (HP-SPME-GC-MS) was employed to determine and analyze the types and levels of flavor compounds in the navel orange wines produced through the different fermentation methods. The co-fermentation using the three strains significantly enhanced both the quantity and variety of volatile compounds in the navel orange wine, concomitant with heightened total phenol and flavonoid levels. Furthermore, a notable improvement was observed in the free radical scavenging activity. A sensory evaluation was carried out to analyze the differences among the various navel orange wines, shedding light on the impact of different wine yeasts and co-fermentation with LAB on the quality of navel orange wines.

Background: To explore the relationships between hyperuricemia and the risk of cardiovascular diseases (CVD) and chronic kidney disease (CKD) in both the general population and hypertensive patients through meta-analysis., Methods and Results: We systematically searched PubMed, Embase, and Cochrane Library databases from January 2012. The eligibility criteria were predefined, and quality was assessed using the Newcastle-Ottawa Scale (NOS). Stata 15.1 was used for meta-analysis, heterogeneity and sensitivity analysis. Subgroup analysis was used to explore heterogeneity, funnel plots and Egger tests were used to assesse publication bias and applicability. A total of 10,662 studies were retrieved, 45 of which were included in this meta-analysis utilizing a random effects model. Hyperuricemia was significantly associated with an increased risk of new-onset hypertension (RR = 1.36, 95% CI 1.16-1.59; I 2  = 98.8%), total CVD (RR = 1.53, 95% CI 1.23-1.89; I 2  = 93.7%), stroke (RR = 1.97, 95% CI 1.71-2.26, I 2  = 0.0%), coronary heart disease (CHD) (RR = 1.56, 95% CI 1.06-2.30, I 2  = 93.3%), and CKD (RR = 1.71, 95% CI 1.56-1.87; I 2  = 87.3%). However, subgroup analysis showed no significant associations between hyperuricemia and hypertension in non-Asian populations (RR = 0.88, 95% CI 0.59-1.33), or between hyperuricemia and CVD with a follow-up duration <5 years (RR = 1.26, 95% CI 0.97-1.63). Among hypertensive patients, hyperuricemia was significantly associated with total CVD (RR = 2.32, 95% CI 1.31-4.12, I 2  = 90.2%), but not with stroke (RR = 1.48, 95% CI 0.86-2.55; I 2  = 90.7%) or CHD (RR = 1.51, 95% CI 0.98-2.33; I 2  = 71.7%)., Conclusion: Hyperuricemia was significantly associated with an increased risk of new-onset hypertension, total CVD, stroke, CHD, and CKD in the general population. Among hypertensive patients, hyperuricemia was associated with an increased risk of CVD but not stroke or CHD alone., Registration Number: CRD42022370692., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier Ireland Ltd. All rights reserved.)

Control of convection plays an important role in heat transfer regulation, bio/chemical sensing, phase separation, etc. Current convection controlling systems generally depend on engineered energy sources to drive and manipulate the convection, which brings additional energy consumption into the system. Here the use of human hand as a natural and sustainable infrared (IR) radiation source for the manipulation of liquid convection is demonstrated. The fluid can sense the change of the relative position or the shape of the hand with the formation of different convection patterns. Besides the generation of static complex patterns, dynamic manipulation of convections can also be realized via moving of hand or finger. The use of such sustainable convections to control the movement of a floating "boat" is further achieved. The use of human hands as the natural energy sources provides a promising approach for the manipulation of liquid convection without the need of extra external energy, which may be further utilized for low-cost and intelligent bio/chemical sensing and separation., (© 2023 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

The microbial fermentation of food has emerged as an efficient means to eliminate pesticide residues in agricultural products; however, the specific degradation characteristics and mechanisms remain unclear. In this study, a Gram-positive bacterium, Aneurinibacillus aneurinilyticus D-21, isolated from fermented Pixian Douban samples exhibited the capability to degrade 45 mg/L of cyfluthrin with an efficiency of 90.37%. Product analysis unveiled a novel cyfluthrin degradation pathway, involving the removal of the cyanide group and ammoniation of the ester bond into an amide. Whole genome analysis discovered the enzymes linked to cyfluthrin degradation, including nitrilase, esterase, carbon-nitrogen ligases, and enzymes associated with aromatic degradation. Additionally, metabolome analysis identified 140 benzenoids distributed across various aromatic metabolic pathways, further substantiating D-21's catabolic capability toward aromatics. This study underscores the exceptional pyrethroid degradation prowess of A. aneurinilyticus D-21, positioning it as a promising candidate for the biotreatment of pesticide residues in food systems.

Ester-containing deltamethrin pesticides are widely used in farmland and have inevitable side effects on the biosphere and human health. Microbia have been used for efficient degradation of deltamethrin, but the related mechanism and enzyme characteristics have not been elucidated. In this study, a species Brevibacillus parabrevis BCP-09 could degrade up to 75 mg L -1 deltamethrin with a degradation efficiency of 95.41%. Proteomic and genomic methods were used to explore its degradation mechanism. Enzymes belonged to hydrolases, oxidases and aromatic compound degrading enzymes were expressed enhanced and might participate in the deltamethrin degradtion. RT-PCR experiment and enzyme activity analysis verified the degradation of deltamethrin by bacterial protein. Additionally, the formation of endospores can help strain BCP-09 resist the toxicity of deltamethrin and enhance its degradation. This study supplies a scientific evidence for the application of Brevibacillus parabrevis BCP-09 in the bioremediation of environmental pollution and enriches the resources of deltamethrin-biodegradable proteins., Competing Interests: Declaration of competing interest This manuscript has not been published or presented elsewhere in part or in entirety and is not under consideration by another journal. All study participants provided informed consent, and the study design was approved by the appropriate ethics review board. We have read and understood your journal's policies, and we believe that neither the manuscript nor the study violates any of these. There are no conflicts of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: The modified clear twin-block aligner (CTBA) was developed to provide a mandibular advancement appliance for the treatment of mandibular retrognathia. The objective of this study was to analyse the stress distribution changes of CTBA with 45°, 60° and 70° bite blocks., Material and Methods: A three-dimensional model of the craniomaxillofacial bones and teeth was generated from a spiral computed tomography (CT) scan. The models of the articular disc, capsule, periodontal ligament and CTBA were constructed mathematically. After assigning the appropriate material properties and the boundary condition using ABAQUS software, we simulated the CTBA with different bite blocks to analyse the mechanical effects., Results: In the temporomandibular joint (TMJ) region, the posterior aspect of the condyle and glenoid fossa experienced tensile stress that was approximately about 22 times greater at 70° than at 45°. The Von Mises stress distribution on the articular disc tended to be uniform. The strain direction of the condyle was backward. In the maxillary bone, the stress on the labial alveolar bone was about 5.83MPa at 70° and greater than that on the lingual side. The resulting displacement of the dentition revealed a tendency for the upper teeth to shift backward and the lower teeth to move forward by 0.46 to 0.49mm. The foregoing stress and displacement rose as the angle of the bite blocks increased., Conclusions: CTBA with 70° bite blocks constituted an advantageous biomechanical setting for the treatment of mandibular retrognathia in teenagers and provided a superior therapeutic effect., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Introduction: The mechanical distribution of the mandible is an important factor that affects functional orthosis during Twin-block (TB) appliance correction. Changes in the mandible before and after TB appliance correction are also key factors in maintaining the therapeutic effect. Finite element analysis, a powerful numerical, analytical tool, is widely used to predict the stress and strain distribution of the craniofacial bone that orthodontics generates., Methods: The sample was a 14-year-old male patient with Class II malocclusion during growth. A cone-beam computed tomography scan was undertaken at pretreatment and posttreatment. In the Finite element analysis of the pretreatment model, the remote displacement model of the mandible was established with the sella point as the center. A mandibular model under TB appliance loading was established. Its mandibular displacement and von Mises stress were compared before and after loading. Three-dimensional registration was conducted on the pretreatment and posttreatment models to measure the sagittal displacement of the centrosome., Results: The force on the mandible occurred mainly in the condyle neck and medial mandible after the TB appliance moved the mandible. After displacement, the posterior upper margin of the condyle was farther away from the articular fossa. Three-dimensional registration results showed that new bone had formed behind and above the condyle after TB appliance treatment., Conclusion: The TB appliance provides additional advantages in treating skeletal Class II malocclusions by helping to reduce the burden on the temporomandibular joint and promoting the adaptive reconstruction of the mandible., (Copyright © 2023 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

