A sustainable matrix based on eucalyptol essential oil/sawdust was developed and applied on one-sided laminated plywood. This finish aims to serve as a eucalyptol odor slow release. Eucalyptol odor release was monitored with gas chromatography coupled with a flame ionization detector (GC – FID: Limits of Detection and Quantification of 0.70 g/m3 and 2.11 g/m3, respectively, and with linearity up to 18.6 g/m3). Measurement of the eucalyptol odor released was performed during a six-month period and it was found that the release followed a first-order exponential decay with a decay rate constant of 0.0169 per day. The half-life was determined to be of 48 days. The granulometry and particle size porosity of sawdust were analyzed by Scanning Electron Microscopy. Sawdust size fraction between 112 – 200 μm showed best eucalyptol absorption capacity with 1:3 masses ratio (sawdust:eucalyptol). The time capacity of eucalyptol release depends of composite eucalyptol – sawdust quantity. Where this relation was determined: 15.0 grams of composite eucalyptol-sawdust by 0.8 mm diameter aperture gave 6 months of eucalyptol release, that was considered very positive, understanding high volatility of eucalyptol and a small quantity of composite for further products. The new product is characterized by a carbon footprint (considering the industry frontiers) of 5.94 kg CO2eq/m2 of plywood floor.

This study investigated the effect of replacing part of the dietary soybean meal with either polymer-coated urea or gelatinized starch urea on the performance, nutrient digestibility, blood biochemical indexes, ruminal fermentation and rumen microflora of Angus heifers. The urea release profiles of two kinds of slow-release urea were evaluated in vitro and indicated a superior nitrogen retention with the polymer-coated urea. 210 purebred Angus cattle (BW = 314.26 kg) were divided into three groups: no urea group (CON), polymer-coated urea group (PCU), gelatinized starch urea group (GSU), 20g/kg polymer-coated urea or 25g/kg gelatinized starch urea was used to replace part of soybean meal in the concentrate feed respectively according to the principle of iso-metabolic energy and iso-nitrogenous. During the whole experiment, the ADG of PCU group was higher than both the GSU group and the CON group. The feed-weight ratio of the PCU group was significantly lower than both the GSU group and the CON group during the 90-day feeding period. The ADF apparent digestibility in the PCU group was significantly higher than that of the CON group, and extremely significantly higher than that of the GSU group. On the 86th day, the ALB content in the PCU group was significantly higher than that in the CON group. The contents of acetic acid and butyric acid, total volatile fatty acid and propionic acid were significantly higher in the PCU group than in the CON group. Bacterial diversity analysis found that the abundance of Firmicutes was higher in the PCU group than that in the GSU group and the CON group at the phylum level, and inverse result was observed in Bacteroidetes. The abundance of Paraprevotella was higher in the PCU group, whereas higher abundance of Prevotella was found in the GSU group at the genus level. These results indicate that both polymer-coated urea and gelatinized starch urea can replace part of soybean meal in the diet, and the amount of substitution in this trial had no diverse effect on the performance of Angus heifers, and the effect and economic benefits brought by polymer-coated urea were better than gelatinized starch urea.

In the drive towards environmental restoration and sustainable energy solutions, effective utilization and management of agricultural crop residues are vital to mitigate greenhouse gas (GHG) emissions and waste accumulation. Converting biogenic wastes into biofuels and bioproducts has the potential to tackle the energy crisis and contribute to environmental remediation. In this investigation, teff husk, primarily generated in Ethiopia during teff production within the agro-industrial sector, is used as the feedstock for the slow pyrolysis process. In Ethiopia, it is estimated that over 1.75 million tons of teff husk are generated annually, with a significant portion being incinerated in the fields, resulting in substantial environmental pollution. This study focuses on assessing teff husk as a potential material for slow pyrolysis, a crucial stage in biochar production, to tap into its biochar-producing potential. To determine the composition of the biomass, the teff-husk was initially analyzed by thermogravimetry. The significant presence of fixed carbon indicates that teff husk is a viable candidate for pyrolytic conversion into biochar particles. The process of slow pyrolysis took place at three varied temperatures—specifically, at 400, 450, and 500 °C. Process parameters of slow pyrolysis such as reaction time, temperature, and heating rate were enhanced to obtain maximum biochar yields. The highest biochar yield of 43.4 wt% was recorded at optimized reaction time, temperature, and heating rate of 120 min, 400 °C, and 4.2 °C/min, respectively. Furthermore, biochar's physicochemical, SEM-EDX, FTIR, and TGA characterization were performed. The thermal stability and carbon content of biochar were found to rise at higher temperatures. Unlike fuel recovery, the results suggest that teff-husk can be used as a feedstock for biochar production.

In this study, a slow-release urea fertilizer hydrogel was synthesized from hydroxyl propyl methyl cellulose, polyvinyl alcohol and glycerol blends with paper (blended paper) as second layer. The fertilizer hydrogel was characterized by SEM, XRD and FTIR. Its retention in sandy soil, swelling behavior in distilled and tap water as well as slow-release behavior to urea were investigated. The results indicated that the fertilizer had good slow-release properties and ability to retain water in soil. However, the addition of blended paper as a second layer matrix was found to help improve the release properties of the fertilizer. The swelling kinetic of the hydrogel followed the Schott’s Second order model. The release kinetics of urea in water was best described by the Zero order model signifying that the release behavior was independent of fertilizer concentration

The enterprise software sector is experiencing a significant transformation driven by rapid technological progress and evolving business needs. An effective release management process is crucial for the solution providers and customers, as they incorporate the principles of Industry 4.0 and 5.0. With the growing dependence on software solutions and services, ensuring their quality, reliability, and security is highly necessary. The release management process incorporates strategic planning, regression testing, accurate deployment, and continuous monitoring of software updates. However, the rapid advancements in artificial intelligence (AI) and machine learning (ML) create a unique challenge to the release management process. The existing research needs to address the necessary adaptations for Industry 5.0, mainly in product-based software organizations, to the release management process without a change management system. After working with several software solution stakeholders, based on the responses from SaaS project stakeholders, we have presented a revised software release readiness workflow by incorporating a change management module. The preliminary result based on data over a limited period of time indicates that the revised workflow has the potential to improve the management of slippage, particularly by more effectively addressing NFR-related issues, thereby resulting in more predictable and reliable release cycles.

The global usage of veterinary antibiotics is significant. These antibiotics can be released into the aquatic environment and exert toxic effects on non-target organisms. To explore the physiological effects of tetracycline antibiotics on aquatic life, the growth characteristics of and toxin release from the cyanobacterium Microcystis aeruginosa (M. aeruginosa) were studied. Results showed that the toxicity order of the three target antibiotics was TC (tetracycline) > CTC (chlortetracycline hydrochloride) > OTC (oxytetracycline) in terms of inhibition occurrence time and the EC₁₀ and EC₂₅ values. Further, the target antibiotics regulated the production of MC-LR (microcystin-LR) to different degrees. CTC destroyed the M. aeruginosa cells and resulted in a decreased MC-LR release but stimulated the ability to synthesise MC-LR. OTC had a relatively weaker toxicity compared with CTC, while TC was the most toxic among the three antibiotics. Therefore, TC is friendly to the aquatic environment because it simultaneously reduced the intracellular and extracellular MC-LR content. These results aid our understanding of the effects of tetracycline antibiotics on Microcystis aeruginosa, which is important for environmental evaluation and protection. These results are also helpful for guiding the application of veterinary antibiotics in agricultural settings.

We propose that a dietary reduction of Lipopolysaccharide (LPS) could reduce risk and slow the progression of cognitive decline and Alzheimer’s disease. LPS is a component of the highly inflammatory cell membrane of Gram-negative bacteria. The highest dietary sources of LPS are processed meat and dairy products, which can sharply raise plasma LPS within one to two hours. The LPS in these foods is packaged into chylomicrons, which enter the bloodstream. Smaller amounts of LPS from colonic microbiota do not account for the sharp postprandial increase of plasma LPS. Once in the bloodstream, LPS can trigger the release of inflammatory cytokines within three hours. LPS can increase cytokines via LPS binding protein and cluster of differentiation-14, triggering toll-like receptor-4, and activating nuclear factor kappa-B. Nuclear factor kappa-B can increase cytokine levels, including interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha. LPS and inflammatory cytokines are higher in Alzheimer’s disease, both in plasma and in the central nervous system. These cytokines can enter the brain via active transport and induce microglial activation and inflammatory damage in the brain, including loss of synapses and neurons. Elevated brain inflammation from dietary LPS can contribute to cognitive impairment and increased risk of dementia.

Adenoviruses (Ads) have been extensively manipulated for the development of cancer selective replication, leading to cancer cell death or oncolysis. Clinical studies using E1-modified oncolytic Ads have shown that this therapeutic platform was safe, but with limited efficacy, indicating the necessity of targeting other viral genes for manipulation. To improve the therapeutic efficacy of oncolytic Ads, we treated the entire Ad genome repeatedly with UV-light and have isolated AdUV which efficiently lyses cancer cells as reported previously [1]. In this report, we show that no mutations were observed in the early genes (E1 or E4) of AdUV while several mutations were observed within the Ad late genes which have structural or viral DNA packaging functions. This study also reported the increased release of AdUV from cancer cells. In this study, we found that AdUV inhibits tumor growth following intratumoral injection. These results indicate the potentially significant role of the viral late genes, in particular the DNA packaging genes, to enhance Ad oncolysis.

The objective of this study was to evaluate the efficacy of fungal treatment (Pleurotus ostreatus) of urea-treated rice stubble on growth performance in slow-growing goats. Eighteen crossbred Thai native x Anglo-Nubian male goats (average body weight: 20.4 ± 2.0 kg) were randomly assigned to three experimental total mixed rations containing 35% rice stubble (RS) that was either untreated (URS), urea treated (UTRS) or treated with urea and fungi (UFTRS). URS and UTRS were cultivated and harvested from aseptically fungal spawn, incubated at 25-30 °C for 25 days. Indicators of growth performance were monitored and faeces were collected quantitatively to assess nutrient digestibility, during a 12-week feeding trial. All goats remained healthy throughout experiment. The goats fed UFTRS had a lower feed conversion ratio (kg feed/kg growth) compared to goats fed URS or UTRS. Compared to URS, dietary UFTRS increased nutrient digestibility of slow-growing goats, such as OM (+8.5%), CP (+5.5%), NDF (+39.2%), and ADF (+27.4%). Likewise, dietary UFTRS tended to increase rumen ammonia concentrations but rumen pH and volatile fatty acids were not affected by UFTRS. In conclusion, the present study indicates that the fungal treatment of RS is an effective tool to improve the growth performance of slow-growing goats.

Extracellular vesicle (EV) release, which occurs in most eukaryotic cells, has recently been associated with peptidylarginine deiminase (PAD)-driven protein deimination. Evidence points to the involvement of deiminated cytoskeletal proteins and changes in histone deimination. Both PADs and EVs are associated with various pathologies including cancers, autoimmune and neurodegenerative diseases. The elevated PAD expression observed in cancers may contribute to increase in EV shedding observed from cancer cells, contributing to cancer progression. Similarly, elevated PAD expression observed in neurodegenerative diseases may cause increased EV shedding and spread of neurodegenerative EV cargo, contributing to disease progression and pathologies. Pharmacological inhibition of PAD-mediated deimination using pan-PAD inhibitor Cl-amidine, reduced cellular EV release in prostate cancer cells, rendering them significantly more susceptible to chemotherapeutic drugs. Studies on models of central nervous system damage have demonstrated critical functional roles for PADs and neuroprotective effects using PAD inhibitors in vivo, while human neurodegenerative iPSC in vitro models showed evidence of increased protein deimination. Besides using refined PAD inhibitors to selectively manipulate EV biogenesis for novel combination therapies in cancer treatment, we also speculate how EV biogenesis could be targeted via the newly identified PAD-pathway to ameliorate neurodegenerative disease progression.

Starting from the model of a slow-rolling missile with six degrees of freedom (6 DOF) in the body frame, a 6 DOF model in the Resal frame is obtained, which is used to linearize the coupled commanded motion. Based on the linearized model, we obtain the structural scheme of the commanded object and define the quality parameters. The obtained parameters have a complex representation (with real and imaginary parts) due to the coupling between longitudinal channels. Then, the kinematic guidance equations, the seeker equations and the actuator specific to the slow-rolling single-channel missile are defined using a switching function. The guidance kinematic equations, the seeker equations and the actuator model are linearized in the Resal frame, and the structural diagram of the homing missile is constructed. Starting from this, the characteristic polynomial having complex coefficients is determined and then analyzed with the Frank-Wall stability criterion. Based on the analysis, a stability range is determined for the navigation constant and a minimum and possibly a maximum limit for the time to hit the target is obtained. The stability range defined for the navigation constant on the linear model is finally validated on the nonlinear model in the body frame.

Management of chronic inflammation and wounds has always been a key issue in the pharmaceutical and healthcare sector. Curcumin (CCM) is an active ingredient extracted from turmeric rhizomes that has antioxidant, anti-inflammatory, and antibacterial activities, thus showing significant effectiveness toward wound healing. However, its shortcomings such as poor water solubility, poor chemical stability and fast metabolic rate limit its bioavailability and long-term use. In this context, hydrogels appear to be a versatile matrix for carrying and stabilizing drugs due to the biomimetic structure, soft porous microarchitecture, and pleasant biomechanical properties. The drug loading/releasing efficiencies can also be controlled by use of highly crystalline and porous metal organic frameworks (MOFs). Here, a flexible hydrogel composed of sodium alginate (SA) matrix and CCM-loaded MOFs was constructed for long-term drug release and antibacterial activity. The morphology and physicochemical properties of composite hydrogels were analyzed by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), ultraviolet visible spectroscopy (UV-Vis), Raman spectroscopy and mechanical property tests. The results showed that the composite hydrogel was highly twistable and bendable to mechanically comply with human skin. The as-prepared hydrogel could capture efficient CCM for slow drug release as well as effective killing of bacteria. Therefore, such composite hydrogel is expected to provide a new management system for chronic wound dressings.

Extensive evidence indicates that activation of P2X7 receptor (P2X7R), an ATP-gated ion channel highly expressed in immune and brain cells, is strictly associated with the release of extracellular vesicles. Through this process, P2X7R-expressing cells regulate non-classical protein secretion and transfer bioactive components to other cells, including misfolded proteins, participating in inflammatory and neurodegenerative diseases. In this review, we summarize and discuss the studies addressing the impact of P2X7R activation on extracellular vesicle release and their activities.

