There are numerous approaches to model an influence of manufacturing parameters on the dissolution and disintegration of solid dosage forms. A modern approach for modelling and simulating complex and heterogeneous systems such as pharmaceutical tablets focuses on computationally-intensive finite-element or discreet element methods. Industrial challenges such as Process Analytical Technology (PAT) and Quality by Design are stimulating computer-based technologies to design, control and improve the quality of pharmaceutical compacts and their performance. In this study the disintegration and dissolution model based on the numerical solutions of the Noyes-Whitney equation and cellular automata supported disintegration model are proposed and evaluated. The results from in vitro release studies of the mefenamic acid formulations were compared to the calculated release patterns from the tablet structures obtained from microtomography experiments and the purely algorithmically created virtual tablets.

This study aimed to develop extended–release tablets containing 25 mg IMM−H014, an original drug formulated by a direct powder pressing method based on pharmaceutical–grade hydrophilic matrix polymers, such as hydroxypropyl methylcellulose, to establish an in vitro−in vivo corre-lation (IVIVC) to predict bioavailability. The tablets’ mechanical properties and in vitro and in vivo performance were studied. The formulation was optimized using a single factor experiment and the reproducibility was confirmed. The in vitro dissolution profiles of the tablet were de-termined in five dissolution media, in which the drug released from the hydrophilic tablets fol-lowed Ritger–Peppas model kinetics in 0.01 N HCl medium for the first 2 h, and in phosphate buffer saline medium (pH 7.5) for further 24 h. Accelerated stability studies (40°C, 75% relative humidity) proved that the optimal formulation was stable for 6 months. The in vivo pharmaco-kinetics study in beagle dogs showed that compared to the IMM−H014 immediate release prep-aration, the maximum plasma concentration of the extended release (ER) preparation was sig-nificantly decreased, while the maximum time to peak and mean residence time were significantly prolonged. The relative bioavailability was 97.9% based on an area under curve, indicating that the optimal formulation has an obvious ER profile. And a good IVIVC was established, which could be used to predict in vivo pharmacokinetics from the formulation composition.

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].

To keep the global navigation satellite system functional during extreme conditions, it is a trend to employ autonomous navigation technology with inter-satellite link. As in the newly built BeiDou system (BDS-3) equipped with Ka-band inter-satellite links, every individual satellite has the ability of communicating and measuring distances among each other. The system also has less dependence on the ground stations and improved navigation performance. Because of the huge amount of measurement data, centralized data processing algorithm for orbit determination is suggested to be replaced by a distributed one in which each satellite in the constellation is required to finish a partial computation task. In current paper, the balanced extended Kalman filter algorithm for distributed orbit determination is proposed and compared with whole-constellation centralized extended Kalman filter, iterative cascade extended Kalman filter, and increasing measurement covariance extended Kalman filter. The proposed method demands a lower computation power however yields results with a relatively good accuracy.

In this article, our main purpose is to establish a new extension of Mittag-Leffler function by using the known extended beta function $\mathbf{B}_{\omega}(a,b;p)$ introduced in [1]. It led to a novel extension of the applicability of Mittag-Leffler function that introduced them as distributions defined for a specific set of functions. We also, investigate some of its important properties, namely recursion relation, Mellin transform and differential formulas.

The main aim of this paper is to establish two generalized integral formulas involving the extended Mittag–Leffler function based on the well known Lavoie and Trottier integral formula and the obtain results are express in term of extended Wright-type function. Also, we establish certain special cases of our main result.

This paper introduces extensions H4,p and X8,p of Horn’s double hypergeometric function H4 and Exton’s triple hypergeometric function X8, taking into account recent extensions of Euler’s beta function, hypergeometric function, and confluent hypergeometric function. Among the numerous extended hypergeometric functions, the primary rationale for choosing H4 and X8 is their comparable extension type. Next, we present various integral representations of Euler and Laplace type, Mellin and inverse Mellin transforms, Laguerre polynomial representation, transformation formulae and a recurrence relation for the extended functions. In particular, we provide a generating function for the X8,p and several bounding inequalities for the H4,p and X8,p.

In this work we present VaccineHero, an eXtended Reality system that aims to reduce children’s discomfort during vaccination. In our proposal the child wears a headset during vaccination and watches a short story in VR. The story includes a hero touching the child’s arm and the doctor synchronises the insertion of the needle with the VR content, so that the child is distracted efficiently. A clinical trial has been carried out, involving 2 doctors and a cohort of 16 children, and has shown that the use of VaccineHero reduces children’s discomfort during vaccination by a staggering 40% and totally eliminates extreme discomfort. The implemented solution is extremely affordable, as it can be deployed on simple headsets or even Cardboard devices, a feature that makes it a realistic option for any paediatric practice. It can also be extended to support other medical activities that involve needles, such as blood draw and blood donation.

The nervous system is composed of neurons, which conduct the signals, and glial cells that provide metabolic and functional support and protection to neurons. An important component of the nervous system is the myelin sheath, an insulating layer around the nerves of the brain and spinal cord, which allows a fast and efficient nerve conduction and therefore the proper transmission of signal to all tissues and organs. Myelin is made of protein and fatty substances and gives protection for the propagation of the electrical impulse. Myelin alterations determine the onset of several neuropathies as the electrical signal can be slowed or stopped. Myelin is formed by oligodendrocytes in the central nervous system (CNS) and by Schwann cells in the peripheral nervous system (PNS). Differences in myelination in the CNS and PNS have been found and molecules involved in membrane trafficking such as SNAREs and rabs have been proved to contribute to several aspects regarding the formation of myelin or dysmyelination. Here, I will describe the role of these proteins in regulating membrane trafficking and nerve conduction, myelin biogenesis and maintenance.

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.

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.

