Association between constipation and the risk of Parkinson's disease among participants in the UK Biobank.

INTRODUCTION: Constipation is common in patients with Parkinson's disease (PD), but its impact on incident PD remains uncertain. We aimed to prospectively investigate constipation symptoms and the risk of PD. METHODS: Participants without PD at baseline from the UK Biobank were included in the study. Information on the regular use of laxatives, bowel movement frequency, and the frequency of hard or lumpy stools was collected. Incident PD was defined by the ICD-10 code. Cox proportional hazards models were used to assess the association between constipation symptoms and incident PD. RESULTS: In the analysis of regular laxative use and PD, 490,797 participants were included and 2,735 incident PD were detected. The multivariable adjusted HR of PD in participants who regularly used laxatives was 1.99 (95% confidence interval [CI], 1.70-2.33) compared with those not. In the analysis of bowel movement frequency and hard or lumpy stools and PD, 170,017 participants were included and 519 incident PD were detected. The multivariable adjusted HRs were 2.16 (95% CI, 1.74-2.68) and 2.57 (95% CI, 2.00-3.31) for participants with a bowel movement frequency of 3-6 times/week and <3 times/week, respectively, compared with those with a bowel movement frequency of ≥7 times/week; compared with participants who never had hard or lumpy stools, multivariable adjusted HRs were 1.31 (95% CI, 1.07-1.60), 2.32 (95% CI, 1.77-3.05), and 2.94 (95% CI, 2.14-4.05) for those who sometimes had hard or lumpy stools, often had hard or lumpy stools, and most of time/always had hard or lumpy stools, respectively. CONCLUSIONS: Constipation measured by the regular use of laxatives, bowel movement frequency, and the frequency of hard or lumpy stools was significantly associated with an increased risk of incident PD.

Association between Physical Activity and Parkinson's Disease: A Prospective Cohort Study.

BACKGROUND: The burden of Parkinson's disease (PD) is still increasing, and physical activity is a modifiable factor for health benefits. The benefits of physical activity in PD are not well established. Therefore, this study aimed to investigate the association between various types of physical activity and the risk of developing PD. METHODS: Data from 432,497 participants in UK Biobank, who were free of PD at baseline, were analyzed. Physical activity levels were assessed by measuring the duration of walking for pleasure, light and heavy do-it-yourself (DIY) activities, strenuous sports, and other exercises. Physical activity was categorized into daily living activities (walking for pleasure, light DIY, and heavy DIY) and structured exercises (strenuous sports and other exercises). Association between different types of physical activity and PD risk was examined using multivariable adjusted restricted cubic splines and Cox proportional risk models. RESULTS: Over a median follow-up of 13.7 years, 2,350 PD cases were identified. Cubic spline analyses revealed negative linear associations between PD risk and total physical activity, daily living activities, and structured exercise. After multivariable adjustment, the hazard ratios and 95% confidence intervals for incident PD associated with the highest quartile of total physical activity, daily living activities, and structured exercise were 0.72 (0.64-0.81), 0.75 (0.67-0.84), and 0.78 (0.67-0.90), respectively, compared to those in the lowest quartile. Sensitivity analysis confirmed these findings. CONCLUSIONS: Higher levels of both daily living activities and structured exercise were associated with a reduced incidence of PD, underscoring the importance of maintaining physical activity to prevent PD.

Kinetically Controlled Star Copolymer Self-Assembly for Rapid Fabrication of Nanoparticles with High Encapsulation Capacity.

