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.

Preventing or treating infections at implantation sites where the risk of bacterial contamination is high requires the development of intelligent drug delivery systems. In this work, honeycomb structures as a potential drug carrier were obtained for the first time in a fast, one-step anodization process of titanium grade 4, lasting only 60 seconds. Fourth generation oxide nanotube layers were obtained from an aqueous solution of 0.5% AgNO3 in the voltage range from 50 to 80 at 15(1) °C. The FE-SEM method showed the length of the oxide nanotubes from 1.02(2) µm at 50 V to 230(8) nm at 80 V. The EDS analysis revealed that during anodizing, silver particles are deposited on the Ti G4 up to 2.2(5) wt.%. Electrochemical measurements by open circuit potential and anodic polarization curves methods proved the improvement of in vitro corrosion resistance as a result of Ti G4 anodizing. Assessment of the anodized Ti G4 as gentamicin sulfate carrier carried out using ATR-FTIR and UV-VIS absorption spectroscopy revealed that the obtained oxide nanotube layers can be used for application of drugs directly to the tissue around the implant. This method of application allows full use of the therapeutic dose of the antibiotic used.

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.

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.

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.

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.

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 > 12 months between the control and rehabilitation groups at the final follow-up.

In this work, polyacrylic acid-functionalized MCM-41 was synthesized, which was further interacted with calcium ions, to realize enhanced pH-responsive nanocarrier for sustained drug release. First, mesoporous silica nanoparticles (MSNs) were prepared by the sol-gel method. Afterward, (3-trimethoxysilyl)propyl methacrylate (TMSPM) modified surface was prepared by using the post-grafting method, then polymerization of acrylic acid was proceeded. After adding calcium chloride solution, polyacrylic acid-functionalized MSNs with calcium-carboxyl ionic bonds in the polymeric layer, which can prevent the cargo from leaking out of the mesopore, were prepared. The structure and morphology of the modified nanoparticles (PAA-MSNs) were characterized by X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectroscopy, transmission electron microscopy (TEM), and N2 adsorption-desorption analysis, etc. The controlled release of guest molecules was studied by using 5-fluorouracil (5-FU). The drug molecules-incorporated nanoparticles showed different releasing rates under different pH conditions. It is considered that our current materials have the potential as pH-responsive targeted nanocarriers in the field of medical treatment.

Diabetes is a major health concern that the next-generation of on-demand insulin releasing implants may overcome for personalized therapy. Therein, 3D-printed phenylboronic acid-containing subcutaneous implants with on-demand glucose-triggered drug release abilities are produced using high resolution stereolithography technology. To that end, the methacrylation of phenylboronic acid is targeted following a two-step reaction. The resulting photocurable phenylboronic acid derivative is accordingly incorporated within bioinert polyhydroxyethyl methacrylate-based hydrogels at varying loadings. The end result are sub-centimeter scaled 3D-printed bionert implants that can be remotely activated with 1,2-diols and 1,3-diols such as glucose for on-demand drug administration such as insulin. As a proof of concept, varying glucose concentration from hypoglycemia to hyperglycemia levels readily allow the release of pinacol, i.e. a model molecule with similar release properties than insulin, at respectively low and high rates. In addition, the results demonstrated that adjusting the geometry and size of the 3D-printed part is a simple and suitable method for tailoring the release behavior and dosage.

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.

Chronic and non-healing wounds demand personalized and more effective therapies for treating complications and improve patient adherence. This work aims to develop a suitable chitosan-based scaffold to provide 24 hours controlled release of DKT, by taking advantage of chitosan’s thermo-responsive behavior as well as local hyperthermia in wounds. Three formulation prototypes were developed using chitosan (F1), 2:1 chitosan: PVA (F2), and 1:1 chitosan:gelatin (F3). Compatibility tests were done by DSC, TG, and IR spectroscopy. SEM was employed to examine the morphology of the surface and inner layers from the scaffolds. In vitro release studies were performed at 32 °C and 38 °C to evaluate the release profiles, which were later adjusted to different kinetic models for the best formulation. F3 showed the most controlled release of DKT at 32 °C for 24 hours (77.75 ± 2.72 %), and reduced the burst release in the initial 6 hours (40.18 ± 1.00 %), while at 38 °C the release reached 88.52 ± 2.07 % at 12 hours. The release profile for this formulation fits with Hixson-Crowell and Korsmeyer-Peppas kinetic models at both temperatures. Therefore, the developed chitosan/gelatin thermo-responsive scaffold provides a suitable system for wound healing with a controlled release of DKT for 24 hour-use, which can overcome adherence issues and wound complications.

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.

Agriculture technical development exclusively relies on the effective delivery of agrochemicals and water to the plants and reduce the harmful effects of the agrochemicals on the useful organisms in the soil. Wherefore, super absorbent hydrogels were prepared by copolymerization of gum Arabic (GA) with chitosan (CS) or poly(vinyl alcohol) (PVA), and cross-linked by N,’N-methylenebisacrylamide (MBA) chemically (CH) or using sodium hexametaphosphate (SHMP) as physical (PH) cross-linker. The prepared hydrogels include PVA/GA-CH, PVA/GA-PH, CS/GA-CH and CS/GA-PH showed different degree of swelling (DS) in the following swelling medium, deionized water (DW), river water(RW) and buffer solution pH9. PVA/GA-CH and CS/GA-CH hydrogels have showed 84g/g and 63g/g maximum DS in RW respectively, while PVA/GA-PH and CS/GA-PH hydrogels have showed 81g/g and 69g/g maximum DS in pH9 respectively. The water- retention capability of some hydrogels were studied using a mixture of 0.5%(w/w) hydrogel in agricultural soil and the composite showed about 20 days extra retain of water with a control sample of soil alone. The hydrogels were loaded using urea the important fertilizer in agriculture field. The hydrogels of higher DS were only loaded, where PVA/GA-CH hydrogel has shown 89%(w/w) maximum loading percentage (Lmax%), and CS/GA-PH hydrogel reached 79.75%(w/w) of urea. The release behavior in different medium and degree of temperatures of loaded hydrogels were studied. Generally, PVA/GA-CH hydrogel have shown better release profile in RW medium at 10oC, while CS/GA-PH hydrogel showed more controlled release in pH9 medium at 30oC. Different analytical methods of SEM, FTIR of loaded hydrogel and after their release were achieved, whereas XRD,1H NMR and (TGA, DSC) of prepared hydrogels have been characterized.

This study was carried out to formulate and evaluate controlled release (CR) matrix tablets of Acyclovir using combination of hydrophilic and hydrophobic polymers. Acyclovir is a guanine derivative and is its half-life is short hence administered five times a day using immediate release tablets. Six formulations (F1-F6) were developed using Ethocel and Carbopol in equal combinations at drug-polymer (D:P) ratio of 10:5, 10:6, 10:7, 10:8, 10:9 and 10:10. Solubility study was performed using six different solvents. The compatibility studies were carried out using FTIR and DSC. According to USP, Quality Control and dimensional tests (hardness, friability, disintegration and thickness) were executed. In-vitro drug release studies of Acyclovir was carried out in dissolution apparatus using using 0.1 N HCl medium at constant temperature of 37 ± 0.5 ºC. In order to analyze the drug release kinetics, five different mathematical models were applied to the release data. The results showed that there was no incompatibility between drug and polymers. Physical QC tests were found within limits of USP. The release was retarded upto 24 hrs and non-fickian in-vitro drug release mechanism was found. A formulation developed using blend of polymers, showed excellent retention and desired release profiles thus providing absolute control for 24 hrs.

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.