There is a need for alternatives or complements to synthetic fertilizers to enhance agricultural sustainability. Applying organic amendments can play a significant role in this. Insect droppings show high potential, though studies evaluating their agronomic value have only recently begun to emerge. This study compared black soldier fly (Hermetia illucens) and mealworm (Tenebrio molitor) larvae frass with another organic amendment (Nutrimais) derived from composting forestry, agro-industrial, and domestic waste. The experiment also included ammonium nitrate at two rates [the same as the organic amendments, 50 kg ha–1 nitrogen (N) (FullR), and half that rate (HalfR)] and an unfertilized control. The study spanned two growth cycles of lettuce (Lactuca sativa L.) grown in pots, followed by unfertilized oats (Avena sativa L.) to assess the residual effects of the fertilizing treatments. Mealworm larvae frass mineralized rapidly, with an apparent N recovery of 37.4% over the two lettuce growth cycles, indicating its high availability to soil heterotrophic microorganisms. The average dry matter yield (DMY) of lettuce was the highest among all treatments (12.8 and 9.8 g plant–1 in the first and second lettuce cycles), even compared to the FullR treatment (12.2 and 7.8 g plant–1), though without significant differences. Although mealworm larvae frass exhibited a high mineralization rate, the DMY cannot be attributed solely to N supply, as plants in the FullR treatment showed better N nutritional status. Mealworm larvae frass provided strong evidence of a plant biostimulant effect, not explained by the variables measured in this study. Black soldier fly larvae frass exhibited typical behavior of a moderately reactive organic amendment, while Nutrimais showed low reactivity, with a near-neutral mineralization/immobilization balance. The results suggest mealworm larvae frass is recommended for early maturing vegetable crops, whereas Nutrimais appears more suitable for perennial crops with low short-term nutrient requirements.

Purposely slow velocity resistance exercise (i.e., 10 s concentric and eccentric phases) is a popular training method, but limits the loads that can be lifted (e.g., <50% 1 RM). This study compared the biomechanical properties of purposely slow velocity (SLOW) and traditional resistance exercise (TRAD) that uses maximal lifting velocities. Healthy resistance-trained men (n=5) performed two testing sessions (barbell squat and bench press) in random-order; a SLOW session (1 set x 10 repetitions at 28% 1 RM, 10 s concentric & eccentric), and a TRAD session (3 x 10 at 70% 1 RM, controlled eccentric and maximal concentric). A force plate and linear position transducer were used to collect kinetic and kinematic data for every repetition of both protocols (α = 0.05). For both exercises, both concentric and eccentric mean force (N) and power (W) for each repetition was greater for TRAD. When the entire training session (squat + bench press) was examined, SLOW exhibited greater time under tension, while TRAD produced greater work (J) and impulse (N·s). Contrary to suggestions in both the lay and scientific literature, purposely slow resistance exercise produced less force, power, and work than traditional velocity resistance exercise.

In this nano era, nanomaterials and nanostructures are popular in developing novel functional materials. However, the combinations of nanoproducts with materials at micro and macro scale can open new routes for conceiving novel materials with an improved or even new functional performances. In this study, a brand-new hybrid, containing both nanofibers and particles having a microsize, was fabricated using a sequential electrohydrodynamic atomization (EHDA) process. Firstly, the microparticles loaded with drug (berberine hydrochloride, BH) molecules in the cellulose acetate (CA) were fabricated using a solution electrospraying process. Later, these microparticles were suspended into a co-dissolved solution containned BH and a hydrophilic polymer (polypyrrolidone, PVP), and were co-electrospun into the nanofiber/microparticle hybrids. The EHDA processes were clearly recorded, and the resultant products showed a typical hybrid topography, with microparticles distributed all over the nanofibers, which was demonstrated by SEM assessments. FTIR and XRD demonstrated that the components within the hybrids were presented in an amorphous state and have fine compatibility with each other. In vitro dissolution tests verified that the hybrids were able to provide the designed dula-step drug release profiles, a combination of the fast release step of BH from the hydrophilic PVP nanofibers through an erosion mechanism and the sustained release step of BH from the insoluble CA microparticles via a typical Fickian diffusion mechanism. The present protocols pave a new way for developing trans-scale functional materials.

In the contest of childhood epilepsies, the concept of continuous spike-waves during slow sleep (CSWS) includes several childhood-onset heterogeneous conditions, sharing an electroencephalogram (EEG) characterized by a high frequency of paroxysmal abnormalities during sleep which are attributed negative effects on the cognitive development and behavior of the child. These negative effects may have the characteristics of a clear regression or of a slowdown in development. Seizures are very often present, but not constantly. The above makes it clear why CSWS have been included in epileptic encephalopathies, in which by definition the frequent EEG paroxysmal abnormalities have an unfavorable impact on the cognitive functions, including socio-communicative skills causing autistic features, even regardless of the presence of clinically overt seizures. Although several decades have passed since the original descriptions of the electroclinical condition of CSWS, there are still many areas that are little known and deserve to be further studied, including the EEG diagnostic criteria, the most effective electrophysiological parameter for monitoring the evolution, the role of the thalamus in the CSWS pathogenesis, the long-term evolution, the nosographic location of Landau-Kleffner syndrome, the standardized neuropsychological and behavioral assessment, the pharmacological and non-pharmacological therapies.

The flow field around a straight chain of multiple slip spherical particles rotating steadily in an incompressible Newtonian fluid about their line of centers is analyzed at low Reynolds numbers. The particles may vary in radius, slip coefficient, and angular velocity, and they are permitted to be unevenly spaced. Through the use of a boundary collocation method, the Stokes equation governing the fluid flow is solved semi-analytically. The interaction effects among the particles are found to be noteworthy under appropriate conditions. For the rotation of two spheres, our collocation results for their hydrodynamic torques are in good agreement with the analytical asymptotic solution in the literature obtained by using a method of twin multipole expansions. For the rotation of three spheres, the particle interaction effect indicates that the existence of the third particle can influence the torques exerted on the other two particles noticeably. The interaction effect is stronger on the smaller or less slippery particles than on the larger or more slippery ones. Torque results for the rotation of chains of many particles visibly show the shielding effect among the particles.

Bionic robotic hand can perform many movements similar to human hand. But there is still a significant gap in manipulation between robot and human hand. It is necessary to understand the finger kinematics and motion patterns of human hand to improve the performance of robotic hand. This study aimed to comprehensively investigate normal hand motion patterns by evaluating the kinematics of hand grip and release in healthy individuals. The data corresponding to rapid grip and release were collected from the dominant hand of 22 healthy people by sensory glove. The kinematics of 14 finger joints were analyzed, including the dynamic range of motion (ROM), peak velocity, joint sequence and finger sequence. The results show that the proximal interphalangeal (PIP) joint had a largest dynamic ROM than metacarpophalangeal (MCP) and distal interphalangeal (DIP) joints. Besides, the PIP joint had the highest peak velocity, both in flexion and extension. For joint sequence, the PIP joint moved prior to the DIP or MCP joints during flexion, while extension started in DIP or MCP joints, followed by PIP joint. Regarding the finger sequence, the thumb started to move before four fingers, and stopped moving after the fingers during both grip and release. This study explored the normal motion patterns in hand grip and release, which provided kinematic reference for the design of robotic hand and thus contribute to its development.

The aim of this paper was to determine the soil phosphorus release risk from drained and re-wetted peatlands under different landcovers. The study was carried out at 10 soil profiles (organic soils, frequently with mursh in the topsoil, developed from low peat with various degrees of decomposition, on mineral subsoil or gyttja) located south-west of Lake Kośno nature reserve in northern-central Europe (north-eastern Poland). The soil samples were collected from the depths of 0-30 cm, 50-80 cm and 100-130 cm during spring, summer and autumn (in April, July, and October). In the laboratory, the following soil properties were determined: ash content, soil reaction, content of total organic carbon, total nitrogen, total and plant-available phosphorus. Gyttja formations and hemic peats had the highest total P content (6.77 g∙kg-1 and 2.29 g∙kg-1, respectively). Murshes contained twice less P (1.18 g∙kg-1). In spring, more plant-available phosphorus (AP sp) was released in murshes (0.29 g∙kg-1) than in peats (0.07-0.14 g∙kg-1). In the summer, higher amounts of plant-available P were stated in fiber peats (0.37 g∙kg-1) than in murshes (0.26 g∙kg-1), whereas in autumn, the amounts of P in murshes (0.22 g∙kg-1) and peats (0.21-0.23 g∙kg-1) did not vary. Generally, average contents of AP were the highest in murshes (0.26 g∙kg-1) and fiber peats (0.25 g∙kg-1), and the lowest in sapric peats (0.15 g∙kg-1). The release of phosphorus from organic compounds or binding of P by organic matter (immobilization) depends on the C:P ratio in plant residues and soil. If it is wide (&gt;300), P is bound, if it is narrower (150–200), P is released. In the tested soil formations, the C:P ratio was frequently above 300. Only in some murshes and gyttjas the C:P ratio was below 150, which may indicate a risk of phosphorus release to groundwaters.

Renewable resources gain increasing interest as source for environmentally benign biomaterials, such as drug encapsulation/release compounds, and scaffolds for tissue engineering in regenerative medicine. Being the second largest naturally abundant polymer, the interest in lignin valorization for biomedical utilization is rapidly growing. Depending on resource and isolation procedure, lignin shows specific antioxidant and antimicrobial activity. Today, efforts in research and industry are directed toward lignin utilization as renewable macromolecular building block for the preparation of polymeric drug encapsulation and scaffold materials. Within the last five years, remarkable progress has been made in isolation, functionalization and modification of lignin and lignin-derived compounds. However, literature so far mainly focuses lignin-derived fuels, lubricants and resins. The purpose of this review is to summarize the current state of the art and to highlight the most important results in the field of lignin-based materials for potential use in biomedicine (reported in 2014–2018). Special focus is drawn on lignin-derived nanomaterials for drug encapsulation and release as well as lignin hybrid materials used as scaffolds for guided bone regeneration in stem cell-based therapies.

In bovine embryos, microRNA (miRNA) expression has been profiled at each stage of early development in-vitro. miRNAomic analysis of spent media has the potential to reveal characteristics of embryo health, however, applications are limited without categorizing miRNA profiles by embryo quality. Time-lapse imaging has shown the timing of embryo development in-vitro may be indicative of their developmental potential. The aim of the study was to profile miRNAs in the spent media of slow and fast-growing bovine embryos throughout the pre-implantation period. Bovine cumulus-oocyte-complexes were aspirated from ovaries, fertilized, and cultured to blastocyst stage of development. At 2-cell, 8-cell, and blastocyst stage, each microdrop of 30 presumptive-zygotes were classified as slow or fast-growing based on the percentage of embryos that had reached the desired morphological stage. Following hybridization on a GeneChip miRNA 4.0 array, comparative analysis was conducted between spent media of slow and fast-growing embryos. In total, 34 differentially expressed miRNAs were identified between the comparison groups, with 14 of the miRNAs detected in the 2-cell samples, 7 miRNAs detected in the 8-cell samples, and 12 miRNAs detected in the blastocyst samples. The results demonstrate distinct miRNAs populations can be identified between slow and fast-growing embryos, highlighting novel biomarkers of developmental potential at each stage of pre-implantation development.

Our previous retrospective observational study demonstrated the safety of laparoscopically assisted subtotal colectomy with ileorectal anastomosis and preservation of the superior rectal artery (SRA), without instances of leakage, in patients with slow-transit constipation (STC). Thus, we extended the enrollment period and enlarged the sample size to detect the differences in the post-operative complications, and surgical and functional outcomes between patients who underwent laparoscopically assisted subtotal colectomy with and without SRA preservation. We conducted a retrospective single-center analysis of patients with STC who underwent laparoscopically assisted subtotal colectomy between 2016 and 2020. The diagnosis of STC was based on the colonic transit and anal functional tests, and barium enema to exclude secondary causes. Patients were divided into group A that underwent surgery with SRA preservation, and group B that underwent ligation of the SRA during surgery. Outcome assessments for both groups included the incidence of anastomotic breakdown, intraoperative complications, length of hospital stay, estimated blood loss, time to first flatus, and complications. Propensity-score matching allocated 34 patients to groups A and B each. Postoperative bowel function, including time to first flatus, stool, and oral intake, recovered better in group A than that in group B. Anastomotic leakage, a significant postoperative complication, was less frequent in patients with SRA preservation. Preservation of the SRA in patients undergoing laparoscopically assisted subtotal colectomy with ileorectal anastomosis for STC is associated with favorable postoperative bowel function recovery and lower anastomotic leakage rates.

Mosquitoes carrying endosymbiotic bacteria called Wolbachia are being released in mosquito and arbovirus control programs around the world. Open field releases of Wolbachia-infected male mosquitoes have achieved over 95% population suppression, while the replacement of populations with Wolbachia-infected females is self-sustaining and can greatly reduce local dengue transmission. Despite many successful interventions, significant questions and challenges lie ahead. Wolbachia, viruses and their mosquito hosts can evolve, leading to uncertainty around the long-term effectiveness of a given Wolbachia strain, while few ecological impacts of Wolbachia releases have been explored. Wolbachia strains are diverse and the choice of strain to release should be made carefully, taking environmental conditions and the release objective into account. Mosquito quality control, thoughtful community awareness programs and long-term monitoring of populations are essential for all types of Wolbachia intervention. Releases of Wolbachia-infected mosquitoes show great promise, but existing control measures remain an important way to reduce the burden of mosquito-borne disease.

Sustained-release drug delivery systems have evolved significantly over the years, playing a pivotal role in pharmaceutical research and enhancing patient care [1]. This abstract synthesizes key insights from various references to highlight the noteworthy advancements in this field. Recent research has emphasized the importance of understanding drug properties and their impact on sustained-release system design [2] [9]. These advancements enable tailoring drug delivery to optimize therapeutic outcomes [2] [9]. Incorporating innovative technologies such as nanotechnology [1], biodegradable polymers [3], and matrix systems [4] has led to the development of more efficient and patient-friendly sustained-release systems [1] [3] [4] Moreover, the concept of personalized medicine is gaining prominence [5], opening doors to individualized drug delivery strategies [5]. These strategies promise to enhance treatment efficacy while minimizing adverse effects [5]. Theoretical analyses, as exemplified by Higuchi’s work [6], continue to shape the understanding of sustained-release mechanisms [6]. Furthermore, studies on enteric-coated timed-release tablets [10]. highlight advancements in specific drug formulations to meet patient needs [10]. In conclusion, advancements in sustained-release drug delivery systems reflect a dynamic landscape where drug properties, innovative technologies, and personalized approaches converge to improve patient outcomes and drug therapy [7] [8] [10].