With extended reality (XR) technology on the rise in aviation education, we evaluated the perceptions of Thai students on an inexpensive and classroom-friendly virtual reality (VR) system and software combination, as an introduction to flying an aircraft. In addition to cost-effectiveness, consumer grade technology also provides greater portability than traditional full-flight simulators. Third year aeronautical engineering and commercial pilot undergraduate program international students were exposed to a brief VR experience using a PlayStation 4 console (PS4) with PlayStation VR (PSVR) and Ultrawings software. Subsequently, in-depth qualitative interviews were analyzed via thematic coding. The student responses were mostly positive and enthusiastic, but also identified issues with hardware and software (screen door effect, limited peripheral vision, less than optimal interaction controls, and lack of haptic feedback). Using thematic coding, responses were categorized into; head mounted device, controls and controllers, plausibility illusion, place illusion, embodiment illusion, academic value and entertainment value. Following respondents’ positive responses on certain identified critical points, we recommend further study using other hardware and software combinations.

Our objective was to investigate the effects of topically applied neuropeptide Y (NPY) on ischemic wounds. Initially, the animal model for ischemic wound healing was validated using 16 male Sprague-Dawley albino rats. In the intervention study, an additional 28 rats were divided into three groups: NPY (0.025%), the positive control insulin-like growth factor-I (IGF-I, 0.0025%), and the hydrogel carrier alone (control). The hydrogel was selected due to its capacity to prolong NPY release (p < 0.001), as demonstrated in a Franz diffusion cell. In the animals, an 8-mm full-thickness wound was made in a pedunculated dorsal ischemic skin flap. Wounds were then treated and assessed for 14 days, and procured at the end of the experiment for in situ hybridization analysis (RNAscope®) targeting NPY receptor Y2R and for meticulous histologic examination. Wound healing rates, i.e. the percentage wound area changes, did not show an increase with NPY (p = 0.938) but did with rhIGF-I (p = 0.039) compared to the control. Y2R mRNA was not detected in the wounds or adjacent skin but was identified in the rat brain (positive control). Light microscopic examination revealed trends of increased angiogenesis and enhanced inflammatory cell infiltration with NPY compared to control. An interesting secondary discovery was the presence of melanophages in the wounds. Our findings suggest the potential of NPY to enhance neovascularization under ischemic wound healing conditions, but further optimization of the carrier and dosage is necessary. The mechanism is elusive but likely involves NPY receptor subtypes other than Y2R.

The manuscript studies the release kinetic of fluorescein from colloidal liquid crystals made up from monoglyceride and different non-ionic surfactants. The release experiments were carried out under sink conditions, and mathematical models were described as extrapolations from solutions of diffusion equation in different initial and boundary conditions imposed by pharmaceutical formulations. The diffusion equation was solved, using Laplace and Fourier transformed functions for the release kinetic from infinite reservoirs in a semi-infinite medium. Solutions represents a general square root law and can be applied for the release kinetic of fluorescein from monoglyceride colloidal liquid crystals. Akaike, Schwartz and Imbimbo criteria were used to establish the appropriate mathematical model and the hierarchy of performances of different models applied to the release experiments. The Fisher statistic test was applied to perform significance of differences among mathematical models. Differences evaluated by mathematical criteria demonstrated that small or no significant statistic differences were carried out between various applied models and colloidal formulations. Phenomenological models were preferred over to empirical and semi-empirical ones. The general square root model shows that the diffusion-controlled release of fluorescein is the mathematical models extrapolated for monoglyceride colloidal liquids, in the first part of the process.

The main objective of this paper is to introduce a further extension of extended (p, q)-beta function by considering two Mittag-Leffler function in the kernel. We investigate various properties of this newly defined beta function such as integral representations, summation formulas and Mellin transform. We define extended beta distribution and its mean, variance and moment generating function with the help of extension of beta function. Also, we establish an extension of extended (p, q)-hypergeometric and (p, q)-confluent hypergeometric functions by using the extension of beta function. Various properties of newly defined extended hypergeometric and confluent hypergeometric functions such as integral representations, Mellin transformations, differentiation formulas, transformation and summation formulas are investigated.

A new generalization of extended beta function and its various properties, integral representations and distribution are given in this paper. In addition, we establish the generalization of extended hypergeometric and con uent hypergeometric functions using the newly extended beta function. The properties these extended and con uent hypergeometric functions such as integral representations, Mellin transformations, dif- ferentiation formulas, transformation and summation formulas are also investigated.

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.

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.

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.

Herein, we report a stimuli responsive hydrogel with inhibitory activity against Escherichia coli prepared by chemical crosslinking of carboxymethyl chitosan (CMCs) and hydroxyethyl cellulose (HEC). The hydrogels were prepared by esterification of chitosan (Cs) with monochloroacetic acid to produce CMCs which was then chemically crosslinked to HEC using citric acid as the crosslinking agent. To impart a stimuli responsiveness property to the hydrogels, polydiacetylene-zinc oxide (PDA-ZnO) nanosheets were synthesized in-situ during the crosslinking reaction followed by photopolymerization of the resultant composite. To achieve this, ZnO was anchored on carboxylic groups in 10,12-pentacosadiynoic acid (PCDA) layers to restrict movement of alkyl portion of PCDA during crosslinking CMCs and HEC hydrogels. This was followed by irradiating the composite with UV radiation to photopolymerize the PCDA to PDA within the hydrogel matrix so as to impart thermal and pH responsiveness to the hydrogel. From the results obtained, the prepared hydrogel had a pH dependant swelling capacity as it absorbed more water in acidic media as compared to basic media. Incorporation of PDA-ZnO resulted in a thermochromic composite responsive to pH evidenced by a visible colour transition from pale purple to pale pink. Upon swelling, PDA-ZnO-CMCs-HEC hydrogels had inhibitory activity against E. coli attributed to the slow release of the ZnO nanoparticles as compared to CMCs-HEC hydrogels.