In this paper, we introduce a novel controlled quantum communication protocol utilizing a quantum random walk involving one sender, one receiver, and multiple controllers. Inspired by classical random walk theory, quantum random walk serves as the foundation of our proposed protocol. With this protocol, we demonstrate the ability to transfer any n- dimensional quantum state to any party facilitated by any m number of controllers. Furthermore, any of the (m+1) individuals has the freedom to accept the role of the receiver. Rigorous testing of the protocol’s performance is conducted through quantum state tomography. We have run different variations of the circuits in IBMQ QASM simulator. Additionally, we explore the effectiveness of a weak measurement-based protocol designed to mitigate amplitude-damping noise’s detrimental effects on quantum states. By analyzing fidelity versus amplitude damping noise-strength plots for scenarios with and without the weak measurement protocol, we provide valuable insights into its protective capabilities across various levels of noise. These find- ings illuminate the protocol’s potential applications in quantum information processing

Exogenous melatonin, a nutraceutical for maintaining a healthy sleep-wake cycle and managing sleep disorders, requires large, repeated doses due to low bioavailability and short half-life. This necessitates the development of a sustained-release formulation with a longer half-life and sustained plasma concentration. Therefore, exogenous novel 5 mg sustained-release melatonin capsules (Melatonin-SR, test product) were formulated. This open-label cross-over study compared the pharmacokinetics (maximum concentration [Cmax], time to reach Cmax [Tmax], area under the curve [AUC] and elimination half-life [t1/2]) and safety of Melatonin-SR with 5 mg immediate-release melatonin capsules (Melatonin-IR, reference product) after single-dose oral administration in healthy fasting adults. Sixteen participants (aged 18-45 years) were randomized (1:1) to receive either Melatonin-SR or Melatonin-IR in two periods with a 7-day washout period. Melatonin-SR reported lower Cmax (11446.87 pg/mL) compared to Melatonin-IR (22786.30 pg/mL). The mean Tmax of Melatonin-SR and Melatonin-IR was 1.26 h and 0.87 h, respectively. The mean t1/2 of Melatonin-SR (5.10 h) was prolonged by five-fold compared to Melatonin-IR (1.01 h). One adverse event (vomiting) was reported following administration of the Melatonin-IR. Melatonin-SR resulted in higher and sustained plasma melatonin concentrations for an extended period and was well-tolerated. Hence, Melatonin-SR may be a promising nutraceutical for maintaining healthy sleep.

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.

: Background: Brain-derived neurotrophic factor (BDNF) is a crucial mediator of neuronal plasticity. Here, we investigated the effects of controlled normobaric hypoxia (NH) combined with physical inactivity on BDNF blood levels and executive functions. Methods: Twenty-five healthy adults (25.8±3.3 years, 15 female) were analyzed in a randomized, controlled cross-over study. Each intervention began with a 30 min resting phase under normoxia (NOR), followed by a 90 min continuation of NOR or NH (peripheral oxygen saturation [SpO₂] 85-80%). Serum and plasma samples were collected every 15 min. Heart rate and SpO₂ were continuously measured. Before and after each exposure, cognitive tests were performed and after 24 h another follow-up blood sample was taken. Results: NH decreased SpO₂ (p<.001, η_p²=.747) and increased heart rate (p=.006, η_p²=.116) significantly. The 30-min resting phase under NOR led to a significant BDNF reduction in serum (p <.001, η_p²=.581) and plasma (p <.001, η_p²=.362). Continuation of NOR further significantly reduced BDNF after another 45 min (p=.018) in serum and after 30 min (p=.040) and 90 min (p=.005) in plasma. There was no significant BDNF decline under NH. 24 h Follow-up examination showed a significant decline of serum BDNF, both after NH and NOR. Conclusion: Our results show that NH has the potential to counteract physical inactivity-induced BDNF decline. Therefore, our study emphasizes the need for a physically active lifestyle and its positive effects on BDNF. This study also demonstrates the need for a standardized protocol for future studies to determine BDNF in serum and plasma.

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.

The new unique technology for granulation of metals and nonmetallic melts is presented in the paper. It was created on the newly developed controlled film flow disintegration with rapid cooling of the droplets and solidified granules in amorphous state. Three new phenomena discovered by us created the base for 3 different methods for granulation of metals and nonmetallic melts in a wide range of granules’ sizes. Electromagnetic resonance method allows producing granules of metals in the range of 1 mm and over. The soliton-like vibrational regime is available for production of any granulation material in the range 0.1-1 mm. Moreover, the shockwave regime is applicable for producing particles from 10 micrometers by size. All methods produce particles of the stated size with a narrow distribution by size: deviation from the average size no more than 50%. The other known methods do not produce granules with such high cooling rate, which can realize the amorphous state and cannot regulate size of particles in such bright but narrow range from 10 micrometers to 1-2 mm.

Background: Spine shape parameters, such as leg length, kyphotic or lordotic angle, are influenced by low back pain. There is also evidence that the thoracolumbar fascia plays a role in such pa-thologies. This study examined the immediate effects of a myofascial release technique (MFR) on the thoracolumbar fascia and of an osteopathic treatment (OMT) on postural parameters in pa-tients with acute low back pain (aLBP). Methods: This study was a single-blind randomized pla-cebo-controlled trial. Seventy-one subjects (43.8 ± 10.5 years) suffering from aLBP were randomly and blinded assigned to three groups to be treated with MFR, OMT or a placebo intervention. Spinal shape parameters (functional leg length discrepancy (fLLD), kyphotic angle, lordotic an-gle) were measured before and after the intervention using video raster stereography. Results: Within the MFR group, fLLD reduced by 5.2 mm, p < 0.001 and kyphotic angle by 8.2 degrees, p < 0.001. Within the OMT group, fLLD reduced by 4.5 mm, p < 0.001 and kyphotic angle by 8.4 °, p = 0.007. Conclusion: MFR and OMT have an influence on fLLD and the kyphotic angle in aLBP patients. The interventions could have a regulating effect on the impaired neuromotor control of the lumbar muscles.

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.

Acute myocardial infarction (AMI) results from vulnerable plaque rupture, causing ischemic cardiomyocyte necrosis and intense inflammation. Paradoxically, this inflammation releases factors that aid heart repair. Recent findings suggest a role for extracellular vesicles (EVs) in intercellular communication during post-AMI cardiac repair. However, EVs’ tissue origin and chemokine profile in the blood of patients with AMI remains unclear. This study characterized EV tissue origin and chemokine receptor profile in the coronary and peripheral blood of patients with AMI. The results reveal that vesicles isolated from coronary and peripheral blood plasma are enriched in tetraspanin (CD9) and express CD81+, CD90+, and CD144+. The vesicle size ranged between 145 and 162 nm, with the control group exhibiting smaller vesicles than the AMI group. Furthermore, all vesicles expressed CCR6+ and CXCR3+, whereas a small percentage expressed CCR4+. In addition, a decrease in CXCR3+ and CCR6+ positivity was observed in coronary and peripheral blood vesicles compared with the control. Non-difference was found in the coronary and peripheral blood for the CXCR3+ and CCR6+ markers. In conclusion, our study demonstrates, for the first time, changes in the number of extracellular vesicles expressing CD144+, CXCR3+, and CCR6+ in the peripheral circulation of patients with AMI. Extracellular vesicles present in the peripheral circulation of patients with AMI hold excellent promise as a potential diagnostic tool.

Polar stratospheric clouds (PSCs) form in polar regions typically between 15 and 25 km, when the local temperature is sufficiently low. PSCs play an important role in the ozone chemistry and the dehydration and denitrification of the stratosphere. Lidars with a depolarization channel may be used to detect and classify different classes of PSCs. The main PSC classes are water ice, nitric acid trihydrate (NAT) and supercooled ternary solutions (STS), the latter being liquid droplets consisting of water, nitric acid and sulphuric acid. PSCs have been observed at the lidar observatory at Concordia Station from 2014 on. The harsh environmental conditions at Concordia during winter render successful lidar operation difficult. In order to facilitate the operation of the observatory several measures have been put in place to achieve an almost complete remote control of the system. PSC occurrence is strongly correlated with local temperatures and is affected by dynamics, as the PSC coverage during the observation season shows.