Rapid and scalable self-assembly of an amphiphilic 21-arm star copolymer, (polystyrene-block-polyethylene glycol)21 [(PS-b-PEG)21 ] in aqueous solution has been performed by reverse solvent exchange procedure. Transmission electron microscope (TEM) and nanoparticle tracking analysis (NTA) reveal the formation of nanoparticles with narrow size distribution. Further investigation indicates a kinetically controlled self-assembly mechanism of the copolymers, in which the star topology of the amphiphilic copolymer and deep quenching condition by reverse solvent exchange are key to accelerate intrachain contraction of the copolymer during phase separation. When interchain contraction dominant over interchain association, nanoparticles with low aggregation number could be formed. Thanks to the high hydrophobic contents of the (PS-b-PEG)21 polymers, the resulted nanoparticles could encapsulate a high capacity of hydrophobic cargo up to 19.84 %. The kinetically controlled star copolymer self-assembly process reported here provides a platform for the rapid and scalable fabrication of nanoparticle with high drug loading capacity (LC), which may find broad range of applications in, for example drug delivery, nanopesticide.

Multicompartment Nanoparticles by Crystallization-Driven Self-Assembly of Star Polymers: Combining High Stability and Loading Capacity.

Herein novel multicompartment nanoparticles (MCNs) that combine high stability and cargo loading capacity are developed. The MCNs are fabricated by crystallization-driven self-assembly (CDSA) of a tailor-made 21 arm star polymer, poly(L-lactide)[poly(tert-butyl acrylate)-block-poly(ethylene glycol)]20 [PLLA(PtBA-b-PEG)20 ]. Platelet-like or spherical MCNs containing a crystalline PLLA core and hydrophobic PtBA subdomains are formed and stabilized by PEG. Hydrophobic cargos, such as Nile Red and chemotherapeutic drug doxorubicin, can be successfully encapsulated into the collapsed PtBA subdomains with loading capacity two orders of magnitude higher than traditional CDSA nanoparticles. Depolarized fluorescence measurements of the Nile Red loaded MCNs suggest that the free volume of the hydrophobic chains in the nanoparticles may be the key for regulating their drug loading capacity. In vitro study of the MCNs suggests excellent cytocompatibility of the blank nanoparticles as well as a dose-dependent cellular uptake and cytotoxicity of the drug-loaded MCNs.

Asymmetric Incorporation of Silver Nanoparticles in Polymeric Assemblies by Coassembly of Tadpole-Like Nanoparticles and Amphiphilic Block Copolymers.

A general approach to asymmetrically localize nanoparticles (NPs) in larger polymeric nanostructures is demonstrated by coassembly of tadpole-like silver NPs (AgNPs) and amphiphilic block copolymers (BCPs). The tadpole-like AgNPs are prepared by template synthesis using a tailor-made A(BC)20 star polymer, namely poly(ethylene glycol)[poly(acrylic acid)-block-polystyrene]20 [PEG(PAA-b-PS)20 ], as template resulting in AgNPs decorated with twenty short PS chains and one long PEG chain, named Ag@PEG(PS)20 . The asymmetric distribution of these AgNPs in various polymeric nanostructures, e.g., spherical micelles, cylindrical micelles, vesicles, and sponge phase, is achieved via coassembly of the as-prepared Ag@PEG(PS)20 and PEG-b-PS in solution driven by the anisotropic nature of the Ag@PEG(PS)20 . This report not only provides a new strategy for the fabrication of tadpole-like NPs but also offers opportunity for off-center distributing NPs in hybrid assemblies, which may find applications in, e.g., sensing, catalysis, and diagnostics.

Degradable ketal-based block copolymer nanoparticles for anticancer drug delivery: a systematic evaluation.