Information and communication technologies play an increasingly important role in the process of acquiring knowledge from a territory and managing it at different scales. ICTs allow a rapid diffusion of data not only through institutional channels but also through social networks where the smart community share experiences and perceptions. In this sense, ICTs become strategic to support the promotion of sustainable tourism development of territories. An important tool to implement it, can be a circular smart dashboard, a decision support system in which the digital data are organized and processed to produce an information output, to be used, after the evaluation by the decision makers, as a new input for the system. The present paper deals with a wider research the authors are involved in, related to the reconversion and valorization of a former mining area towards slow tourism, as the Santa Barbara Walk (SBW), an ancient mining route in the Sulcis Iglesiente area (Sardinia, Italy) . In particular, we here focus on the design proposal of a dashboard, capable of organizing information concerning the main features of the walk, in order to facilitate a shared governance for an effective tourism promotion. The paper is based on a thorough recognition of the main characteristics of the Walk, both the material ones and the digital, immaterial ones. The SBW represents in fact a network connecting the main points of interest along the Walk. On the contrary, its digital network – consisting of intangible infrastructure and flows - is however fragmented in terms of policies and contents Also a state of disorganization in slow tourism promotion activities can be observed. The goal of this paper is to present and analysis of the area, and to propose an evaluation and planning tool as the design of a circular dashboard of the SBW.

Empirical models help us understand the process of plant residue decomposition and nutrient release into the soil. The objective of this study was to determine an appropriate model to describe the decomposition of hairy vetch (Vicia villosa Roth) and cereal rye (Secale cereale L.) cover crop (CC) residue and nitrogen (N) release. Data pertaining to above and belowground CC residue mass loss and N release for up to 2633 cumulative decomposition degree days (112 d) after litterbag installation were obtained from two cropping system experiments, one conducted in 2015 and the other in 2017 and 2018 at the humid subtropical environment of southern IL, USA. Six exponential and two hyperbolic models were fit to percent mass and N remaining data to find the one with minimum Akaike Information Criterion (AIC) and residual sum of squares. Modified three-parameter single exponential and two- or three-parameter hyperbolic models best met the assumed criteria of selection for above and belowground CC residue, respectively. Fitting a double exponential model to a combined data for percent mass and N remaining, which identified two mass and N pools, a fast and a slow pool with different rate constants. A five-parameter double exponential with an asymptote met the preset criteria and passed all tests for normally distributed population, constant variance, and independence of residuals at α = 0.05 when fit to combined data of hairy vetch shoot mass and N remaining. However, a two-parameter hyperbolic and three-parameter asymptotic hyperbolic model provided the best fit to a combined data of cereal rye shoot mass and N remaining, respectively. Both hyperbolic decay models showed a good fit for belowground mass decomposition and N release for both CCs. Cereal rye had poorer fit than hairy vetch for mass and N remaining of both above and belowground mass. The best-selected decay models can be used to estimate the decomposition and N release rates of hairy vetch and cereal rye above and belowground residue in a similar environment.

The pyrolysis process has emerged as an attractive option for waste treatment. In this technology, inorganic compounds play catalytic effects in the pyrolytic reaction of organic materials, increa-sing the char's yield, porosity, and physicochemical properties. The present research investigates and compares the slow pyrolysis of spent coffee grounds (SCG) using potassium hydroxide (KOH) (weight ratio of 1:1) and landfill leachate membrane concentrate (LLMC) residue (weight ratio of 1:1) as pyrolitic additives. We hypothesized that the high content of alkali and alkaline earth metals in LLMC could enhance the yield or improve the quality of the carbon-based material produced in pyrolysis. This strategy could be a sustainable alternative for valorizing SCG and landfill wastes, replacing catalyzing agents such as steam, CO2, and chemical additives used on an industrial scale. The char yields in slow pyrolysis ranged from 18 to 24%. The SCG had a low specific surface area (4.5 m2 g-1), contrasting with the notable surface areas observed in both ac-tivated chars. In particular, the KOH-activated char displayed a higher surface area than the LLMC-activated char (1960 vs. 1130 m2 g-1). On the other hand, the combustion enthalpy of the LLMC-activated material was estimated at 22 MJ kg-1. This value was 22% higher than the energy enthalpy of SCG and KOH-activated char used for comparison. Our findings confirm that pyrolysis of SCG with KOH produces a microporous material with a high specific surface area. In contrast, the resulting LLMC-activated char demonstrates a higher calorific value. Our findings could contribute to establishing potential industrial applications for SCG and LLMC residues to produce energy and high-value materials.

Severe cancer pain significantly diminishes patients' quality of life, leading to increased reliance on caregivers. Although opioid analgesics are effective, they may induce opioid-induced bowel dysfunction (OIBD) with symptoms such as nausea, vomiting, drowsiness, and constipation. While controlled-release oxycodone is a viable option, its prolonged use can lead to opi-oid-induced constipation (OIC). Addressing this, a relative novel formulation - a fixed 2:1 ratio of oxycodone and naloxone in prolonged release - aims to provide analgesia while alleviating OIC. This review critically assesses the evidence on the efficacy, safety, and patient experience of ox-ycodone/naloxone prolonged release in managing severe cancer pain, emphasizing the necessity for a targeted approach in this patient population.

Introduction: Established predictors for COVID-19 related mortalities are diverse, with cytokine release syndrome (CRS), a key intermediator to the case fatalities being dominant and multi-faceted. The impact of these several risk factors on coronavirus mortality have been previously reported in several meta‐analyses limited by small sample sizes and premature data, and CRS not fully being accounted for. The objective of this systematic review and meta-analysis was to evaluate the evidence on the risk of COVID-19 related CRS and mortality with HIV serostatus using published data, and a meta-regression to account for possible covariates. Method: Electronic databases including Google Scholar, Cochrane Library, Web of Sciences (WOS), EMBASE, Medline/PubMed, COVID-19 Research Database, and Scopus, were systematically searched till 30th February, 2022. All human studies were included irrespective of publication date or region. Twenty-two studies with a total of 19,783,097 patients detailing COVID-related mortality and eleven with a total of 2,005,274 were included. To pool the estimate, a random-effects model with risk ration as the effect measure was used. Moreover, publication bias and sensitivity analysis were evaluated followed by meta-regression. The trial was registered (CRD42021264761) on the PROSPERO register. Results: The findings were consistent in stating the contribution of HIV infection for COVID-19 related CRS and mortality. The cumulative COVID-19 related mortality and CRS was 110270 (0.6%) and 48863 (2.4%) with total events of 2010 (3.6%), 108260 (0.5%) and 837(4.6%), 48026 (2.4%) among HIV-positive and negative persons respectively. HIV infection showed an increased risk of COVID-19 related CRS and mortality [RR= 1.48, 95% CI (1.16, 1.88) (P=0.002)] and [RR =1.19, 95% CI (1.02 -1.39) (P=0.00001)] respectively, both with substantial heterogeneity (I² > 80%). The true effects size in 95% of all the comparable populations fell between 0.64 to 2.22 and 0.67 to 3.29 for mortality and CRS respectively. MC studies and COVID-19 mortality with HIV infection showed a significant association [RR = 1.305, 95% CI (1.092 -1.559) (P = 0.003)], similar to studies conducted in America (RR = 1.422, 95% CI 1.233–1.639) and South Africa (RR = 1.123, 95% CI 1.052–1.198). HIV infection showed a risk for ICU admission [(P=0.00001) (I² = 0%)] and mechanical ventilation [(P=0.04) (I² = 0%)] as parameters of CRS. Furthermore, risk of COVID-19 related CRS is influenced by the year a study was conducted (R² = 0.55) and the region (R² = 0.11) same for mortality (R² = 0.60). The variance proportion explained by covariates was significant for CRS (I² = 86.5%, Q = 73.99, df = 10, P = 0.0000) (R² = 0.78) and mortality (I² = 87.5%, Q = 168.02, df = 21, p = 0.0000) (R² = 0.67). Conclusion: Our updated meta-analysis indicated that HIV infection was significantly associated with an increased risk for both COVID-19 – CRS and mortality, which might be modulated by regions, study setting and year. Risk for ICU admission and mechanical ventilation are the key indicators of CRS. We believe the updated data further anchoring CRS will contribute to more substantiation of the findings reported by similar earlier studies (Dong et al., 2021; K. W. Lee et al., 2021; Massarvva, 2021; Mellor et al., 2021; Ssentongo et al., 2021)

Zero-rate output (ZRO) drift induces deteriorated micro-electromechanical system (MEMS) gy-roscope performances, severely limiting its practical applications. Hence, it is vital to explore an effective method toward ZRO drift reduction. In this work, we conduct an elaborate investigation on the impacts of the internal and packaging stresses on the ZRO drift at the thermal start-up stage, and propose a temperature-induced stress release method to reduce the duration and magnitude of ZRO drift. Self-developed high-Q dual mass tuning fork gyroscopes (TFGs) are adopted to study the correlations between temperature, frequency and ZRO drift. Furthermore, a rigorous finite element simulation model is built based on the actual device and packaging structure, revealing the temperature and stresses distribution inside TFGs. Meanwhile, the relationship between temperature and stresses are deeply explored. Moreover, we introduce a temperature-induced stress release process to generate thermal stresses and reduce the temperature-related device sensitivity. By this way, the ZRO drift duration is drastically reduced from ~2000 s to ~890 s, and the drift magnitude decreases from ~0.4 °/s to ~0.23 °/s. This stress release method achieves a small bias instability (BI) of 7.903 °/h and a low angle random walk (ARW) of 0.792 °/√h, and the long-term bias performance is significantly improved.

The calculation of the release of liquid hazardous chemicals storage tanks is an important part of the quantitative risk assessment of accidents. This paper mainly establishes a continuous real–time release model based on the instantaneous mass flow Q_m model. Meanwhile, the software function module was analyzed, and programming software was developed using C# language for model solving. A series of experiments for repeated leakage tests was designed and the discharges through three small holes with different heights for 200 s were observed. The results show that the continuous real–time leakage model is effective, and the deviation between theoretical and experimental release amounts are within a reasonable range. The higher the liquid level above the leak hole is, and the smaller the height of the leak hole from the ground is, the greater the flow rate at the leak orifice is and the smaller discharge rate change is. Therefore, the deviation between the theoretical release amount M_t and the experimental average release amount Ma is greater while the height of the leak hole from the ground is smaller, which indicates that the smaller the distance from the leak orifice to the ground, the greater the influence of the empirical discharge coefficient C₀ on the release amount M.

The central nervous system (CNS) controls movements and regulates joint stiffness with muscle coactivation, but until now few studies have examined muscle pairs during running. This study aims to investigate differences in lower limb muscle coactivation during gait at different speeds from walking to running. Nineteen healthy runners walked and ran at speeds ranging from 0.8 km/h to 9.3 km/h. Twelve lower limb muscles' coactivation was calculated using the time-varying multi-muscle coactivation function (TMCf) with global, flexor-extension, and rostro-caudal approaches. Spatiotemporal and kinematic parameters were also measured. We found that TMCf, spatiotemporal and kinematic parameters were significantly affected by gait speed for all approaches. Significant differences were observed in the main parameters of each coactivation approach, and in the spatiotemporal, and kinematic parameters at the transition between walking and running. Positive and negative strong correlations were found between global coactivation parameters and center of mass displacements, as well as some spatiotemporal parameters, regardless of gait speed. Our findings suggest that walking and running have different coactivation patterns and kinematic characteristics, with the whole-limb stiffness exerted more synchronously and stably in running. The coactivation indexes and kinematic parameters could be the result of global coactivation, which is a sensory-control integration process used by the CNS to deal with more demanding and potentially unstable tasks like running.

Extracellular vesicles (EVs), such as exosomes or oncosomes are released with molecules unfavorable for survival from cells. In addition, accumulating evidence has shown that tumor cells often eject anti-cancer drugs such as chemotherapeutics and targeted drugs within EVs, a novel mechanism of drug resistance. The EV-releasing, drug resistance phenotype is often coupled with cellular dedifferentiation and transformation, cells undergoing epithelial-mesenchymal transition (EMT) and taking on a cancer stem cell phenotype. Recent studies have shown that the release of EVs is also involved in immunosuppression. The concept of the resistance-associated secretory phenotype (RASP) is reviewed herein.

Plasmonic nanocomposites have the ability to enhance light-matter interaction due to the 1 plasmonic effects leading to promising potential applications. In this paper, we theoretically study the 2 group index of the silver nanoparticle-gold nanoparticle-quantum dot plasmonic hybrid system in 3 the optical region of the electromagnetic spectrum using the density matrix approach. The quantum 4 dot is considered to be a three-level atomic system of a lambda configuration, interacting with strong 5 control and weak probe fields. We find that the plasmonic hybrid system exhibits at near resonance a 6 strong switching between slow and fast light, which can be controlled by the inclination angle of the 7 gold nanoparticle and the size of the metals nanoparticles, in addition to the strength and detuning 8 of the control field. Thus, the silver nanoparticle-gold nanoparticle-quantum dot could potentially be 9 used in optoelectronic devices.10

Plasmonic nanocomposites have the ability to enhance light-matter interaction due to the plasmonic effects leading to promising potential applications. In this paper, we theoretically study the group index of the silver nanoparticle-gold nanoparticle-quantum dot plasmonic hybrid system in the optical region of the electromagnetic spectrum using the density matrix approach. The quantum dot is considered to be a three-level atomic system of a lambda configuration, interacting with strong control and weak probe fields. We find that the plasmonic hybrid system exhibits at near resonance a strong switching between slow and fast light, which can be controlled by the inclination angle of the gold nanoparticle and the size of the metals nanoparticles, in addition to the strength and detuning of the control field. Thus, the silver nanoparticle-gold nanoparticle-quantum dot could potentially be used in optoelectronic devices.