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.

Aedes albopictus is considered one of the major invasive species in the world and can transmit viruses such as dengue, Zika, or chikungunya. The Sterile Insect Technique (SIT) can be used to suppress the native populations of Ae. albopictus. To support the development of the release strategy during the SIT application, Mark-Release-Recapture (MRR) studies are crucial. Mean-while, weather conditions can affect the MRR trial’s results and it is critical to understand the influence of climatic factors on the results. In October 2022 in Faro, Southern Portugal, 84,000 ir-radiated sterile males were released for three consecutive weeks and mosquitoes were recapture by Human Landing Collections (HLC) one, two, four and six days after. Generalised linear models with a negative binomial family and log function were used to estimate the factors asso-ciated with the number of recaptured mosquitoes, prevalence ratios, and the 95% confidence in-tervals (CI). A total of 84,000 sterile male mosquitoes were released, with 528 recaptured (0.8%) by HLC. The prevalence of recaptured mosquitoes was 23% lower when the wind intensity was moderate. Sterile-marked males had an average median distance travelled of 88.7 m. Median probability of daily survival and the average life expectancy were 61.6% and 2.1, respectively. Wild male population estimates was 443.33 males/ ha. Despite no statistically significant asso-ciation was found with humidity, temperature and precipitation, it is crucial to consider weather conditions during MRR trials analyses to obtain the best determinants estimation and a more ef-ficient application of SIT in an integrated vector management program.

This study aimed to explore the fermentation behavior of selected potential probiotic strains during sorghum fermentation, considering their microbial counts, pH levels, and antibacterial activity, their ability to break down starch. The fermentation processes were conducted in the presence and absence of glucose, and the lactic acid bacterial strains underwent controlled fermentation to assess microbial counts, amylase activity, pH, and lactic acid levels in the presence and absence of glucose. In addition, the inhibitory activity of these potential probiotic strains against pathogenic bacteria (Salmonella typhimurium, Escherichia coli, and Staph-ylococcus aureus) was examined through co-culturing. The results demonstrated that all nine Lactobacillus strains exhibited robust growth in both sugar and sugar-free fermentation experiments. Glucose supple-mentation significantly enhanced lactic acid yield which was in a range of 0.19-0.52 % compared to fer-mentation without glucose with a range of 0.03-0.29 %. The selected Lactobacillus strains effectively lowered the pH to less than 4 after 24 hours, producing substantial lactic acid. Notably, in the absence of glucose, only Lb. helveticus D7 and Lb. amylolyticus D12 achieved pH levels below 4 after 8 hours, producing the highest lactic acid amounts of 0.27 and 0.29 % after 24 hours, respectively. Amylase activity was detected on two strains D7 and D12. Furthermore, most of the tested Lactobacillus strains demonstrated complete inhibition of pathogen growth after 24 hours of co-culturing, suggesting their potential for enhancing the safety quality of sorghum-based fermented products.

This paper presents geometric analyses of welded frames after free relaxing and vibratory stress relief (VSR). Respected frames were tested components of a prototype packaging machine. Two types of relaxation were carried out to remove stresses introduced as a result of welding process. One of the frame was subjected to free relaxing, while the other one to accelerated vibration relaxing. Detection of the frame geometry changes was performed using a photogrammetric system. In addition, an evaluation of the geometry change was conducted for fifteen variants of steel frame support. A comparative analysis of the geometric deviations of the frames after free and vibratory stress relief confirmed the assumption that the frame after vibration stress relief better reproduces the nominal dimensions. Nevertheless, it should be emphasized that after vibratory stress relief the frame is not subject to further deformation, which is a desirable effect. In the case of free relaxing, the frame undergoes dimensional changes in a random manner. In summary, carrying out accelerated vibratory stress relief allows control of spontaneous dimensional changes in the designed frame of a packaging machine resulting from spontaneous relaxation of stresses arising from the welding process. The shortening of the relaxation process of the welded frame is also an unquestionable advantage.

Amidst increasing awareness of diet-health relationships, plant-derived bioactive peptides are recognized for their dual nutritional and health benefits. This study investigates bioactive peptides released after Alcalase hydrolysis of protein from chachafruto (Erythrina edulis), a nutrient-rich South American leguminous plant, focusing on their behavior during simulated gastrointestinal digestion. Evaluating their ability to scavenge radicals, mitigate oxidative stress, and influence immune response biomarkers, the study underscores the importance of understanding peptide interactions in digestion. Methods included previous enzymatic hydrolysis with Alcalase to obtain peptides, and results show significant radical scavenging and oxidative stress protection by chachafruto peptides. These findings highlight the potential of chachafruto bioactive peptides in functional foods and nutraceuticals, supporting human health through dietary interventions.

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.

Novel pH responsive semi-interpenetrating polymer hydrogels based on tamarind gum-co-poly(acrylamidoglycolic acid) (TMGA) polymers have been synthesized using simple free radical polymerization in the presence of bis[2-(methacryloyloxy)ethyl] phosphate as a crosslinker and potassium persulfate as a initiator. In addition, these hydrogels have been used as templates for green synthesis of silver nanoparticles (13.4±3.6 nm in diameter, TMGA-Ag) by using leaf extract of Teminalia bellirica as reducing agent. Swelling kinetics and equilibrium swelling behavior of the TMGA hydrogels have been investigated in various pH environment the maxium % equilibrium swelling behavior observed i.e., 2882±1.2. The synthesized hydrogels and silver nanocomposites have been characterized by the UV, FTIR, XRD, SEM and TEM. TMGA and TMGA-Ag hydrogels have been investigated to study the characteristics of drug delivery and antimicrobial study. Doxorubicin hydrochloride, a chemotherapeutic agent successfully encapsulated with maximum encapulstaion efficiency i.e., 69.20±1.2 and performed in vitro release studies in pH physiological and gastric environment at 37 ℃. The drug release behavior is examined with kinetic models such as zero order, first order, Higuchi, Hixson Crowell, Korsmeyer-Peppas. These release data was the best fitted with the Korsemeyer-Peppas transport mechanism with n=0.91. Treatment effect on HCT116 Cell, human colon cancer cells were assessed with cell viability and cell cycle analysis. Antimicrobial activity of TMGA-Ag hydrogels is studied against to Staphylococcus aureus and Klebsiella pneumonia. Finally, the results demonstrate that TMGA and TMGA-Ag are promising candidates for anti-cancer drug delivery and inactivation of pathogenic bacteria, respectively.

Background: This study stands as a pioneer in the histological evaluation of the biological behavior of a novel implant design featuring decompressive cervical blades. Hence, the aim of the present study was to evaluate the healing outcome in cortical regions at where decompressive protocols were adopted using implants equipped with blades. Materials and methods: Blades with varying diameters were integrated into the coronal portion of the implant to prepare the cortical region of rabbit tibiae. The blade diameters differed from the implant collar by the following amounts: control group (0 µm), +50 µm, and +200 µm. Results: No marginal bone loss was detected. Instead, all implants exhibited new bone formation in the coronal region. Complete closure was observed in the CG-0 group, as well as in the TG-50 and TG-200 groups, despite the presence of marginal gaps without primary bone contact at installation. In the apical region, most implants breached the cortical layer. Nevertheless, new bone formation in this region completely closed the osteotomy, effectively isolating the internal environment of the tibia from the external. Conclusions: The use of a blade attached to the implant body enabled precise preparation of the cortical layer, allowing for controlled decompression in the targeted area. This technique resulted in optimal osseointegration with no loss of marginal bone, and complete restoration of marginal gaps ranging from 0 µm to 200 µm.

