Detection of alkaline phosphatase activity with a CsPbBr3/Y6 heterojunction-based photoelectrochemical sensor.

An ultra-sensitive photoelectrochemical (PEC) sensor based on perovskite composite was developed for the determination of alkaline phosphatase (ALP) in human serum. In contrast to CsPbBr3 or Y6 that generated anodic current, the heterojunction of CsPbBr3/Y6 promoted photocarriers to separate and generated cathodic photocurrent. Ascorbic acid (AA) was produced by ALP hydrolyzing L-ascorbic acid 2-phosphate trisodium salt (AAP), which can combine with the holes on the photoelectrode surface, accelerating the transmission of photogenerated carriers, leading to enhanced photocurrent intensity. Thus, the enhancement of PEC current was linked to ALP activity. The PEC sensor exhibits good sensitivity for detection of ALP owing to the unique photoelectric properties of the CsPbBr3/Y6 heterojunction. The detection limit of the sensor was 0.012 U·L-1 with a linear dynamic range of 0.02-2000 U·L-1. Therefore, this PEC sensing platform shows great potential for the development of different PEC sensors.

The association between device-measured sitting time and cardiometabolic health risk factors in children.

BACKGROUND: There is limited evidence of the associations between postural-derived sitting time, waist-worn derived sedentary time and children's health and the moderation effect of physical activity (PA). This study examined associations of children's device-measured sitting time with cardiometabolic health risk factors, including moderation by physical activity. METHODS: Cross-sectional baseline data from children (mean-age 8.2 ± 0.5 years) in Melbourne, Australia (2010) participating in the TransformUs program were used. Children simultaneously wore an activPAL to assess sitting time and an ActiGraph GT3X to assess sedentary time and physical activity intensity. Cardiometabolic health risk factors included: adiposity (body mass index [BMI], waist circumference [WC]), systolic and diastolic blood pressure (SBP, DBP), high-density lipoprotein (HDL), low-density lipoprotein (LDL), cholesterol, triglycerides, fasting plasma glucose (FPG), serum insulin, and 25-hydroxyvitaminD (25[OH]D). Linear regression models (n = 71-113) assessed associations between sitting time with each health risk factor, adjusted for different PA intensities (i.e. light [LIPA], moderate-vigorous intensities [MVPA], separately on each model), age, sex, adiposity, and clustering by school. Interaction terms examined moderation. The analyses were repeated using device-measured sedentary time (i.e. ActiGraph GT3X) for comparison. RESULTS: Sitting time was positively associated with SBP (b = 0.015; 95%CI: 0.004, 0.026), DBP (b = 0.012; 95%CI:0.004, 0.020), and FPG (b = 0.001; 95%CI: 0.000, 0.000), after adjusting for higher PA intensities. The association between sitting time and insulin (b = 0.003; 95%CI: 0.000, 0.006) was attenuated after adjusting for higher PA intensities. When the models were adjusted for LIPA and MVPA, there was a negative association with LDL (b=-0.001; 95%CI: -0.002, -0.000 and b=-0.001; 95%CI: -0.003, -0.000, respectively). There was a negative association of sedentary time with WCz (b=-0.003; 95%CI: -0.005, 0.000) and BMIz (b=-0.003; 95%CI: -0.006, -0.000) when the models were adjusted by MVPA. Sedentary time was positively associated with triglycerides (b = 0.001; 95%CI: 0.000, 0.001) but attenuated after adjusting for MVPA. No evidence of moderation effects was found. CONCLUSIONS: Higher volumes of sitting and sedentary time were associated with some adverse associations on some cardiometabolic health risk factors in children. These associations were more evident when sitting time was the predictor. This suggests that reducing time spent sitting may benefit some cardiometabolic health outcomes, but future experimental research is needed to confirm causal relationships and identify the biological mechanisms that might be involved. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12609000715279.

Racial Discrimination and Metabolic Syndrome in Young Black Adults.