Fusion device and its structure may be designed by various means. Two of most popular are; weight basis (described in previous study by author) and energy basis. In present research, later method is explored and described. Energy basis is based on amount of energy released from device upon detonation followed by explosion. Its beneficial in a sense that device size can be kept as independent variable as compared to dependent in former case. Further, it shortens the design procedure. For example, heat transfer pattern in such approach directly helps in quantifying wall thickness which dictates material, fabrication, and manufacturing route. It may also eliminate anisotropy as wall thickness is direct function of amount of heat at which it will rupture and can be much thinner. Device geometry can also be flexibility controlled as it is no longer dependent on pay load bay capacity. This allows more freedom in designing subsystems (compartments, their locations, focusing, switches, and mixers). Such devices can be more compact and simpler. Few such design configurations are proposed.

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)

(1) Background: Although manual therapy for pain relief has been used as an adjunct in treatments for chronic low back pain (CLBP), there is still the belief that a single session of myofascial release would be effective. This study aimed to investigate whether a single session of a specific technique reduces pain and disability. (2) Methods: This was a crossover clinical trial in which 41 participants over 18 years old with CLBP were randomly enrolled into 3 situations - experimental, placebo, control, in a balanced and cross-over manner. The subjects underwent a single session of myofascial release on thoracolumbar fascia and compare it with the control and placebo. Outcome were pain and functionality, evaluated using the numerical pain rating scale (NPRS), pressure pain threshold (PPT) and Oswestry (ODI). (3) Results: There was no effects between-, within-tests, and interaction for all the outcomes, i.e., NPRS (η 2 = 0.32, F = 0.48, p = 0.61), PPT (η2 = 0.73, F = 2.80, p = 0.06), ODI (η 2 = 0.02, F = 0.02, p = 0.97). (4) Conclusion: A single trial of thoracolumbar myofascial release technique was not enough to reduce pain and disability in subjects with CLBP.

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

Paclitaxel is a natural, highly lipophilic anti proliferative drug widely used in medicine. We have studied the release of tritium-labeled paclitaxel (³H-PTX) from matrices destined for the coating of vascular stents and produced by the electrospinning method from the solutions of polycaprolactone (PCL) with paclitaxel (PTX) in hexafluoisoropropanol (HFIP) and/or solutions of PCL with PTX and human serum albumin (HSA) in HFIP or HIFP-dimethyl sulphoxide (DMSO) blend. The release of PTX has been shown to depend on the solvent and the composition of electrospinning solution, as well as the composition of the surrounding medium, particularly the concentration of free PTX and PTX-binding biomolecules present in human serum. It was shown that 3D matrices can completely release PTX without weight loss. Two-phase PTX release from optimized 3D matrices was obtained: ~27% of PTX was released in the first day, another 8% were released over the next 26 days. Wherein ~2.8%, ~2.3%, and ~0.25% of PTX was released on day 3, 9, and 27, respectively. Considering PTX toxicity, the rate of its diffusion through the arterial wall, and the data obtained the minimum cytostatic dose of the drug in the arterial wall will be maintained for at least three months.

The study presents the evaluation of integrating Extended Reality applications in situ to foster visitors' experience at the Tomato Industrial Museum "D. Nomikos". This paper firstly provides an outline of the methodological, technological, and museological approaches undertaken to integrate XR in a quest to enhance visitors’ meaningful engagement with the industrial heritage-related exhibition. Storytelling and narration are key elements of the museums’ museological design [1] through audio tours and interactive AR-based visualization of the machinery’s role as well as internal function. This paper presents and discusses the evaluation findings. We adopted the User Experience Questionnaire method as the main vehicle for gathering quantitative data and analyzing the results with the use of corresponding metrics and benchmarks embedded in this evaluation tool. Moreover, we conducted semi-structured interviews and combined the qualitative data accrued in the form of accounts, suggestions, and remarks to reach more rich and dependable conclusions. This paper aims to offer both an instance of practice to the research community and a broader discussion of the challenges and prospects connected to the quest of employing emerging technologies and assessing their impact on visitors’ museum experience.

Recently, Artificial Intelligence (AI)-based algorithms have revolutionized the medical image segmentation processes. Thus, the precise segmentation of organs and their lesions may contribute to an efficient diagnostics process and a more effective selection of targeted therapies as well as increasing the effectiveness of the training process. Thus, AI may contribute to the automatization of the image scan segmentation process and increase the quality of the resulting 3D objects, which may lead to the generation of more realistic virtual objects. In this paper, we focus on the AI-based solutions applied in the medical image scan segmentation, and intelligent visual-content generation, i.e. computer-generated three-dimensional (3D) images in the context of Extended Reality (XR). We consider different types of neural networks used with a special emphasis on the learning rules applied, taking into account algorithm accuracy and performance, as well as open data availability. This paper also attempts to summarize the current development of AI-based segmentation methods in medical imaging and intelligent visual content generation that are applied in XR. Finally, this paper concludes with possible developments and open challenges in AI application in Extended Reality-based solutions. Finally, the future lines of research and development directions of Artificial Intelligence applications both in medical image segmentation and Extended reality-based medical solutions are discussed.