The release of the active substance from the matrix modified-release tablets based on Kollidon®SR and chitosan depends on its solubility in the dissolution medium and on the composition of the matrix-forming polymers. The study is based on new oral matrix tablets based on Kollidon®SR and chitosan, formulated to optimize the low oral bioavailability of chlorzoxazone, a non-steroidal anti-inflammatory drug, a class II Biopharmaceutical Classification System. Nine types of chlorzoxazone matrix tablets were obtained using the direct compression method, and their combination at 1:1, 1:2, 1:3 chlorzoxazone/ excipients, 20%-40% (w/w) Kollidon®SR, 3-7% (w/w) chitosan and the auxiliary substances were formulated in constant concentrations. Pharmaco-technical characterization included the analysis of flowability and compressibility properties (flow time, friction coefficient, angle of repose, Hausner ratio, Carr Index), and of pharmaco-chemical characteristics (mass and dose uniformity, thickness, diameter, mechanical strength, Friability, degree of softening, in vitro release profile) of the tablets. Based on the initial evaluation of the pharmaco-technical analysis, pharmaco-chemical characteristics, and in vitro release profile, only three matrix tablet formulations (F1b, F2b, and F3b) were further tested. They were evaluated through Fourier-transform infrared spectrometry, X-ray Diffraction, thermogravimetry, differential scanning calorimetry, and in vitro dissolution tests. The three formulations were comparatively studied regarding the release kinetics of active substances using in vitro release testing. The results were analyzed by fitting into four representative mathematical models for the modified release oral formulations. In vitro kinetic study reveals a complex mechanism of release occurring in the first (0 - 2 hours) and second (2.0 hours – 36 hours) steps of drug release. Two factors have been calculated to assess the release profile of chlorzoxazone: f1 - the similarity factor and f2 - the factor difference. The results have shown that both Kollidon®SR and chitosan may be used as matrix-forming agents when combined with chlorzoxazone. In vitro dissolution tests revealed the F2b sample, data suggesting a faster drug release. The three formulations showed optimum pharmaco-technical properties and in vitro kinetic study, and they had tremendous potential to be used in oral pharmaceutical products for the controlled delivery of chlorzoxazone.

Metasurface constitutes one of the most promising technologies for holographic imaging; however, the work for terahertz (THz) metasurface holographic imaging is relatively limited. Here, we propose a THz dielectric geometric-propagation phase metasurface, which can operate dual-mode (reflection and transmission) and reconfigurable multifunctional holographic imaging. The dual-mode is realized by controlling the Fermi energy level (Ef) of the graphene integrated into the metasurface unit, and the reconfigurable three-channel holographic imaging in reflection or transmission mode are achieved by switching the feed polarization among left-handed circular polarization (LCP), right-handed circular polarization (RCP) and linear polarization (LP). The metasurface is designed based on the transmission mode, and a physical model for switching to the reflection mode is established. For the first time to the best of our knowledge, a reflection-transmission dynamic modulation THz holographic imaging metasurface has been developed. The holographic metasurface operates in transmission mode at Ef = 0.1 eV, and in reflection mode at Ef = 0.9 eV. Compared with recently published holographic imaging metasurfaces, the proposed metasurface offers the following advantages: high holographic efficiencies (42.5% to 49%), more holographic imaging channels, dynamic modulation dual-mode operations, and reconfigurability.

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 crystallization conditions from the solution play an important role in determining the mor-phology, phase composition, and photovoltaic properties of perovskite films. Post-processing of the obtained films can have a crucial role in increasing the grain size of perovskite and enhancing its crystallinity. It has been shown that the formation of crystal nuclei can be utilized to accelerate crystallization. In this case, crystallization occurs through the growth of seed crystals created in the solution, enabling the formation of relatively large crystals. For the deposition of CH3NH3PbI3 hybrid halide perovskite films from a solution of the perovskite in dimethylformamide the spin coating technique was employed. Pre-crystallization was achieved by annealing the films at a temperature of 100 or 110 °C. The dissolution process involved adding a drop of dimethylformamide onto the substrate surface and allowing it to partially dissolve the perovskite film. Subsequently, residual solvent was removed through spin coating. The mor-phological analysis of the perovskite film surface after recrystallization at temperatures ranging from 80 to 130 °C was performed. The infrared transmission spectra of the obtained perovskite films were investigated, and their light absorption characteristics were studied through transmission spectra. The perovskite structure in the obtained films was confirmed by the peaks observed in the X-ray diffraction patterns.

This research presents a novel algorithmic implementation to improve the analysis of visually controlled interception and accompanying motor action through the computational application of harmonic ratios and stimulation invariants. Unlike traditional models that focus mainly on psychological aspects, our approach integrates the relevant constructs into a practical mathematical framework. This allows for dynamic prediction of interception points with improved accuracy and real-time perception-action capabilities, essential for applications in neurorehabilitation and virtual reality. Our methodology uses stimulation invariants as key parameters within a mathematical model to quantitatively predict and improve interception outcomes. The results demonstrate the superior performance of our algorithms over conventional methods, confirming their potential for ad-vancing robotic vision systems and adaptive virtual environments. By translating complex theo-ries of visual perception into algorithmic solutions, this study provides innovative ways to im-prove motion perception and interactive systems. This study aims to articulate the complex inter-play of geometry, perception, and technology in understanding and utilizing cross-ratios at infin-ity, emphasizing their practical applications in virtual and augmented reality settings.

Abstract Octreotide is the first synthetic peptide hormone, consisted of eight amino acids, that mimics the activity of somatostatin, a natural hormone in the body. During the past decades, advanced instrumentation and crystallographic software established X-ray Powder Diffraction (XRPD) as a valuable tool for extracting structural information of biological macromolecules. The latter was demonstrated by the successful structural determination of octreotide at a remarkably high d-spacing resolution (1.87 Å) (PDB code: 6vc1). This study focuses on the response of octreotide to different humidity levels and temperatures, with a particular focus on the stability of the polycrystalline sample. XRPD measurements were accomplished employing an Anton Paar MHC-trans humidity-temperature chamber installed within a laboratory X’Pert Pro diffractometer (Malvern Panalytical). The chamber is employed to control and maintain precise humidity and temperature levels of samples during XRPD data collection. Pawley analysis of the collected data sets revealed that the octreotide polycrystalline sample is remarkably stable and no structural transitions were observed. The compound retains its orthorhombic symmetry (space group: P212121, a = 18.57744(4) Å, b = 30.17338(6) Å, c = 39.70590(9) Å, d~ 2.35 Å). However, a characteristic structural evolution in terms of lattice parameters and volume of the unit-cell is reported mainly upon controlled relative humidity variation. In addition, an improvement of signal-to-noise ratio in the XRPD data under a cycle of dehydration/rehydration is reported. These results underline the importance of considering the impact of environmental factors, as humidity and temperature, in the context of structure-based drug design, thereby contributing to the development of more effective and stable pharmaceutical products.

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.

Lifestyle interventions can prevent type 2 diabetes (T2DM). However, some in-dividuals do not experience anticipated improvements despite weight loss. Bi-omarkers to identify such individuals at early stages are lacking. IGF-1 and IGFBP-1 were shown to predict T2DM onset in prediabetes. We assessed if these markers also predict the success of lifestyle interventions, thereby possibly guid-ing personalized strategies. We analyzed fasting serum levels of IGF-1, IGFBP-1 and IGFBP-2 in relation to changes in metabolic and anthropometric parameters, including intrahepatic li-pids (IHL) and visceral adipose tissue (VAT) volume measured by MRI, in 345 high-risk prediabetic participants (54% female; aged 36-80 years). Participants were enrolled in three randomized dietary intervention trials and assessed both at baseline and one year post-intervention. Statistical analyses were performed using IBM SPSS Statistics (version 28), significance set at p

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.

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].