Importance: Metabolic syndrome (MetS) is a common health condition that predisposes individuals to cardiovascular disease (CVD) and disproportionately affects Black and other racially and ethnically minoritized people. Concurrently, Black individuals also report more exposure to racial discrimination compared with White individuals; however, the role of discrimination in the development of MetS over time and associated mediators in these pathways remain underexplored. Objective: To evaluate the association between racial discrimination and MetS in rural Black individuals transitioning from late adolescence into early adulthood and to identify potential mediating pathways. Design, Setting, and Participants: This longitudinal cohort study included Black adolescents enrolled in the Strong African American Families Healthy Adults (SHAPE) Project between June 2009 and May 2021. Families resided in rural counties of Georgia, where poverty rates are among the highest in the nation. Analyses included 322 of the 500 participants who originally enrolled in SHAPE and who were eligible to participate. Guardians provided information about socioeconomic disadvantage. Analyses were conducted in April 2023. Exposures: Youths reported exposure to racial discrimination annually from ages 19 to 21 years. Main Outcomes and Measures: MetS was the main health outcome and was measured at ages 25 and 31 years. MetS was diagnosed according to the International Diabetes Federation guidelines, which requires central adiposity (ie, waist circumference ≥94 cm for males and ≥80 cm for females) and at least 2 of the 4 additional components: signs of early hypertension (ie, systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥85 mm Hg); elevated triglyceride levels (ie, >150 mg/dL); elevated fasting glucose level (ie, ≥100 mg/dL); or lowered high-density lipoprotein levels (ie, <40 mg/dL in men and <50 mg/dL in women). At age 25 years, markers of inflammatory activity (ie, soluble urokinase plasminogen activator receptor [suPAR]) and sleep problems were collected to consider as potential mediators. Results: In 322 participants (210 [65.2%] female) ages 19 to 21 years, more frequent exposure to racial discrimination was associated with higher suPAR levels (b = 0.006; 95% CI, 0.001-0.011; P = .01) and more sleep problems at age 25 years (b = 0.062; 95% CI, 0.028-0.097; P < .001) as well as a 9.5% higher risk of MetS diagnosis at age 31 years (odds ratio [OR], 1.10; 95% CI, 1.01-1.20; P = .03). Both suPAR (b = 0.015; 95% CI, 0.002-0.037) and sleep problems (b = 0.020; 95% CI, 0.002-0.047) at age 25 years were significant indirect pathways. No significant interactions between sex and discrimination emerged. Conclusions and Relevance: This study suggests that racial discrimination in late adolescence is associated with MetS among Black young adults through biobehavioral pathways. Thus, health interventions for MetS in Black adults will need to contend with sleep behaviors and inflammatory intermediaries as well as address and reduce exposure to racial discrimination to narrow disparities and promote health equity.

Serial mediation effect of physical activity and sleep quality between dietary behaviour and depression symptoms: A nationwide cross-sectional survey.

Background: Substantial studies have revealed the potential mechanisms underlying the link between dietary behaviour and depression symptoms. This study investigated the relationship between depression symptoms and dietary behaviour, physical activity, and sleep quality in a nationwide sample of Chinese residents. Methods: A total of 18 819 Chinese Residents completed the dietary behaviour, patient health questionnaire, international physical activity questionnaire, and Pittsburgh sleep quality index. We used the Hayes' serial mediation model to investigate the correlation between the variables. Results: Among the participants, 85.5% were aged between 18 and 59, 41.2% were male, and 73.8% were urban residents. There is a negative correlation between dietary behaviour and physical activity (r = -0.038, P < 0.001), while there is a positive correlation with depression symptoms (r = 0.238, P < 0.001) and sleep quality (r = 0.115, P < 0.001). Additionally, depression shows a positive correlation with physical activity (r = 0.024, P < 0.001) and sleep quality (r = 0.298, P < 0.001), while there is a negative correlation between physical activity and sleep quality (r = -0.035, P < 0.001). Dietary behaviour was found to be connected with depression symptoms via three mediation pathways: (1) physical activity (B = -0.003, 95% confidence interval (CI) = -0.016, -0.007), (2) sleep quality (B = 0.034, 95% CI = 0.126, 0.164), and (3) physical activity and sleep quality (B = 0.001, 95% CI = 0.001, 0.003). Conclusions: These findings highlight the significance of psychological and physical factors in exploring the mechanisms through which dietary behaviour is related to depression symptoms. Overall, this study showed the important role of lifestyle factors in depression symptoms, suggesting that appropriate dietary behaviours, appropriate physical activity, and good sleep quality are necessary for the avoidance or improvement of depression symptoms.

