Long-term Release Research Articles

Remediation of petroleum-contaminated site soil by bioaugmentation with immobilized bacterial pellets stimulated by a controlled-release oxygen composite

Bioaugmentation techniques still show drawbacks in the cleanup of total petroleum hydrocarbons (TPHs) from petroleum-contaminated site soil. Herein, this study explored high-performance immobilized bacterial pellets (IBPs) embed Microbacterium oxydans with a high degrading capacity, and developed a controlled-release oxygen composite (CROC) that allows the efficient, long-term release of oxygen. Tests with four different microcosm incubations were performed to assess the effects of IBPs and CROC on the removal of TPHs from petroleum-contaminated site soil. The results showed that the addition of IBPs and/or CROC could significantly promote the remediation of TPHs in soil. A CROC only played a significant role in the degradation of TPHs in deep soil. The combined application of IBPs and CROC had the best effect on the remediation of deep soil, and the removal rate of TPHs reached 70%, which was much higher than that of nature attenuation (13.2%) and IBPs (43.0%) or CROC (31.9%) alone. In particular, the CROC could better promote the degradation of heavy distillate hydrocarbons (HFAs) in deep soil, and the degradation rates of HFAs increased from 6.6% to 33.2%–21.0% and 67.9%, respectively. In addition, the IBPs and CROC significantly enhanced the activity of dehydrogenase, catalase, and lipase in soil. Results of the enzyme activity were the same as that of TPH degradation. The combined application of IBPs and CROC not only increased the microbial abundance and diversity of soil, but also significantly enhanced the enrichment of potential TPH-biodegrading bacteria. M. oxydans was dominant in AP (bioaugmentation with addition of IBPs) and APO (bioaugmentation with the addition of IBPs and CROC) microcosms that added IBPs. Overall, the IBPs and CROC developed in this study provide a novel option for the combination of bioaugmentation and biostimulation for remediating organic pollutants in soil.

Estimating internal phosphorus loading for a water quality model using chemical characterisation of sediment phosphorus and contrasting oxygen conditions

The Finnish Archipelago Sea (AS) has long been subject to intensive anthropogenic phosphorus (P) loading. The area suffers from seasonal hypoxia and cyanobacterial blooms despite reductions in nutrient discharge from the catchment and point sources. Internal loading may even dominate the P budget. Previous estimates of internal P loading have limitations (e.g., in spatial coverage and infrequent measurements). We present the first area-wide estimates of the magnitude of internal P loading based on the long-term release of P stored in the sediments.Modelling the internal P loading in the AS is challenging due to the complexity of biogeochemical processes in the sediment-water interface, as well as the heterogenic topography of the seafloor. Instead, we calculated estimates of internal P loading based on data from previous studies on sequential chemical extraction of sediment P, sediment physical characteristics (e.g., organic content, location of muddy seabed substrates), and near-bottom oxygen (O2) conditions. The estimates in three scenarios of contrasting O2 conditions were based on potentially mobile P pools in the sediments, recycled from sediment to water (i.e., loosely-bound or exchangeable P, P bound to reducible iron oxy(hydr)oxides, and labile organic P). The potentially mobile P pools were determined by chemical extraction methods (modified from Psenner et al., 1984 and Ruttenberg, 1992). The internal P loading under presumable O2 conditions was estimated to be fivefold that of waterborne P input to the AS; comparable to previous estimates for hypoxic areas in the Baltic Sea.Our estimates revealed wide spatial variability in the internal P loading, depending on O2 conditions and seabed sediment substrate. The site-specific P release estimates are included in a water quality model used by regional authorities, which increases the model's reliability for estimating the impact of human activities on the water quality across the AS.