The interface of a structural system in the soil is usually unsaturated. A decrease in the shear strength of the soil-structure interface can degrade the structure, especially under humid conditions. Studying the shear characteristics of the silt-concrete interface using a shear apparatus. Suction-controlled ring shear tests were carried out on the silt-concrete interface for three interface roughness values. The influence of the matric suction (s) and interface roughness (R) on the shear strength index of the silt-concrete interface was analyzed. The test results showed that high values of s and R improved the shear strength of the interface, but the result was affected by the net normal stress (NNS). High values of NNS and R improved the strain-hardening characteristics. NNS, s, and R significantly affected the interface shear shrinkage. The internal friction angle of the saturated interface was smaller than that of saturated silt, whereas the opposite occurred in the unsaturated state. The cohesion and internal friction angle of the interface rose with an increase in R, and they were larger than that of silt. A shear strength model of the silt and interface was established.

This study aims to investigate the interfacial tension, emulsion stability, and the impact on oil displacement effectiveness of mixed systems containing nonionic surfactants and amphoteric surfactants at different ratios. To achieve this, three different emulsion stability formulations were prepared by mixing betaine and nonionic surfactants in ratios of 1:1, 3:2, and 3:1 respectively. By adjusting the proportions of betaine and nonionic surfactants, variations in interfacial tension and emulsion formation among the three mixed systems were studied to analyze the mechanism of interaction between betaine and nonionic surfactants and evaluate their effects on crude oil displacement and enhanced oil recovery in reservoirs. Subsequently, microscopic and macroscopic oil displacement experiments were conducted on the three mixed systems, along with experiments on emulsion flow resistance. The aim was to verify the oil displacement effectiveness of different mixed systems and further understand their potential applications in reservoirs. By comprehensively analyzing the experimental results, optimal ratios and conditions for the mixed systems were determined. The experimental results indicate that the emulsification system formed by mixing betaine and nonionic surfactants at a ratio of 3:1 achieves molecular synergies through electrostatic interactions and mixed adsorption with betaine, resulting in a compact arrangement of interface membranes and demonstrating a synergistic effect in reducing interfacial tension to an ultra-low value of 10 -4 mN/m. Additionally, as the proportion of betaine surfactant increases, the viscosity of the aqueous phase liquid film increases, the rate of thinning of the liquid film slows down, the rate of water release slows down, and the stability of the emulsion increases. Microscopic oil displacement experiments verified that the three mixed systems increase oil washing efficiency through low interfacial tension and emulsification stripping action, thereby increasing the oil displacement mechanism's coefficient. Emulsion flow resistance experiments demonstrated that as the proportion of betaine surfactant increases, the system exhibits better plugging ability. However, macroscopic oil displacement experiments revealed differences in compatibility between different emulsion stability solutions and rocks with different permeabilities. The mixed system of betaine and nonionic surfactants at a ratio of 3:1 exhibits the best emulsification plugging ability in rocks with a permeability of 109mD, while the 1:1 mixed system performs best in rocks with a permeability of 12mD. This holds significant theoretical and practical significance for reservoir development and enhanced production.

Childhood overweight/obesity (OV/OB) is a major public health problem, of greater concern when accompanied with comorbidities such as hypertension and insulin resistance leading to metabolically unhealthy obesity (MUO). Aetiologic associations between meal patterns, OV/OB risk and MUO are limited. The aim of this systematic review was to explore associations between meal patterns and the risk of childhood OV/OB and MUO. Longitudinal studies and randomised controlled trials from PUBMED and Scopus published between January 2013 - April 2024 were retrieved. Twenty-eight studies were included, all of which reported on OV/OB risk; none on MUO risk. Regular consumption of breakfast and family meals and avoiding dining while watching TV may be protective factors against childhood OV/OB, whereas meal skipping (primarily breakfast) may be a detrimental factor. Mixed effects of meal frequency on OV/OB risk were observed; no effects of frequency of lunch or of fast-food consumption and of meals served at school were found. There was insufficient evidence to support the role of other patterns (meal timing, eating in other social contexts). Meals were mainly participant-identified, leading to increased heterogeneity. Research focusing on childhood MUO and improved methodological approach (e.g. harmonised definitions) regarding the assessment of meal patterns are highly warranted.

Background Lower respiratory tract infections (LRTIs), particularly pneumonia, are a leading cause of morbidity and mortality among children worldwide, especially in low-resource settings. The World Health Organization (WHO) Integrated Management of Childhood Illness (IMCI) guidelines currently recommend antibiotic treatment for all case of with pneumonia based on clinical signs along, which can lead to over-prescription of antibiotics and contribute to antimicrobial resistance (AMR). Point of care Lung Ultrasound (LUS) has emerged as a promising diagnostic tool in this context and has demonstrated potential in distinguishing between bacterial and viral pneumonia, thus enabling more targeted antibiotic use. This study aims to explore whether integrating LUS into the IMCI-based management of clinical pneumonia will better identify those who would benefit from antibiotic treatment, reducing antibiotic overuse without compromising health outcomes. Methods An open label randomized controlled trial will enrol 3500 children aged 60 days to 12 years presenting with IMCI-defined pneumonia. Participants will be enrolled in Senegal, Tanzania, and South Africa. Participants will be randomly assigned in a ratio of 1:1, stratified by site and age group (<5years, 5-12years) to either an intervention group, where LUS will guide antibiotic prescriptions utilising a predefined interpretation framework, or a control group receiving routine IMCI-based care. The co-primary outcomes of this study are the reduction in antibiotic use on the day of enrolment (Day 1) and rate of clinical failure by Day 8, using an acceptable clinical difference of 1.5x as a non-inferiority margin (delta of 2.5%). Secondary outcomes will include adverse drug reactions, cure rates, hospital admissions including in-patient duration, and cost-effectiveness. Data will be collected at baseline (Day 1), Day 8, and Day 29 post-enrolment. Discussion This study seeks to provide evidence on the clinical and public health benefits of using LUS to improve the diagnosis and management of paediatric pneumonia in low-resource settings. If this intervention proves effective it could contribute significantly toward reducing unnecessary antibiotic prescriptions, thereby addressing AMR. The potential for LUS to be integrated into routine clinical practice could revolutionize pneumonia management, especially in areas with limited access to advanced diagnostic tools. Trial Registration This trial will be registered on ClinicalTrials.gov and The South African National Clinical Trials Register (SANCTR) prior to participant enrolment.

Corticosterone, an end product of the hypothalamic-pituitary-adrenal (HPA) axis, is a crucial stress hormone. Dysregulated HPA axis and corticosterone release play pivotal roles in the onset and persistence of symptoms of stress-related psychiatric disorders such as anxiety. The intake of nutrients, probiotics, and prebiotic supplements decreases blood corticosterone levels. The dipeptide L-carnosine is composed of beta-alanine and L-histidine and is commercially available as a nutritional supplement for recovery from fatigue. L-carnosine is involved in stress-induced corticosterone responses and anxiety behaviors in rodents. Here, we assessed the effect of L-carnosine in CD157 knockout (KO) mice, a murine model of autism spectrum disorder (ASD). The uptake of L-carnosine suppressed the increase in plasma corticosterone levels in response to acute stress and attenuated anxiety-like behaviors in CD157 KO mice. These results suggest that L-carnosine supplementation may relieve anxiety by suppressing excessive stress responses in individuals with ASD.

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.