In European countries many measures are carried out to improve the disadvantaged conditions and socio-economic marginality of rural areas in comparison with central places. These conditions also affect the quality of travel for visitors and tourists. Therefore, in response to a 'new' tourist demand, motivated also by the restrictions following the spread of the Covid-19 virus in recent years, the institutions and the different local actors are working more incisively to improve rural areas. The rural tourism services offer, combined with the Green Infrastructure (GI) project, at different scales - from local to regional - prove to be interesting territorial development strategies to achieve the Agenda 2030 objectives. This contribution considers the Sulcis Iglesiente - Guspinese area, in the Sardinia Region (IT), as a case study. In this area, the landscape context is marked by past mining activity and the project of a path of historical, cultural and religious values has proved to be an activator of regenerative processes, in environmental, social and economic terms. The present study proposes a methodological approach to develop an index (FI - Feasibility Index) to assess the feasibility of the Stop Places (SPs) schemes along a horse trail to integrate the current slow mobility by bicycle and pedestrian in the bioregion.

Providing safe drinking water to people in developing countries is an urgent world-wide water problem and a main issue in the UN Sustainability Goals. One of the most efficient and cheapest methods to attain these goals is the use of slow sand filters. Slow sand filters can efficiently provide safe drinking water to people living in small rural communities not served by central water supply systems. The purpose of this review article is to critically summarize and synthesize features and advantages of slow sand filtration methods to improve the quality of drinking water with special focus on less-developed countries. Even though slow sand filtration is an old technique, its efficiency and cost-effectiveness make it important to continue to develop the method in parallel to other chemical and biological methods. Thus, there are needs to continue to develop methods for slow sand filtration combined with simple disinfection techniques for treatment of microbiological pollutants such as bacteria, microbes, viruses, and parasites. These techniques can be applied before or after the sand filter application. Studies are also needed to investigate other types of porous material in areas where suitable sand and gravel are not readily available. Methods are needed to reduce the contents of emerging environmental pollutants such as surfactants and microplastics. Also, further studies are needed to determine design criteria (particle size distribution, depth of media, residence time, temperature, etc.) for different types of pollutants, existing and emerging. Finally, further research is needed to advise on life cycle time, operation (e.g., batch or continuous flow), and maintenance procedures (cleaning of media, back-flushing, etc.) for used porous media in slow the sand filtration.

We present a model of infection dynamics that might explain slower approaching the herd immunity during the covid-19 epidemy in Sweden than it was predicted by a variety of other models; see graphs Fig. \ref{GROWTH2}. The new model takes into account the hierarchic structure of social clusters in the human society. We apply the well developed theory of random walk on the energy landscapes represented mathematically with ultrametric spaces. This theory was created for applications to spin glasses and protein dynamics. To move from one social cluster (valley) to another, the virus should cross a social barrier between them. The magnitude of a barrier depends on the number of social hierarchy's levels composing this barrier. As the most appropriate for the recent situation in Sweden, we consider linearly increasing (with respect to hierarchy's levels) barriers. This structure of barriers matches with a rather soft regulations imposed in Sweden in March 2020. In this model, the infection spreads rather easily inside a social cluster (say working collective), but jumps to other clusters are constrained by social barriers. This model's feature matches with the real situation during the covid-19 epidemy, with its cluster spreading structure. Clusters need not be determined solely geographically, they are based on a number of hierarchically ordered social coordinates. The model differs crucially from the standard models of spread of disease, such as the SIR-model. Our model describes such a specialty of spread of covid-19 virus as the presence of ``super-infectors'' who by performing a kind of random walk on a hierarchic landscape of social clusters spreads infection. In future, this model will be completed by adding the SIR-type counterpart. But, the latter is not a specialty of covid-19 spreading.

Differences in the physical and chemical properties of reclaimed water (RW) and natural surface water (SW) lead to the differences in terms of nitrogen and phosphorus release when pipeline sediments enter these water bodies. The nitrogen and phosphorus release kinetics from pipe sediments with different particle sizes have been investigated. The results demonstrated that both SW and RW had a pH buffering effect after sediment addition, and the final pH (approximately 8.1) of RW was lower. The release of total phosphorus (TP) and ammonia nitrogen ( NH₄⁺-N) fitted the first-order kinetic model where the release of TP reached equilibrium; TP release was inhibited in both SW and RW, where RW exhibited the lowest (by a factor of 1.23~2.44) release (0.002 mg/g). The release of NH4+-N was promoted in both SW and RW; the maximum release in RW was 0.0188 mg/g. The amounts of NH₄⁺-N released in SW and RW were 1.02-1.40 and 1.30-1.80 times that of the control group (CG), respectively. The percentage of TP and NH₄⁺-N release in the three groups was highest in 75-154 μm pipe sediment, reaching 34.53% and 43.51% in SW and RW, respectively. These results can assist in the development of water quality evolution models for specific urban scenarios, and provide important guidance for the precise regulation of recharge water quality during and after rainfall.

A field experiment was conducted for 2 years in Green Tea Laboratory of Saitama Prefectural Agriculture and Forestry Research Center, Iruma, Saitama, Japan from March 2014 to December 2015. Controlled release fertilizers (CRF) or organic fertilizers (ORG) which is the mixture of chicken manure and oil cakewere applied with the amount of 450 kg N ha^-1 yr^-1 in 2014 and 397 kg N ha^-1 yr^-1 in 2015. Nitrous oxide (N₂O) emissionsfrom soil in green tea fields were measured by closed chamber method. The results showed that CRF has significantly lower N₂O compared to ORG. The cumulative N₂O emissions from CRF accounted for 51% of N₂O emissions from ORG fields and 138% of control with no fertilizer treatment. The N₂O flux from the row was higher than that of under the canopy, since fertilizer were applied on the row. However the total emission from the area between the rows was lower than that under the canopy because of the area ratio of row and canopy was 1:5.

A visual study of spiral galaxies from a subset of spiral galaxies in the Dark Energy Survey Data Release 2 finds that a significant number show long tails of baryonic matter, often much longer than the apparent diameter of the galaxy. Examples from less than 10% of the candidates are shown here and their possible origin is discussed. The tails were only seen connected to spiral galaxies; no examples of tails connected to elliptical galaxies or to artifacts were found. In many examples the tail is associated with what appears to be a colliding galaxy, but in many others there is no sign of one. An intriguing possibility is that in the latter cases the tails are produced by an encounter with an unseen object, either a massive black hole or a compact galaxy with mostly dark matter.

Severe disease and uremia are risk factors for neurological complications of coronavirus disease-2019 (COVID-19). An in-depth analysis of a case series was conducted to describe the neurological manifestations of patients with COVID-19 and gain pathophysiological insights that may guide clinical decision-making – especially with respect to the cytokine release syndrome (CRS). Extensive clinical, laboratory, and imaging phenotyping was performed in five patients. Neurological presentation included confusion, tremor, cerebellar ataxia, behavioral alterations, aphasia, pyramidal syndrome, coma, cranial nerve palsy, dysautonomia, and central hypothyroidism. Neurological disturbances were remarkably accompanied by laboratory evidence of CRS. SARS-CoV-2 was undetectable in the cerebrospinal fluid. Hyperalbuminorachy and increased levels of the astroglial protein S100B were suggestive of blood-brain barrier (BBB) dysfunction. Brain MRI findings comprised evidence of acute leukoencephalitis (n = 3, of whom one with a hemorrhagic form), cytotoxic edema mimicking ischemic stroke (n = 1), or normal results (n = 2). Treatment with corticosteroids and/or intravenous immunoglobulins was attempted – resulting in rapid recovery from neurological disturbances in two cases. Patients with COVID-19 can develop neurological manifestations that share clinical, laboratory, and imaging similarities with those of chimeric antigen receptor-T cell-related encephalopathy. The pathophysiological underpinnings appear to involve CRS, endothelial activation, BBB dysfunction, and immune-mediated mechanisms.

Perception of flavor is a dynamic process during which the concentration of aroma molecules at the olfactory epithelium varies with time as they are released progressively from the food in the mouth during consumption. The release kinetics depends on the food matrix itself, but also on food oral processing, such as mastication behavior and food bolus formation with saliva, for which huge inter-individual variations exist due to physiological differences. Sensory methods, such as time-intensity (TI), or the more recent methods temporal dominance of sensations (TDS) and temporal check-all-that-apply (TCATA), are used to account for the dynamic and time-related aspects of flavor perception. Direct injection mass spectrometry (DIMS) techniques that measure in real-time aroma compounds directly in the nose (nosespace), aimed at obtaining data that reflect the pattern of aroma release in real-time during food consumption, supposed to be representative of perception, have been developed since 25 years. Examples obtained with MS operated in chemical ionization mode at atmospheric or sub-atmospheric pressure (atmospheric pressure chemical ionization APCI or proton transfer reaction PTR) will be given, with emphases on studies conducted with simultaneous dynamic sensory evaluation. Inter-individual variations in terms of aroma release and their relevance for understanding flavor perception will be discussed, as well as evidenced cross-modal interactions.

In the present study the synthesis of gold nanoparticles (AuNPs) loaded with methotrexate (MTX) has been carried out in order to obtain controlled size and monodispersed nanocarriers, around 20nm. Characterization study shows metallic AuNPs with MTX polydispersed on the surface. MTX is linked by a replacement of citrate by the MTX carboxyl group. The drug release profiles showed faster MTX release when it is conjugated, which leads to the best control of plasma concentration. Also, the enhanced release observed at pH 5 could take advantage of the pH gradients that exist in tumor microenvironments to achieve high local drug concentrations. AuNPs-MTX conjugates were tested by flow cytometry against lung (A-549) and colon (HTC-116) cancer cell lines. Results for A-549 showed a lighter dose-response effect than for colon cancer ones. This could be related to the presence of folate receptors in line HTC-116 on the contrary than line A-549, supporting the specific uptake of folate-conjugated AuNPs-MTX by folate receptor positive tumor cells. Conjugates exhibited considerably higher cytotoxic effects compared with the effects of equal doses of free MTX. Anexin V-PI test sustain as cell death mechanism apoptosis, which is normally disabled in cancer cells.

Tumor cells exhibit a resistance-associated secretory phenotype involving extracellular vesicles (EVs) and heat shock proteins (HSPs). This response occurs in response to cell stress and cancer therapeutics. HSPs are stress-responsive molecular chaperones promoting proper protein folding, while also being released from cells with EVs as well as in free form as alarmins. We have here investigated the secretory phenotype of castration-resistant prostate cancer (CRPC) cells using proteome analysis. We have also examined the roles of the key co-chaperone CDC37 in stressome release, epithelial-to-mesenchymal transition (EMT), and tumor progression. A number of HSP family members and their common receptor CD91/LRP1 were enriched at high levels in CRPC cell-derived EVs among over 700 other protein species. The small EVs (30 to 200 nm in size, potentially exosomes) were released even in a non-heated condition from the prostate cancer cells, whereas EMT-coupled release of EVs (200 to 500 nm, likely ectosomes) with associated HSP90α was increased after heat shock stress (HSS). Lactate dehydrogenase, a marker of membrane leakage/damage of cells, was also released upon HSS from the prostate cancer cells. During this stress response, intracellular CDC37 was also transcriptionally inducible by heat shock factor 1, and knockdown of CDC37 decreased EMT-coupled release of EVs. Triple knockdown of CDC37, HSP90α, and HSP90β was required for efficient reduction of the chaperone trio and to reduce tumorigenicity of the CRPC cells in vivo. Taken together, the data indicated that CDC37 and HSP90 are essential for stressome release and for tumorigenesis in resistant cancer.

Information and communication technologies play an increasingly important role in the process of knowledge and management of places at different scales. ICTs allow a rapid diffusion of data not only through institutional channels but also through social networks where the smart community share experiences and perceptions. In this sense, ICTs become strategic tools to support the promotion of sustainable tourism development of territories, especially if the digital data are organised within a circular smart dashboard. This research focuses on the case study of the Santa Barbara Walk (SBW), an ancient mining route in the Sulcis Iglesiente region (Sardinia, Italy), where the authors have recognized a state of disorganization in slow tourism promotion activities. In fact, if the SBW represents a network - material infrastructure - which connects the main points of interest along the Walk, its digital network - intangible infrastructure - is fragmented in terms of policies and contents. The goal of this study is to provide a comprehensive set of data and to propose the architecture and design for a circular dashboard of the SBW, capable of organizing information concerning the main features of the walk, in order to facilitate a shared governance for an effective tourism promotion.

The cycling of soil phosphorus (P) is inherently linked with soil organic carbon-iron (C-Fe) cycling, yet empirical integration of these processes within paddy soils remains scarce. In this study, we conducted a microcosm experiment using paddy soils subjected to six distinct fertilization regimes involving varying P inputs for five years. In addition to evaluating P activation under reflooding conditions, we assessed the Fe reduction process and characterized the properties of dissolved organic matter (DOM) at the molecular level using Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS), alongside profiling the composition of soil microbial communities with high-throughput sequencing. Our findings revealed that after 25 days of reflooding, soil Olsen-P content increased by an average of 73% compared to its initial state, showing a strong correlation with the Fe reduction process. Specifically, treatments involving pig manure application exhibited higher Fe reduction rates and enhanced P activation, highlighting the role of organic matter in facilitating Fe reduction. Investigations on the relative abundance of typical iron-reducing microbes further supported their importance in P activation, but the rate of iron reduction is limited by soil organic matter content. Delving deeper into DOM properties, soil DOM composition profiling and network analysis suggested that high-molecular-weight DOM, particularly lignins, served as the primary resources driving Fe reduction by iron-reducing microbes, consequently promoting Fe reduction and P release. Taken together, our study assembled the C-Fe-P cycling dynamics in paddy soils, emphasizing the pivotal role of microbial-driven Fe reduction facilitated by soil DOM in P availability and subsequently sustainable agricultural practices.

In this study, we focus on the effects of fuel bed representation and fire heat and smoke distribution in a coupled fire-atmosphere simulation platform for two landscape-scale fires: the 2018 Camp Fire and the 2021 Caldor Fire. The fuel bed representation in the coupled fire-atmosphere simulation platform WRF-Fire currently includes only surface fuels. Thus, we enhance the model by adding canopy fuel characteristics and heat release, for which a method to calculate the heat generated from canopy fuel consumption is developed and implemented in WRF-Fire. Furthermore, the current WRF-Fire heat and smoke distribution in the atmosphere is replaced with a heat-conserving Truncated Gaussian (TG) function and its effects are evaluated. The simulated fire perimeters of case studies are validated against semi-continuous, high-resolution fire perimeters derived from NEXRAD radar observations. Furthermore, simulated plumes of the two fire cases are compared to NEXRAD radar reflectivity observations followed by buoyancy analysis using simulated temperature and vertical velocity fields. The results show that while the improved fuel bed and the TG heat release scheme have small effects on the simulated fire perimeters of the wind-driven Camp Fire, they affect the propagation direction of the plume-driven Caldor Fire, leading to better-matching fire perimeters with the observations. However, the improved fuel bed representation together with the TG heat smoke release scheme leads to more realistic plume structure in comparison to the observations in both fires. The buoyancy analysis also depicts more realistic fire-induced temperature anomalies and atmospheric circulation when the fuel bed is improved.