Constraint programming for reservoir operation optimization of Bhumibol dam

The modern constraint programming (CP) was adopted to minimize water scarcity and excessive water which are the critical issues in reservoir operation of Bhumibol Dam (BB) to solve consecutive droughts in the Chao Phraya River Basin (CPYRB), Thailand. The situations of the severe droughts have been frequently occurred in a broad area of CPYRB due to an extremely low rainfall leading to unusually low water levels and inflow in major reservoirs. Therefore, multi-objective optimization was conducted to characterize the actual operation and physical reservoir system of BB Dam. Two different CP models with seasonal and yearly constraints were manipulated using MiniZinc programming language and the constraint solver IPOPT to find the optimal daily release scheme from 2000 to 2018 of BB Dam. The potential of downstream flow conditions was also considered to partially supply downstream water demand and store savable water in a reservoir for subsequent use during possible future droughts. The results reveal that CP models can diminish some extent of yearly reservoir release, while daily long-term release scheme conforms well with the actual operation particularly during dry and wet seasons in specific drought years. These mean that amount of reservoir water of approximately 47.12–103.83 MCM/year can be saved and stored in reservoir for subsequent use in CPYRB when CP models are deployed. This results in a reservoir storage increase of 7.10–7.94% at the end of the wet season for seasonal and yearly CP models, respectively. When potential side flow is considered, the increase climbs up to 10.49%. This envisages the higher possibility of supplying reservoir water for agricultural water needs over the dry season in the Greater Chao Phraya Irrigation Scheme. As the potential hydraulic head is subject to increased reservoir water storage, therefore, the increase in hydropower production is definitely found of ranging from + 6.10% to + 13.79% by these two sorts of CP models. In addition, handling with huge volumes of flood and drought by CP models is well managed as the specific release constraints during refilled and drawdown periods are used to define the constraint satisfaction problem.

Comprehensive investigation of pollution levels and potential bioavailable risks of 7 potentially toxic elements in Qinghai-Tibet soils by using diffusive gradients in thin-films (DGT)

ABSTRACT Seven potentially toxic elements (PTEs) including Cr, Ni, Cd, Zn, Cu, Pb and As of soil samples from Qinghai-Tibet Plateau (QTP) were measured to assess the degree of contaminations. To have a comprehensive understanding of PTEs’ risks in QTP, the single-step nitric acid extraction and diffusive gradients in thin-films (DGT) technique were employed in this study for the determination of PTEs’ total amount as well as bioavailable content, respectively. Haibei state of Qinghai province was the most contaminated sites by PTEs. Behaviors of PTEs should be highly concerned as they can produce continuous bioavailable effects to ecological systems. High DGT concentrations of Zn and Cr showed their remarkable available risks in soils. In the environment with insufficient organic matter and slight pH variations, phosphorus level was the main contributor to affect the mobility of labile PTEs, especially for Pb and Ni. Concentration ratio between DGT measurement and soil solution and correlation analysis confirmed the high bioavailability of Pb, Zn and Cr, leading to short-term mixture effects on ecological systems, while the long-term release dynamics were found for As and Cu. Results from road-side and river-side soils of QTP evidenced the short-term bioavailable risks were possibly attributed to intensive anthropogenic activities including traveling industries and vehicle driving, whereas long-term bioavailable risks was from the natural transportation and deposition.

#2084 Biologic effect evaluation of de novo long-term release tacrolimus on metabolizer phenotype and T cell composition after kidney transplantation