Background: Evidence suggests that children and young people (CYP) who present to the emergency department (ED) for mental health (MH) difficulties may have extended lengths of stay (LOS); however, there is a paucity of research in Australia regarding the factors associated with extended LOS. This study aimed to determine the factors associated with extended LOS for paediatric MH-related presentations to the EDs in South Western Sydney (SWS), a multicultural community in Australia. Methods: We analysed electronic medical records (eMR) of 7,409 MH-related ED encounters of CYP aged 0 up to 18 years from all six public hospitals in SWS from January 2016 to April 2022. Extended LOS was defined as encounters of more than 4 hours. We assessed factors associated with extended LOS using a multilevel logistic regression model, accounting for hospital-level clustering. Results: Approximately 57.6% of all ED presentations for paediatric MH involved extended LOS. ED presentations by adolescents (adjusted odds ratio (AOR) 2.23, 95% CI 1.20-4.17 for 12-14 years and AOR 2.69, 95% CI 1.44-5.00 for 15-17 years), and patients with a preferred language other than English (AOR 1.47, 95% CI 1.15-1.89) had increased odds of extended LOS compared to their counterparts. Deliberate self-harm related presentations, the most commonly presented MH condition, had higher odds of extended LOS than other MH-related presentations (AOR 1.77, 95% CI 1.59-1.98). Patients with MH presentations that required urgent evaluation (triage levels 1-2) had higher odds of extended LOS (AOR 1.38, 95% CI 1.15-1.65) compared to triage level 3, whereas those with triage levels 4-5 had lower odds (AOR 0.66, 95% CI 0.58-0.74). Further, patients with MH-related presentations that came by ambulance (compared to other mode of presentations) and presentations that happened at night and late at night (compared to early morning and daytime presentations). The odds of extended LOS were considerably lower during the COVID-19 period compared to the pre-COVID-19 period (AOR 0.74, 95% CI 0.67-0.82). Additionally, extended paediatric LOS for MH issues in the ED showed notable hospital-level heterogeneity. Conclusion: A large proportion of extended LOS in ED and sociodemographic disparities reflect inequality in access to paediatric MH care. Our findings highlight the need for equitable distribution of resources directed towards at-risk CYP to improve MH outcomes and reduce health system burden.

The recent Planck Legacy release confirmed the presence of an enhanced lensing amplitude in the cosmic microwave background (CMB) power spectra, which prefers a positively curved early Universe with a confidence level exceeding 99%. In this study, the pre-existing curvature is incorporated to extend the field equations where the derived wavefunction of the Universe is utilised to model Universe evolution with reference to the scale factor of the early Universe and its radius of curvature upon the emission of the CMB. The wavefunction reveals both positive and negative solutions, implying that matter and antimatter of early Universe plasma evolved in opposite directions as distinct Universe sides, corroborating the axis of CMB. The wavefunction indicates that a nascent hyperbolic expansion away from early plasma is followed by a first phase of decelerating expansion during the first 10 Gyr, and then, a second phase of accelerating expansion in reverse directions, whereby both sides free-fall towards each other under gravitational acceleration. The predicted conformal curvature evolution demonstrates the fast orbital speed of outer stars owing to external fields exerted on galaxies as they travel through conformally curved space-time. Finally, the wavefunction predicts an eventual time-reversal phase comprising rapid spatial contraction that culminates in a Big Crunch, signalling a cyclic Universe. These findings show that early plasma could be separated and evolved into distinct sides of the Universe that collectively inducing its evolution, physically explaining the effects attributed to dark energy and dark matter.

Since its inception, evolutionary theory has experienced a number of extensions. The most important of these took the forms of the Modern Evolutionary Synthesis (MES), embracing genetics and population biology in the early 20^th century, and the Extended Evolutionary Synthesis (EES) of the last thirty years, embracing, among other factors, non-genetic forms of inheritance. While we appreciate the motivation for this recent extension, we argue that it does not go far enough, since it restricts itself to widening explanations of adaptation by adding mechanisms of inheritance and variation. A more thoroughgoing extension is needed, one that widens the explanatory scope of evolutionary theory. In addition to adaptation and its various mechanisms, evolutionary theory must recognize as a distinct intellectual challenge the origin of what we call “historical kinds.” Under historical kinds we include any process that acquires a quasi-independent and traceable lineage-history in biological and cultural evolution. We develop the notion of a historical kind in a series of paradigmatic exemplars, from genes and homologues to rituals and music, and we propose a preliminary characterization.

Authors present The First Results of the National Extended Newborn Screening (ENS) in Slovakia in the majority (M) and the Roma (R ) ethnic populations. The follow-up of the ethnicity has been introduced in Newborn Screening for Cystic Fibrosis (NSCF) and after to entire ENS program comprising of 23 Hereditary Metabolic Disorders (HMD). Results: In 2013-2015, a total of 165,648 newborns were investigated in ENS, 23,321 of them (15,3%) were the R ethnic group, a total of 313 positive cases were discovered (total ENS prevalence = 1:529, M=1:758, R=1:198). In the R ethnic group, there was slightly higher prevalence in cong. hypothyreosis (CH), only one case of CF, and no cases of CAH in the R ethnic group. The ENS prevalence of HMD detected by MS/MS was expressively higher in the R ethnic group than in M group (M=1:1670 vs. R=1:234, OR:7,13). Significant differences in the prevalence of individual types of HMD were found. Whereas the PKU and spectrum of aminoaciduria and organic acidurias dominate in the M group, the fatty acids oxidation disorders (MCAD, SCAD) and carnitine defects (CUD) were frequent in the R newborn group. Conclusion: Despite the presented results are preliminary, the ethnic approach to ENS is enabling the recording of the ethnic differences in the screening prevalence of individual disorders, which would be missing during unitary approach.

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.

Hydrogels can provide instant relief to pain and facilitate the fast recovery of wounds. Currently the incorporation of medicinal herbs/plants in polymer matrix is being investigated due to their anti-bacterial and wound healing properties. Herein, we investigated the novel combination of chitosan (CS), chondroitin sulfate (CHI) and garlic (Gar) to synthesize hydrogels through freeze gelation process for faster wound healing and resistance to microbial growth at the wound surface. The synthesized hydrogels were characterized via Fourier transform infrared spectroscopy (FTIR), which confirmed the presence of relevant functional groups. The scanning electron microscopy (SEM) images exhibited the porous structure of the hydrogels, which is useful for the sustained release of Gar from the hydrogels. The synthesized hydrogels showed significant inhibition zones against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Furthermore, cell culture studies confirmed the cyto-compatibility of the synthesized hydrogels. Thus, the novel hydrogels presented in this study can offer antibacterial effect during wound healing and promote tissue regeneration.