Mediterranean diet, featuring sourdough bread, shows promise in managing metabolic syndrome. This study explored the effects of two sourdough breads with differing fermentation times but similar nutritional profiles on inflammation, satiety, and gut microbiota composition in adults with metabolic syndrome. The double-blind clinical trial randomized participants to consume over two-months Elias Boulanger® long fermentation (48h) sourdough bread (EBLong) or Elias Boulanger® short fermentation (2h) sourdough bread (EBShort). We assessed clinical parameters, inflammatory- and satiety-related biomarkers; and richness and abundance of gut microbiota at baseline and follow-up. 31 individuals (mean age: 67, 55.7% female) participated. EBShort was associated with reduced soluble intercellular adhesion molecule (sICAM) levels, and irrespective of the adjudicated intervention, all participants had a decrease in sICAM and diastolic pressure relative to baseline (p&lt;0.017). At follow-up, plasminogen activator inhibitor-1 (PAI-1) levels were lower in EBShort (-744 pg/mL; 95%CI: -282 to -1210 pg/mL) compared to EBLong. High-quality sourdough bread may offer mild benefits in blood pressure and inflammation for those with metabolic syndrome, however, only EBLong was associated to reduced Enterobacteriaceae abundance. Further research is needed to understand potential benefits and mechanisms of sourdough bread in managing metabolic syndrome and improving cardiovascular health.

Objectives: To assess the short-term impact of a single global stretching session on plantar pressures and lumbar range of motion (RoM) over one week in sedentary university students. Design: A randomised controlled trial with two parallel groups. Participants: Sixty-four university students were randomly assigned to a stretching group or control group. The stretching group received a single session of global stretching and the control group remained seated for the same length of time as the stretching session. Main outcome measures: Lumbar RoM and plantar pressures were assessed before, immediately after, 48 hours after, and 7 days after intervention. Results: Group-by-time interaction was significant for lumbar lateral flexion (p = 0.044), right maximal pressure (p = 0.003), left maximal pressure (p = 0.008), right mean pressure (p = 0.025), left mean pressure (p = 0.002), and maximal pressure minus mean pressure in right foot (p = 0.007). The model with plantar pressures showed a significant difference for group-by-time interaction (p = 0.010).Conclusion: Global stretching seems to counteract the ill-effects of prolonged sitting up to seven days with respect to plantar pressure in standing without improving lumbar ROM

This article describes rationales and limitations for making inferences based on data from randomized controlled trials (RCTs). We argue that obtaining a representative random sample from a patient population is impossible for a clinical trial because patients are accrued sequentially over time and thus comprise a convenience sample, subject only to protocol entry criteria. Consequently, the trial’s sample is unlikely to represent a definable patient population. We use causal diagrams to illustrate the difference between random allocation of interventions within a clinical trial sample and true simple or stratified random sampling, as done in surveys. We argue that group-specific statistics, such as a median survival time estimate for a treatment arm in an RCT, have limited meaning as estimates of larger patient population parameters. In contrast, random allocation between interventions facilitates comparative causal inferences about between-treatment effects, such as hazard ratios or differences between probabilities of response. Comparative inferences also require the assumption of transportability from a clinical trial’s convenience sample to a targeted patient population. We focus on the consequences and limitations of randomization procedures in order to clarify the distinctions between pairs of complementary concepts of fundamental importance to data science and RCT interpretation. These include internal and external validity, generalizability and transportability, uncertainty and variability, representativeness and inclusiveness, blocking and stratification, relevance and robustness, forward and reverse causal inference, intention to treat and per protocol analyses, and potential outcomes and counterfactuals.

The increasing prevalence of obesity and sedentary lifestyles has led to an increased incidence of metabolic syndrome (MetS) worldwide. In Taiwan, middle-aged women are at a greater risk of MetS, type 2 diabetes, and cardiovascular disease than men are because they have more subcutaneous fat and larger waist circumferences compared to men with equal visceral fat levels. This study investigated the effects of calorie restriction supplemented with fish oil (CRF) in middle-aged women with MetS. For 12 weeks, 75 eligible participants were randomly assigned either calorie restriction (CR) or CRF. Both dietary intervention groups were further divided into two age groups: ≤45 and >45 years. The changes in MetS severity, inflammatory status, iron status, and red blood cell fatty acid profile were evaluated. Seventy-one participants completed the trial. Both dietary interventions significantly ameliorated MetS and improved the participants’ inflammatory status. CR significantly increased total iron binding capacity, whereas CRF increased hepcidin levels. Furthermore, CRF significantly increased the n-6/n-3 and arachidonic acid/docosahexaenoic acid ratios. In conclusion, CR and CRF improved the anthropometric and MetS characteristics of early-middle aged women, including body weight, blood glucose levels, triglyceride levels, as well as the scores for the homeostasis model assessment of insulin resistance and quantitative insulin sensitivity cheque index. Dietary intervention was more effective in >45-year-old women than ≤45-year-old women.

The paper explores the features of numerical simulation to analyze the dynamic behavior of drives controlled by pulse-width modulators. Modern motor control systems widely use pulse width modulation. Effective numerical modeling of such systems has specific features because the models employed are continuous-event and have hybrid behavior due to the presence of nonlinear links with discontinuities of the first kind. Therefore, it is essential to have special integration methods with variable steps, which should be factored in when developing the model. The paper shows how these problems are solved when modeling an electric drive with a DC motor in the SimInTech software.

Plantar fasciitis is one of the most common causes of foot pain; in a significant percentage it is also associated with bone edema of the heel. A prospective randomized clinical trial was designed, in which 48 patients suffering from plantar fasciitis, with or without bone edema, were treated with temperature controlled high energy adjustable multi-mode emission laser and exercises (laser group) or with exercises only (control group). Patients were evaluated at recruitment (T0), at 2 (T1) and 6 months (T2), monitoring pain (with Visual Analogue Scale), functionality (with Foot Function Index) and perception of improvement (with Roles and Maudsley Score) and fascia thickness (with ultrasound examination). In both groups there was a significant improvement in pain, functional recovery, perception of remission and a reduction in plantar fascia thickness at T1 and T2. The laser group presented statistically better values at T2 for the Roles and Maudsley Score (z: 2.21; 0.027). Regression analysis showed that a greater reduction in fascia thickness occurred in the laser group (p-value: 0.047). In conclusion, the two conservative treatments were effective in patients suffering from plantar fasciitis, even in the presence of bone edema, but with lesser results.

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.

Despite the expansion of financial institutions and proliferation of mobile financial services, reaching the unbanked and bringing them under formal financial services has become a policy concern in many developing countries. Due to the lack of financial accounts, unbanked people prefer informal, risky, and inconvenient mechanisms for receiving, sending and transferring money. Previous studies rely much on common intervention like no account maintenance and opening fees, easy documentation processes and money subsidies for opening financial accounts. This study aims to examine the impact of the motivational workshop on opening savings accounts through causality among the unbanked people in a setting where the respondents are unbanked despite having all the requirements and many institutional offers for opening savings accounts. We encouraged the unbanked people through a one-hour-long motivational workshop to open saving account. Based on our cross-sectional data and randomized controlled trial experiment among 505 unbanked Village Defense Party (VDP) members at Dhubil Union under Sirajganj in Bangladesh, we have the evidence that motivational workshop positively impacts opening ac-counts by 32.33 percent. However, the account opening rate differs in terms of respondent’s pref-erence for financial institutions. Our study also finds that unbanked people have the highest pref-erence for mobile financial services for opening accounts resulting in 15.33 percent. The result of the study has some policy implications for adopting effective strategies of financial access in many developing countries.

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.

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.

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.

In this pilot study, 84 subjects with a history of poor oral hygiene were enrolled in an interventional, randomized, prospective, open-label controlled trial. The aim was to provide preliminary clinical data on the products, the recruitment monthly rate, and patient satisfaction to estimate resources for the main study, as well as descriptive data on oral microbiota rebalancing. The population was divided into five groups: 20 participants received delicate mint toothpaste, 12 mint toothpaste, 20 mint mouthwash, and 20 delicate mint toothpaste and mint mouthwash using a specifically custom-designed toothbrush. The 12 subjects in the control group continued to use their oral care products without changing their normal routine. The study duration was 28 days.All subjects tolerated the products well, and there were no adverse events. Recruitment capability and procedures allowed a realistic estimation for the future main trial. The products did not cause any changes in tooth color. The participants who completed the treatment consisting of delicate mint toothpaste, mint mouthwash, and the specifically custom-designed toothbrush showed the gingival sensitivity best results (p≤0.000). The products induced a statistically significant decrease in plaque in all treated groups (p≤0.000) and an improvement of gingival sensitivity (delicate mint toothpaste, p≤0.005; mint toothpaste, p≤0.015; and mint mouthwash, p≤0.015). All the products were effective in stabilizing the oral microbiota.The tested products showed an optimal safety profile. They also stabilized the biodiversity of the oral microbiota, making it less susceptible to microbial fluctuations than the control group.