Ascorbyl palmitate ameliorates inflammatory diseases by inhibition of NLRP3 inflammasome.

The aberrant activation of NLRP3 inflammasome contributes to pathogenesis of multiple inflammation-driven human diseases. However, the medications targeting NLRP3 inflammasome are not approved for clinic use to date. Here, we show that ascorbyl palmitate (AP), a lipophilic derivative of ascorbic acid (AA) and a safe food additive, is a potent inhibitor of NLRP3 inflammasome. Compared with AA, AP inhibited the activation of NLRP3 inflammasome with increased potency and specificity. Mechanistically, AP directly scavenged mitochondrial reactive oxygen species (mitoROS) by its antioxidant activity and blocked NLRP3-NEK7 interaction and NLRP3 inflammasome assembly. Moreover, AP showed more significant preventive effects than AA in LPS-induced systemic inflammation, dextran sulfate sodium (DSS)-induced colitis and experimental autoimmune encephalomyelitis (EAE). Thus, our results suggest that AP is a potential therapeutic combating NLRP3-driven diseases.

An application of the reasoned action approach to clinical students' intention toward a career in geriatrics.

Guided by the reasoned action approach, this study examined select individual, information, and social factors that influence intention toward pursuing a career in geriatrics among 314 clinical medical and nursing students in Ghana. A Poisson regression showed attitude toward older persons was a significant influencing factor of intention to choose a career in geriatrics for medical students (B = 0.015, SE = 0.0048, p = 0.002) but not nursing students (B = 0.009, SE = 0.0145, p = 0.512). Personal interest was, however, a significant influencing factor for both medical and nursing students (B = 0.462, SE = 0.0592, p = 0.000) and (B = 0.015, SE = 0.0048, p = 0.002), respectively. Nursing students with moderate to strong interest were 1.6 times more likely to express an intention to specialize in geriatrics, and medical students were 1.5 times more likely to express an intention to specialize in geriatrics. The results show that the most important factor influencing geriatric career intention is students' personal interest in the field. Evidence-based interventions such as early educational and practice exposure to the field and interactions with older adults are recommended.

The impact of kidney function on plasma neurofilament light and phospho-tau 181 in a community-based cohort: the Shanghai Aging Study.

BACKGROUND: The blood-based biomarkers are approaching the clinical practice of Alzheimer's disease (AD). Chronic kidney disease (CKD) has a potential confounding effect on peripheral protein levels. It is essential to characterize the impact of renal function on AD markers. METHODS: Plasma phospho-tau181 (P-tau181), and neurofilament light (NfL) were assayed via the Simoa HD-X platform in 1189 dementia-free participants from the Shanghai Aging Study (SAS). The estimated glomerular filter rate (eGFR) was calculated. The association between renal function and blood NfL, P-tau181 was analyzed. An analysis of interactions between various demographic and comorbid factors and eGFR was conducted. RESULTS: The eGFR levels were negatively associated with plasma concentrations of NfL and P-tau181 (B = - 0.19, 95% CI - 0.224 to - 0.156, P < 0.001; B = - 0.009, 95% CI - 0.013 to -0.005, P < 0.001, respectively). After adjusting for demographic characteristics and comorbid diseases, eGFR remained significantly correlated with plasma NfL (B = - 0.010, 95% CI - 0.133 to - 0.068, P < 0.001), but not with P-tau181 (B = - 0.003, 95% CI - 0.007 to 0.001, P = 0.194). A significant interaction between age and eGFR was found for plasma NfL (Pinteraction < 0.001). In participants ≥ 70 years and with eGFR < 60 ml/min/1.73 m2, the correlation between eGFR and plasma NfL was significantly remarkable (B = - 0.790, 95% CI - 1.026 to - 0,554, P < 0.001). CONCLUSIONS: Considering renal function and age is crucial when interpreting AD biomarkers in the general aging population.