Low solubility of potent (anticancer) drugs is a major driving force for the development of noncytotoxic, stimuli-responsive nanocarriers, including systems based on amphiphilic block copolymers. In this regard, we investigated the potential of block copolymers based on 2-hydroxyethyl acrylate (HEA) and the acid-sensitive ketal-containing monomer (2,2-dimethyl-1,3-dioxolane-4-yl)methyl acrylate (DMDMA) to form responsive drug nanocarriers. Block copolymers were successfully synthesized by sequential reversible addition-fragmentation chain transfer (RAFT) polymerization, in which we combined a hydrophilic poly(HEA)x block with a (responsive) hydrophobic poly(HEAm-co-DMDMAn)y copolymer block. The DMDMA content of the hydrophobic block was systematically varied to investigate the influence of polymer design on physicochemical properties and in vitro biological performance. We found that a DMDMA content higher than 11 mol % is required for self-assembly behavior in aqueous medium. All particles showed colloidal stability in PBS at 37 °C for at least 4 days, with sizes ranging from 23 to 338 nm, proportional to the block copolymer DMDMA content. Under acidic conditions, the nanoparticles decomposed into soluble unimers, of which the decomposition rate was inversely proportional to the block copolymer DMDMA content. Flow cytometry and confocal microscopy showed dose-dependent, active in vitro cellular uptake of the particles loaded with hydrophobic octadecyl rhodamine B chloride (R18). The block copolymers showed no intrinsic in vitro cytotoxicity, while loaded with paclitaxel (PTX), a significant decrease in cell viability was observed comparable or better than the two commercial PTX nanoformulations Abraxane and Genexol-PM at equal PTX dose. This systematic approach evaluated and showed the potential of these block copolymers as nanocarriers for hydrophobic drugs.

One-Pot Preparation of Inert Well-Defined Polymers by RAFT Polymerization and In Situ End Group Transformation.

A one-pot procedure that straightforwardly combines reversible addition-fragmentation chain transfer (RAFT) polymerization and end group transformation to remove the RAFT end groups is developed for the synthesis of well-defined poly(meth)acrylates and polyacrylamides with inert end groups. This procedure only requires the addition of an amine at the end of the standard RAFT polymerization procedure, which avoids the separation and purification of the intermediate polymers and, hence, extremely reduces the working time and utilized amount of solvents. Upon addition of the amine, a thiol group is formed by aminolysis of the thiocarbonylthio group, which subsequently undergoes Michael addition with unreacted monomer leading to an inert thioether functionalized polymer.

Tuning the LCST and UCST thermoresponsive behavior of poly(N,N-dimethylaminoethyl methacrylate) by electrostatic interactions with trivalent metal hexacyano anions and copolymerization.

Poly(N,N-dimethylaminoethyl methacrylate) (PDMAEMA) has been reported to show both upper critical solution temperature (UCST) and lower critical solution temperature (LCST) behavior in presence of trivalent metal hexacyano anions, which is attractive for the development of smart materials. In this communication, the influence of the double thermoresponsive behavior of PDMAEMA driven by electrostatic interactions is investigated by comparing systems with [Co(CN)6 ](3-) , [Fe(CN)6 ](3-) , and [Cr(CN)6 ](3-) as trivalent anions. Furthermore, tuning of double thermoresponsive behavior of PDMAEMA by incorporating hydrophilic or hydrophobic comonomers is also discussed in the presence of [Fe(CN)6 ](3-) as trivalent ion.

Acid-Labile Thermoresponsive Copolymers That Combine Fast pH-Triggered Hydrolysis and High Stability under Neutral Conditions.

Biodegradable polymeric materials are intensively used in biomedical applications. Of particular interest for drug-delivery applications are polymers that are stable at pH 7.4, that is, in the blood stream, but rapidly hydrolyze under acidic conditions, such as those encountered in the endo/lysosome or the tumor microenvironment. However, an increase in the acidic-degradation rate of acid-labile groups goes hand in hand with higher instability of the polymer at pH 7.4 or during storage, thus posing an intrinsic limitation on fast degradation under acidic conditions. Herein, we report that a combination of acid-labile dimethyldioxolane side chains and hydroxyethyl side chains leads to acid-degradable thermoresponsive polymers that are quickly hydrolyzed under slightly acidic conditions but stable at pH 7.4 or during storage. We ascribe these properties to high hydration of the hydroxy-containing collapsed polymer globules in conjunction with autocatalytic acceleration of the hydrolysis reactions by the hydroxy groups.

RAFT polymerization of 4-vinylphenylboronic acid as the basis for micellar sugar sensors.