Objectives: To compare the effects of high-velocity resistance training to slow-velocity re-sistance training on neuromuscular and functional parameters and to analyze the relationship between changes in walking speed and improvements in neuromuscular parameters following intervetions. Methods: 40 participants were randomly assigned to either a high-speed resistance training group (GHS, n = 18; age = 80.41 ± 10.12 years; BMI = 23.81 ± 3.45 kg/m²) or a low-speed resistance training group (GLS, n = 22; age = 82.89 ± 5.32 years; BMI = 23.81 ± 3.45 kg/m²). Before and after the interventions, gait speed (m/s) was assessed using a 10-minute walking test, and relative maximal force (Relative F max, N/kg) was evaluated during maximal voluntary isometric con-traction of the plantar flexors. From the force-time curve, early (0 – 50 ms) and late (100 – 200 ms) rates of force development (RFD) were extracted from the linear slopes (Δ force / Δ time). Results: Gait speed significantly improved in both groups (p < 0.05). However, the improvement was more pronounced in the GHS compared to the GLS (p < 0.05). Relative Fmax showed a more significant increase in the GLS than in the GHS (p < 0.05). Moreover, a significant 10% increase in early RFD in the GLS and a 20.1% increase in the GHS were observed (p < 0.05). The improvement in early RFD was greater in the GHS (p < 0.05). Additionally, late RFD improved significantly only in the GHS (+20.4%, p < 0.05). Conclusion: High-velocity resistance training appears particularly effective in improving the ability to rapidly generate force, which is essential for many daily activities re-quiring explosive movements and quick responses.

Metabolic dysfunction associated fatty liver disease (MAFLD), a globally prevalent chronic liver disease, has only limited pharmacological options. Both metformin and Ganwei, a botanical supplement containing a potent inducer for glycine N-methyltransferase (GNMT), have shown great promise for MAFLD. We conducted a 4-arm, randomized, placebo-controlled trial to investigate the safety and efficacy of metformin and Ganwei for MAFLD. Between September 2021 and March 2023, 64 patients with MAFLD were received metformin alone, Ganwei alone, combination of metformin and Ganwei, and placebo for 6 months. The primary MAFLD outcome was assessed by control attenuation parameter (CAP) and kilopascal (kPa) scores for liver steatosis and fibrosis, utilizing FibroScan. At 6 months after treatment, significant MAFLD improvements were observed in patients treated with Ganwei alone (repeated measures ANOVA test, p = 0.048 for both CAP and kPa scores). By employing a 6-point steatosis grade scale, the Ganwei alone arm exhibited a statistically better improvement than the placebo-controlled arm (mean score 1.1±1.9 vs. 0.1±0.7, p &lt; 0.01). In addition, patients in the Ganwei alone arm showed significant quality-of-life improvements. There was no serious adverse events observed. Our study demonstrated that Ganwei can be an effective treatment option for MAFLD patients. Clinical trial registration: NCT06244550.

Saprotrophic fungi are key in global carbon cycling, capable of decomposing lignocellulose in wood. This study, for the first time, explores the influence of oxygen (O2) and temperature on methane (CH4) production by two fungi, Laetiporus sulphureus and Pleurotus sapidus. We examined CH4 formation under varying O2 levels (0 to 98%) and temperatures (17, 27, and 40 °C) when the fungi grew on pine wood, beech wood, and grass under sterile conditions. Our findings reveal a strong dependency of fungal CH4 production on O2 mixing ratios. Methane formation was highest when O2 levels exceeded 5%, whilst no CH4 formation was observed after complete O2 consumption by the fungi. Reintroducing O2 immediately resumed fungal CH4 production. When CH4 formation was normalized to O2 consumption (CH4_norm) a different pattern between species was observed. L. sulphureus showed higher CH4_norm rates with higher O2 levels, whereas P. sapidus showed elevated rates between 0-5% O2. Temperature also significantly influenced CH4 and CH4_norm rates, with the highest production at 27 °C, and comparatively lower rates at 17 and 40 °C. These results demonstrate that O2 levels and temperature are critical in controlling fungal CH4 emissions, a consideration necessary for future CH4 source predictions.

The strictness of the result of an excavation, whether mechanical or by means of explosives, is naturally conditioned by the objective, and therefore by the type of technique applied to achieve it. To attain the best results in terms of rock breakage and respect of the final profile, it’s important to evaluate the excavation specific energy and its optimization. This research focuses on evaluating the effects of different techniques on the quality of final walls in open-pit and underground operations. Different geometries and configurations can be applied to both quarrying and tunnelling blasts. The research is aimed to push contour blasts to their limits, and the main aspects are discussed in order to improve the blast parameters in the daily practice.

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.

Laser ablation of silicon under an external applied magnetic field with different orientations was investigated in respect to the scanning direction and polarisation of the laser beam, by observation of the ablation patterns and debris deposition. Ultra-short ∼230 fs laser pulses of 1030 nm wavelengths were used in the single and multi-pulse irradiation modes. Ablation with an externally applied magnetic B-field (B ≈ 0.1 T) is shown to strongly affect debris formation. The mechanism of surface plasmon polariton (SPP) wave can explain the ablated periodic patterns observed with alignment along the magnetic field lines.

Using polymethylmethacrylate (PMMA) bone cement is widespread in orthopedic surgeries for implant fixation and as a carrier for antibiotic delivery to prevent and treat infections. This review comprehensively evaluates in vitro studies investigating the antibiotic elution profiles and mechanical properties of PMMA bone cement. We explore the kinetics of antibiotic release, factors influencing elution efficiency, and the impact of various antibiotics on the mechanical properties of PMMA composites. At the same time, we examine how the inclusion of antibiotics affects the mechanical integrity of PMMA, including parameters such as compressive strength, tensile strength, and fatigue resistance. Through a detailed analysis of these studies, this review aims to provide insights into optimizing PMMA bone cement formulations for enhanced therapeutic efficacy and structural performance.

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.

EUS–TA in unresectable pancreatic cancer requires not only a tissue diagnosis but also tissue collection in anticipation of comprehensive genomic profiling. However, the optimal puncture target remains controversial. Therefore, the Primary and Metastatic Lesions in Pancreatic Cancer (PRIMATE) study was designed to clarify the optimal target by comparing the success rates for meeting OncoGuide NCC Oncopanel (NOP) analysis criteria on pre-check primary and metastatic lesion specimens obtained during the same EUS–TA session in patients with invasive pancreatic ductal adenocarcinoma. In this ongoing prospective study, two specimens, each from primary and metastatic lesions, are obtained by EUS–TA (typically using a 19G fine-needle biopsy needle) in patients with invasive pancreatic ductal adenocarcinoma. The primary endpoint is the proportion of EUS–TA specimens that meet NOP analysis criteria during pre-check (i.e., tumor cellularity ≥ 20% and tissue area ≥ 4 mm2), which are then compared between primary and metastatic lesions. This study has been approved by the National Cancer Center Institutional Review Board (Research No. 2022-168). The results of this study will be reported at an international conference and published in an international peer-reviewed journal. The trial registration number is UMIN 000048966.