We consider the problem of scheduling $n$ jobs with identical processing times and given release as well as delivery times on $m$ uniform machines. The goal is to minimize the makespan, i.e., the maximum full completion time of any job. This problem is well-known to have an open complexity status even if the number of jobs is fixed. We present a polynomial-time algorithm for the problem which is based on the earlier introduced algorithmic framework blesscmore (``branch less and cut more''). We extend the analysis of the so-called behavior alternatives developed earlier for the version of the problem with identical parallel machines and show how the earlier used technique for identical machines can be extended to the uniform machine environment if a special condition on the job parameters is imposed. The time complexity of the proposed algorithm is $O(\gamma m^2 n\log n)$, where $\gamma$ can be either $n$ or the maximum job delivery time $q_{\max}$. This complexity can even be reduced further by using a smaller number $\kappa<n$ in the estimation describing the number of jobs of particular types. However, this number $\kappa$ becomes only known when the algorithm has terminated.

Aerococcus urinae is an aerobic Gram-positive coccus that grows as tiny alpha-hemolytic colonies. Actinotignum schaalii is a slow-growing facultative anaerobic Gram-positive rod. These bacteria are part of the urogenital microbiota of healthy patients, but can also be involved in urinary tract infections (UTIs), particularly in elderly men and young children [1–3]. Because A. urinae and A. schaalii are fastidious and are difficult to identify with phenotypic methods, they are underestimated causes of UTIs. Their growth is slow and requires a blood-enriched medium and an incubation time of 48 hours under anaerobic or 5% CO2 atmosphere. Furthermore, accurate identification is only possible using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) or molecular-based methods. In rare cases, these bacteria can be responsible for invasive infections. We describe here the second case of bacteremic UTI caused by both A. schaalii and A. urinae in an 89-year-old woman who presented dyspnea and asymptomatic bacteriuria. This challenging clinical and microbiological diagnosis was made by our laboratory by Gram staining urine with a leucocyte count &gt;50/μL and/or a bacterial count &gt;14/μL, urinary culture on blood agar plate, and direct bacterial identification on positive blood culture bottles (BCBs) by MALDI-TOF MS. After 10 days of antimicrobial treatment consisting of 2g amoxicillin PO t.i.d the patient was discharged with complete clinical and biological recovery. A. schaalii and A. urinae are probably still underestimated causes of UTIs. Microbiologists should assess the presence of these two bacteria in urine using the appropriate culture and identification methods where direct examination is positive for small Gram-positive cocci or rods, and a urinary dipstick is negative for nitrites and associated with leukocyturia.

Cognitive impairment and sarcopenia may share common risk factors and pathophysiological pathways. This study was performed to examine the association between impairments in specific cognitive domains and sarcopenia (and its defining components) in a large group of community-dwelling older adults. Cross-sectional analysis was performed on the baseline data of 3,014 adults aged 70–84 years enrolled in the Korean Frailty and Aging Cohort Study (KFACS). The final analysis included 1,887 adults underwent dual-energy X-ray absorptiometry and cognitive function assessments. Those with disability in activities of daily living, dementia, severe cognitive impairment, Parkinson’s disease, musculoskeletal complaints, neurological disorders, or who were illiterate were excluded. Cognitive function was assessed using the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Assessment Packet, the Frontal Assessment Battery. For sarcopenia, we used the diagnostic criteria of the Asian Working Group for Sarcopenia. The prevalence of sarcopenia was 9.6% for men and 7.6% for women. Sarcopenia (odds ratio [OR] 1.76, 95% confidence interval [CI] 1.04–2.99) and slow gait speed (OR 2.58, 95% CI 1.34–4.99) were associated with cognitive impairment in men. Only slow gait speed (OR 1.88, 95% CI 1.05–3.36) was associated with cognitive impairment in women. Sarcopenia is associated with cognitive impairment mainly due to slow gait speed. Our results suggested that cognitive impairment domains, such as processing speed and executive function, are associated with sarcopenia-related slow gait speed.

This study evaluated the effect of newly introduced calcium silicate-based temporary intracanal medicament Bio-C Temp and calcium hydroxide-based material UltraCal XS on the release of transforming growth factor β1 (TGF-β1) from root canal dentin. Twenty-two intact and fully developed human premolars from patients aged 15 – 18 were shaped and irrigated according to the current clinical recommendations. The teeth were then gently split in half, and the root canal dentin of paired samples was covered with Bio-C Temp or UltraCal XS. After 3 weeks of incubation, the specimens were conditioned with 17% EDTA and the collected solution was subjected to quantification of released TGF-β1 by performing ELISA. One-way analysis of variance (ANOVA), followed by Tukey’s test, was selected to determine the statistically significant differences between the groups at the 0.95 confidence level. The highest mean value of released TGF-β1 (1993.1 pg/ml) was detected in the control group, where root canal dentin was conditioned with 17% EDTA alone. Regarding experimental groups, Bio-C Temp released a statistically significant higher amount of TGF-β1 (282.14 pg/ml) compared to UltraCal XS (114.28 pg/ml; p = 0.0158). Bio-C Temp affected the release of growth factors from root canal dentin less than UltraCal XS and may therefore serve as an intracanal medicament for regenerative endodontic procedures.

This study develops a vitamin C controlled-release system trackable via color changes as a function of vitamin C release. The system is composed of coaxial microfibers prepared via coaxial electrospinning, with a core of poly(ethylene oxide) (PEO) incorporating vitamin C, and a shell composed of polycaprolactone (PCL) containing polydiacetylene (PDA) as the color-changing material. The shell thickness was controlled by adjusting the amount of PCL ejected during electrospinning, allowing the regulation of the release rate of vitamin C. When vitamin C added to PEO penetrated the PCL layer, the color of PDA changed from blue to red, indicating a color change. The results of this study can be applied to devices that require immediate detection of vitamin C release levels.

The influence of lignin modification on drug release and pH-dependent releasing behaviour of oral solid dosage form was investigated using three different formulations. The first formulation contains microcrystalline cellulose (MCC101) as excipient and paracetamol as active pharmaceutical ingredient (API). The second formulation includes Alcell lignin and MCC 101 as excipient and paracetamol, and the third formulation consists of carboxylated Alcell lignin, MCC 101 and paracetamol. Direct compaction was carried out in order to prepare the tablets. Lignin can be readily chemically modified due to the existence of different functional groups in its structure. The focus of this investigation is on lignin carboxylation and its influence on paracetamol control release behaviour at varying pH. Results suggest that carboxylated lignin tablets had the highest drug release, which is linked to their faster disintegration and lower tablet hardness.

Antimicrobial peptides (AMPs) can directly kill Gram-positive bacteria, Gram-negative bacteria, mycobacteria, fungi, enveloped viruses and parasites. At sublethal concentrations some AMPs and also conventional antibiotics can stimulate bacteria response to increase their resilience, also called the hormetic response. That can include stimulation of growth, mobility, and biofilm production. Here, we have discovered AMPs that stimulate the growth of certain mycobacteria. Peptide 14 for example showed growth stimulating effect on M. tuberculosis, M. bovis, M. avium subsp. paratuberculosis (MAP), M. marinum, M. avium-intracellulare, M. celatum and M. abscessus. The effect was more pronounced at low bacterial inocula. The peptides induce a faster transition from the lag phase to the log phase and keep the bacteria longer in the log phase before entering the stationary phase compared to non treated control. In some cases, an increase in the division rate was observed. An initial screen using MAP and a collection of 75 peptides revealed 13 peptides with a hormetic effect. For M. tuberculosis a collection of 25 artificial peptides were screened and 9 were found to reduce the time to positivity (TTP), improving growth. A screen of 43 naturally occurring peptides, 11 fragments of naturally occurring peptides and 5 designed peptides, all taken from the APD3, identified a further 44 peptides that also lowered TTP by at least 5%. Lasioglossin LL-III (Bee) and Ranacyclin E (Frog) were the most active natural peptides, the human cathelicidin LL37 fragment GF-17 and a porcine cathelicidin protegrin-1 fragment was the most active fragment of naturally occurring peptides. Peptide 14 showed growth-stimulating activity between 50 ng/ml and 10 µg/ml whereas the stability-optimised peptide 14D had a narrow activity range of 0.1 - 1 µg/ml. Peptides identified in this study are now part of novel products improving the diagnosis of mycobacteria in humans and animals.

Slow-roll inflation may simultaneously solve the horizon problem and generate a near scale-free fluctuation spectrum $P(k)$. These two processes are intimately connected via the initiation and duration of the inflationary phase. But a recent study based on the latest {\it Planck} release suggests that $P(k)$ has a hard cutoff, $k_{\rm min}\not=0$, inconsistent with this conventional picture. Here we demonstrate quantitatively that most---perhaps all---slow-roll inflationary models fail to accommodate this minimum cutoff. We show that the small parameter $\epsilon$ must be $\gtrsim 0.9$ throughout the inflationary period to comply with the data, seriously violating the slow-roll approximation. Models with such an $\epsilon$ predict extremely red spectral indices, at odds with the measured value. We also consider extensions to the basic picture (suggested by several earlier workers) by adding a kinetic-dominated or radiation-dominated phase preceding the slow-roll expansion. Our approach differs from previously published treatments principally because we require these modifications to---not only fit the measured fluctuation spectrum, but to simultaneously also---fix the horizon problem. We show, however, that even such measures preclude a joint resolution of the horizon problem and the missing correlations at large angles.

Currently the bimatoprost implant (DURYSTA) is approved for a single administration secondary to concern for progressive corneal endothelial cell (CEC) loss with intracameral administration. In order to better understand the cause of CEC loss and other adverse events (AEs) with intracameral administration, multimodal imaging of the implant utilizing optical coherence topography (OCT), robotic ultrasound and bio microscopy video recording was utilized. Inherently the anterior chamber is a non-confined space. In certain examples the implant assumed a round and spotted structure as it picked up iris pigment as it migrated around the anterior chamber. Accordingly, we explored delivery of the implant in the middle segment behind the iris and in front of the pseudophakic lens. We then evaluated the suitability of various imaging modalities to assess the implant in this location. For middle segment administration, the ArcScan Insight 100 robotic ultrasound provided resolution and repeatability sufficient to monitor the implant behind the iris. This preliminary study hypothesizes that DURYSTA migration in the anterior chamber is the main source of AEs. Through use of a confined location, the middle segment, the implant is unlikely to migrate and cause CEC loss while also delivering drug closer to its site of action, the ciliary body. Further efforts are underway to understand the suitability of the middle segment for serial DURYSTA administration to maximize intraocular pressure lowering while minimizing AEs.

In this work, we designed and fabricated a multifunctional nanocomposite system which consists of chitosan, raspberry-like silver nanoparticles and graphene oxide. Room temperature atmospheric pressure microplasma (RT-APM) process provides a rapid, facile, and environment-friendly method for introducing silver nanoparticles into the composite system. By loading different drugs onto the polymer matrix and/or graphene oxide, our composite can achieve a pH controlled dual drug release with release profile specific to the drugs used. In addition to its strong antibacterial ability against E. coli and S. aureus, our composite also demonstrates excellent photothermal conversion effect under irradiation of near infrared lasers. These unique functionalities point to it’s the potential of nanocomposite system in multiple applications areas such as multimodal therapeutics in healthcare, water treatment, and anti-microbial, etc.

Blood Concentrates (BCs) are autologous non-transfusional therapeutical preparations with biological properties applied in tissue regeneration. These BCs differ in the preparation method, in fibrin network architecture, growth factors release as well as in platelet/cell content. Methodological changes result in distinct matrices that can compromise their clinical effectiveness. The present study evaluated the influence of different g-forces and types of tubes in the release of vascular endothelial growth factor (VEGF) from platelet-rich fibrin (PRF) as a function of time. The PRF-like samples were obtained with three g-forces (200, 400, and 800 x g) for 10 minutes in pure glass tubes or in polystyrene-clot activator tubes. Scanning and Transmission electron microscopy was used to morphometric analyzes of PRF’s specimens and flow cytometry was used to quantify VEGF slow release until 7 days. Our results showed that platelets were intact and adhered to the fibrin network, emitting pseudopods and in degranulation. The fibrin network was rough and twisted with exosomic granulations impregnated on its surface. An increase in the concentration of VEGF in the PRF supernatant was observed until 7 days for all g forces (200, 400 or 800 x g), with the highest concentrations observed with 200 x g, in both tubes, glass or plastic. Morphological analyzes showed a reduction in the diameter of the PRF fibers after 7 days. Our results showed that g-force interferes with the shape of the fibrin network in the PRF, as well as affect the release of VEGF stored into platelets. This finding may be useful in applying PRF to skin lesions, in which the rapid release of growth factors can favor the tissue repair process. Our observations point to a greater clarification on the methodological variations related to obtaining PRF matrices, as they can generate products with different characteristics and degrees of effectiveness in specific applications.

The evolution of release factors catalyzing the hydrolysis of the final peptidyl-tRNA bond and the release of the polypeptide from the ribosome has been a longstanding paradox. While the components of the translation apparatus are generally well-conserved across extant life, structurally-unrelated release factor peptidyl hydrolases (RF-PHs) emerged in the stems of the bacterial and archaeo-eukaryotic lineages. We analyze the diversification of RF-PH domains within the broader evolutionary framework of the translation apparatus. Thus, we reconstruct the possible state of translation termination in the Last Universal Common Ancestor with possible tRNA-like terminators. Further, evolutionary trajectories of the several auxiliary release factors in ribosome quality control (RQC) and rescue pathways point to multiple independent solutions to this problem and frequent transfers between superkingdoms including the recently-characterized ArfT, which is more widely-distributed across life than previously appreciated. The eukaryotic RQC system was pieced together from components with disparate provenance, which include the long-sought Vms1/ANKZF1 RF-PH of bacterial origin. We also uncover an under-appreciated evolutionary driver of innovation in rescue pathways: effectors deployed in biological conflicts that target the ribosome. At least three rescue pathways (centered on the prfH/RFH, baeRF-1, and C12orf65 RF-PH domains), were likely innovated in response to such conflicts.