Abstract Background and Aims Kidney transplantation (KTX) is the current treatment of choice in patients with kidney failure. Since immunosuppressive medication to prevent acute rejection is still needed in high doses with frequent adverse events, new strategies to achieve risk-appropriate personalization of immunosuppression are needed. Calcineurin inhibitors are the cornerstone of T cell suppression, currently available in different release formulations including once daily long-term release tacrolimus (LCPT) and regular twice daily immediate release tacrolimus (IRT). Little is known about the temporal evolution of tacrolimus metabolism potentially influencing T cell composition and clinical endpoints between different tacrolimus formulations after KTX. Method To evaluate the influence of de novo LCPT on clinical endpoints, metabolizer phenotype and immune cell composition after KTX, subgroup analysis of a single-center, prospective, observational cohort study including 32 patients started on LCPT (0.1 mg/kg) and 55 patients started on IRT (0.1 mg/kg) was conducted. Peripheral blood mononuclear cells were isolated from whole blood samples drawn before KTX, 2 months and 12 months after KTX for flow cytometry analysis. Study visits were simultaneously conducted to obtain tacrolimus dosing, plasma levels, acute rejection and infection incidence. Statistical analysis was done using GraphPad Prism (v10), accepting significance for p < 0.05, and flow cytometry analysis was done using FlowJo (v10) software. Results The cohort represented KTX recipients with a median age of 60 years and similar distributions of gender, HLA-mismatches and induction therapy. Clinical outcome data showed a trend towards lower acute rejection rate, lower serum-creatinine values and increased incidence of BK-viremia in LCPT treated patients. Rejection rate was associated with a fast-metabolizer phenotype (HR 3.9; 1.1-6.8, p < 0.01) and HLA mismatch > 3 (HR 4.0; 1.2-7.3, p < 0.01) while this effect was blunted in the LCPT group (HR 1.9; 0.7-3.2, p = 0.67 and HR 0.9; 0.3-1.4, p = 0.38 respectively) in a multivariate Cox-regression model. Cluster exploration and tSNE analysis of flow cytometry data revealed diminution of activated-proliferative effector and regulatory T cell trajectories, with significant reduction in cell counts of CD4+CD15s+/CD45RA-Ki67+Foxp3+ Treg and in CD4+CD147high/CD45RA-LAP+HLADR+FcRL3+ effector T cells in LCPT treated patients after KTX. Conclusion Induction with de novo LCPT was associated with a blunted influence of metabolizer phenotype and HLA-mismatch on acute rejection in our cohort. Major changes were detected in peripheral T cell composition after transplantation, with signs of a stronger immunosuppressive effect of LCPT on circulating activated T cells. Therefore, LCPT may be considered for KTX recipients with higher HLA-mismatch (i.e. “old-for-old”) or fast-metabolizer phenotype. Inclusion of changes in T cell composition as biologic effect measures may be worthwhile in future studies evaluating biomarkers to guide immunosuppression and predict complications after KTX.

Microencapsulation efficiency of fruit peel phytonutrient-based antimicrobial to mitigate rumen emission using in vitro fermentation technique

This research investigated the protecting properties of polyphenols and flavonoids in phytonutrient pellets formulated from lemongrass powder and mangosteen peel (LEMANGOS pellets) through the microencapsulation and named microencapsulated LEMANGOS (mLEMANGOS). For this purpose, the effects of mLEMANGOS supplementation at various R:C ratios of 60:40 and 20:80 were evaluated and compared with monensin (antibiotic) supplementation under an in vitro study technique. Treatments were randomly assigned in a 2 × 4 × 2 factorial arrangement in a completely randomised design consisting of factors A: R:C ratios (60:40 and 80:20), factor B: mLEMANGOS supplementation (0, 2, 4, and 6% DM), and factor C: monensin supplementation (0 and 20% DM). There was an interaction between the R:C ratio and both mLEMANGOS and monensin supplements on the in vitro gas production kinetics, ruminal by-product fermentation, methane production, and rumen microbial population (p < 0.001, 0.01, 0.05). Results indicated that each supplementation influenced the gas production kinetics, while there was decreased cumulative gas production in the mLEMANGOS supplemented. Consequently, the supplemented group buffered ruminal pH and increased the in vitro dry matter degradability (IVDMD) and ammonia nitrogen (NH3-N) concentrations. Moreover, the additional treatment of mLEMANGOS supplementation (6% DM at R:C ratios of 60:40 and 20:80) significantly reduced the number of Methanobacteriales to 53.5% and 50.4% after 24 h, respectively. Results from those supplements can reduce methane production to 99.2% and 97.9% (p < 0.001), respectively. This research suggests that phytonutrient-based antimicrobial in the mLEMANGOS supplement could potentially be used as ruminant feed additives and as antimicrobial substances. HIGHLIGHT Microencapsulated LEMANGOS was formulated by biopolymer using green technique to retain the phytonutrients and their long-term release. The mLEMANGOS supplementation (at 6% of total DM) can be used as a synthetic bio-antibiotic for inhibiting methanogens-archaea population. The mLEMANGOS supplementation (at 6% of total DM) can enhance rumen nutrients degradability, ruminal end-products, and mitigate methane production.

Study on the Long-Term Salt Release Characteristics of Self-Melting Ice Asphalt Mixtures and Their Impact on Pavement Performance.