Hybrid gelatin-ascorbyl phosphate scaffolds accelerate diabetic wound healing via ROS scavenging, angiogenesis and collagen remodeling.

Skin wound healing, particularly diabetic wound healing, is challenging in clinical management. Impaired wound healing is associated with persistent oxidative stress, altered inflammatory responses, unsatisfactory angiogenesis and epithelialization. Magnesium ascorbyl phosphate (MAP), which is an ascorbic acid derivative and active ingredient in cosmetics, has been reported to scavenge reactive oxygen species (ROS), and is considered a potential therapeutic agent for diabetic wounds. Herein, we report a hybrid gelatin-MAP scaffolds that can reduces oxidative stress damage, enhances angiogenesis and collagen remodeling to accelerate diabetic wound repair. Preliminary insights based on network pharmacology indicate that MAP may accelerate wound repair through multiple biological pathways, including extracellular matrix remodeling and anti-apoptosis. In vitro studies showed that the hybrid hydrogel scaffold had suitable mechanical properties, excellent biocompatibility and bioactivity. Further animal experiments demonstrated that the hydrogel accelerated full-thickness wound repair in diabetic mice (repair rate MAP vs Control=91.791±3.306 % vs 62.962±6.758 %) through antioxidant, neuroangiogenesis, collagen remodeling, and up-regulated the expression of the related factors COL-1, CD31, VEGF, and CGRP. Overall, we developed a bioactive hybrid hydrogel encapsulating MAP that synergistically promotes diabetic wound repair through multiple biological effects. This potentially integrated therapeutic scaffold may enrich future surgical approaches for treating diabetic wounds.

Impact of country governance mechanisms on carbon emissions performance of multinational entities.

This study investigates the impact of country governance mechanisms on carbon emissions performance of private sector organisations, using empirical evidence from 336 top multinational entities (MNEs) over a 15-year period. The results show that, at the aggregate level, Control of Corruption (b = -0.021, p < 0.01) and Voice & Accountability (b = -0.015, p < 0.05) are significantly and negatively associated with carbon emissions rate. While Political Stability (b = 0.007, p < 0.05) and Government Effectiveness (b = 0.018, p < 0.05) have significant positive impact on carbon emissions rate, the impact of Regulatory Quality and Rule of Law is negative but insignificant. Empirical evidence supports the conclusion that the existing institutional environment is not sufficient to deliver the net zero transition. There is a need for more coordination, strategic planning, and delivery monitoring in government institutions to achieve decarbonisation targets. The study contributes to knowledge within the context of the identified research gaps. First, the study adds to the limited literature on the impact of country governance on carbon emissions reduction, particularly with reference to scope 3 emissions. Second, with the sustainable development goals (SDGs) set to expire by 2030, the study provides empirical evidence on efforts governments of countries are making in achieving decarbonisation targets through improvement in country governance quality. Third, the study shows that the impact of the country governance on the carbon emissions performance of MNEs is contextual and varies across jurisdictions/geographical regions. Finally, the paper contributes to the debate on the actualisation of Agenda 2030, because presenting empirical evidence on the impact of country governance mechanisms on carbon emissions reduction-particularly scope 3 emissions-is an important discourse in the realisation of the SDGs.

Insomnia moderates the association between psychotic-like experiences and suicidal ideation in a non-clinical population: a network analysis.

Psychotic-like experiences (PLEs) have been associated with poor sleep quality and increased suicide risk. However, the association between PLEs, insomnia and suicide risk has not been thoroughly investigated in prior studies. In this study, we aimed to explore as to whether insomnia moderates the association between PLEs and suicidal ideation. The study was performed in 4203 young adults (aged 18-35 years, 63.8% females). Data were collected using self-reports. Moderation analysis demonstrated that PLEs are associated with higher levels of the current suicidal ideation only in participants with greater severity of insomnia (B = 0.003, p < 0.001). This analysis included age, gender, education, occupation and depressive symptoms as covariates. Moreover, the network analysis demonstrated that nodes representing PLEs are connected to the node of current suicidal ideation only in participants with greater severity of insomnia. The nodes of PLEs connected to the current suicidal ideation node captured PLEs representing deja vu experiences, auditory hallucination-like experiences and paranoia (edge weights between 0.011 and 0.083). Furthermore, nodes representing PLEs were the three most central nodes in the network analysis of individuals with higher levels of insomnia (strength centrality between 0.96 and 1.10). In turn, the three most central nodes were represented by depressive symptoms in the network analysis of individuals with lower levels of insomnia (strength centrality between 0.67 and 0.79). Findings from this study indicate that insomnia might be an important risk factor of suicide in people with PLEs, especially those reporting deja vu experiences, auditory hallucination-like experiences and paranoia.