Astaxanthin (AX) is a carotenoid that exerts potent antioxidant activity and acts in the lipid bilayer. This study aimed to investigate the effects of AX on muscle atrophy-mediated disturbance of mitochondria that have a lipid bilayer. Tail suspension was used to establish muscle- atrophied mouse models. AX diet fed to tail-suspension mice prevented loss of muscle weight and decreased myofiber size in the soleus muscle. Additionally, AX improved down-regulation of mitochondrial respiratory chain complexes II and III in the soleus muscle after tail suspension. To confirm the AX phenotype in the soleus muscle, we examined its effects on mitochondria using Sol8 myotubes derived from the soleus muscle. We found that AX was preferentially detected in the mitochondrial fraction; it significantly suppressed mitochondrial complex III-driven production of reactive oxygen species in Sol8 myotubes. Moreover, AX inhibited the activation of caspase 3 via inhibiting the release of cytochrome c into the cytosol in antimycin A-treated Sol8 myotubes. These results suggested that AX inhibited mitochondrial oxidative stress through a mitochondria-mediated apoptosis pathway and thus prevented muscle atrophy.

Neuronal timing is critical for many brain functions such as perception and learning. At the level of the chemical synapse, the synaptic delay is determined by the presynaptic release probability (Pr) and the waveform of the presynaptic action potential (AP). Depolarization-induced analogue-digital facilitation (d-ADF) is a form of context-dependent synaptic facilitation that is induced by constant depolarization of the presynaptic neuron and is mediated by voltage inactivation of presynaptic Kv1 channels. Whether synaptic delay is modulated during d-ADF remains unclear. We show here that despite Pr is elevated during d-ADF at L5-L5 synapses, the synaptic delay is surprisingly unchanged, suggesting that both Pr- and AP-dependent changes in synaptic delay compensate for each other. We conclude that in contrast with other short- or long-term modulation of presynaptic release, timing is not affected during d-ADF because of the opposite interaction of Pr- and AP-dependent modulations of synaptic delay.

Ferroptosis is an iron-dependent cell death pathway that involves depletion of intracellular glutathione (GSH) levels and iron-mediated lipid peroxidation. Ferroptosis is experimentally caused by inhibition of the cystine/glutamate antiporter xCT, which depletes cells of GSH, or by inhibition of Glutathione peroxidase 4 (GPx4), a key regulator of lipid peroxidation. The events that occur between GPx4 inhibition and the execution of ferroptotic cell death are currently a matter of active research. Previous work has shown that calcium release from the endoplasmic reticulum (ER) mediated by ryanodine receptor (RyR) channels contributes to ferroptosis-induced cell death in primary hippocampal neurons. Here, we used SH-SY5Y neuroblastoma cells, which do not express RyR channels, to test if calcium release mediated by the inositol 1,4,5-trisphosphate receptor (IP3R) channel plays a role in this process. We show that inhibition of GPx4 by RAS Selective Lethal Compound 3 (RSL3) generated an increase in reactive oxygen species (ROS), increased cytoplasmic and mitochondrial calcium levels, increased lipid peroxidation and caused cell death. The RSL3-induced calcium signals were inhibited by Xestospongin B, an inhibitor of the ER-resident IP3R calcium channel, by decreasing IP3R levels with carbachol and by IP3R1 knock-down. The intracellular calcium chelator BAPTA-AM inhibited RSL3-induced calcium signals, which were not affected by extracellular calcium depletion. We propose that GPx4 inhibition activates IP3R-mediated calcium release in SH-SY5Y cells, leading to increased cytoplasmic and mitochondrial calcium levels, which in turn stimulate the production of ROS and induce lipid peroxidation and ferroptotic cell death in a noxious positive feedback cycle.

This work deals with the synthesis of bare and curcumin (CUR)-loaded chitosan (CS)-based macroparticles by ionic gelation using sodium hydroxide (NaOH) or sodium tripolyphosphate (TPP) as cross-linking agents. The resulting spherical-shaped macroparticles were studied using various characterization techniques, Scanning Electron Microscopy (SEM), Fourier Transformed Infrared Spectroscopy (FTIR), Thermogravimetric Analysis (TGA), and Differential Scanning Calorimetry (DSC). The release of CUR from the CS-based particles with respect to time was analyzed, and the encapsulation efficiency and degree of swelling were studied. All formulations showed excellent CUR trapping efficiency, exceeding 90%. In particular, the TPP-crosslinked macrobeads released 34 wt% of the charged CUR within minutes, while the remaining 66 wt% was released slowly due to the biodegradation of CS. The results indicate that the correct choice of gelling agent and its concentration leads to spherical particles capable of encapsulating CUR and releasing it in a wide range of kinetics depending on the specific application.

Prospects for predicting the fragmentation of polypeptide chains during their enzymatic hydrolysis using proteolysis models are considered. The opening of the protein substrate during proteolysis and the exposure of its internal peptide bonds for a successful enzymatic attack, the so-called demasking process, were taken into account. The two-step model of proteolysis was used, including the parameters of peptide bond demasking and hydrolysis rate constants for various peptide bonds. Herein, we presented an algorithm for calculating the concentrations of peptide fragments depending on the hydrolysis time or the degree of hydrolysis. The intermediate peptide fragments with two or one internal specific bonds were considered. The fragmentation of β-lactoglobulin (b-LG) with trypsin was predicted, and the calculated concentration curves for peptide fragments were compared with the experimental dependences of concentrations on the degree of hydrolysis. Numerical parameters characterizing the kinetic curves were proposed for the intermediate and final peptide fragments, and they were used to compare the calculated and experimental dependences. The predicted distribution of peptide fragments corresponded to the experimental data on the peptide release during proteolysis of b-LG by trypsin.

Objectives: In December 2019 a novel human-infecting coronavirus, SARS-CoV-2, has emerged. The WHO has stated the epidemic as a “public health emergency of international concern”. A drammatic situation has emerged with thousands of deaths, occurring mainly in the aged and very ill people. Epidemiological studies suggest that immune system function is impaired in elderly individuals and these subjects often present a severe deficiency in nutrients as fatsoluble and hydrosoluble vitamins. Design: In this first part of the review about Cov2 in aged people, we searched for reviews describing the characteristics of autoimmune diseases and the available therapeutic protocols for their treatment. We sed them as a paradigm with the purpose to retrieve pathogenetic mechanisms in common among these pathological conditions and SARS-CoV-2 infection, as well as the alteration induced in immune system function by this virus, or by its homologous SARS-CoV. Results: SARS-CoV-2 infection induces an important immune system dysfunction with the development of an exhuberant proinflammatory response in the host, and with the development of a life-threatening condition defined as Cytokine Release Syndrome (CRS). This leads to the Acute Respiratory Syndrome (ARDS), mainly in the aged people. High mortality and lethality rates have been observed in the elderly subjects with CoV-2-related infection. Conclusion: These diseases may serve as a paradigm for the study of CRS emerging in the course of SARS CoV-2 infection. This review discusses about the possible activity of Vitamin A, D, E and C in restoring normal antiviral Immune System function or the potential therapeutic role of these micronutrients as a part of a multi-treatment strategy against SARS- CoV-2 infection.

Developing prolonged antigen delivery systems that mimick the long-term exposure to pathogens appears as a promising, still poorly explored approach to reach durable immunities. In this study, we have used a simple technology by which his-tagged proteins can be assembled, assisted by divalent cations, as supramolecular complexes with progressive complexity, namely protein-only nanoparticles and microparticles. Microparticles produced out of nanoparticles are biomimetics of secretory granules from the mammalian hormonal system. Upon subcutaneous administration, they slowly disintegrate, acting as an endocrine-like secretory system, and rendering the building block nanoparticles progressively bioavailable. The performance of such materials, previously validated for drug delivery in oncology, has been tested here regarding the potential for time-prolonged antigen release. This has been done by taking, as building blocks, a nanostructured version of p30, a main structural immunogen from the African swine fever virus (ASFV). By challenging the system in both mice and pigs, we have observed unusually potent pro-inflammatory activity in porcine macrophages, and long-lasting humoral and cellular responses in vivo, which might overcome the need for an adjuvant. The robustness of both innate and adaptive responses tag, for the first time, these dynamic depot materials as a novel and valuable instrument with transversal applicability in immune stimulation and vaccinology.

Background: There is a high bureaucratic and administrative burden associated with health care tasks (test requesting, visits scheduling, supporting documents provision) that has historically largely fallen on health care professionals, which is one among the factors contributing to low job satisfaction and lower productivity. Incorporating new professional roles that help to better respond to the needs of both patients and professionals can increase the quality and efficiency of service provision. Objective: To evaluate the impact of the clinical assistant’s introduction in the Sant Joan de Déu Barcelona Children’s Hospital’s pediatric oncology department, in terms of displacement of activity loads carried out by this new professional role and the consequent time freed up for physicians. Methodology: Observational and retrospective study using administrative data based on the analysis of the type of activity performed by clinical assistants and the measurement of the time freed up in favor of the physicians, based on in situ timekeeping, to approximate the potential skill mix productivity increase. Results: Since its implementation in the pediatric oncology department, clinical assistants have performed 13,553 requests (69.93% of the total), representing a total saving of 266.83 hours or 6.67 workweeks of 40 hours. They performed 74.25% of outpatient surgical requests in the oncology department, 87.5% of day hospital requests and 54.13% of total requests in the outpatient consultations area. Conclusion: The introduction of clinical assistants in the oncology department could be efficient to the extent that it displaces a good part of the bureaucratic and administrative tasks previously performed by health care professionals. This delegation allows them to work more closely to the maximum of their competences and the physicians to have more time for higher added value clinical tasks. In terms of efficiency, this role change enables to optimize the clinical process, reducing the cost by 56% compared to the conventional model.

In article questions of development low-waste technologies of processing of steel-smelting slag are considered, gland allowing by extraction and its connections from steel-smelting slag to receive additional raw materials for production became, and the remains to use in building industry. Studying of gravitational methods of enrichment of steel-smelting slag and heat treatment the ore-fuel of pellets is the basis for work. Proceeding from it, in work modern physic-mechanical, chemical and physical and chemical methods of researches (UV-spectroscopy, electronic microscopy, the granulometric analysis) are used.

The soma, dendrites and axon of neurons may display calcium-dependent release of transmitters and peptides. Such release is named extrasynaptic for occurring in the absence of synaptic structures. This review describes cooperative actions of three calcium sources on somatic exocytosis. Emphasis is given to the release of serotonin by the classical serotonergic leech Retzius neuron, which has allowed detailed studies of each step between excitation and exoctytosis. Trains of action potentials induce transmembrane calcium entry through L-type channels. If the frequency of action potentials is above 5 Hz, summation of calcium transients upon individual action potentials increases the intracellular calcium concentration to activate calcium–induced calcium release. The amplified calcium wave activates motochondrial ATP synthesis that fuels the transport of vesicles to the plasma membrane. Serotonin that is released activates autoreceptors coupled to phospholipase C. Production of IP3 produces release of calcium that sustains the large-scale exocytosis. The swiss-clock workings of the release machinery for somatic exocytosis has a striking disadvantage. The essential calcium-releasing endoplasmic reticulum that lays between resting vesicles and the plasma membrane becomes an obstacle for the vesicle transport. Such architecture reduces drastically the thermodynamic efficiency of the vesicle transport and elevates its energy cost..

Polyphenol ellagic acid (EA) possesses anti-oxidant, anti-inflammatory, anti-carcinogenic, anti-diabetic and cardio protection activities, remarking it an interesting multi-targeting profile. EA also controls the central nervous system (CNS) since it was proven to reduce the immobility time of mice in both the forced swimming and the tail-suspension tests, with an efficiency comparable to that of classic antidepressants. Interestingly, the anti-depressant-like effect was almost nulled by the concomitant administration of selective antagonists of the noradrenergic receptors, suggesting the involvement of these cellular targets in the central effects elicited by EA and its derivatives. By in silico and in vitro studies, we discuss how EA engages with human α2A-ARs and α2C-AR catalytic pockets, comparing EA behaviour with those ones of known agonist and antagonist. Structurally, the hydrophobic residues surrounding α2A-AR pocket confer specificity on the intermolecular interactions and hence lead to favourable binding of EA in the α2A-AR, with respect to α2C-AR. Moreover, EA seems to better accommodate within α2A-ARs into TM5 area, closely to S200 and S204 which play a crucial role for activation of aminergic GPCRs such as the α2-AR, highlighting its promising role as a partial agonist. Consistently, EA mimics clonidine in inhibiting noradrenaline exocytosis from hippocampal nerve endings in an yohimbine-sensitive fashion that confirms the engagement of naïve α2-ARs in the EA-mediated effect.

Nizatidine is a gastroprotective drug with a short biological half-life and narrow absorption window. This study aimed at developing floating tablets of nizatidine using various HPMC viscosity grades, namely K4M, E4M, K15 and K200M. Directly compressed tablets revealed an excellent uniformity in hardness, thickness and weight and nizatidine was evenly distributed within the matrix floating tablets. Buoyancy study revealed floating lag time as low as 18–38 s, and tablets remain buoyant for upto 24 h. However, the later depended upon viscosity grade of HPMC and that the higher the viscosity, the less was the total floating time. In vitro dissolution indicated viscosity dependent nizatidine release from the floating tablets. HPMC K4M and E4M based floating tablets released almost 100% drug in 12 h, whilst higher viscosity polymers such as K15 and K200M only released 81.88% and 75.81% drug, respectively. The drug release followed non-Fickian diffusion from tablets formulated with K4M, K15 and K200M, whilst super case II transport was observed with E4M based tablets. More interestingly, K4M and E4M polymers have similar viscosity yet exhibited different drug release mechanism. This was attributed to the difference in degree of substitution of methoxyl- and hydroxypropoxyl- groups on polymer backbone.

Motivated by experimental success in designing linear amphiphilic copolymers with selective demicellization capabilities through head-to-tail depolymerization triggered by specific stimuli, we advanced the design paradigm by increasing the number of triggering groups on the copolymer chain through architectural modifications. Utilizing molecular dynamics simulations, we explored the demicellization and cargo release dynamics of linear and miktoarm copolymers, featuring one, two and three hydrophobic block or branches, each capable for head-to-tail depolymerization. Our findings revealed that, under stoichiometric trigger molecule concentrations, miktoarms with three branches exhibited consistently faster depolymerization rates than those with two branches and linear copolymers. Conversely, at constant trigger molecule concentrations, the depolymerization rates of copolymers exhibited more complex behavior influenced by two opposing factors: the excess of trigger molecules, which increased with a decrease in the number of hydrophobic branches or blocks, and simultaneous head-to-tail depolymerization, which intensified with an increasing number of branches. Our study elucidates the intricate interplay between copolymer architecture, trigger molecule concentrations, and depolymerization dynamics, providing valuable insights for the rational design of amphiphilic copolymers with tunable demicellization and cargo release properties.