In this paper, multiresponsive actuators based on asymmetric design of graphene-conjugated poly(3,4-ethylene dioxythiophene): poly(styrenesulfonate) (PEDOT:PSS) gradient films have been developed by a simple drop casting method. The biomimetic actuation is attributed to the hygroscopic expansion property of PEDOT:PSS and the gradient distribution of graphene sheets within the film, which resembles the hierarchical swelling tissues of some plants in nature. Graphene-conjugated PEDOT:PSS (GCP) actuators exhibit reversible bending behavior under multistimuli such as moisture, organic vapor, electrothermal, and photothermal heating. Noticeably, the bending curvature reaches 2.15 cm -1 under applied voltage as low as 1.5 V owing to the high electrical conductivity of GCP actuator. To mimic the motions of nyctinastic plants, a GCP artificial flower that spreads its petals under sunlight illumination has been fabricated. GCP actuators have been also demonstrated as intelligent light-controlled switches for light-emitting diodes and smart curtains for thermal management. Not only do the GCP gradient films exhibit potential applications in flexible electronics and energy harvesting/storage devices but also the facile fabrication of multiresponsive GCP actuators may shed light on the development of soft robotics, artificial muscles, wearable electronics, and smart sensors.

This study examines the impact of the Chinese regional emission trading system (ETS) pilots on enterprise transformation from the perspective of diversification. We use data on Chinese A-share listed companies from 2004 to 2021, and adopt the staggered difference-in-differences (DID) and difference-in-difference-in-differences (DDD) models. The empirical results show that first, the ETS significantly increases the product quantity and revenue diversification of regulated firms. Second, the ETS promotes enterprise diversification through three channels: emission cost, emission risk, and market efficiency. Third, the ETS has a greater impact on the diversification of state-owned enterprises, firms with high business concentration, and firms with low innovation investment. Fourth, the ETS-driven diversification has not been successful as it has increased firms' costs and reduced their profitability. We recommend introducing industrial policies to guide the transformation of enterprises, encourage them to improve their innovation capabilities, and choose appropriate transformation strategies., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Beta-cypermethrin (β-CY) is an organic compound that is widely used as a synthetic pesticide in agriculture and family. Excessive accumulation of β-CY inevitably causes environmental pollution, which has led to food safety and human health concerns. Identification of microorganisms from food sources that are capable of β-CY biodegradation may help prevent pollution due to β-CY accumulation. Here, Gordonia alkanivorans GH-1, which was isolated from the traditional Sichuan fermented food, Pixian Doubanjiang, could not only degrade 82.76% of 50 mg/L β-CY at 96 h, but also degraded the intermediate degradation products including dibutyl phthalate (DBP), benzoic acid (BA) and phenol (Ph). This bacterial strain, thus, effectively improved the efficiency of removal of β-CY and its related metabolites, without being limited by toxic intermediates. Whole genome sequencing and transcriptomics analyses have demonstrated that the bacteria affected the transcription of genes related to cell response and material transport under the stress induced by β-CY, and thereby promoted degradation and transformation of β-CY. Moreover, a complete pathway of β-CY degradation is proposed based on the key genes involved in degradation. This study provides important theoretical significance and reference value for eliminating pesticide residues in agricultural products and food to ensure food safety., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Edible and medicinal plants (EMPs) are widely used but are easily infected by harmful fungi which produce mycotoxins. Herein, 127 samples from 11 provinces were collected to investigate 15 mycotoxins based on geographic, demographic, processing, and risk characteristics. A total of 13 mycotoxins were detected, and aflatoxin B 1 (0.56~97.00 μg/kg), deoxynivalenol (9.41~1570.35 μg/kg), fumonisin B 1 (8.25~1875.77 μg/kg), fumonisin B 2 (2.74~543.01 μg/kg), ochratoxin A (0.62~19.30 μg/kg), and zearalenone (1.64~2376.58 μg/kg) occurred more frequently. Mycotoxin levels and species were significantly different by region, types of EMPs, and method of processing. The margin of exposure (MOE) values was well below the safe MOE (10,000). AFB 1 exposure from Coix seed and malt consumption in China was of high health concern. The hazard Index (HI) method showed the range of 113.15~130.73% for malt, indicating a public health concern. In conclusion, EMPs should be concerned because of the cumulative effects of co-occurred mycotoxins, and safety management strategies should be developed in follow-up studies.

Background and Aims: Hepatocellular carcinoma (HCC) is a common cause of cancer-related death in humans. Increasing evidence indicates that an imbalance in N6-methyladenosine (m6A) methylation is linked to the occurrence and development of cancer. We then developed a prognostic model as an independent risk factor with which predict the prognosis of HCC., Methods: We obtained the gene expression and clinical data of HCC patients from the TCGA databases. The prognostic value of m6A methylation-related genes in patients who had HCC were subjected to comprehensive bioinformatics analysis. We use Risk Score = ∑ i = 1 n Coe f i × X i to construct the risk scoring formula. We collected pathological specimens from 68 patients who had HCC, and conducted immunohistochemical staining experiments on the specimens., Results: There was a significant correlation between candidate m6A methylation-related genes (YTHDF2, METTL14 and ZC3H13) overall survival of HCC patients. Among the 68 HCC patient specimens that underwent immunohistochemical staining, all cancer tissues were positive for METTL14, YTHDF2, and ZC3H13 staining in contrast to the adjacent tissues. We conducted a Kaplan-Meier survival analysis. The results showed that patients who had low METTL14 expression had a longer survival time than those of patients who had high METTL14 expression. Also, patients with low YTHDF2 expression had a longer survival time than patients with high YTHDF2 expression. Finally, patients with high ZC3H13 expression lived longer than those with low ZC3H13 expression. This result is consistent with the bioinformatics analysis conclusion above., Conclusions: Generally, the prognostic model that was based on m6A methylation-related genes in this study can effectively predict the prognosis of HCC patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Zheng, Zhang, Wang, He, Zhang, Ren, Yan and Yuan.)