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

Voltage-gated Ca²⁺ (Ca_v) channels play pivotal roles in regulating gene transcription, neuronal excitability, and neurotransmitter release. In order to meet the spatial and temporal demands of visual signaling, Ca_v channels exhibit unusual properties in the retina compared to their counterparts in other areas of the nervous system. Here, we review current concepts regarding the specific subtypes of Ca_v channels expressed in the retina, their intrinsic properties and forms of modulation, and how their dysregulation could lead to retinal disease.

We explore the possibility to form a physical theory in $C^4$. We argue that the expansion of our usual 4-d real space-time to a 4-d complex space-time, can serve us to describe geometrically electromagnetism and nuclear fields and unify it with gravity, in a different way that Kaluza-Klein theories do. Specifically, the electromagnetic field $A_\mu$, is included in the free geodesic equation of $C^4$. By embedding our usual 4-d real space-time in the symplectic 8-d real space-time (symplectic $R^8$ is algebraically isomorphic to $C^4$), we derive the usual geodesic equation of a charged particle in gravitational field, plus new information which is interpreted. Afterwards, we formulate and explore the extended special relativity and extended general relativity an $C^4$ or$R^8$. After embedding our usual 4-d space-time in $R^8$, two new phenomena rise naturally, that are interpreted as "dark matter" and "dark energy". A new cosmological model is presented, while the geometrical terms associated with "dark matter" and "dark energy" are investigated. Similarities, patterns and differences between "dark matter", "dark energy", ordinary matter and radiation are presented, where "dark energy" is a dynamic entity and "dark matter" reveal itself as a "mediator" betwen ordinary matter and "dark energy". Moreover, "dark matter" is deeply connected with "dark energy". Furthermore, the extended Hamilton-Jacobi equation of the extended space-time, is transformed naturally as an extended Klein-Gordon equation, in order to get in contact with quantum theories. By solving the Klein-Gordon equation analytically, we derive an eigenvalue for Higg's boson mass value at 125,173945 $Gev/c^{2}$. The extended Klein-Gordon equation, also connects Higg's boson (or vacuum) with Cosmology, due to the existence of our second "time" T (cosmological time), which serve us to connect quantum theories with Cosmology. Afterwards, in the general case, we explore the symmetries of the curved Hamilton-Jacobi equation locally, in order to investigate the consequences of a $C^4$ space-time in Standard Model. An extension to Standard Model is revealed, especially in the sector of strong nuclear field. The Stiefel manifold $SU(4)/SU(2)$ seems capable not only to describe the strong nuclear field but give us,as well, enough room to explore in the future, the possibility to explain quark confinment. Our extension, flavors firstly the unification of nuclear fields and afterwards the unification of nuclear fields with electromagnetic field. The desired grand unification, is achieved locally, through the symmetry group $GL(4,C)\simeq SO(4,4)\cap U(4)$ and we present a potential mechanism to reduce the existing particle numbers to just six. Afterwards,23 present the extended Dirac equation in $C^4$ space-time (Majorana-Weyl representation) plus a preliminary attempt to introduce a pure geometric structure for fermions. Finally, we consider a new geometric structure through n-linear forms in order to give geometric explanation for quantisation

A PLS-based quality prediction method is proposed for batch processes using two-dimensional extended windows. To realize the adoption of information in the direction of sampling time and batch, a new definition region of support (ROS), k-i-back-extended region of support (KIBROS), is proposed to establish the extended window, which including the data of the previous sampling times in the same batch, the data of the same sampling time in the historical batches, the data of the previous sampling times in the historical batches and the data of the later sampling times in the historical batches. According to these regions of support, extended windows are established, and different models are proposed based on the extended windows for batch processes quality prediction. Further, using a typical batch process as an example, the injection molding process, the proposed quality prediction method is experimentally verified, proving that the proposed methods have higher prediction accuracy than the traditional method and the prediction stability is also improved.

Background. Metronidazole treats obligate anaerobic bacterial and protozoal infections, with an elimination half-life of around eight hours. The long elimination half-life, the favorable ratio of steady-state serum levels to minimum inhibitory concentration, and the presence of active metabolites lead to consideration of metronidazole use at 12-hour dosage intervals. This systematic review aimed to compare the clinical outcomes of twice-daily and thrice-daily metronidazole dosing. Methods. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. PubMed, Scopus, Science Direct, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials to systematically identify all relevant studies published up to June 16, 2023. Results. The final analysis included two published retrospective cohort studies; a single site (n = 200) and a multisite study (n = 85) of ‘good’ quality, as measured by the Newcastle-Ottawa scale. The reported baseline characteristics of the 8-hour and 12-hour dosing groups were comparable, and neither study identified significant differences in primary and secondary clinical outcomes. Meta-analysis of the need to escalate antibiotic therapy also showed no statistically significant differences using the Mantel-Haenszel fixed-effect method (95% CI: 47.6% lower to 6.4 times higher risk, p = 0.342) and inverse-variance method (RR: 1.87, 95% CI: 0.52-6.65, p = 0.336). Conclusions. Dosing metronidazole every 12 hours is as effective as every 8-hour dosing for anaerobic infections. Healthcare systems may consider the adoption of every 12-hour metronidazole dosing with continued evaluation of patient outcomes.