Mechanical properties of simulated dentin caries treated with metal cations and L-ascorbic acid 2-phosphate.

This pH cycling study aimed to investigate the effects of L-Ascorbic acid 2-phosphate (AA2P) salts of Mg, Zn, Mn, Sr, and Ba on the surface microhardness, compressive strength, diametral tensile strength (DTS), and solubility of root canal dentin. 186 cylindrical dentin specimens from 93 teeth were fortified with optimal concentrations of AA2P salts of Mg (0.18 mM), Zn (5.3 µM), Mn (2.2 × 10-8 M), Sr (1.8 µM), and Ba (1.9 µM). Saline was used as the control group. These dentin specimens underwent a 3-day cycling process simulating dentin caries formation through repeated sequences of demineralization and remineralization. Surface microhardness at 100 and 500 µm depths (n = 10/subgroup), scanning electron microscopy (n = 3/group), compressive strength (n = 10/group), DTS (n = 6/group), and solubility (n = 5/group) tests were performed to analyze the dentin specimens. Data were analyzed using Kolmogorov-Smirnov, one-way ANOVA, and Post Hoc Tukey tests (p < 0.05). The control group had significantly lower microhardness at both depths (p < 0.001), reduced DTS (p = 0.001), decreased compressive strength (p < 0.001), and higher weight loss (p < 0.001) than all other groups. The Sr group had the highest compressive strength and microhardness among all the groups. The microhardness was significantly higher for the 500 µm depth than the 100 µm depth (p < 0.001), but the difference in microhardness between depths across groups was not significant (p = 0.211). All fortifying solutions provided some protection against artificial caries lesions. Therefore, these elements might have penetrated and reinforced the demineralized dentin against acid dissolution.

Fabrication and characterization of l-ascorbyl palmitate and phospholipid-based hybrid liposomes and their impacts on the stability of loaded hydrophobic polyphenols.

The aim of this study was to evaluate the influence of l-ascorbyl palmitate (LAP) as an additive to liposome formulations by self-assembling with soy lecithin to form hybrid liposomes, in order to enhance the physical stability and bioactivator-loaded retention ratio of the LAP incorporated liposomes (LAP-LP). The addition of LAP significantly increased its surface negative charge and strong hydrophobic interactions occurred between the hydrophobic tails of LAP and phospholipids resulting in more compactly ordered, rigid and hydrophobic phospholipid bilayers as indicated by surface tension, fluorescence probes and DSC. These changes enhanced the stability of hydrophobic polyphenol loaded LAP-LP during storage. Particularly, after four weeks storage at 37 °C for naringenin loaded liposomes, the retention ratio of pure liposome decreased dramatically to 12.5 %, while the LAP-LP remained above 74.5 %. This study opens up the potential for the LAP-LP to be developed as a food-grade multifunctional formulation for encapsulating and delivering bioactivators.

Encapsulation of ascorbyl palmitate in corn starch matrix by extrusion cooking: Release behavior and antioxidant activity.

The main limitation associated with the oral delivery of ascorbyl palmitate, a potent food antioxidant, is its susceptibility to oxidative deterioration. The main objective of the current research was to encapsulate ascorbyl palmitate into corn starch matrix using extrusion cooking and evaluate its release behavior and oxidative stability. Results showed that ascorbyl palmitate was efficiently encapsulated (96.06-99.28%) in the starch matrix using the extrusion technique. The release behavior of ascorbyl palmitate from the extruded starch matrix during simulated upper gastrointestinal tract conditions was slow but steady (18.92-28.32% after 180 min) and presented a sustainable antioxidant activity. Acid treatment (pH 2.0) increased the release rate of ascorbyl palmitate from the extruded starch matrix. Furthermore, the antioxidant capacity of ascorbyl palmitate released from the extruded samples stored in both darkness and under UV radiation at 40 °C was found to be remarkably retained (p > 0.05) for up to three months.