Self-melting ice asphalt pavement materials inhibit pavement freezing and improve driving safety. This paper aims to study the long-term salt release characteristics of self-melting ice asphalt mixtures and the impact on pavement after complete salt release. Firstly, a method to accelerate the rapid release of salt based on the Los Angeles abrasion tester. Then, long-term salt release patterns were elucidated under the influence of deicing agent dosage, type of asphalt, and type of gradation. Finally, a quantitative analysis of the pavement performance after complete salt release is conducted. The results indicate that the release efficiency of the Los Angeles abrasion tester method has increased by 91 times compared to the magnetic stirrer immersion flushing method and by 114 times compared to the natural soaking method. The SBS-modified self-melting ice asphalt mixture possesses a longer duration of salt release, but the uniformity of salt release is inferior. Salt release duration is directly proportional to the dosage of deicing agents. SMA-13 self-melting ice asphalt mixture exhibits poorer uniformity in salt release. After complete salt release, high-temperature stability of self-melting ice asphalt mixtures decreased by 31.6%, low-temperature performance decreased by 15.4%, water stability decreased by 26.7%, and fatigue life decreased by 35.9%.

RETRACTED: In vitro and in vivo assessment of curcumin-quercetin loaded multi-layered 3D-nanofibroporous matrix prepared by solution blow-spinning for full-thickness burn wound healing

Burn wounds (BWs) cause impairment of native skin tissue and may cause significant microbial infections that demand immediate care. Curcumin (Cur) and quercetin (Que) exhibit antimicrobial, hemocompatibility, ROS-scavenging, and anti-inflammatory properties. However, its instability, water insolubility, and low biological fluid absorption render it challenging to sustain local Cur and Que doses at the wound site. Therefore, to combat these limitations, we employed blow-spinning and freeze-drying to develop a multi-layered, Cur/Que-loaded gelatin/chitosan/PCL (GCP-Q/C) nanofibroporous (NFP) matrix. Morphological analysis of the NFP-matrix using SEM revealed a well-formed multi-layered structure. The FTIR and XRD plots demonstrated dual-bioactive incorporation and scaffold polymer interaction. Additionally, the GCP-Q/C matrix displayed high porosity (82.7 ± 2.07 %), adequate pore size (∼121 μm), enhanced water-uptake ability (∼675 % within 24 h), and satisfactory biodegradation. The scaffolds with bioactives had a long-term release, increased antioxidant activity, and were more effective against gram-positive (S. aureus) and gram-negative (E. coli) bacteria than the unloaded scaffolds. The in vitro findings of GCP-Q/C scaffolds showed promoted L929 cell growth and hemocompatibility. Additionally, an in vivo full-thickness BW investigation found that an implanted GCP-Q/C matrix stimulates rapid recuperation and tissue regeneration. In accordance with the findings, the Gel/Ch/PCL-Que/Cur NFP-matrix could represent an effective wound-healing dressing for BWs.

Integration of metformin-loaded MIL-100(Fe) into hydrogel microneedles for prolonged regulation of blood glucose levels

The transdermal drug delivery based on microneedles (MNs) provides a suitable and painless self-administration for diabetic patients. In this work, the hydrogel-forming MNs were firstly fabricated using poly(vinyl alcohol) (PVA) and chitosan (CS) as matrix. A hypoglycemic drug, metformin (Met), had been loaded into MIL-100(Fe). Then, both of free Met and Met-loaded MIL-100(Fe) were integrated into hydrogel-forming MNs for regulation of blood glucose levels (BGLs) on diabetic rats. After penetrated into the skin, the free Met could be firstly released from MNs. Due to the absorption of interstitial fluid and subsequent release of loaded Met from MIL-100(Fe), leading to a sustainable and long-term drug release behaviors. A notable hypoglycemic effect and low risk of hypoglycemia could be obtained on diabetic rat models in vivo. The as-fabricated hydrogel-forming MNs expected to become a new type of transdermal drug delivery platform for transdermal delivery of high-dose drugs to form a long-term hypoglycemic effect.