Background: Preserving health and physical fitness is critical to ensure independent living across the lifespan. Lower levels of physical fitness are associated with age-related cognitive decline and a higher prevalence of mild cognitive impairment (MCI). Thus, this study investigates the influence of a six-month dance intervention on selected measures of physical fitness in older adults with MCI. Methods: In this randomized controlled trial 55 patients with MCI were randomized into a sportive dance training (IG; n=26; Age: 70.7 +/- 5.6 years; 62% female) or an inactive control group (CG; n=24; Age: 69.1 +/- 6.8 years; 46% female).The dance group received two 90-minute dance training sessions per week over a duration of six-months, which focused on learning dance movement patterns. During the training sessions, heartrate was measured to control exercise intensity. Physical fitness was assessed using cardiopulmonary exercise testing (CPET), lower limb functional fitness via sit-to-stand test, handgrip strength and heart rate variability (HRV). Results: We observed that the dance intervention preserved the cardiorespiratory fitness as measured by maximal oxygen uptake (VO2max) during CPET, which decreased in the CG. Furthermore, participants in the IG demonstrated increases in leg and handgrip strength although not statistically significant. HRV displayed a nonsignificant decrease following the intervention. Conclusion: The results of this randomized controlled trial suggest that sportive dance training can preserve physical fitness in older adults with MCI. Although improvements in the other parameters were statistically non-significant, likely due to the small sample size, stabilizing muscular fitness and preventing age-related decline in older adults with MCI is important for maintaining functional independence.

This study aimed to investigate the efficacy of manual therapy and exercise versus synchronized telerehabilitation with self-manual therapy and exercise in treating Subacromial Pain Syndrome (SAPS). Sixty individuals diagnosed with SPS, aged 18-50 years, were randomly assigned to home exercise (HE), manual therapy (MT), and telerehabilitation (TR) groups. Treatment protocols were administered over 8 weeks and included specific exercises and therapy interventions. Out-come measures included Visual Pain Scale (VAS), shoulder range of motion (ROM) via gonio-metric measurements, Quick Disability Arm-Shoulder-Hand Problems Survey (Q-DASH), and patient satisfaction. Results revealed that both MT and TR groups exhibited reduced pain, in-creased ROM, lower Q-DASH scores, and higher patient satisfaction compared to the HE group. However, no significant differences were found between MT and TR groups in pain levels, ROM, Q-DASH scores, or patient satisfaction. The study concludes that both telerehabilitation and manual therapy effectively alleviate pain and are well-received by patients with SPS. Addition-ally, manual therapy demonstrates superiority in enhancing functional levels compared to exer-cise-based interventions. (Registration: NCT05200130)

The control of alumina morphology is crucial yet challenging for its various applications. Un-fortunately, traditional methods for preparing alumina particles suffer from several limitations such as irregular morphology, poor dispersibility, and restricted application areas. In this study, we develop a novel method for preparing spherical mesoporous alumina using chitin and Plu-ronic P123 as mixed templates. The effects of reaction temperature, time, and the addition of mixed templates on the phase structure, micromorphology, and optical absorption properties of the samples were investigated. The experimental results indicate that lower temperature and shorter reaction time facilitated the formation of spherical mesoporous alumina with excellent CO2 adsorption capacity. The periodic density functional theory (DFT) calculations demonstrate that both (110) and (100) surfaces of γ-Al2O3 can strongly adsorb CO2. The difference in the amount of CO2 adsorbed by Al2O3 is mainly due to the different surface areas, which give dif-ferent number of exposed active sites. This approach introduces a novel strategy for utilizing bi-ological compounds to synthesize spherical alumina and greatly enhances mesoporous alu-mina's application efficiency in adsorption fields. Moreover, the study explored the electro-chemical performance of the synthesized product using cyclic voltammetry and discovered im-proved loading of electrocatalysts and enhanced electrocatalytic activity.

The field of controlled polymerization is growing and evolving at unprecedented rates, facilitating polymer scientists to engineer the structure and property of polymer materials for a variety of applications. However, the lack of degradability, particularly in vinyl polymers, is a general concern for not only environmental sustainability but also biomedical applications. In recent years, there has been a significant effort to develop reversible polymerization approaches in those well-established controlled polymerization systems. Reversible polymerization typically involves two steps including (i) forward polymerization which converts small monomers into macromolecules, and (ii) depolymerization capable of regenerating original monomers. Furthermore, recycled monomers can be repolymerized into new polymers. In this perspective, we highlight recent developments of reversible polymerization in those controlled polymerization systems and offer insight into the promise and utility of reversible polymerization systems. More importantly, the current challenges and future directions to solve those problems are discussed. We hope this perspective can serve as an “initiator” to promote continuing innovations in this fairly new area.

This pilot randomized controlled trial (RCT) aimed to explore whether depression and anxiety could be reduced by psychiatric home healthcare supporters offering brief cognitive behavioral therapy for psychosis (CBTp) at home using a workbook for patients with schizophrenia. Eighteen patients with schizophrenia treated in a psychiatric home nursing service were randomly assigned to two groups: one group received CBTp in addition to usual care (CBTp + TAU group; n=8) and the other received only usual care (TAU group; n=8); 2 patients were excluded due to hospitalization or withdrawal of consent. Eight weekly CBTp sessions were conducted; anxiety/depression, quality of life, self-esteem, and overall functioning were assessed at baseline, week 9, and week 13. There was no significant difference in the primary evaluation; however, a significant improvement (p=0.014) was observed in the secondary evaluation of quality of life. The effect size was 0.95 for primary evaluation and 1.33 for the secondary evaluation, indicating a large effect. This study showed that nurses and occupational therapists can provide CBTp in psychiatric home care for patients with schizophrenia to potentially alleviate anxiety and depression compared to standard psychiatric home care alone. Therefore, larger RCTs with larger sample sizes are recommended.

As the world’s population age, Cognitive Frailty (CF) is becoming one of the most serious health problems and elucidating its biological mechanisms along with prevention and treatments becomes increasingly important also considering the associated health costs. This pilot study aims to investigate the potential cognitive and neuropsychological effects of a 5-week treatment with a therapy based on the regenerative properties of ozone (O3) in a cohort of patients stratified according to CF. We also study the potential effects of O3 on blood-based biomarkers indicative of specific biological systems that may be altered in CF. Seventy-five older persons have been recruited and randomly assigned to receive the active treatment (150cc of oxygen-O2-O3 mixture at the concentration of 30ug of O3 per cc of O2) or O2, or the placebo (air) for 5 weeks. The primary endpoint is a change in the scores of clinical scales from baseline (T0) to weeks 3 (T3), 9 (T9), 15 (T15) after treatment. The secondary endpoint is a change in biomarkers levels resulting from transcriptomics, proteomics and metabolomic patterns at the same times. This study will evaluate whether an intervention with the O2-O3 therapy could have potential cognitive, neuropsychological and biological effects on CF.

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.

With the increasing occurrence of rotator cuff injuries every year, there is a great need for a reliable treatment option. Wharton’s Jelly contains several components that can positively impact the replacement and repair of musculoskeletal defects. The overall objective of this study is to evaluate the improvement of patient-reported pain scales after applying Wharton’s Jelly (WJ) in rotator cuff defects. Eighty-seven patients with rotator cuff defects who failed at least eight weeks of conservative treatment were selected from the retrospective repository. 2cc of WJ flowable allograft was applied to the specific affected anatomy, the most common being supraspinatus tendon, biceps tendon insertion, labral tear, and subscapularis tear. No adverse reactions were reported. Statistically significant improvements were found from the initial to Day 90 in all scales. Patient satisfaction was calculated using minimal clinically important differences. No statistically significant differences were found in mean changes between gender, BMI, and age. Scanning Electron Microscopy images reveal the similarities between the collagen matrix in WJ and the rotator cuff. The significant improvement in patient outcomes coincides with current literature analyzing WJ applications with other structural defects around the body. WJ is a promising alternative for musculoskeletal defects when the standard of care fails.

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.

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.

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.

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.

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.

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.