In this work, we observed size-dependent behavior of filler on both the thermal and electrical conductivities of nacre-like graphene-conjugated conducting polymer films and demonstrated the display of apparent Wiedemann-Franz law and tunability of Lorenz constant in such films. The maximum thermal and electrical conductivities of as-fabricated films can reach over 73 W·m -1 ·K -1 and 1200 S·cm -1 , respectively. Furthermore, the maximum value of electromagnetic interference shielding reaches 54 dB with SSE/ t over 16000 dB·cm 2 ·g -1 . These films can not only show high-quality electromagnetic interference shielding performance with small thickness and low filler ratio but also achieve simultaneous thermal management during electromagnetic shielding. The findings in this work offer new insight into designing flexible graphene-conjugated polymers with customizable thermal and electrical properties in the broad fields of thermal management systems, electromagnetic defense systems, and flexible electronic systems.

Objective: The purpose of this research was to use a new method the human and bar combination barycenter to exposit the differences between successful and failed characteristics of snatch attempts in competition. Try to establish an effective biomechanical method that can uncover the main factors for the failed snatch. The obtained results will provide valuable information for weightlifters to improve the success rate in snatch by altering their technical issues accordingly., Methods: A 3-D video analysis method was used to compare the characteristics of the heaviest successful and failed attempts of ten elite weightlifters in the men's 73 kg category. The video was captured under competitive conditions at the 2019 World Weightlifting Championships, the 2019 Asian Weightlifting Championships, and the 2020 China Olympic Trial. The video data were digitized using the SIMI°Motion7.50 3-D system (Germany)., Results: Significant difference ( P > 0.05) was not found between the successful and failed attempts in the parameters, such as the maximal vertical rising velocity, the maximal vertical height, and the vertical displacement of the barbell. The maximal descending acceleration of the human body, the time duration, the angles of the hip, and knee joints were no significant difference. However, significant differences were found in the variation of the human and bar combination barycenter on the X- axis in the inertial ascent stage and the squat support stage ( t = 2.862, P < 0.05; t = 3.376, P < 0.05)., Conclusions: A probable cause of the failed snatch is that the displacement of human and bar combination barycenter on the X- axis is not enough to reach the position for supporting barbell during the inertial ascent stage and the squat support stage. The reason is that the strength of reclining of torso at the end of the force phase is insufficient. Insufficient knee flexion in the knee flexion phase ( M 2), which leads to a lower maximum vertical velocity of barbell, may be an indirect factor leading to the failed snatch. The cumulative variation of human and bar combination barycenter on the X- axis can effectively determine the technical characteristics between the success and failure in snatch., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Gongju Liu et al.)

This report presents nanoparticles composed of a liquid gallium core with a reduced graphene oxide (RGO) shell (Ga@RGO) of tunable thickness. The particles are produced by a simple, one-pot nanoprobe sonication method. The high near-infrared absorption of RGO results in a photothermal energy conversion of light to heat of 42.4%. This efficient photothermal conversion, combined with the large intrinsic thermal expansion coefficient of liquid gallium, allows the particles to be used for photoacoustic imaging, that is, conversion of light into vibrations that are useful for imaging. The Ga@RGO results in fivefold and twofold enhancement in photoacoustic signals compared with bare gallium nanoparticles and gold nanorods (a commonly used photoacoustic contrast agent), respectively. A theoretical model further reveals the intrinsic factors that affect the photothermal and photoacoustic performance of Ga@RGO. These core-shell Ga@RGO nanoparticles not only can serve as photoacoustic imaging contrast agents but also pave a new way to rationally design liquid metal-based nanomaterials with specific multi-functionality for biomedical applications.

Objective: Studies have shown that chronic stress is closely linked to the occurrence and development of cardiovascular disease. To date, few studies have focused on perceived stress in coronary heart diseases (CHD) patients and the possible factors influencing the stress. This study aims to investigate the perceived stress of patients with CHD and determine the individual attributes closely associated with it., Design: A cross-sectional study., Participates: A total of 2215 patients with CHD were enrolled and perceived stress was assessed with the Chinese version Perceived Stress Scale (CPSS). Participants were divided into two groups due to CPSS score and binary logistic regression was applied to analyse the factors that affected perceived stress level., Results: The mean CPSS score of Chinese patients with CHD was 27.16±6.35 Compared with participants who received senior middle school education or below, those with a university degree had a higher probability of high perceived stress (OR 1.453, 95% CI 1.206 to 1.750); this difference was more evident in participants with a master or doctoral degree (OR 1.928, 95% CI 1.290 to 2.882). Also engaging in mental labour (OR 1.389, 95% CI 1.144 to 1.686), having children (OR 2.226, 95% CI 1.098 to 4.515) and having a habit of risky alcohol consumption (OR 1.492, 95% CI 1.146 to 1.944) were associated with perceived stress., Conclusion: Patients who had higher educational attainment, engaged in mental labour, had children, and had a habit of risky alcohol consumption were much easier to perceive the stress., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

This paper reports an interfacial evaporation-driven approach for self-assembly of a gold nanoparticle (AuNP) film at the interface of liquid/air. We have designed colloidal plasmonic AuNPs capped with different types and surface coverage densities of ligands ( i.e. purified and unpurified oleylamine-capped or thiol-protected AuNPs) and studied the impact of surface chemistry on the self-assembly of AuNPs using the optically excited plasmonic heating effect. By employing the extended DerjaguinLandau-Verwey-Overbeek model, the calculated lowest potential energies of the assembled AuNPs capped with purified oleylamine or alkyl thiols are between -1 k B T and -2 k B T , which is close to the room temperature thermal energy and represents a meta-stable assembly, indicating the reversible self-assembly of the AuNP film observed from the experiment. Furthermore, we observed the superheating phenomenon in well-dispersed nanoparticle solution while normal boiling occurred in the solutions with AuNP assemblies. The SERS activity of the as-prepared AuNP film has also been studied using rhodamine 6G as a molecular probe. This work not only provides a new aspect of the boiling phenomena of optically heated colloidal plasmonic nanoparticle solutions, but also provides inspiration for a new approach in designing surface ligands on the nanoparticles to realize reversible self-assembly via interfacial evaporation.