Macrophage-mediated controlled release of cysteine protease inhibitor from PLGA-PEG/hydroxyapatite microspheres for targeting cathepsin S in Alzheimer’s disease

The cause of Alzheimer’s disease (AD) remains unknown; however, studies have indicated the increased expression of cathepsin S (CTSS) in AD brains. Cathepsin S acts as a β-secretase, prompting the release of amyloid-β peptides and stimulating microglial cell activation, causing microglial migration, and contributing to neuroinflammation and disease progression. In this study, CT001, an inhibitor of the cysteine protease CTSS, was encapsulated in poly(lactic-co-glycolic acid)-polyethylene glycol microspheres combined with hydroxyapatite microspheres (CPPMs/HAMs) to achieve a constant and long-term drug release for AD. The results showed that CPPMs/HAMs had a uniform diameter of approximately 1 μm, enabling macrophage endocytosis and facilitating sustained CT001 release into the bloodstream, ultimately reaching the brain for AD treatment. The developed CPPMs/HAMs demonstrated excellent anti-inflammatory properties and mitigated CTSS expression in an in vitro inflammation microglial model. Intramuscular administration of CPPMs/HAMs improved learning and memory in AD mice during behavioral assessments. Furthermore, CPPMs/HAMs reduced CTSS expression, amyloid-beta accumulation, and deposition in vivo. This study demonstrated the potential of CT001 delivered via CPPMs/HAMs as a promising approach for managing AD in patients.

Tunable Release of Ions from Graphene Oxide Laminates for Sustained Antibacterial Activity in a Biomimetic Environment.

Silver has long been recognized for its potent antimicrobial properties, but achieving a slow and longer-term delivery of silver ions presents significant challenges. Previous efforts to control silver ion dosages have struggled to sustain release for extended periods in biomimetic environments, especially in the presence of complex proteins.This challenge is underscored by the absence of technology for sustaining antimicrobial activity, especially in the context of orthopedic implants where long-term efficacy, extending beyond 7days, is essential. In this study, the tunable, slow, and longer-term release of silver ions from the two-dimensional (2D) nanocapillaries of graphene oxide (GO) laminates incorporated with silver ions (Ag-GO) for antimicrobial applications are successfully demonstrated. To closely mimic a physiologically relevant serum-based environment, a novel in vitro study model using 100% fetal bovine serum (FBS) is introduced as the test medium for microbiology, biocompatibility, and bioactivity studies. To emulate fluid circulation in a physiological environment, the in vitro studies are challenged with serum exchange protocols on different days. The findings show that the Ag-GO coating can sustainably release silver ions at a minimum dosage of 10µgcm-2day-1, providing an effective and sustained antimicrobial barrier for over ten days.

Hydrogel forming microneedles loaded with VEGF and Ritlecitinib/polyhydroxyalkanoates nanoparticles for mini-invasive androgenetic alopecia treatment

Androgenetic alopecia (AGA), the most prevalent clinical hair loss, lacks safe and effective treatments due to downregulated angiogenic genes and insufficient vascularization in the perifollicular microenvironment of the bald scalp in AGA patients. In this study, a hyaluronic acid (HA) based hydrogel-formed microneedle (MN) was designed, referred to as V-R-MNs, which was simultaneously loaded with vascular endothelial growth factor (VEGF) and the novel hair loss drug Ritlecitinib, the latter is encapsulated in slowly biodegradable polyhydroxyalkanoates (PHAs) nanoparticles (R-PHA NPs) for minimally invasive AGA treatment. The integration of HA based hydrogel alongside PHA nanoparticles significantly bolstered the mechanical characteristics of microneedles and enhanced skin penetration efficiency. Due to the biosafety, mechanical strength, and controlled degradation properties of HA hydrogel formed microneedles, V-R-MNs can effectively penetrate the skin's stratum corneum, facilitating the direct delivery of VEGF and Ritlecitinib in a minimally invasive, painless and long-term sustained release manner. V-R-MNs not only promoted angiogenesis and improve the immune microenvironment around the hair follicle to promote the proliferation and development of hair follicle cells, but also the application of MNs to the skin to produce certain mechanical stimulation could also promote angiogenesis. In comparison to the clinical drug minoxidil for AGA treatment, the hair regeneration effect of V-R-MN in AGA model mice is characterized by a rapid onset of the anagen phase, improved hair quality, and greater coverage. This introduces a new, clinically safer, and more efficient strategy for AGA treatment, and serving as a reference for the treatment of other related diseases.

Preparation of Liposome Gel by Calcium Cross-Linking Induces the Long-Term Release of DOX to Improve the Antitumor Effect.