Development of hemp seed oil nanoemulsions loaded with ascorbyl palmitate: Effect of operational parameters, emulsifiers, and wall materials.

The perceived health properties of hemp seed oil, as one of the few plant-basedsources of omega-3 and omega-6 fatty acids with an ideal ratio of 1:3, suggest its incorporation in food-grade emulsions to improve its water solubility and oxidative stability. The current research's main aim was nanoemulsification of hemp seed oil using the oil-in-water emulsification method followed by ultrasonication. The entrapment efficiency of the nanoemulsions for antioxidant ascorbyl palmitate and its impact on oxidative stability of the oil was also evaluated. Gum arabic: maltodextrin in 75:25 ratio could result in nanoemulsion with entrapment efficiency of 97.10 % for ascorbyl palmitate and radical scavenging activity of oil-soluble bioactives of 92.13 %. Moreover, incorporation of ascorbyl palmitate could effectively retard the oxidation, specifically in nanoemulsions containing gum Arabic. The optimum formulation of nanoemulsion having an average droplet size of 293 nm can be applied as an ideal vegetarian source of omega-3 fatty acids.

Enzymatic synthesis of ascorbyl oleate and evaluation of biological activities.

Compounds that reduce or neutralize free radicals have been evaluated for use as nutraceutical or antioxidant additives in processed foods. This study aimed to enzymatically produce ascorbyl oleate and assess its biological properties. The synthesis was performed under previously maximized conditions (L-ascorbic acid/oleic acid 1:9 molar ratio, 70 °C, 1 h reaction). Immobilized commercial lipase from Candida antarctica (NS 88011) was used as biocatalyst. The reaction product was isolated, and its structure was confirmed by High-Performance Liquid Chromatography and Nuclear Magnetic Resonance. Ascorbyl oleate showed antioxidant and antimicrobial activity, besides no toxicity, did not influencing blood coagulation and also not presenting hemolytic profile. Better storage stability was achieved under refrigerated conditions, and the oxidative stability demonstrated free radicals fighting efficiency, increasing olive oil's shelf life. In vitro gastrointestinal simulation showed that ascorbyl oleate maintained antioxidant potential up to the duodenum stage during the digestive process. Therefore, the synthesized natural compound presented a high potential to be applied in the food and pharmaceutical industries.

Natural 8-C-ascorbyl-(-)-epigallocatechin as antidiabetic agent: α-glucosidase and PTP-1B signaling pathway dual regulators.

α-Glucosidase and protein tyrosine phosphatase 1B (PTP1B) signaling pathway dual regulators decrease postprandial blood glucose levels and improve insulin sensitivity, making it a new treatment strategy for type 2 diabetes. This study examined in vitro antidiabetic activities of 8-C-ascorbyl-(-)-epigallocatechin (AE), found in oolong tea. AE inhibited α-glucosidase (IC50 = 142.8 µM) with activity higher than that of acarbose (IC50 = 250.2 µM). AE significantly promoted glucose-consumption and activated the insulin signaling pathway through enhancing the protein levels of p-GSK3ß and p-Akt and inhibiting the expression of PTP1B, along with slightly inhibitory activity against PTP1B. Docking analysis showed AE inhibited α-glucosidase activity via binding to the catalytic site through hydrogen bonds and Pi-Pi interactions, as well as a good shape match to the active pocket. In addition, AE could relieve oxidative damage and possessed good antioxidant capacity. Taken together, the results of this study indicate that AE exhibits antidiabetic activity in vitro, making it a potential functional food ingredient and drug candidate for management of type 2 diabetes.

Mechanism Study on Nanoparticle Negative Surface Charge Modification by Ascorbyl Palmitate and Its Improvement of Tumor Targeting Ability.