Well-defined homo and mPEGylated block (co)polymers of the commercially available unprotected 4-vinylphenylboronic acid (4-VBA) monomer are reported based on reversible addition-fragmentation chain transfer (RAFT) polymerization. The polymerization kinetics are studied in detail for homo and block (co)polymerizations with different chain transfer agents (CTAs) to optimize the preparation of well-defined polymer structures, eventually leading to comparatively low dispersities (D ≤ 1.25). Subsequently, block (co)polymers with methoxy poly(ethylene glycol) mPEG-b-P(4-VBA) are prepared using a mPEG-functionalized CTA. The formed block copolymer mPEG114 -b-P(4-VBA)30 is demonstrated to be pH and glucose responsive as its micellization behavior is dictated by pH as well as the presence of glucose. The glucose-responsive pH window of mPEG114 -b-P(4-VBA)30 is found to be pH 9-10 based on the DLS and TEM measurement.

The association of early life factors with depression and anxiety in adults aged 40-69 years: a population-based cohort study.

This study was aimed to explore the longitudinal association of five early life factors (breastfeeding, maternal smoking around birth, birth weight, being born in a multiple birth, and adoption) during the in-utero, perinatal, and early childhood development stages with incidence of depression and anxiety in adults aged 40-69 years. We used data from the UK biobank, 5,02,394 participants aged 40-69 years were recruited between 2006 and 2010. Participants provided information on early life exposures through touchscreen questionnaires or verbal interviews at baseline. The primary outcomes, depression, and anxiety, were defined according to the International Classification of Diseases, 10th Revision. Hazard ratios (HR) and 95% confidence intervals (CI) for each factor were reported. During a median follow-up of 13.6 years, 16,502 (3.55%) participants developed depression, and 15,507 (3.33%) developed anxiety. After adjusting for potential confounders, increased risk of depression was found to be significantly associated with non-breastfeeding (HR, 1.08; 95% CI, 1.04-1.13), maternal smoking around birth (HR, 1.19; 95% CI, 1.14-1.23), being born in multiple births (HR, 1.16; 95% CI, 1.05-1.27), low birth weight (HR, 1.14; 95% CI, 1.07-1.22), and being an adoptee (HR, 1.42; 95% CI, 1.28-1.58). Increased risk of anxiety was associated with non-breastfeeding (HR, 1.09; 95% CI, 1.04-1.13), maternal smoking around birth (HR, 1.11; 95% CI, 1.07-1.16), being born in a multiple births (HR, 1.05; 95% CI, 0.95-1.17), low birth weight (HR, 1.12; 95% CI, 1.05-1.20), and being an adoptee (HR, 1.25; 95% CI, 1.10-1.41). Each of these five early life factors can be considered as early life risk factors for incident depression and anxiety in adulthood independently. The dose-response relationship was also observed, suggesting that with an increase in the number of early life risk factors, the likelihood of experiencing depression and anxiety also increased. These findings highlighted the imperative consideration of early life factors in comprehending the susceptibility to mental health disorders later in life, including non-breastfeeding, maternal smoking around birth, being born in multiple births, low birth weight, and being an adoptee.

Associations of computer gaming with incident dementia, cognitive functions, and brain structure: a prospective cohort study and Mendelian randomization analysis.

BACKGROUND: Computer gaming has recently been suggested to be associated with benefits for cognition, but its impact on incident dementia remains uncertain. We aimed to investigate the observational associations of playing computer games with incident dementia, cognitive functions, and brain structural measures, and further explore the genetic associations between computer gaming and dementia. METHODS: We included 471,346 White British participants without dementia at baseline based on the UK Biobank, and followed them until November 2022. We estimated the risk of dementia using Cox proportional hazard models, and assessed the changes of cognitive functions and brain structural measures using logistic regression models and linear regression models. Mendelian randomization (MR) analyses were performed to examine the association between genetically determined computer gaming and dementia. RESULTS: High frequency of playing computer games was associated with decreased risk of incident dementia (HR, 0.81 [95% CI: 0.69, 0.94]). Individuals with high frequency of playing computer games had better performance in prospective memory (OR, 1.46 [1.26, 1.70]), reaction time (beta, -0.195 [-0.243, -0.147]), fluid intelligence (0.334 [0.286, 0.382]), numeric memory (0.107 [0.047, 0.166]), incorrect pairs matching (-0.253 [-0.302, -0.203]), and high volume of gray matter in hippocampus (0.078 [0.023, 0.134]). Genetically determined high frequency of playing computer games was associated with a low risk of dementia (OR, 0.37 [0.15, 0.91]). CONCLUSIONS: Computer gaming was associated with a decreased risk of dementia, favorable cognitive function, and better brain structure, suggesting that computer gaming could modulate cognitive function and may be a promising target for dementia prevention.