Background: Heart failure (HF) is considered one of the most common complications of coronary heart disease (CHD), with a higher incidence of readmission and mortality. Thus, exploring the risk factors related to the prognosis is necessary. Moreover, the effect of the waist-to-hip ratio (WHR) on HF patients with revascularized CHD is still unclear. Thus, we aimed to assess the influence of WHR on the prognosis of HF patients with revascularized CHD. Methods: We collected data of HF patients with revascularized CHD who were referred to the Cardiac Rehabilitation Clinic of PLA Hospital from June 30, 2015, to June 30, 2019. Cox proportional hazard regression analysis was used to determine the relationship between WHR and prognosis of HF patients with revascularized CHD. Patients were divided into higher and lower WHR groups based on the cutoff WHR value calculated by the X-tile software. Cox regression analysis was used to analysis the two groups. We drew the receiver operating characteristic curve (ROC) of WHR and analyzed the differences between the two groups. Endpoints were defined as major adverse cardiac events (MACE) (including all-cause mortality, non-fatal myocardial infarction, unscheduled revascularization, and stroke). Results: During the median follow-up of 39 months and maximum follow-up of 54 months, 109 patients were enrolled, of which 91.7% were males, and the mean age was 56.0 ± 10.4 years. WHR was associated with the incidence of MACE in the Cox regression analysis ( p = 0.001); an increase in WHR of 0.01 unit had a hazard ratio (HR) of 1.134 (95%CI: 1.057-1.216). The WHR cutoff value was 0.93. Patients in the higher WHR group had a significantly higher risk of MACE than those in the lower WHR group (HR = 7.037, 95%CI: 1.758-28.168). The ROC area under the curve was 0.733 at 4 years. Patients in the higher WHR group had a higher body mass index (BMI; 26.7 ± 3.5 vs. 25.4 ± 2.4, P = 0.033) than patients in the lower WHR group. Conclusions: WHR is an independent risk factor of the long-term prognosis of Chinese HF patients with revascularized CHD. Patients with WHR ≥ 0.93 require intensified treatment. Higher WHR is related to higher BMI and ΔVO2/ΔWR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Zhang, Shi, Dong, Mu, Wang, Gao, Hu, Xu, Chen and Ma.)

Background: Treadmill exercise testing (TET) is commonly used to measure exercise capacity. Studies have shown that cardiopulmonary exercise testing (CPET) is more accurate than TET and is, therefore, regarded as the "gold standard" for testing maximum exercise capacity and prescribing exercise plans. To date, no studies have reported the differences in exercise capacity after percutaneous coronary intervention (PCI) using the two methods or how to more accurately measure exercise capacity based on the results of TET. Aims: This study aims to measure maximum exercise capacity in post-PCI patients and to recommend exercise intensities that ensure safe levels of exercise. Methods: We enrolled 41 post-PCI patients who were admitted to the Cardiac Rehabilitation Clinic at the First Medical Center, the Chinese PLA General Hospital, from July 2015 to June 2016. They completed CPET and TET. The paired sample t -test was used to compare differences in measured exercise capacity, and multiple linear regression was applied to analyze the factors that affected the difference. Results: The mean maximum exercise capacity measured by TET was 8.89 ± 1.53 metabolic equivalents (METs), and that measured by CPET was 5.19 ± 1.23 METs. The difference between them was statistically significant ( p = 0.000) according to the paired sample t -test. The difference averaged 40.15% ± 2.61% of the exercise capacity measured by TET multiple linear regression analysis showed that the difference negatively correlated with waist-hip ratio (WHR). Conclusion: For the purpose of formulating more accurate exercise prescription, the results of TET should be appropriately adjusted when applied to exercise capacity assessment. Clinical Trial Registration: http://www.chictr.org.cn/ number, ChiCTR2000031543., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Gao, Feng, Hu, Zhang, Shi, Xu and Ma.)

The identification of genome-wide selection signatures can provide insights on the mechanisms of natural and/or artificial selection and uncover genes related to biological functions and/or phenotypes. Tibetan sheep are an important livestock in Tibet, providing meat and wool for Tibetans who are renown for breeding livestock that adapt well to high altitudes. Using whole-genome sequences with an effective sequencing depth of 5×, we investigated the genomic diversity and structure and, identified selection signatures of White Tibetan, Oula and Poll Dorset sheep. We obtained 30,163,679 Single Nucleotide Polymorphisms (SNPs) and 5,388,372 indels benchmarked against the ovine Oar&#95;v4.0 genome assembly. Next, using F ST , ZHp and XP-EHH approaches, we identified selection signatures spanning a set of candidate genes, including HIF1A, CAPN3, PRKAA1, RXFP2, TRHR and HOXA10 that are associated with pathways and GO categories putatively related to hypoxia responses, meat traits and disease resistance. Candidate genes and GO terms associated with coat color were also identified. Finally, quantification of blood physiological parameters, revealed higher levels of mean corpuscular hemoglobin measurement and mean corpuscular hemoglobin concentration in Tibetan sheep compared with Poll Dorset, suggesting a greater oxygen-carrying capacity in the Tibetan sheep and thus better adaptation to high-altitude hypoxia. In conclusion, this study provides a greater understanding of genome diversity and variations associated with adaptive and production traits in sheep.

Economic loss of postharvest wheat under poor storage conditions due to fungal spoilage and mycotoxin contamination is severe. In order to study the influencing factors of the aggravation of mildew in natural wheat during storage, we assessed changes in Fusarium mycotoxins by high performance liquid chromatography, changes in fungal communities by high-throughput sequencing, and changes in biochemical components in wheat stored under artificial simulation conditions. Deoxynivalenol was the dominant Fusarium mycotoxin, reaching 1103 μg/kg at 25 °C with 75% relative humidity after 30 weeks. Under these conditions, Fusarium dominated the fungal communities, and Fusarium graminearum was significantly negatively correlated with glutenin ( p < 0.05). Low storage temperatures and low humidity result in lower levels of Fusarium mycotoxins. Different fungi tended to consume different wheat components, and the interaction between environmental and biological factors eventually leads to the deterioration of wheat quality. These findings might provide valuable information for control strategies of mildew occurrence during grain storage.

Clofazimine, a drug previously used to treat leprosy, has recently been identified as a potential new drug for the treatment for cryptosporidiosis: a diarrheal disease that contributes to 500 000 infant deaths a year in developing countries. Rapid dissolution and local availability of the drug in the small intestine is considered key to the treatment of the infection. However, the commercially available clofazimine formulation (Lamprene) is not well-suited to pediatric use, and therefore reformulation of clofazimine is desirable. Development of clofazimine nanoparticles through the process of flash nanoprecipitation (FNP) has been previously shown to provide fast and improved drug dissolution rates compared to clofazimine crystals and Lamprene. In this study, we investigate the effects of milk-based formulations (as possible pediatric-friendly vehicles) on the in vitro solubilization of clofazimine formulated as either lecithin- or zein/casein-stabilized nanoparticles. Milk and infant formula were used as the lipid vehicles, and time-resolved synchrotron X-ray scattering was used to monitor the presence of crystalline clofazimine in suspension during in vitro lipolysis under intestinal conditions. The study confirmed faster dissolution of clofazimine from all the FNP formulations after the digestion of infant formula was initiated, and a reduced quantity of fat was required to achieve similar levels of drug solubilization compared to the reference drug material and the commercial formulation. These attributes highlight not only the potential benefits of the FNP approach to prepare drug particles but also the fact that enhanced dissolution rates can be complemented by considering the amount of co-administered fat in lipid-based formulations to drive the solubilization of poorly soluble drugs.