The practical application of a pH-responsive Nanoparticle Drug Delivery System (NDDS) in cancer treatment is often hampered by several issues such as the protection of therapeutic molecules from external stresses, inefficient targeted delivery, sustained drug release, and poor efficacy. This study presents an effective design strategy for the synthesis of a pH-sensitive controlled hydrophobic drug delivery method based on the formulation of chitosan (CS)-coated mesoporous silica nanoparticles (MSNs) through the sol-gel method, where hydrolysis takes place in the acidic medium followed by polycondensation of the hydrolyzed products. For this purpose, NH2 modified-MSNs were prepared by using tetraethyl orthosilicate (TEOS) as precursor and cetyltrimethylammonium bromide (CTAB) as a template, and 3-aminopropyltriethoxysilane (APTES) for amine modification, followed by hydrophobic drug loading and CS coating of various concentrations. Camptothecin (CPT) was used as a model drug. Fabricated monodispersed functionalized nanoparticles had sizes ranging from 200nm to 245nm with an encapsulation efficiency as high as 90%. The highest encapsulation efficiency was found for 1% CS coating, which released 50% drug in 120h at pH 6.4 and 20% at pH 7.4 respectively. These nanoformulations exhibited pH-responsive release patterns of CPT under two different pH values (pH=7.4 and pH=6.4). These results contribute to the optimization of NDDS, with potential implications for nanoformulations designed for controlled and sustained drug release particularly to tumors without affecting healthy cells owing to differences in the pH of the tumor microenvironment and the normal physiological environment of cells.

Drug delivery through Liposomes has shown tremendous potential in terms of the therapeutic application of nanoparticles. There are several drug-loaded liposomal formulations approved for clinical use that help mitigate harmful effects of life-threatening diseases. Developments in the field of liposomal formulations and drug delivery have made it possible for clinicians and researchers to find therapeutic solutions for complicated medical conditions. A key aspect in the development of drug-loaded liposomes is a careful review of optimization techniques to improve the overall formulation stability and efficacy. Optimization studies help in improving/modulating the various properties of drug-loaded liposomes and are vital for the development of this class of delivery systems. A comprehensive overview of the various process variables and factors involved in the optimization of drug-loaded liposomes is presented in this review. The influence of different independent variables on drug release and loading properties with the application of a statistical experimental design is also explained in this article.

The objective of this study aimed to develop biodegradable calcium alginate microspheres carrying doxorubicin (Dox) at the micrometer-scale for sustained-release and the capacity of pH regulatory for transarterial chemoembolization. Ultrasonic atomization and CaCl2 cross-linking technologies were used to prepare the microspheres. A 4 by 5 experiment was first designed to identify imperative parameters. The concentration of CaCl2 and the flow rate of the pump were found to be critical to generate microspheres with a constant volume median diameter (~ 39 m) across 5 groups with different alginate:NaHCO3 ratios using each corresponding flow rate. In each group, the encapsulation efficiency was positively correlated to the Dox-loaded efficiency. Fourier-transform infrared spectroscopy showed that NaHCO3 and Dox were step-by-step incorporated into the calcium alginate microspheres successfully. Microspheres containing alginate:NaHCO3 = 1 exhibited rough and porous surfaces, high Young’s modulus and hardness. In each group with the same alginate:NaHCO3 ratio, the swelling rates of microspheres were higher in PBS containing 10% FBS compared to those in PBS alone. Microspheres with relative high NaHCO3 concentrations in PBS containing 10% FBS maintained better physiological pH and higher accumulated Dox release ratios. In two distinct hepatocellular carcinoma-derived cell lines, treatments with microspheres carrying Dox demonstrated that the cell viabilities decreased in groups with relative high NaHCO3 ratios in time- and dose-dependent manners. Our results suggested that biodegradable alginate microspheres containing relative high NaHCO3 concentrations improved the cytotoxicity effects in vitro.

Curcumin has restrained clinical applications due to poor bioavailability. This study aimed to synthesize cockle shell-derived calcium carbonate (aragonite) nanoparticles (CSCaCO3NP) for delivery of curcumin and to evaluate its kinetic release in vitro. CSCaCO3NP was synthesized and conjugated with curcumin (Cur-CSCaCO3NP) using a simple top down approach and characterized for its physicochemical properties as a potential curcumin carrier. In vitro release profile was assessed using dialysis bag membrane method. The release data were fitted to Korsmeyer-Peppas, Zero order and Higuchi models to evaluate the mechanism of release pattern. A spherical shaped CSCaCO3NP with a surface area of 14.48±0.1 m2/g, average mean diameter size of 21.38±2.7 nm and a zeta potential of -18.7 mV was synthesized which has a high loading content and encapsulation efficiency. The FT-IR and XRD revealed less observable changes on the peaks after conjugation. In vitro kinetic release profile demonstrated sustained release and best fitted to the Higuchi equation model. The results of this study showed the capacity of the synthesized CSCaCO3NP to encapsulate curcumin efficiently with a stable release in vitro. This could give an insight and supportive ideas on the potentials of CSCaCO3NP for curcumin delivery. Therefore, CSCaCO3NP holds future prospects in preclinical framework to enhance curcumin efficacy for oral therapeutic applications.

Diabetes is one of the metabolic syndromes that demands the great concern affecting millions of people all over the world. Viral infections were also considered as responsible for diabetes. Though, variety of medications for prevention and treatment of diabetes are available, numerous limitations are also prevailing that cannot be neglected. Precise drug-targetability, controlled drug-release, oral bioavailability, minimizing side effects are a few to consider. To address most of these shortcomings of traditional drug-delivery models, nanoformulation has been employed therein a wide range of nanoformulation models are developed. The pharmacology of a drug can be greatly enhanced through nanoformulation models in diabetes treatment in terms of enhanced bioavailability, prolonged and sustained drug-lease, maintain maximum drug concentration in serum, higher intestinal absorption, and protection from enzymatic degradation. In this review work, recently designed nanoformulation models for efficient insulin delivery and the other properties concerning diabetes such as reducing blood glucose level, total cholesterol, triglycerides, lipid profile, wound healing, elevating antioxidant enzymes etc. are discussed. Classification of the nanoformulation models is done based on the nature of the fabricating material employed in nanoformulation. This review may be helpful in designing a more efficient nanoformulation model for diabetes treatment.

Reducing the use of stabilizers is one of the main challenges in food emulsions, especially for beverages. This work aimed to produce oleogel structured nanoemulsions (NEs) without additional surfactants. Lecithin-stearic acid (LSa) and lecithin-sorbitan tristearate (LSt) oleogels formed stable NEs under optimized sonication conditions. Microscopy and rheometry revealed that the presence of self-assembled fibrous networks (SAFiNs) in both dispersed and continuous phases provided steric stabilization to NEs. Lecithin acted as crystal habit modifier of SAFiNs and facilitated their phase partitioning. Notably, short fibers of LSt showed better emulsifying efficiency than the long fibers of LSa. Curcumin release studies under simulated gastrointestinal conditions demonstrated that SAFiNs affect the release capabilities of NEs. Polydispersity index, zeta potential and oil syneresis data showed that emulsions are stable for six months. Moreover, NEs showed thermal stability upon curcumin release at 25 and 50 °C. These results suggested that the developed oleogel-based NEs are suitable for delivery of bioactive agents for beverages and other food applications.

Curcumin, a nontoxic and cheap natural medicine, has high therapeutic efficacy for many diseases including diabetes and cancers. Unfortunately, its exceedingly low water-solubility and rapid degradation in the body severely limit its bioavailability. In this work, we prepare a series of biocompatible poly(vinyl anisole)@nonlinear poly(ethylene glycol) (PVAS@PEG) core-shell nanogels with different PEG gel shell thickness to provide high water solubility, good stability, and controllable sustained release of curcumin. The PVAS nanogel core is designed to attract and store curcumin molecules for high drug loading capacity and the hydrophilic nonlinear PEG gel shell is designed to offer water dispersibility and thermo-responsive drug release. The obtained nanogels are monodispersed in spherical shape with clear core-shell morphology. The size and shell thickness of the nanogels can be easily controlled by changing the core-shell precursor feeding ratios. The optimized PVAS@PEG nanogels display a high curcumin loading capacity of 38.0 wt%. The nanogels can stabilize the curcumin from degradation at pH =7.4 and release the curcumin in response to heat in the physiologically important temperature range. The nanogels can enter cells effectively and exhibit negligible cytotoxicity to both the B16F10 and HL-7702 cells at a concentration up to 2.3 mg/mL. Such designed PVAS@PEG nanogels have a great potential to be used for delicate drug delivery.

In this paper we intend to present a dataset that contain a collection of tweets generated as reactions of the release of 50 different movies. The dataset can be used for gaining useful insights regarding the conversation that is generated around a particular movie. It is particularly suitable for conducting sentiment analysis and other NLP techniques. The dataset contains approximately 2.5 million tweets with their related meta data and cover 50 movies. For each movie, its IMDb rating is included. The movies are the 25 releases with the highest number of votes during 2020 and 2021. The collected tweets represent the reactions of the twitter community during the first week of the release date in US of that particular movie. The tweets per movie ranged from 1.000 to approximately 200.000 tweets with an average of 50.000 per release. We used The Internet Archive Wayback Machine in order to retrieve the IMDb movie rating after one week of the US release date. The tweets and related metadata have been collected using the Tweet Downloader tool.

Lipid nanoparticles (LNPs) have attracted extensive attention in tumor immunotherapy in recent years. The strategy of targeting immune cells in cancer therapy has become a research area of great interest. mRNA vaccines are a potential choice for tumor immunotherapy due to their ability to directly encode antigen proteins and stimulate a strong immune response. However, the mode of delivery and lack of stability of mRNA are key issues limiting its application. LNPs are an excellent mRNA delivery vector, and their structural stability and biocompatibility make them an effective means to deliver mRNA to specific targets. This study summarizes the research progress in LNP delivery vector-assisted targeted controlled release mRNA vaccines in tumor immunity. The role of LNPs in improving mRNA stability, immunogenicity and targeting is discussed. In addition, combined with the cutting-edge research results, the potential mechanisms and application prospects of LNP-mRNA vaccines in tumor immunotherapy were further analyzed. This review aims to systematically summarize the latest research progress in LNP delivery carrier-assisted targeted controlled-release mRNA vaccines in tumor immunity to provide new ideas and strategies for tumor immunotherapy and provide more effective treatment plans for patients.

Contamination by microplastics (MP) in aquatic ecosystems is largely due to the release of millions of these particles from treated effluents from Wastewater Treatment Plants (WWTP). Due to the lack of policies and regulations that establish criteria for the control and elimination of MP from WWTP effluents, this research evaluated the presence of MP for particle sizes of 38 and 150 µm in influents and effluents from three WWTP in the port of Acapulco, Mexico. Using optical microscopy and Fourier transform infrared spectroscopy (FTIR) techniques, the MP detected were polyethylene (PE), polypropylene (PP), polyethylene terephthalate (PET) and polyvinyl chloride (PVC). MP removal efficiencies of 82.5 to 98.7% (38 µm) and 86.8 to 97.5% (150µm) were obtained; the MP average daily emissions to the receiving bodies of these three WWTPs were in the ranges of 9.5 x 106 - 4.70 x 108 particles and the annual emissions in the range of 3.05 x 109 - 1.72 x 1011 particles. This work reveals the urgency of implementing regulatory policies to avoid the continuous emission of MP to aquatic ecosystems from WWTPs in Acapulco, Mexico.

Nutrient release from marine sediments in Osaka Bay has a significant impact on nutrient concentrations in seawater. A tsunami induced by the Nankai Trough earthquake may disturb marine sediments in the inner part of Osaka Bay. An incubation experiment to estimate the release rates of NH4-N and PO4-P was conducted to understand the present conditions and to quantify the changes caused by tsunamis. Two types of cores were created: a "control core" representing the current sediment, and a "redeposition core" representing the redeposition after the tsunami. The release rates have been decreasing since the year 2000 and have remained low. The experimental results suggest that the release rate after exposure to an aerobic environment by a tsunami may decrease to approximately 70% for NH4-N and 60% for PO4-P of the current level. In the past, the release rates were values experienced in the inner part of Osaka Bay. However, the reduction in the release rate by tsunamis may be more limiting for primary production under the current situation where the contribution of release for nutrients in seawater is significant.

Background: Antibiotic-containing carrier systems are one option that offers the advantage of releasing active ingredients over a longer period of time. In vitro sustained drug release from a carrier system consisting of microporous β-TCP ceramic and alginate has been reported in previous works. Alginate dialdehyde (ADA) gelatin gel showed both better mechanical properties when loaded into a β-TCP ceramic and higher biodegradability than pure alginate. Methods: Dual release of daptomycin and BMP-2 was measured on days 1, 2, 3, 6, 9, 14, 21, and 28 by HPLC and ELISA. After release, the microbial efficacy of the daptomycin was verified and the biocompatibility of the composite was tested in cell culture. Results: Daptomycin and the model compound FITC protein A (n=30) were released from the composite over 28 days. A Daptomycin release above the minimum inhibitory concentration (MIC) by day 9 and a burst release of 71.7 ± 5.9 % were observed in the loaded ceramics. Low concentrations of BMP-2 were released from the loaded ceramics over 28 days.

Hydrogels obtained from the combination of different polymers are an interesting strategy for the development of controlled release system platforms and tissue engineering scaffolds. In this study, the applicability of sodium alginate-g-(QCL-co-HEMA) hydrogels for these biomedical applications was evaluated. Hydrogels were synthesized by free-radical polymerization using different concentration of the components. The hydrogels were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, and swelling degree; betamethasone release as well as the in vitro cytocompatibility with chondrocytes and fibroblast cells were also evaluated. Scanning electron microscopy confirmed the porous surface morphology of the hydrogels in all cases. The swelling percent was determined at different pH and was observed to be pH-sensitive. The controlled release behavior of betamethasone from the matrices was investigated in PBS media (pH = 7.4) and the drug was released in a controlled manner up to 8 h. Human chondrocytes and fibroblasts were cultured on the hydrogels. The MTS assay shown that almost all hydrogels are cytocompatibles and an increase the proliferation in both cell types after one week of incubation was observed by Live/Dead® assay. These results demonstrate that these hydrogels are attractive materials for pharmaceutical and biomedical applications due to their characteristics, their release kinetics and biocompatibility.