Twenty-four-hour blood pressure trajectories and clinical outcomes in patients who had an acute ischaemic stroke.

OBJECTIVE: The management of blood pressure (BP) in acute ischaemic stroke remains a subject of controversy. This investigation aimed to explore the relationship between 24-hour BP patterns following ischaemic stroke and clinical outcomes. METHODS: A cohort of 4069 patients who had an acute ischaemic stroke from 26 hospitals was examined. Five systolic BP trajectories were identified by using latent mixture modelling: trajectory category 5 (190-170 mm Hg), trajectory category 4 (180-140 mm Hg), trajectory category 3 (170-160 mm Hg), trajectory category 2 (155-145 mm Hg) and trajectory category 1 (150-130 mm Hg). The primary outcome was a composite outcome of death and major disability at 3 months poststroke. RESULTS: Patients with trajectory category 5 exhibited the highest risk, while those with trajectory category 1 had the lowest risk of adverse outcomes at 3-month follow-up. Compared with the patients in the trajectory category 5, adjusted ORs (95% CIs) for the primary outcome were 0.79 (0.58 to 1.10), 0.70 (0.53 to 0.93), 0.64 (0.47 to 0.86) and 0.47 (0.33 to 0.66) among patients in trajectory category 4, trajectory category 3, trajectory category 2 and trajectory category 1, respectively. Similar trends were observed for death, vascular events and the composite outcome of death and vascular events. CONCLUSION: Patients with persistently high BP at 180 mm Hg within 24 hours of ischaemic stroke onset had the highest risk, while those maintaining stable BP at a moderate-low level (150 mm Hg) or even a low level (137 mm Hg) had more favourable outcomes.

Poisoning by Purity: What Stops Stereocomplex Crystallization in Polylactide Racemate?

Formation of stereocomplex crystals (SC) is an effective way to improve the heat resistance and mechanical performance of poly(lactic acid) products. However, at all but the slowest cooling rates, SC crystallization of a high-molecular-weight poly(l-lactic acid)/poly(d-lactic acid) (PLLA/PDLA) racemate stops at a high temperature or does not even start, leaving the remaining melt to crystallize into homochiral crystals (HC) or an SC-HC mixture on continuous cooling. To understand this intriguing phenomenon, we revisit the SC crystallization of both high- and low-molecular-weight PLLA/PDLA racemates. Based on differential scanning calorimetry (DSC), supplemented by optical microscopy and X-ray scattering, we concluded that what stops the growth of SC is the accumulation of the nearly pure enantiomer, either PDLA or PLLA, that is rejected from the SC ahead of its growth front. The excess enantiomer is a result of random compositional fluctuation present in the melt even if the average composition is 1:1. The situation is more favorable if the initial polymer is not fully molten or is brought up to just above the melting point where SC seeds remain, as proven by DSC and X-ray scattering. Moreover, we find that not only is SC growth poisoned by the locally pure enantiomer but also that at lower temperatures, the HC growth can be poisoned by the blend. This explains why SC growth, arrested at high temperatures, can resume at lower temperatures, along with the growth of HC. Furthermore, while some previous works attributed the incomplete SC crystallization to a problem of primary nucleation, we find that adding a specific SC-promoting nucleating agent does not help alleviate the problem of cessation of SC crystallization. This reinforces the conclusion that the main problem is in growth rather than in nucleation.