The delivery of fermentable substrate(s) to subsurface environments stimulates Fe(III)-bioreduction and achieves detoxification of organic/inorganic contaminants. Although, much research has been conducted on the microbiology of such engineered systems at lab and field scales, little attention has been given to the phage-host interactions and virus community dynamics in these environments. The objective was to determine the responses of soil bacterial communities and viral assemblages to stimulated anaerobic Fe(III)-bioreduction following electron donor (e.g. acetate) addition. Microbial communities, including viral assemblages, were investigated after 60 days of Fe(III)-bioreduction in laboratory-scale columns continuously fed with acetate-amended artificial groundwater. Viral abundances were greatest in the influent section and decreased along the flow path. Acetate availability was important in influencing bacterial diversity, microbial interactions and viral abundance and community composition. The impact of acetate addition was most evident in the influent section of the columns. The increased relative abundance of Fe(III)-reducing bacteria coincided with an increase in viral abundance in areas of the columns exhibiting the most Fe(III) reduction. The genetic composition of viruses in these column sections also differed from the control column and distal sections of acetate-treated columns suggesting viral communities responded to biostimulated Fe(III)-bioreduction., (© 2019 Society for Applied Microbiology and John Wiley & Sons Ltd.)

Background: OZ439 is a new chemical entity which is active against drug-resistant malaria and shows potential as a single-dose cure. However, development of an oral formulation with desired exposure has proved problematic, as OZ439 is poorly soluble (BCS Class II drug). In order to be feasible for low and middle income countries (LMICs), any process to create or formulate such a therapeutic must be inexpensive at scale, and the resulting formulation must survive without refrigeration even in hot, humid climates. We here demonstrate the scalability and stability of a nanoparticle (NP) formulation of OZ439. Previously, we applied a combination of hydrophobic ion pairing and Flash NanoPrecipitation (FNP) to formulate OZ439 NPs 150 nm in diameter using the inexpensive stabilizer hydroxypropyl methylcellulose acetate succinate (HPMCAS). Lyophilization was used to process the NPs into a dry form, and the powder's in vitro solubilization was over tenfold higher than unprocessed OZ439., Methods: In this study, we optimize our previous formulation using a large-scale multi-inlet vortex mixer (MIVM). Spray drying is a more scalable and less expensive operation than lyophilization and is, therefore, optimized to produce dry powders. The spray dried powders are then subjected to a series of accelerated aging stability trials at high temperature and humidity conditions., Results: The spray dried OZ439 powder's dissolution kinetics are superior to those of lyophilized NPs. The powder's OZ439 solubilization profile remains constant after 1 month in uncapped vials in an oven at 50 °C and 75% RH, and for 6 months in capped vials at 40 °C and 75% RH. In fasted-state intestinal fluid, spray dried NPs achieved 80-85% OZ439 dissolution, to a concentration of 430 µg/mL, within 3 h. In fed-state intestinal fluid, 95-100% OZ439 dissolution is achieved within 1 h, to a concentration of 535 µg/mL. X-ray powder diffraction and differential scanning calorimetry profiles similarly remain constant over these periods., Conclusions: The combined nanofabrication and drying process described herein, which utilizes two continuous unit operations that can be operated at scale, is an important step toward an industrially-relevant method of formulating the antimalarial OZ439 into a single-dose oral form with good stability against humidity and temperature.

More than 40% of newly developed drug molecules are highly hydrophobic and, thus, suffer from low bioavailability. Kinetically trapping the drug as a nanoparticle in an amorphous state enhances solubility. However, enhanced solubility can be compromised by subsequent recrystallization from the amorphous state during drying processes. We combine Flash NanoPrecipitation (FNP) to generate nanoparticles with spray-drying to produce stable solid powders. We demonstrate that the continuous nanofabrication platform for nanoparticle synthesis and recovery does not compromise the dissolution kinetics of the drug. Lumefantrine, an anti-malaria drug, is highly hydrophobic with low bioavailability. Increasing the bioavailability of lumefantrine has the potential to reduce the dose and number of required administrations per treatment, thus reducing cost and increasing patient compliance. The low melting temperature of lumefantrine (Tm = 130 °C) makes the drying of amorphous nanoparticles at elevated temperatures potentially problematic. Via FNP, we produced 200-400 nm nanoparticles using hydroxypropyl methylcellulose acetate succinate (HPMCAS), lecithin phospholipid, and zein protein stabilizers. Zein nanoparticles were spray-dried at 100 °C and 120 °C to study the effect of the drying temperature. For zein powders, at two hours the dissolution kinetics under fasted conditions reached 85% release for the 100 °C sample, but only 60% release for the 120 °C sample. Powder X-ray diffraction, differential scanning calorimetry, and solid state nuclear magnetic resonance indicate that the lumefantrine in the nanoparticle core is amorphous for samples spray-dried at 100 °C. Dissolution under fed state conditions showed similar release kinetics for both temperatures, with 90-95% release at two hours. Zein and HPMCAS nanoparticles spray-dried at 100 °C showed release profiles in fasted and fed state media that are identical to those of lyophilized samples, i.e. those dried at cryogenic conditions where no transformation to the crystalline state can occur. Thus, spray drying 30 °C below the melting transition of lumefantrine is sufficient to maintain the amorphous state. These inexpensive formulations have potential to be developed into future therapies for malaria, and the results also highlight the potential of combining FNP and spray-drying as a versatile platform to assemble and rapidly recover amorphous nanoparticles in a solid dosage form.