Doxorubicin (DOX) is one of the most commonly used anticancer drugs; however, its clinical application is greatly limited due to its toxicity and chemotherapy resistance. The delivery of DOX by liposomes (Lipos) can improve the blood circulation time in vivo and reduce toxic side effects, but the drug's accumulation in the tumor is often insufficient for effective treatment. In this study, we present a calcium cross-linked liposome gel for the encapsulation of DOX, demonstrating its superior long-term release capabilities compared to conventional Lipos. By leveraging this enhanced long-term release, we can enhance drug accumulation within tumors, ultimately leading to improved antitumor efficacy. Lipos were prepared using the thin-film dispersion method in this study. We utilized the ion-responsiveness of glutathione-gelatin (GSH-GG) to form the gel outside the Lipos and named the nanoparticles coated with GSH-GG on the outside of Lipos as Lipos@GSH-GG. The average size of Lipos@GSH-GG was around 342.9 nm, with a negative charge of -25.6 mV. The in vitro experiments revealed that Lipos@GSH-GG exhibited excellent biocompatibility and slower drug release compared to conventional Lipos. Further analysis of cellular uptake and cytotoxicity demonstrated that Lipos@GSH-GG loading DOX (DOX&Lipos@GSH-GG) exhibited superior long-term release effects and lower toxic side effects compared to Lipos loading DOX (DOX&Lipos). Additionally, the findings regarding the long-term release effect in vivo and the tumor accumulation within tumor-bearing mice of Lipos@GSH-GG suggested that, compared to Lipos, it demonstrated superior long-term release capabilities and achieved greater drug accumulation within tumors. In vivo antitumor efficacy experiments showed that DOX&Lipos@GSH-GG demonstrated superior antitumor efficacy to DOX&Lipos. Our study highlights Lipos@GSH-GG as a promising nanocarrier with the potential to enhance efficacy and safety by means of long-term release effects and may offer an alternative approach for effective antitumor therapy in the future.

Intra-Articular Injection of PLGA/Polydopamine Core-Shell Nanoparticle Attenuates Osteoarthritis Progression.

Osteoarthritis (OA) is a common joint disease characterized by progressive cartilage degeneration. Unfortunately, currently available clinical drugs are mainly analgesics and cannot alleviate the development of OA. Kartogenin (KGN) has been found to promote the differentiation of bone marrow mesenchymal stem cells (BMSCs) into chondrocytes for the treatment of cartilage damage in early OA. However, KGN, as a small hydrophobic molecule, is rapidly cleared from the synovial fluid after intra-articular injection. This study synthesized a KGN-loaded nanocarrier based on PLGA/polydopamine core/shell structure to treat OA. The fluorescence signal of KGN@PLGA/PDA-PEG-E7 nanoparticles lasted for 4 weeks, ensuring long-term sustained release of KGN from a single intra-articular injection. In addition, the polyphenolic structure of PDA enables it to effectively scavenge reactive oxygen species, and the BMSC-targeting peptide E7 (EPLQLKM) endows KGN@PLGA/PDA-PEG-E7 NPs with an effective affinity for BMSCs. As a result, the KGN@PLGA/PDA-PEG-E7 nanoparticles could effectively induce cartilage in vitro and protect the cartilage and subchondral bone in a rat ACLT model. This therapeutic strategy could also be extended to the delivery of other drugs, targeting other tissues to treat joint diseases.

Deep CO2 release and the carbon budget of the central Apennines modulated by geodynamics

Recent studies increasingly recognize the importance of critical-zone weathering during mountain building for long-term CO2 drawdown and release. However, the focus on near-surface weathering reactions commonly does not account for CO2 emissions from the crust, which could outstrip CO2 drawdown where carbonates melt and decarbonize during subduction and metamorphism. We analyse water chemistry from streams in Italy’s central Apennines that cross a gradient in heat flow and crustal thickness with relatively constant climatic conditions. We quantify the balance of inorganic carbon fluxes from near-surface weathering processes, metamorphism and the melting of carbonates. We find that, at the regional scale, carbon emissions from crustal sources outpace near-surface fluxes by two orders of magnitude above a tear in the subducting slab characterized by heat flow greater than 150 mW m–2 and crustal thickness of less than 25 km. By contrast, weathering processes dominate the carbon budget where crustal thickness exceeds 40 km and heat flow is lower than 30 mW m–2. The observed variation in metamorphic fluxes is one to two orders of magnitude larger than that of weathering fluxes. We therefore suggest that geodynamic modulations of metamorphic melting and decarbonation reactions are an efficient process by which tectonics can regulate the inorganic carbon cycle.