Surface charge polarity and density influence the immune clearance and cellular uptake of intravenously administered lipid nanoparticles (LNPs), thus determining the efficiency of their delivery to the target. Here, we modified the surface charge with ascorbyl palmitate (AsP) used as a negatively charged lipid. AsP-PC-LNPs were prepared by dispersion and ultrasonication of AsP and phosphatidylcholine (PC) composite films at various ratios. AsP inserted into the PC film with its polar head outward. The pKa for AsP was 4.34, and its ion form conferred the LNPs with negative surface charge. Zeta potentials were correlated with the amount and distribution of AsP on the LNPs surface. DSC, Raman and FTIR spectra, and molecular dynamics simulations disclosed that AsP distributed homogeneously in PC at 1−8% (w/w), and there were strong hydrogen bonds between the polar heads of AsP and PC (PO2−), which favored LNPs' stability. But at AsP:PC > 8% (w/w), the excessive AsP changed the interaction modes between AsP and PC. The AsP−PC composite films became inhomogeneous, and their phase transition behaviors and Raman and FTIR spectra were altered. Our results clarified the mechanism of surface charge modification by AsP and provided a rational use of AsP as a charged lipid to modify LNP surface properties in targeted drug delivery systems. Furthermore, AsP−PC composites were used as phospholipid-based biological membranes to prepare paclitaxel-loaded LNPs, which had stable surface negative charge, better tumor targeting and tumor inhibitory effects.

[Comparison of three α-glucosidases from different sources in the synthesis of L-ascorbic acid 2-glucoside].

L-ascorbic acid 2-glucoside (AA-2G) is a derivative of L-ascorbic acid (L-AA). Compared with L-AA, it has good stability and is easily decomposed by enzyme in the human body. α-Glucosidase (AG) was the first enzyme found capable of producing AA-2G. However, researches on this enzyme is still in infancy. We took AG derived from Aspergillus niger (AAG), Japanese rice (JrAG) and Rattus rattus (RAG), and compared their specific enzymatic activity and transglycosidation rate, with the aim to improve the synthesis of AA-2G by the transglycosidation of AG. The genes encoding these three different AG were cloned and expressed in engineered yeast. The conditions for the transglycosidation reaction of these three enzymes were optimized and the transglycosidation efficiency and yield of AA-2G under the optimized conditions were compared. The specific activity of AAG reached 1.0 U/mg, while the yield of AA-2G reached 153.1 mg/L with a transglycosidation rate of 0.5%. The specific activity of RAG reached 0.4 U/mg, while the yield of AA-2G reached 861.0 mg/L with a transglycosidation rate of 2.5%. JrAG showed the highest specific activity and transglycosidation rate. The enzyme specific activity of JrAG reached 1.9 U/mg, while the yield of AA-2G reached 2 577.2 mg/L with a transglycosidation rate of 7.6%, much higher than that of the other two glucosidases. JrAG may thus have potential to improve the synthesis of AA-2G.

Efficient dermal delivery of ascorbic acid 2-glucoside with photoacoustic waves.

OBJECTIVE: Ascorbic acid (i.e., vitamin C) is an important antioxidant present in skin. The protective role of vitamin C against photoaging motivated numerous attempts to promote its topical delivery, with a success limited by its chemical instability and poor skin permeability. Vitamin C precursors, such as ascorbic acid 2-glucoside (AA2G), which are metabolized to vitamin C by enzymes present in the skin, solve the problem of stability but are limited by low skin permeability. We developed a 2% (w/v) gel formulation of AA2G application (viscosity 4.30 × 104 Pa.s, pH 5.94) and compared its passive dermal delivery with the delivery promoted by photoacoustic waves that transiently perturb the skin barrier. METHODS: Photoacoustic (PA) waves were generated by laser pulses absorbed by piezophotonic (light-to-pressure) transducers. Pig skin samples were exposed to the 2% AA2G formulation alone or combined with 5 min of PA waves. One hour later, AA2G was extracted from the skin and quantified by reverse-phase HPLC. AA2G transdermal fluxes using Franz cells with 760 µm thick pig skin samples were also measured. RESULTS: Photoacoustic waves transiently enhanced skin permeability and increased dermal delivery of AA2G. AA2G was released from the formulation nearly quantitatively (92.6 ± 6.2%) in 24 h, showing a non-Fickian behaviour controlled by diffusion and swelling. AA2G dermal delivery with exposure for 5 min to PA waves was compared with passive delivery to pig skin. PA waves increased the delivery of AA2G to the skin by a factor of 15-fold with respect to passive delivery, as measured from skin extracts after 1 h of contact of the formulation with the skin. CONCLUSION: Five minutes of exposure to PA waves is a safe and effective method to deliver large quantities of AA2G to the skin.