Multiple mycotoxins can contaminate foods simultaneously leading to increased risks for human health. To assess exposure and health risks of 9 mycotoxins, we employed a multiple immunoaffinity column - high performance liquid chromatography method to determine their concentrations of 35 whole wheat flour and 50 refined wheat flour samples from China. The recoveries of the validated method were 75.78-118.24%, and the limits of detection and quantification were 1.5-20 and 5.0-60 µg kg -1 , respectively. Multiple mycotoxins were detected in 37.1% of whole wheat flour and 8% of refined wheat flour. In the worst-case scenario, the hazard index was 222.69% for male and 253.97% for female with a cumulative exposure to Fusarium mycotoxins through consuming whole wheat flour, and deoxynivalenol was the main mycotoxin detected. In conclusion, whole wheat flour should be regarded with more health concern because of cumulative effects of co-occurred mycotoxins., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The change of atom density induced structural collapse in the transformation process from metal-organic frameworks (MOFs) to their inorganic counterparts is a major challenge to the achievement of porous hollow structures. Herein, we develop an amino acid-mediated strategy for transformation of NH 2 -MIL-125(Ti) to successfully synthesize well-defined porous cages of titanium oxides (PCT) due to sheets serving as structural scaffolds. On this basis, PCT supported Pt-based nanoparticles are generated via a similar synthetic route, and are utilized to study the selective hydrogenation of carbonyl groups in α,β-unsaturated aldehydes, benefiting from the specific structures of PCT and tunable electronic structures of Pt mainly affected by doping with metal species such as Co. In this case, Pt-Co/PCT composites give 96% selectivity for cinnamyl alcohol at 100% conversion of cinnamaldehyde under 0.2 MPa H 2 and 80 °C for 3 h. This research would offer a promising strategy for important organic transformations in academic and industrial research to selectively synthesize high-value-added products.

Cobalt layered double hydroxides (Co-LDHs) obtained by an imidazole-assisted route were used as precursors to prepare dual-functional electrocatalysts CoP/Co 2 P. CoP/Co 2 P showed an enhanced electrocatalytic performance for HER and OER. The reason was attributed to porous sheets providing more catalytic sites and multi-components improving conductivity and substrate adsorption capability.

The production of Pleurotus eryngii by selenium (Se) biofortification is an effective way to improve the demand for Se in humans. In order to investigate the Se bioaccessibility and speciation of Se-enriched P. eryngii during the growing stage, the Se distribution in biochemical fractions, and the molecular weight and the Se species of Se-containing compounds derived from in vitro simulated gastrointestinal fluids were analyzed by size exclusion and anion exchange-high performance liquid chromatography and inductively coupled plasma mass spectrometry. The results showed that albumin had the highest Se content among biochemical fractions, approximately 34.40% of total Se, followed by glutelin, globulin and gliadins. Selenomethionine that was proved to be the major Se species would increase with P. eryngii growing from 45.85% to 59.32%, while selenocysteine would decrease from 40.68% to 15.17% of total Se. In conclusion, selenocysteine would gradually convert to selenomethionine, and thus the bioaccessibility of Se was greater in mature P. eryngii than in younger mushrooms.

Malaria poses a major burden on human health and is becoming increasingly difficult to treat due to the development of antimalarial drug resistance. The resistance issue is further exacerbated by a lack of patient adherence to multi-day dosing regimens. This situation motivates the development of new antimalarial treatments that are less susceptible to the development of resistance. We have applied Flash NanoPrecipitation (FNP), a polymer-directed self-assembly process, to form stable, water-dispersible nanoparticles (NPs) of 50-400 nm in size containing OZ439, a poorly orally bioavailable but promising candidate for single-dose malaria treatment developed by Medicines for Malaria Venture (MMV). During the FNP process, a hydrophobic OZ439 oleate ion paired complex was formed and was encapsulated into NPs. Lyophilization conditions for the NP suspension were optimized to produce a dry powder. The in vitro release rates of OZ439 encapsulated in this powder were determined in biorelevant media and compared with the release rates of the unencapsulated drug. The OZ439 NPs exhibit a sustained release profile and several-fold higher release concentrations compared to that of the unencapsulated drug. In addition, XRD suggests the drug was stabilized into an amorphous form within the NPs, which may explain the improvement in dissolution kinetics. Formulating OZ439 into NPs in this way may be an important step toward developing a single-dose oral malaria therapeutic, and offers the possibility of reducing the amount of drug required per patient, lowering delivery costs, and improving dosing compliance.

While the formulation of nanoparticle (NP) suspensions has been widely applied in materials and life science, the recovery of NPs from such a suspension into a solid state is practically important to confer long-term storage stability. However, solidification, while preserving the original nanoscale properties, remains a formidable challenge in the pharmaceutical and biomedical applications of NPs. Herein we combined flash nanoprecipitation (FNP) and spray-drying as a nanofabrication platform for NP formulation and recovery without compromising the dissolution kinetics of the active ingredient. Clofazimine was chosen to be the representative drug, which has been recently repurposed as a potential treatment for cryptosporidiosis. Clofazimine was encapsulated in NPs with low-cost surface coatings, hypromellose acetate succinate (HPMCAS) and lecithin, which were required by the ultimate application to global health. Spray-drying and lyophilization were utilized to produce dried powders with good long-term storage stability for application in hot and humid climatic zones. The particle morphology, yield efficiency, drug loading, and clofazimine crystallinity in the spray-dried powders were characterized. The in vitro release kinetics of spray-dried NP powders were compared to analogous dissolution profiles from standard lyophilized NP samples, crystalline clofazimine powder, and the commercially available formulation Lamprene. The spray-dried powders showed a supersaturation level of up to 60 times the equilibrium solubility and remarkably improved dissolution rates. In addition, the spray-dried powders with both surface coatings showed excellent stability during aging studies with elevated temperature and humidity, in view of the dissolution and release in vitro. Considering oral delivery for pediatric administration, the spray-dried powders show less staining effects with simulated skin than crystalline clofazimine and may be made into minitablets without additional excipients. These results highlight the potential of combining FNP and spray-drying as a feasible and versatile platform to design and rapidly recover amorphous NPs in a solid dosage form, with the advantages of satisfactory long-term storage stability, low cost, and easy scalability., Competing Interests: The authors declare no competing financial interest.

Antibiotic resistance and recurrence of bacterial vaginosis (BV), a polymicrobial infection, justify the need for novel antimicrobials to counteract microbial resistance to conventional antibiotics. Previously, two series of cationic amphiphiles (CAms) which self-assemble into supramolecular nanostructures with membrane-lytic properties were designed with hydrophilic head groups and nonpolar domains. The combination of CAms and commonly prescribed antibiotics is suggested as a promising strategy for targeting microorganisms that are resistant to conventional antibiotics. Activities of the CAms against Gardnerella vaginalis ATCC 14018, a representative BV pathogen, ranged from 1.1 to 24.4 μM. Interestingly, the tested healthy Lactobacillus species, especially Lactobacillus plantarum ATCC 39268, were significantly more tolerant of CAms than the selected pathogens. In addition, CAms prevented biofilm formation at concentrations which did not influence the normal growth ability of G. vaginalis ATCC 14018. Furthermore, the biofilm minimum bactericidal concentration (MBC-Bs) of CAms against G. vaginalis ATCC 14018 ranged from 58.8 to 425.6 μM, while much higher concentrations (≥850 μM) were required to produce ≥3-log reductions in the number of biofilm-associated lactobacilli. The conventional antibiotic metronidazole synergized strongly with all tested CAms against planktonic cells and biofilms of G. vaginalis ATCC 14018. The synergism between CAms and the tested conventional antibiotic may be considered a new, effective, and beneficial method of controlling biofilm-associated bacterial vaginosis., (Copyright © 2017 American Society for Microbiology.)