Evidence for differential associations of distinct trait mindfulness facets with acute and chronic stress

Stress and stress-associated disease are considered the health epidemic of the 21st century. Interestingly, despite experiencing similar amounts of stress than those falling ill, some individuals are protected against the “wear and tear of daily life”. Based on the notion that mindfulness training strengthens stress resilience, we explored whether facets of trait mindfulness, prior to training intervention, are linked to acute psychosocial stress reactivity and chronic stress load. To assess different mindfulness facets, over 130 participants completed the Five Facet Mindfulness Questionnaire (FFMQ) and the Freiburg Mindfulness Inventory (FMI). For acute stress induction, a standardized psychosocial stress test was conducted. Subjective stress, sympathetic and parasympathetic activity, and levels of the hypothalamic-pituitary-adrenal axis end hormone cortisol were assessed repeatedly. Additionally, levels of hair cortisol and cortisone as indices of the long-term physiological stress load were collected. We found differential associations of different facets of mindfulness with subjective stress, cortisol, and hair cortisone levels. Specifically, the trait mindfulness facets FMI “Acceptance” and the ability to put one’s inner experience into words (FFMQ “Describing”) were associated with lower acute subjective and cortisol stress reactivity. Contrarily, monitoring-related trait mindfulness facets (FFMQ “Acting with Awareness” and “Observing”) were associated with higher acute cortisol and marginally higher long-term cortisone release. Our results suggest granularity of the mindfulness construct. In accordance with the “Monitor and Acceptance Theory”, especially acceptance-related traits buffered against stress, while monitoring-related traits seemed to be maladaptive in the context of stress. The current results give valuable guidance for the conceptualization of mindfulness-based interventions geared towards stress reduction.

Application of ultrasound-assisted compression and 3D-printing semi-solid extrusion techniques to the development of sustained-release drug delivery systems based on a novel biodegradable aliphatic copolyester

The purpose of this study was to investigate the ability of two advanced hot-processing technologies, Ultrasound-Assisted Compression (USAC) and 3D-printing Semi-solid Extrusion (SSE), to manufacture sustained-release drug delivery systems based on a novel biodegradable aliphatic copolyester. The copolymer was synthesized from ω-pentadecalactone (PDL), 1,4-cyclohexanedimethanol (CHDM) and dimethyl succinate (DMS) (monomer ratio PDL/CHDM/DMS 70/30/30) by enzymatic ring opening polymerization and two-step melt polycondensation processes and has a random microstructure, a high molecular weight (107,100 g mol−1) and a relatively low melting point (∼65 °C). The antibacterial agent metronidazole (MTZ) was chosen as model drug and binary physical mixtures copolymer:drug were prepared at 90:10 and 70:30 w/w ratios. Thermal analysis studies evidenced that the formulations could be processed below their degradation temperatures. Drug delivery devices with dense and meshed structures were manufactured using USAC and SSE techniques, respectively, with USAC devices exhibiting more reproducible physical properties than the SSE systems. Powder X-ray diffraction and scanning electron microscopy studies showed a partial sintering of the copolyester during USAC processing while MTZ remained mostly crystalline. In contrast, the copolymer melted and the drug underwent some amorphization when processed using SSE. In vitro drug release studies in phosphate buffer (pH 6.8) showed that, after an initial burst release of metronidazole, USAC and SSE devices exhibited a prolonged and/or sustained drug release over 20 days. The initial burst release was dependent on the manufacturing technique and the drug/polymer ratio, being minimized for SSE devices containing 10 wt% MTZ. The whole drug release profiles fitted well to the Peppas-Sahlin model, being drug diffusion the predominant release mechanism. After the burst release, the sustained release period of USAC and SSE devices containing 10 wt% MTZ showed a good fit to the zero-order kinetic model, with faster drug release from the SSE devices due to the larger surface area of their meshed structure. In conclusion, this work demonstrates that processing the aliphatic copolyester by both USAC and SSE technologies provides an attractive strategy to manufacture biodegradable drug delivery systems for long-term release of metronidazole.