Nanofibers with homogeneous heparin distribution and protracted release profile for vascular tissue engineering.

In clinic, controlling acute coagulation after small-diameter vessel grafts transplantation is considered a primary problem. The combination of heparin with high anticoagulant efficiency and polyurethane fiber with good compliance is a good choice for vascular materials. However, blending water-soluble heparin with fat-soluble poly (ester-ether-urethane) urea elastomer (PEEUU) uniformly and preparing nanofibers tubular grafts with uniform morphology is a huge challenge. In this research, we have compounded PEEUU with optimized constant concentration of heparin by homogeneous emulsion blending, then spun into the hybrid PEEUU/heparin nanofibers tubular graft (H-PHNF) for replacing rats' abdominal aorta in situ for comprehensive performance evaluation. The in vitro results demonstrated that H-PHNF was of uniform microstructure, moderate wettability, matched mechanical properties, reliable cytocompatibility, and strongest ability to promote endothelial growth. Replacement of resected abdominal artery with the H-PHNF in rat showed that the graft was capable of homogeneous hybrid heparin and significantly promoted the stabilization of vascular smooth muscle cells (VSMCs) as well as stabilizing the blood microenvironment. This research demonstrates the H-PHNF with substantial patency, indicating their potential for vascular tissue engineering.

Electrospun PCL/collagen hybrid nanofibrous tubular graft based on post-network bond processing for vascular substitute.

Inhibiting thrombus formation and intimal hyperplasia is essential for orthotopic tissue-engineered vascular grafts. The matching mechanical properties of autologous blood vessels and inhibition of platelet aggregation are considered as two points to improve the success rate of transplantation. The poly(ε-caprolactone)/collagen/heparin composite vascular graft (PCLHC) with three-dimensional network structure were constructed by electrospinning, which can mimic natural vascular biomechanics and enhance the viability of cells viability in vitro. The hybrid collagen matrix network nanofibers formed by electrospinning exhibited uniform and smooth morphology. The results of mechanical experiments showed that PCLHC had similar mechanical properties to natural blood vessels. And the addition of heparin enhanced the anticoagulation of PCLHC. Simultaneous three-component hybrid nanofibers showed a potentially reliable ability to promote the proliferation of human umbilical vein endothelial cells (HUVECs). In summary, all the results showed that the three-dimensional network structure of PCLHC presented the potential to heal injured vessels.

An Intelligent Nanovehicle Armed with Multifunctional Navigation for Precise Delivery of Toll-Like Receptor 7/8 Agonist and Immunogenic Cell Death Amplifiers to Eliminate Solid Tumors and Trigger Durable Antitumor Immunity.

Cancer immunotherapy is revolutionary in oncology and hematology. However, a low response rate restricts the clinical benefits of this therapy owing to inadequate T lymphocyte infiltration and low delivery efficiency of immunotherapeutic drugs. Herein, an intelligent nanovehicle (folic acid (FA)/1-(4-(aminomethyl) benzyl)-2-butyl-1H-imidazo[4,5-c]quinolin-4-amine (IMDQ)-oxaliplatin (F/IMO)@CuS) armed with multifunctional navigation is designed for the accurate delivery of cargoes to tumor cells and dendritic cells (DCs), respectively. The nanovehicle is based on a near infrared-responsive inorganic CuS nanoparticles, acting as a photosensitizer and carrier of the chemotherapeutic agent oxaliplatin, and enters tumor cells owing to the presence of folic acid on the surface of CuS upon intratumoral injection. Furthermore, a toll-like receptor (TLR) 7/8 agonist-conjugated polymer, anchored on the surface of CuS, is modified with mannose to bind with DCs in the tumor microenvironment. Upon exposure to laser irradiation, nanovehicles disassemble, releasing oxaliplatin, to ablate tumor cells and amplify immunogenic cell death in combination with photothermal therapy. Mannose-modified polymer-TLR7/8 agonist conjugates are subsequently exposed, leading to the activation of DCs and proliferation of T cells. Collectively, these intelligent nanovehicles reduce tumor burden, exert a robust antitumor immune response, and generate long-term immune protection to prevent tumor recurrence.