Superstar Learning System is an interactive information platform, where teachers and students can not only have an easy access to various learning resources, but also interact in the whole teaching and learning process. Although there have been a large number of studies devoted to the use of Superstar Learning System in education, very few of them explored its behavioral intention. In order to deal with this missing link in literature, we adopt a random sampling technique and a questionnaire survey to collect data. This study concludes that performance expectancy, effort expectancy, lecturer influence, peer influence, user innovativeness, interface simplicity, and multiple functions exert a positive influence on behavioral intention to use Superstar Learning System. We form a fit extended technology acceptance model (TAM) by including innovative constructs, i.e. lecturer and peer influences, user innovativeness, interface simplicity, and multiple functions. Interdisciplinary research is needed to explore an extended TAM to use Superstar Learning System in the future.

The loose and porous structure and abundant pores of biochar provide conditions for being a suitable fertilizer carrier. Biochar loaded with beneficial microorganisms will greatly promote plant growth and soil improvement. In this work, an environmentally friendly Paenibacillus mucilaginosus loaded biochar-based fertilizer (B@PM) with high nutrient content, good slow-release effect and increased biological activity was prepared. The released mechanism of P-K-Ca from B@PM and the synergistic effect on the soil nutrients and plant growth were also analyzed. The experimental results showed that the release behavior of P, K and Ca from B@PM was diffusive and dissolved, which conforms to the Power function and Parabolic diffusion models, respectively. The potting experiment showed that the root length (30.77%), leaf width (71.67%), and plant height (81.08%) of Chinese cabbage were enhanced after the application of B@PM, and the organic matter, available phosphorus, available potassium, and total calcium in the soil were also substantially enhanced. In addition, the abundance of the Proteobacteria, Actinobacteria, Bacteroidetes and Firmicutes in the in the rhizosphere soil was increased, as well as the activities of catalase (82.84%) and alkaline phosphatase (39.64%). The results of RDA analyses showed that B@PM increased the content of the environmental factors, such as OM, URE, EC, TCa, AK, CAT, AP and ALP, thus improving soil quality and plant length.

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

Sewage sludge is an organic waste generated in waste-water treatment plants with certain content of nutrients, what may potentially be used as a source of slow release fertilizer, especially as phosphorus (P) source, but it demands some pre-treatment and the content of P is much lower compared to soluble mineral fertilizers. For these reasons, composted sewage sludge was used to manufacture pelletized organomineral fertilizers, mixing it with the inorganic sources monoammonium phosphate (MAP) and AshDec® (ASD) (thermochemically incinerated sewage sludge). The fertilizers were physiochemically characterized and evaluated as to the dynamics of soil P solubilization, and the forms of P remaining according to its lability. The sources evaluated were: organic compost of sewage sludge powder (SSC), pelletized SSC (SCP), pelletized organominerals SSC+MAP (S+MAP) and SSC+ASD (S+ASD), ASD alone, all compared to a soluble mineral fertilizer (MAP), and a control without P fertilizer. A test was conducted in leaching columns with 50 g of soil (Oxisol), where the fertilizers were applied at a dose of 100 mg P/column, and 30 mL of water or 2% citric acid were added daily for 30 consecutive days. The collected leachates had pH measured and P content determined. Pelletizing process resulted in denser products and promoted more gradual P release. The organomineral S+MAP was the most water-soluble recycled source, solubilizing about 70% of the total P, while the others presented much lower solubilization (<20%). In contrast, all fertilizers showed high solubility in 2% citric acid (except for S+ASD). After leaching, the greatest amount of P remaining in the soil as labile and moderately labile. Composting and the AshDec process produced materials with slow P solubilization, which would be favoured to solubilize in acidic soils and acidic rhizosphere conditions. In turn, the organomineral mixture of SSC with a highly soluble mineral fertilizer (MAP) resulted in a promising product with intermediate nutrient solubility, better synchronized with crop demand, thus increasing efficiency in P use.

Many redox diseases, including diabetes, are associated with an imbalance of calcium homeostasis, regulated mainly by a Ca2+-ATPase pump (SERCA). Dysfunction of this enzyme may be prevented by natural polyphenolic compounds, representing a possible supporting treatment. Compounds that increase SERCA activity/expression may be useful for the treatment of diabetic complications. Stimulation of SERCA1 activity was analyzed experimentally and by molecular modeling. SERCA1 activity under methylglyoxal- and palmitate-induced oxidative stress was evaluated. The viability of INS-1E cells and insulin secretion were determined. [6]-Gingerol, resveratrol, and ellagic acid increased SERCA1 activity and exerted a protective effect under oxidative stress in the noncellular system. We found for the first time that the binding of polyphenols ([6]-gingerol, resveratrol, ellagic acid) to Glu439 in the SERCA1 P-domain may be critical for the stimulation of its activity. Moreover, this binding may also be important in the protective effects against oxidative stress. Direct stimulation of SERCA1 activity by ellagic acid was observed for the first time. In INS-1E cells, these compounds increased insulin secretion.

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.

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.

There is an increasing clinical need to develop novel biomaterials that combine regenerative and biocidal properties. In this work, we present the preparation of silver /silica based glassy bioactive (ABG) compositions via a facile, fast (20h), and low temperature (80 °C) approach and their characterization. The fabrication process included the synthesis of the bioactive glass (BG) particles followed by the surface modification of the bioactive glass with silver nanoparticles. The microstructural features of ABG samples before and after exposure to simulated body fluid (SBF) as well as their ion release behavior during SBF test were evaluated using infrared spectrometry (FTIR), ultraviolet- visible (UV-Vis) spectroscopy, X-ray diffraction (XRD), electron microscopies (TEM and SEM) and optical emission spectroscopy (OES). The antibacterial properties of the experimental compositions were tested against Escherichia coli (E. coli). The results indicated that the prepared ABG materials possess antibacterial activity against E. coli, which is directly correlated with the glass surface modification.