The influence mechanism of environmental factors on DGT adsorbing sulfonamides and the migration between water and sediment

Obtaining the sulfonamides (SAs) concentrations in the water body and sediment bulk was a prerequisite to reveal their transport and partitioning behavior in sediment-water environments and accurately assess their ecological risk. In the present study, the influences of multifactor interactions on the performance of o-DGTs with XAD-18 binding gels were analyzed by central combination experiments and response surfaces analysis, in which the target compounds were 9 SAs. The results indicated that dissolved organic matter (DOM), pH, and suspended particulate matter (SS) had significant effects on the o-DGT sampling, whereas this o-DGT was independent of the ionic strength (IS). Concentning the composite influence of the four factors, the interaction between DOM and SS posed the most significant effect on all 9 SAs compounds. Subsequently, an o-DGT and DIFS model was applied to explore the SAs migration between the water-sediments interface. The difference between desorption rate (kb) and adsorption rates (kf) values suggested that the kinetics of SAs was dominated by adsorption. Moreover, the short-term sediment-water partitioning of SAs was clarified on the basis of distribution coefficient (Kdl) for the labile SAs, among which the sulfadiazine (SDZ) had the largest labile pool. The ability of sediments to release SAs to the liquid phase as a sink was determined by response time (Tc). Among the 9 SAs, the long-term release of soseulfamethoxypyridazine (SMP) from the solid phase of sediments would have a potential risk to the aquatic environment, to which more attention should be paid in the future.

Encapsulation and characterization of ω-3 medium- and long-chain triacylglycerols microencapsulated with different proteins as wall materials

In this study, ω-3 medium- and long-chain triacylglycerols (MLCTs) microcapsules with excellent performance were obtained using soy protein as the wall component to address the oxidation-related problems of MLCTs. Additionally, the effect of soy, whey, or pea proteins on microcapsules in terms of the changes in their structure and physicochemical properties was investigated. The results showed that the small particle size, low PDI (polydispersity index) and zeta potential, fast adsorption rate, and low interfacial tension of these protein-based samples fabricated through the O/W template method were conducive to maintaining the integrity of microcapsules during spray-drying. The microcapsules, characterized by a spherical shape, exhibited superior encapsulation efficiency of 94.56%, surpassing the findings of previous investigations. Overall, these microcapsules exhibited long-term storage stability and low controllable release rates, which could be utilized as carriers for liposoluble actives.

A dual dynamically cross-linked hydrogel promotes rheumatoid arthritis repair through ROS initiative regulation and microenvironment modulation-independent triptolide release

High oxidative stress and inflammatory cell infiltration are major causes of the persistent bone erosion and difficult tissue regeneration in rheumatoid arthritis (RA). Triptolide (TPL) has become a highly anticipated anti-rheumatic drug due to its excellent immunomodulatory and anti-inflammatory effects. However, the sudden drug accumulation caused by the binding of “stimulus-response” and “drug release” in a general smart delivery system is difficult to meet the shortcoming of extreme toxicity and the demand for long-term administration of TPL. Herein, we developed a dual dynamically cross-linked hydrogel (SPT@TPL), which demonstrated sensitive RA microenvironment regulation and microenvironment modulation-independent TPL release for 30 days. The abundant borate ester/tea polyphenol units in SPT@TPL possessed the capability to respond and regulate high reactive oxygen species (ROS) levels on-demand. Meanwhile, based on its dense dual crosslinked structure as well as the spontaneous healing behavior of numerous intermolecular hydrogen bonds formed after the breakage of borate ester, TPL could remain stable and slowly release under high ROS environments of RA, which dramatically reduced the risk of TPL exerting toxicity while maximized its long-term efficacy. Through the dual effects of ROS regulation and TPL sustained-release, SPT@TPL alleviated oxidative stress and reprogrammed macrophages into M2 phenotype, showing marked inhibition of inflammation and optimal regeneration of articular cartilage in RA rat model. In conclusion, this hydrogel platform with both microenvironment initiative regulation and TPL long-term sustained release provides a potential scheme for rheumatoid arthritis.