Polyzwitterions with LCST Side Chains: Tunable Self-Assembly.

Manipulation of self-assembly behavior of copolymers via environmental change is attractive in the fabrication of smart polymeric materials. We present tunable self-assembly behavior of graft copolymers, poly(sulfobetaine methacrylate)-graft-poly[oligo(ethylene glycol) methyl ether methacrylate)-co-di(ethylene glycol) methyl ether methacrylate] (PSBM-g-P(OEGMA-co-DEGMA)). Upon heating the aqueous solutions, the graft copolymers undergo a transition from micelles with PSBM cores to unimers (i.e., individual macromolecules) and then to reversed micelles with P(OEGMA-co-DEGMA) cores, thus demonstrating the tunability of the self-assembling through temperature change. In the presence of salt the temperature response of PSBM is eliminated, and the structure of the micelles with the P(OEGMA-co-DEGMA) core changes. Moreover, for the graft copolymer with long side chains, micelles with aggregation number ∼ 2 were formed with a PSBM core at low temperature, which is ascribed to the steric effect of the P(OEGMA-co-DEGMA) shell.

Morphology and interfacial action of nanocomposites formed from ethylene-vinyl acetate copolymers and organoclays.

The effect of the polarity of modifier and polymer matrixes on the morphology and interfacial action of nanocomposites was studied by molecular dynamics (MD) and inverse gas chromatography (IGC) based on ethylene-vinyl acetate (EVA) /organic montmorillonite (OMMT), where vinyl acetate (VA) concentrations are 9.3 and 18 wt %, respectively. It is found that EVA with higher VA concentration displays a higher surface energy than that with lower VA concentration. Modifier with two long alkyl tails will lower the surface energy of montmorillonite (MMT) more effectively. Combined with transmission electron microscopy (TEM) photography of EVA/OMMT nanocomposites, it is found that the surface energies of organic montmorillonite and EVAs make great contributions to the dispersion of the OMMT in polymer matrixes. OMMT modified by two long alkyl tails displays weaker acid and base properties which will have a better interaction with EVAs through acid-base interaction. Molecular simulation (MD) proved that nonpolar interaction determines the binding between EVAs and organoclays, otherwise electrostatic interaction in polar polymer/organoclay systems. Binding energies were calculated by MD, and the results show stronger interaction between 20A (organoclay made from two long alkyl tails surfactant) and EVA. Interfacial action between filler and polymer matrix should be accountable for the mechanical properties of the nanocomposite.

Photodynamic Antifungal Activity of Hypocrellin A Against Candida albicans.

Many studies have reported that hypocrellin A (HA) exhibits effective antimicrobial activities with proper irradiation. However, its antifungal activity and the involved mechanism have not been fully defined. In this study, HA-mediated cytotoxicity in Candida albicans cells was evaluated after antimicrobial photodynamic therapy (aPDT). The results showed that 1.0 µg/ml HA significantly decreased the survival rate of C. albicans cells with light illumination. Moreover, the ROS levels were also remarkably elevated by HA. Further study found that HA combined with illumination led to cell membrane potential depolarization and cell membrane integrity damage. To investigate the form of cell death, a series of apoptosis-related parameters, including mitochondrial transmembrane potential, metacaspase activity, DNA fragmentation, nuclear condensation, and cytosolic and mitochondrial calcium, were analyzed. Data showed that all the above mentioned apoptosis hallmarks were affected after treatment with HA, indicating that HA induced C. albicans cell apoptosis. Finally, HA-mediated aPDT was demonstrated to be low-toxic and effective in treating cutaneous C. albicans infections. This study highlights the antifungal effect and mechanism of HA-mediated aPDT against C. albicans and provides a promising photodynamic antifungal candidate for C. albicans skin infections.