Clofazimine, a lipophilic (log P = 7.66) riminophenazine antibiotic approved by the US Food and Drug Administration (FDA) with a good safety record, was recently identified as a lead hit for cryptosporidiosis through a high-throughput phenotypic screen. Cryptosporidiosis requires fast-acting treatment as it leads to severe symptoms which, if untreated, result in morbidity for infants and small children. Consequently, a fast-releasing oral formulation of clofazimine in a water-dispersible form for pediatric administration is highly desirable. In this work, clofazimine nanoparticles were prepared with three surface stabilizers, hypromellose acetate succinate (HPMCAS), lecithin, and zein, using the flash nanoprecipitation (FNP) process. Drug encapsulation efficiencies of over 92% were achieved. Lyophilization and spray-drying were applied and optimized to produce redispersible nanoparticle powders. The release kinetics of these clofazimine nanoparticle powders in biorelevant media were measured and compared with those of crystalline clofazimine and the currently marketed formulation Lamprene. Remarkably improved dissolution rates and clofazimine supersaturation levels up to 90 times equilibrium solubility were observed with all clofazimine nanoparticles tested. Differential scanning calorimetry indicated a reduction of crystallinity of clofazimine in nanoparticles. These results strongly suggest that the new clofazimine nanoparticles prepared with affordable materials in this low-cost nanoparticle formulation process can be used as viable cryptosporidiosis therapeutics.

Kojic acid (KA) is a naturally occurring fungal metabolite that is utilized as a skin-lightener and antibrowning agent owing to its potent tyrosinase inhibition activity. While efficacious, KA's inclination to undergo pH-mediated, thermal-, and photodegradation reduces its efficacy, necessitating stabilizing vehicles. To minimize degradation, poly(carbonate-esters) and polyesters comprised of KA and natural diacids were prepared via solution polymerization methods. In vitro hydrolytic degradation analyses revealed KA release was drastically influenced by polymer backbone composition (e.g., poly(carbonate-ester) vs polyester), linker molecule (aliphatic vs heteroatom-containing), and release conditions (physiological vs skin). Tyrosinase inhibition assays demonstrated that aliphatic KA dienols, the major degradation product under skin conditions, were more potent then KA itself. All dienols were found to be less toxic than KA at all tested concentrations. Additionally, the most lipophilic dienols were statistically more effective than KA at inhibiting melanin biosynthesis in cells. These KA-based polymer systems deliver KA analogues with improved efficacy and cytocompatible profiles, making them ideal candidates for sustained topical treatments in both medical and personal care products.

Inspired by high promise using naturally occurring antimicrobial peptides (AMPs) to treat infections caused by antimicrobial-resistant bacteria, cationic amphiphiles (CAms) were strategically designed as synthetic mimics to overcome associated limitations, including high manufacture cost and low metabolic stability. CAms with facially amphiphilic conformation were expected to demonstrate membrane-lytic properties and thus reduce tendency of resistance development. By systematically tuning the hydrophobicity, CAms with optimized compositions exhibited potent broad-spectrum antimicrobial activity (with minimum inhibitory concentrations in low μg/mL range) as well as negligible hemolytic activity. Electron microscope images revealed the morphological and ultrastructure changes of bacterial membranes induced by CAm treatment and validated their membrane-disrupting mechanism. Additionally, an all-atom molecular dynamics simulation was employed to understand the CAm-membrane interaction on molecular level. This study shows that these CAms can serve as viable scaffolds for designing next generation of AMP mimics as antimicrobial alternatives to combat drug-resistant pathogens., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Long-circulating liposomes are typically prepared with poly(ethylene glycol)- (PEG-) modified lipids, where the lipid portion is inserted in the lipid bilayers as an anchor and the hydrophilic PEG coats the surface to prevent liposome aggregation and rapid clearance in vivo. However, these steric protection effects are compromised upon systemic administration due to low retention of PEGylated lipids within liposome membranes upon dilution. Hence, a series of PEGylated bolaamphiphiles (PEG-bolas) were for the first time developed to increase retention in the lipid bilayer, presumably leading to enhanced integrity of the PEG protective layer upon dilution. We hypothesized that PEG-bolas with a sufficiently long hydrophobic domain and rigid central group could predominantly adopt a membrane-spanning configuration, taking full advantage of steric protection offered by PEG and enhanced retention in liposomes enabled by the bola geometry. In this paper, liposomes stabilized by PEG-bolas comprised of a biphenyl core and twelve-carbon alkyl chain not only exhibited similar storage and biological stability compared to conventional PEGylated lipid stabilized liposomes, but also significantly improved retention upon dilution. Our findings facilitate new designs of liposome-stabilizing agents and can be applied to improve the delivery efficiency of liposomal delivery vehicles in vivo., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Atherosclerosis, a leading cause of mortality in developed countries, is characterized by the buildup of oxidized low-density lipoprotein (oxLDL) within the vascular intima, unregulated oxLDL uptake by macrophages, and ensuing formation of arterial plaque. Amphiphilic polymers (AMPs) comprised of a branched hydrophobic domain and a hydrophilic poly(ethylene glycol) (PEG) tail have shown promising anti-atherogenic effects through direct inhibition of oxLDL uptake by macrophages. In this study, five AMPs with controlled variations were evaluated for their micellar and structural stability in the presence of serum and lipase, respectively, to develop underlying structure-atheroprotective activity relations. In parallel, molecular dynamics simulations were performed to explore the AMP conformational preferences within an aqueous environment. Notably, AMPs with ether linkages between the hydrophobic arms and sugar backbones demonstrated enhanced degradation stability and storage stability, and also elicited enhanced anti-atherogenic bioactivity. Additionally, AMPs with increased hydrophobicity elicited increased atheroprotective bioactivity in the presence of serum. These studies provide key insights for designing more serum-stable polymeric micelles as prospective cardiovascular nanotherapies., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Sugar-based polymers have been extensively explored as a means to increase drug delivery systems' biocompatibility and biodegradation. Here,we review he use of sugar-based polymers for drug delivery applications, with a particular focus on the utility of the sugar component(s) to provide benefits for drug targeting and stimuli responsive systems. Specifically, numerous synthetic methods have been developed to reliably modify naturally-occurring polysaccharides, conjugate sugar moieties to synthetic polymer scaffolds to generate glycopolymers, and utilize sugars as a multifunctional building block to develop sugar-linked polymers. The design of sugar-based polymer systems has tremendous implications on both the physiological and biological properties imparted by the saccharide units and are unique from synthetic polymers. These features include the ability of glycopolymers to preferentially target various cell types and tissues through receptor interactions, exhibit bioadhesion for prolonged residence time, and be rapidly recognized and internalized by cancer cells. Also discussed are the distinct stimuli-sensitive properties of saccharide-modified polymers to mediate drug release under desired conditions. Saccharide-based systems with inherent pH- and temperature-sensitive properties, as well as enzyme-cleavable polysaccharides for targeted bioactive delivery, are covered. Overall, this work emphasizes inherent benefits of sugar-containing polymer systems for bioactive delivery.