Halloysite nanotubes (HNTs) are natural occurring mineral clay nanotubes that have excellent application potential in different fields. However, HNTs are heterogeneous in size, surface charge and formation of surfacial hydrogen bond, which lead to weak affinity and aggregation at a certain extent. It is very important to modify the HNTs’ surface to expand its applications. In this review, the structural characteristics, performance and the related applications of surface-modified HNTs are reviewed. We focus on the surface-modified variation of HNTs, the effects of surface modification on the materials and related applications in various regions. In addition, future prospects and the meaning of surface modification were also discussed in HNTs studies. This review provides a reference for the application of HNTs modifications in the field of new nanomaterials.

Hydrogels evolved as an outstanding carrier material for local and controlled drug delivery that tend to the shortcomings of old conventional dosage forms for small drugs (NSAIDS) and large peptides and proteins. Aqueous swellable and crosslinked polymeric network structure of hydrogels is composed of various natural, synthetic and semisynthetic biodegradable polymers. Hydrogels have remarkable properties of functionality, reversibility, sterilizability, and biocompatibility. All these dynamic properties of hydrogels have increased the interest in their use as a carrier for peptides and proteins to be released slowly in a sustained manner. The therapeutical peptide and proteins are remarkable therapeutic agents in today’s world that allows the treatment of severe, chronic and life‐threatening diseases, such as diabetes, rheumatoid arthritis, hepatitis in an easy manner. Despite few limitations, hydrogels provide fine tuning of proteins and peptides delivery with enormous impact in clinical medicine. The primary objective of this article is to review current issues concerned with the therapeutics peptides and proteins and impact of remarkable properties of hydrogels on these therapeutic agents. Different routes for pharmaceutical peptides and proteins and superiority over other drugs candidates are presented. The article will also review literature concerning classification of hydrogels on different basis, polymers used, release mechanisms their physical and chemical characteristics and diverse applications.

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.

Flomoxef (FMX) may be a potential alternative to carbapenems for dogs infected with Enterobacterales producing extended-spectrum β-lactamase (ESBL-E). However, the appropriate dosage of FMX in dogs with ESBL-E infections has yet to be established. This study was carried out to establish appropriate treatment regimens for FMX against ESBL-E infections in dogs by a pharmacokinetics–pharmacodynamics (PK–PD) approach. Five dogs received an intravenous bolus dose of FMX (40 mg/kg). Serum FMX concentrations were evaluated using high-performance liquid chromatography-tandem mass spectrometry, and PK indices were determined based on non-compartmental model. The cumulative fraction of response (CFR) was calculated based on the distribution of minimum inhibitory concentrations among wild-type ESBL-E from companion animals. As the results, the dosage regimens of 40 mg/kg q8h and q6h were estimated to achieve a CFR of >90% for wild-type isolates of ESBL-producing Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis for dogs. In contrast, all regimens exhibited a CFR of <80% for ESBL-producing Enterobacter cloacae. Our results indicated that dosage regimens of 40 mg/kg FMX q8h and q6h can be a non-carbapenem treatment for dogs infected with ESBL-producing isolates of Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, but not for those infected with ESBL-producing Enterobacter cloacae.

Water conflicts have been a significant issue in Brazil, especially in the Sao Francisco River basin. Subseasonal forecasts, up to a 60-day forecast range, can provide information to support decision-makers in managing water resources in the river basin, especially before drought events. Predictability in the subseasonal forecasts range is a research topic as this range contains mixed dependence on weather and seasonal phenomena. Numerical models may inherit this mixed dependence on their skills. The objective of this paper is to evaluate the Eta Model simulations to reproduce the drought events between the years 2011 and 2016. Two sets of 60-day simulations were produced; one started in September (SO) and the other in January (JF) each year. These months were chosen to evaluate the model skill to reproduce the onset and the middle of the rainy seasons in Central Brazil, where the Upper Sao Francisco River is located. The SO simulations reproduced the observed spatial distribution of precipitation but underestimated the amounts. Precipitation errors exhibit large variability across the subbasins. The JF simulations also reproduced the observed precipitation distribution but overestimated it in the Upper and Lower subbasins. The JF simulations better captured the interannual variability of precipitation. The 60-day simulations were discretized in six 10-day accumulations to assess the intra-monthly variability. They showed that simulations can capture the onset of the rainy season and the small amounts of the rainy months that occurred in these severe drought years.

Randomized block Kaczmarz Method and randomized extended block Kaczmarz Method are proposed for solving matrix equation AXB=C, where the matrix A and B may be full rank or rank deficient. These methods are iterative methods without matrix multiplication, and are especially suitable for solving large-scale matrix equations. It is theoretically proved these methods converge to the solution or least square solution of the matrix equation. The numerical results show that these methods are more efficient than the existing algorithms for high-dimensional matrix equations.

In applied mathematics, statistics, operation research, physics, and engineering mathematics, confluent representations of hypergeometric functions in one and two variables are known to exist, and their occurrence in a variety of applications is also well recognised. In this article, we intend to present a new derivation of the extended Watson summation theorem for the Kim et al. given series 4F3. We assessed four attractive integrals involving generalized hypergeometric function as an application. With a few particular cases, this note will come to an end. In the results given above, symmetry appears on its own.

In the context of Kalman filters, the predicted error covariance matrix $\mathbf{P}_{k+1}$ and measurement noise covariance matrix $\mathbf{R}$ are used to represent the uncertainty of state variables and measurement noise, respectively. However, in real-world situations, these matrices may vary with time due to measurement faults. To address this issue in CubeSat attitude estimation, an adaptive extended Kalman filter has been proposed that can dynamically estimate the predicted error covariance matrix and measurement noise covariance matrix using an expectation-maximization approach. Simulation experiments have shown that this algorithm outperforms existing methods in terms of attitude estimation accuracy, particularly in sunlit and shadowed phases of the orbit, with the same filtering parameters and initial conditions.