The expression of polysialic acid (polySia) on the neuronal cell adhesion molecule (NCAM), is called NCAM-polysialylation, which is strongly related to the migration and invasion of tumor cells and with aggressive in the clinic. Thus, it’s important to select a proper drug to block tumor cell migration for clinic treatment. In this study, we proposed that lactoferrin (LFcinB11) may be a more ideal candidate for inhibition of NCAM polysialylation comparing with CMP and low molecular weight heparin (LMWH), which were determined based on our NMR studies. On the other hand, because neutrophil extracellular traps (NET) is the most dramatic stage in cell death process, and NETs’ release are related to pathogenesis of autoimmune and inflammatory disorders, with proposed involvement in glomerulonephritis, chronic lung disease, sepsis and vascular disorders. In this study, the molecular mechanism of inhibition of NETs’ release using LFcinB11 as inhibitor was also determined. Based on these results, LFcinB11 is proposed to be bifunctional inhibitor for inhibiting both NCAM polysialylation and NETs releases.

The molecular clusters ((HO)3Si-O-Si(OH)3, and (HO)3Al-O-Si(OH)3 ) representative of aluminosilicate mineral surface were employed to study the dissolution of aluminosilicate in acidic condition via density functional theory with the M06-2X+G(d,p) methodology. The surface termination sites (Si and Al) were both tetra-coordinated and the terminal oxygen was protonated in acidic condition. In the dissolution reaction, the calculated barrier height of the six-membered ring transition state complex containing two water molecules was predicted to be lower than that of four-membered ring transition state complex containing one water molecule. In addition, the calculated barrier heights for Al-terminated sites were predicted to be lower than those for the Si-terminated sites, suggesting that breaking the Al-O bond is easier than Si-O bond in the aluminosilicate mineral surface; the barrier heights of the surface termination sites with protonated terminal oxygen were lower than those without protonated terminal oxygen. With the fracture of Si-O and Al-O bonds, the Si and Al release from the aluminosilicate. These results confirm the experimental conclusions that the acidic condition facilitates the release of Si and Al from the aluminosilicate, and the concentration of Al leaching from aluminosilicate is higher than Si.

Extracellular vesicles (EVs) effectively suppress neuroinflammation and induce neuroprotective effects in different disease models. However, the mechanisms by which EVs regulate neuroinflammatory response of microglia remain largely unexplored. Here, we addressed this issue by testing the action of EVs derived from human exfoliated deciduous teeth stem cells (SHEDs) on immortalized human microglial cells. We found that EVs induced a rapid increase in intracellular Ca2+ and promoted a significant ATP release in microglial after 20 min of treatment. Boyden chamber assays revealed that EVs promoted microglial migration by 20 %. Pharmacological inhibition of different subtypes of purinergic receptors demonstrated that EVs activated microglial migration preferentially through the P2X4R pathway. Proximity ligation and co-immunoprecipitation assays revealed that EVs promote association between milk fat globule-epidermal growth factor-factor VIII (MFG-E8) and P2X4 receptor proteins. Furthermore, pharmacological inhibition of αVβ3/αVβ5 integrin suppressed EV -induced cell migration and formation of lipid rafts in microglia. These results demonstrate that EVs promote microglial motility through P2X4 R/ MFG-E8 – dependent mechanisms. Our findings provide novel insights into the molecular mechanisms through which EVs target human microglia that may be exploited for the development of new therapeutic strategies targeting disease associated neuroinflammation.

In eutrophic waters, such as Mikawa Bay, Japan, anoxic bottom water develops in summer. This causes sulfide release into seawater by sulfate reduction in the sediment, leading to environmental problems. The addition of iron to sediments is a method used to improve the sediment environment, which was devised from a natural phenomenon. However, this method has not yet been quantitatively evaluated. In this study, we aim to quantitatively evaluate the suppressive effect of iron on sulfide release. First, we develop a sediment model that focuses on S and Fe. We then attempted to reproduce the observations and experiments on sulfide dynamics using the model. Consequently, the proposed model was able to reproduce field sulfur and Fe dynamics in sediments. Additionally, the model described the characteristics of sulfide release considering the effects of additive iron materials. Finally, we conducted predictive calculations and quantitatively evaluated the effects of adding iron materials to the sediments in terms of sulfur and iron cycles.

In addition to the risk of vaccine failure caused by strain mismatch, the production of inactivated FMD vaccines is dangerous if adequate biosafety cannot be maintained. Using a high-throughput sequencing protocol optimized for short nucleic acid fragments, the composition of a local inactivated vaccine was analyzed in depth. The serotype O strain identified in the vaccine was genetically identical to viruses found in recent FMD outbreaks in Egypt.

A novel scaffold design has been created to enhance tissue engineering and regenerative medicine by optimizing the controlled, prolonged release of hepatocyte growth factor (HGF), a powerful chemoattractant for endogenous mesenchymal stem cells. We present a new stacked scaffold that is made up of three different fibrin gel layers, each of which has HGF integrated into the matrix. The design attempts to preserve HGF's regenerative properties for long periods of time, which is necessary for complex tissue regeneration. These multi-layered fibrin gels have been mechanically evaluated using rheometry, and their degradation behavior has been studied using D-Dimer ELISA. Understanding the kinetics of HGF release from this novel scaffold configuration is essential for understanding HGF's long-term sustained bioactivity. A range of cell-based tests were carried out to verify the functionality of HGF following extended incorporation. These tests included 2-photon microscopy using phalloidin staining to examine cellular morphology, SEM analysis for scaffold-cell interactions, and scratch and scatter assays to assess migration and motility. The analyses show that the novel stacking scaffold promotes vital cellular processes for tissue regeneration in addition to supporting HGF's bioactivity. This scaffold design was developed for in situ tissue engineering. Using the body as a bioreactor, the scaffold should recruit mesenchymal stem cells from their niche thus combining the regenerative abilities of HGF and MSCs to promote tissue remodeling and wound repair.

Euschistus heros (Hemiptera: Pentatomidae) is one of the main pests of soybean. Egg parasitoids such as Telenomus podisi (Hymenoptera: Scelionidae) can be highly effective in attacking E. heros eggs, preventing the establishment at levels of economic damage. This study evaluated two re-lease methods of T. podisi in soybean. The treatments compared results from release of T. podisi adults fed with honey in cardboard capsules and the release of pupae in bulk. Four aerial releas-es per area were carried out via drone (7,500 females/ha) distributed at 10 points. The population density of E. heros, productivity and reproductive aspects of soybean were evaluated. Total pop-ulation of E. heros was lower in adult release treatment and male population was lower with pupae release. Thousand grain weight had higher values in fed adults treatments compared to release of pupae and control. Number of damage grains was lower in both release treatments compared with the control area. Therefore, the use of biological control with inundative release of T. podisi, regardless of the release method, is recommended within IPM programs, supporting production parameters and benefiting the sustainability of the agroecosystem.

The present work evaluates the food effect on the absorption of rivaroxaban (Riva), a BCS II drug, from the orally administered commercial immediate-release tablet (Xarelto IR) using physiologically based pharmacokinetic (PBPK) and conventional in vitro- in vivo correlation (IVIVC) models. The bioavailability of Riva upon oral administration of Xarelto IR tablet is reported to exhibit a positive food effect. The PBPK model for Riva was developed and verified using the previously reported in vivo data for oral solution (5 and 10 mg) and Xarelto IR tablet (5 and 10 mg dose strength). Once the PBPK model was established, the in vivo performance of the tablet formulation with the higher dose strength (Xarelto IR tablet 20 mg in fasted and fed state) was predicted using the experimentally obtained data of in vitro permeability, biorelevant solubility and in vitro dynamic dissolution data using United States Pharmacopeia (USP) IV flow-through cell apparatus. In addition, the mathematical IVIVC model was developed using the in vitro dissolution and in vivo profile of 20 mg strength Xarelto IR tablet in fasted condition. Using the developed IVIVC model, the pharmacokinetic (PK) profile of the Xarelto IR tablet in fed condition was predicted and compared with the PK parameters obtained via the PBPK model. A virtual in vivo PK study was designed using a single-dose, 3-treatment cross-over trial in 50 subjects to predict the PK profile of the Xarelto® IR tablet in the fed state. Overall, the results obtained from the IVIVC model were found to be comparable with that from the PBPK model. The outcome from both the model pointed to the positive food effect on the in vivo profile of the Riva. The developed models thus can be effectively extended to establish bioequivalence for the marketed and novel complex formulations of Riva such as amorphous solid dispersions.

Slow and controlled release systems for drugs, have attracted increasing interest recently. A highly efficient metal-organic gels (MOGs) drug delivery carrier, i.e., MIL-100(Al) gels, has been fabricated by a facile, low cost and environment friendly one-pot process. The unique structure of MIL-100(Al) gels leads to a high loading efficiency (620 mg/g) towards doxorubicin hydrochloride (DOX) as a kind of anticancer drugs. DOX-loaded MOGs exhibited high stability under physiological conditions and sustained release capacity of DOX for up to 3 days (under acidic environments). They further showed sustained drug release behavior and excellent antitumor effects in in vitro experiments on HeLa cells, in contrast with the extremely low biotoxicity of MOGs. Our work provides a promising way for the anticancer therapy, by utilizing this MOGs-based drug delivery system, as an efficient and safe vehicle.

The cross-linked microspheres were prepared and loaded with Favipiravir SARS-CoV-2 antiviral drug, by copolymerization of chitosan (CS) with a polysaccharide extracted from fresh pomegranate peels. Moreover, glutaraldehyde (Glu) has been used as chemical cross-linker ,and sodium hexametaphosphate (SHMP) as physical cross-linker. The extracted polysaccharide was analyzed and different techniques have been used and the analyses leads to the fact that it is pectin .The surface morphology of the prepared microspheres was studied use scanning electron microscope where the size and the shape factor (S) of Glu microspheres have shown high values(74.27μm) and (0.852) respectively means their surfaces are tends to roughness, whereas the SHMP microspheres have shown size particle(20.47μm)and shape factor (0.748) which gives indication that the SHMP microspheres have smooth surfaces. The swelling studies have shown that Glu microspheres have higher degree of swelling which means SHMP microspheres are more compact. The prepared microspheres have shown more Loading percentage of Favipiravir antiviral drug in SHMP microspheres(37%w/w)in comparison with Glu microspheres(35%w/w) where the electrostatic interaction between the Favipiravir ions and SHMP anions help for more loading. The microspheres prepared under different types of cross-linking have shown initially burst release of Favipiravir and followed by a step of controlled release for a certain time where its period depends on the pH of the release media. Both Glu and SHMP cross-linked microspheres have shown high controlled release time in buffered release solution of pH 7.4 and for a less periods in pH 1.3 and pH 9.4 which may related to the type of electrostatic interactions between drug and polymer system and their reactions with release solution ions.

This paper introduces an innovative nanotechnology-based approach that provides a pathway to enhance the energy release efficiency of nanoenergetic materials (nEMs) by harnessing self-synchronized collective atomic vibrations and phonon wave resonance within the transition domains between nanocomponents, without altering the material composition. The key innovation involves incorporating finely-tuned 2D-ordered linear-chain carbon-based multilayer nano-enhanced interfaces as programmable nanodevices into the transition domains using advanced multistage processing and assembly techniques. These programmable nanodevices enable precise control over self-synchronized collective atomic vibrations and phonon wave propagation, leading to synergistic effects. To activate and optimize these effects, a combination of various methods is employed, including energy-driven initiation of allotropic phase transformations, surface acoustic wave-assisted micro/nano-manipulation, heteroatom doping, directed self-assembly using high-frequency electromagnetic fields, and data-driven inverse design approaches. By leveraging a data-driven inverse design strategy and uncovering hidden structure-property relationships, we maximize energy release efficiency using the carbon nano-materials genome approach derived from multifactorial neural network-based predictive models. This approach not only unlocks new functionalities in nEMs but also improves environmental performance and safety levels. By pioneering transformative pathways for nEMs through harnessing phonon wave resonance in low-dimensional nanocarbon transition interfaces, this research brings significant advancements in the field.

Arthroscopic capsular release (ACR) is used for persistent shoulder stiffness after an index surgery. No cases of post-ACR humeral head osteonecrosis have been reported to date. A 56-year-old male patient underwent open reduction and internal fixation using a hook plate for acromioclavicular joint dislocation. Despite hardware removal, the patient presented with unresolved shoulder pain and range-of-motion (ROM) limitation. He had a history of hypertension, chronic hepatitis B infection, and alcohol consumption. Preoperative ROM was forward flexion 90°and internal rotation sacral level. Preoperative functional status was visual analog scale (VAS) score 4, American Shoulder and Elbow Surgeons (ASES) score 51, and Constant–Murley (CMS) score 48, and normal radiography and magnetic resonance imaging. Standard ACR was performed with 360° release of the joint capsule via electrocautery ablation. Six-months post-ACR, ROM (forward flexion: 135°, abduction: 135°, external rotation: 70°, internal rotation: T10 vertebra) and functional outcomes (VAS 2; ASES79; CMS 75) were significantly improved, without interval change in radiographic assessment. However, 21 months later, he had recurrent shoulder pain and decreased ROM. Radiography revealed humeral head osteonecrosis. Patients with intrinsic or extrinsic risk factors related to humeral head circulation disturbance should be monitored for humeral head osteonecrosis post-ACR.

Background: It is not clear whether rehabilitation after surgery for trigger finger is effective. The aim of this study was to reveal the effectiveness for trigger finger. Methods: This study was a randomized, controlled trial that included patients who underwent operations for trigger fingers. The patients in the rehabilitation group had postoperative occupational therapy (OT) for 3 months, while the patients in the control group were not referred for rehabilitation but received advice for a range of motion exercise. We evaluated the severity of trigger finger, Disability of Arm-Shoulder-Hand (DASH) score, pain-visual analogue scale (VAS), grip strength, whether they gained a full range of motion (ROM), and complications before and after surgery. Results: Finally, 29 and 28 patients were included in the control and rehabilitation groups, respectively. DASH score, grip strength, and ROM were significantly improved in the rehabilitation group from that preoperatively at final follow-up. Pain was significantly improved in both groups from that preoperatively at final follow-up. Subgroup analysis showed that there is a significant difference in the DASH score of patients doing housework or light work and those with a duration of symptoms &gt; 12 months between the control and rehabilitation groups at the final follow-up.