A significant limitation of cardiovascular stents is restenosis, where excessive smooth muscle cell (SMC) proliferation following stent implantation causes blood vessel reocclusion. While drug-eluting stents minimize SMC proliferation through releasing cytotoxic or immunosuppressive drugs from polymer carriers, significant issues remain with delayed healing, inflammation, and hypersensitivity reactions associated with drug and polymer coatings. Amphiphilic macromolecules (AMs) comprising a sugar-based hydrophobic domain and a hydrophilic poly(ethylene glycol) tail are noncytotoxic and recently demonstrated a concentration-dependent ability to suppress SMC proliferation. In this study, we designed a series of AMs and studied their coating properties (chemical composition, thickness, grafting density, and coating uniformity) to determine the effect of headgroup chemistry on bioactive AM grafting and release properties from stainless steel substrates. One carboxyl-terminated AM (1cM) and two phosphonate- (Me-1pM and Pr-1pM) terminated AMs, with varying linker lengths preceding the hydrophobic domain, were grafted to stainless steel substrates using the tethering by aggregation and growth (T-BAG) approach. The AMs formed headgroup-dependent, yet uniform, biocompatible adlayers. Pr-1pM and 1cM demonstrated higher grafting density and an extended release from the substrate over 21 days compared to Me-1pM, which exhibited lower grafting density and complete release within 7 days. Coinciding with their release profiles, Me-1pM and 1cM coatings initially suppressed SMC proliferation in vitro, but their efficacy decreased within 7 and 14 days, respectively, while Pr-1pM coatings suppressed SMC proliferation over 21 days. Thus, AMs with phosphonate headgroups and propyl linkers are capable of sustained release from the substrate and have the ability to suppress SMC proliferation during the restenosis that occurs in the 3-4 weeks after stent implantation, demonstrating the potential for AM coatings to provide sustained delivery via desorption from coated coronary stents and other metal-based implants.

Danhong injection (DHI) is a widely used Chinese Materia Medica standardized product for the clinical treatment of ischemic encephalopathy and coronary heart disease. The bindings of eight natural components in DHI between bovine serum albumin (BSA) were studied by fluorescence spectroscopy technology and molecular docking. According to the results, the quenching process of salvianolic acid B and hydroxysafflor yellow A was a static quenching procedure through the analysis of quenching data by the Stern-Volmer equation, the modified Stern-Volmer equation, and the modified Scatchard equation. Meanwhile, syringin (Syr) enhanced the fluorescence of BSA, and the data were analyzed using the Lineweaver-Burk equation. Molecular docking suggested that all of these natural components bind to serum albumin at the site I location. Further competitive experiments of SaB confirmed the result of molecular docking studies duo to the displacement of warfarin by SaB. Base on these studies, we selected SaB as a research target because it presented the strongest binding ability to BSA and investigated the influence of the multi-components coexisting in DHI on the interaction between the components of the SaB-BSA binding system. The participation of these natural components in DHI affected the interaction between the components of the SaB-BSA system. Therefore, when DHI is used in mammals, SaB is released from serum albumin more quickly than it is used alone. This work would provide a new experiment basis for revealing the scientific principle of compatibility for Traditional Chinese Medicine.

Cardiovascular disease initiates with the atherogenic cascade of scavenger receptor- (SR-) mediated oxidized low-density lipoprotein (oxLDL) uptake. Resulting foam cell formation leads to lipid-rich lesions within arteries. We designed amphiphilic macromolecules (AMs) to inhibit these processes by competitively blocking oxLDL uptake via SRs, potentially arresting atherosclerotic development. In this study, we investigated the impact of replacing ester linkages with ether linkages in the AM hydrophobic domain. We hypothesized that ether linkages would impart flexibility for orientation to improve binding to SR binding pockets, enhancing anti-atherogenic activity. A series of tartaric acid-based AMs with varying hydrophobic chain lengths and conjugation chemistries were synthesized, characterized, and evaluated for bioactivity. 3-D conformations of AMs in aqueous conditions may have significant effects on anti-atherogenic potency and were simulated by molecular modeling. Notably, ether-linked AMs exhibited significantly higher levels of inhibition of oxLDL uptake than their corresponding ester analogues, indicating a dominant effect of linkage flexibility on pharmacological activity. The degradation stability was also enhanced for ether-linked AMs. These studies further suggested that alkyl chain length (i.e., relative hydrophobicity), conformation (i.e., orientation), and chemical stability play a critical role in modulating oxLDL uptake, and guide the design of innovative cardiovascular therapies., (Copyright © 2015. Published by Elsevier Ltd.)

A novel series of amphiphilic macromolecules (AMs) composed of a sugar backbone, aliphatic chains, and branched, hydrophilic poly(oligoethylene glycol) methyl ether methacrylate (POEGMA)were developed for drug delivery applications. The branched, hydrophilic domains (POEGMA homopolymers with one hydroxyl group) were prepared via atom transfer radical polymerization (ATRP) of oligo(ethylene glycol) methyl ether methacrylate (OEGMA) monomers using 2-hydroxyethyl-2-bromoisobutyrate (HEBiB) as an initiator and copper bromide/bipyridine (CuBr/Bpy) as the catalyst system. To form the amphiphilic structures, the branched POEGMAs were coupled to hydrophobic domains that were formed via acylation of a sugar backbone. The impact of branching in the hydrophilic domain was investigated by comparing the AMs' solution and thermal properties with those of the linear counterparts. Although these highly branched AMs showed similar critical micelle concentration (CMC) values as compared to linear analogues, they possessed quite low glass transition ( T g ) temperatures. Consequently, these novel AMs with branched hydrophilic domain combine the desirable thermal properties of POEGMA with favorable solution properties of amphiphilic architectures, which make them suitable for injectable drug delivery systems.

A series of starburst oligomers (T1-T3) that contained a fully diarylmethene-bridged triphenylamine core and oligofluorene arms were designed and synthesized through Suzuki cross-coupling reactions. Their thermal, photophysical, and electrochemical properties were also investigated. These materials showed high glass transition, in the range of 123-129 °C, and good film-forming abilities. They displayed deep-blue emission both in solution and as thin films. Solution-processed devices based on these oligomers exhibited highly efficient deep-blue electroluminescence and the device performances were significantly enhanced with the extension of the oligofluorene arms. The double-layered device that contained T3 as an emitter showed a maximum current efficiency of 3.83 cd A(-1) and a maximum external quantum efficiency of 4.19% with CIE coordinates of (0.16, 0.09), which are among the highest values for undoped deep-blue OLEDs that are based on solution-processable starburst oligomers., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)