OBJECTIF: L'acide ascorbique (c.-à-d. la vitamine C) est un antioxydant important présent dans la peau. Le rôle protecteur de la vitamine C contre le photovieillissement a motivé de nombreuses tentatives pour favoriser son administration topique, avec un succès limité par son instabilité chimique et sa mauvaise perméabilité cutanée. Les précurseurs de la vitamine C, tels que l'acide ascorbique 2-glucoside (AA2G), qui sont métabolisés en vitamine C par les enzymes présentes dans la peau, résolvent le problème de stabilité, mais sont limités par une faible perméabilité de la peau. Nous avons développé une formulation type gel à 2 % (p/v) d'AA2G (viscosité 4,30 × 104 Pa.s, pH 5,94) et comparé son administration dermique passive à l'administration favorisée par des ondes photoacoustiques qui perturbent transitoirement la barrière cutanée. MÉTHODES: Les ondes photoacoustiques (PA) ont été générées par des impulsions laser absorbées par des transducteurs piézophotoniques (lumière vers pression). Des échantillons de peau de porc ont été exposés à la formulation d'AA2G à 2 % seule ou associée à 5 min d'ondes PA. Une heure plus tard, l'AA2G a été extrait de la peau et quantifié par chromatographie en phase liquide à haute performance en phase inverse. Les flux transdermiques d'AA2G utilisant des cellules de Franz avec des échantillons de peau de porc épaisse de 760 µm ont également été mesurés. RÉSULTATS: Les ondes photoacoustiques ont amélioré transitoirement la perméabilité de la peau et augmenté l'administration dermique d'AA2G. L'AA2G a été libéré de la formulation presque quantitativement (92,6 ± 6,2 %) en 24 h, montrant un comportement non-Fickian contrôlé par diffusion et gonflement. L'administration cutanée d'AA2G avec une exposition de 5 min aux ondes PA a été comparée à l'administration passive sur peau de porc. Les ondes PA ont augmenté l'administration d'AA2G dans la peau d'un facteur de 15 concernant l'administration passive, mesurée à partir d'extraits cutanés après 1 h de contact de la formulation avec la peau. CONCLUSIONS: Cinq minutes d'exposition aux ondes PA est une méthode sûre et efficace pour administrer de grandes quantités d'AA2G dans la peau.

A ternary system of α-tocopherol with phosphatidylethanolamine and l-ascorbyl palmitate in bulk oils provides antioxidant synergy through stabilization and regeneration of α-tocopherol.

The stabilization of fats and oils against oxidative lipid deterioration is still a great challenge. The synergistic interaction between phospholipids, l-ascorbate, and tocopherols have not yet been comprehensively understood. The mechanism of the synergistic antioxidant effect of 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (PE) in mixtures with l-ascorbyl palmitate (AP) and α-tocopherol (α-Toc) was investigated in an ethyl linoleate model and sunflower oil at 110 °C. The mixture of PE, AP, and α-Toc is stabilized through continuous regeneration of α-Toc from its oxidation product α-tocopherylquinone (α-TQ). This reaction is catalyzed by acids and proceeded through the formation of the α-tocopherone ion (T+) as an intermediate product. In addition to the direct reduction of T+ by AP, PE can also cause regeneration indirectly by reacting with dehydroascorbyl palmitate (DHAP) or other tricarbonyl compounds to form amino reductones. PE and AP undergo an amino-carbonyl reaction to form the condensate PE(AP)2.