Background: Since the advent of virtual reality (VR), it has been used in medical education for surgical training and anatomy teaching. Recently, other modalities of extended reality (XR) such as augmented reality (AR) and mixed reality (MR) has also made its way into medical education. Although there has been research validating XR’s use in medical education, there have been few studies on the research trends of the different XR modalities. The paper aims to compare the research trends of the XR modalities in general and in terms of the medical fields studied and outcomes measured. Methods: Web of Science was searched, and preliminary data was extracted to analyze the general trend. Inclusion and exclusion criteria were then applied, and finalized articles were analyzed and grouped based on the medical field studied and outcomes measured. Results: 31 articles on VR, eight on AR and one on MR were included in the final analysis. We found that there is increasing research in VR since 1990 and AR since 2008. The research in MR is constant. Most of the papers on VR studied endoscopic surgery and anatomy whereas AR studied mostly anatomy and endovascular procedures. Using Miller’s prism of clinical competence, the competency measured most for VR and AR is “show”. Discussion and conclusion: Advancement in computing, communication and display technologies since 1990 may contribute to the increase in research on VR whereas the ubiquity of smartphone since 2008 may explain the increase in research on AR. Although both VR and AR are used in surgical training and anatomy teaching, we found possible strengths of VR in counseling and AR in practical skills. The competency "show" was measured most as most of the papers were on surgery, and the XR simulators used can capture surgical parameters

We propose a new Mamdani fuzzy rule-based system in which the fuzzy sets in the antecedents and consequents are assigned in a discrete set of points and approximated by using the extended inverse fuzzy transforms, whose components are calculated by verifying that the dataset is sufficiently dense with respect to the uniform fuzzy partition. We test our system in the problem of spatial analysis consisting in the evaluation of the liveability of residential housings in all the municipalities of the district of Naples (Italy). Comparisons are done with the results obtained by using trapezoidal fuzzy numbers in the fuzzy rules.

The parameter estimation problem for polynomial phase signals (PPSs) arises in a number of fields, including radar, sonar, biology, etc. In this paper, a fast algorithm of parameter estimation for monocomponent PPS is considered. We propose the so-called LSU-EKF estimator, which combines the least squares unwrapping (LSU) estimator and the extended Kalman filter (EKF). First, the coarse estimates of the parameters of PPS are obtained by the LSU estimator using a small number of samples. Subsequently, these coarse estimates are used to initial the EKF. Monte-Carlo simulations show that the computation complexity of the LSU-EKF estimator is much less than that of the LSU estimator, with little performance loss. Similar to the LSU estimator, the proposed algorithm is able to work over the entire identifiable region. Moreover, in the EKF stage, the accurate estimated results can be output point-by-point, which is useful in real applications.

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

Milled MgH2, NaAlH4, MgH2–10NaAlH4, MgH2–30NaAlH4, MgH2–50NaAlH4, and MgH2–2Ni-10NaAlH4 samples were prepared by milling in hydrogen atmosphere (reactive mechanical milling, RMM). Decomposition temperatures of milled MgH2, NaAlH4, MgH2–10NaAlH4, and MgH2–30NaAlH4 were examined in a Sieverts-type hydrogen-absorption and release apparatus, in which the hydrogen pressures were kept constant during hydrogen absorption or release. As the content of NaAlH4 in the sample increased, the temperature at the highest peak in the ratio of increase in Hr to increase in T, dHr/dT, versus T curve decreased. The higher content of NaAlH4 is believed to have made effects of reactive mechanical milling stronger. Effects of the NaAlH4 content on the temperatures of intermediate reactions were studied for MgH2 – NaAlH4 composites. Phase formation in the cycled MgH2–50NaAlH4 were investigated. The hydrogen-storage properties of MgH2–30NaAlH4 were compared with those of Mg-based alloys in which oxide, halides, or fluoride was added.

This work presents the possibility of using a synthetic membrane for pretracing mucosal penetration studies. The permeability of two types of membranes, porcine oral mucosa and a synthetic Nuclepore membrane, to water was compared. Moreover, the water permeability of membranes modified with waterproofing formulations was measured to study their ability to protect against the penetration of viruses, toxins, etc. A very good correlation was obtained between the transmucosal water loss (TMWL) values of the artificial membrane and the mucosa. These results support the possible use of this synthetic membrane in the screening of the water permeability of formulations. In addition, studies of the permeation of different actives, drugs and biocides through the two membranes were carried out, and these results were compared with their skin permeation data. The synthetic membrane does not seem to discern between compounds in terms of permeability, which could be due to the lack of lipids in the composition of this synthetic membrane. Therefore, Nuclepore alone cannot be used as a model for the release of actives. Additionally, the permeation of caffeine through intact or modified membranes incorporating waterproofing formulations was also studied. In this case, similar permeation profiles through the synthetic membrane and mucosa were found. The results from these assays should lend support to the use of this synthetic membrane when screening formulations to be applied in oral penetration studies.

Regenerative endodontic procedures (REPs) aim at recreating dental pulp tissue using biomaterials such as hydrogels. Their bioactivity is mostly linked to the nature of biomolecules or chemical compounds that will compose the endodontic hydrogel. However, many other parameters, such as hydrogel concentration, type, bioactive molecules solubility, of apex size were reported to influence the hydrogel behavior, leading to the inability to predict the clinical outcome. This lack of knowledge and the various parameters that should be considered, suggest that biological activity of endodontic hydrogel is impossible to anticipate and could hinder the bench to bedside transition. We formulated in this article our opinion that most of these parameters could be identified, described, and studied. A second part of the document lists some challenges and perspectives, including development of future mathematical models able to explain and predict the bioactivity of these endodontic hydrogel in clinic.

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.

Melatonin is a hormone used for treating several disorders. However, its oral administration is problematic due to the variable absorption and extensive first-pass metabolism. The topical application of this drug does not present these disadvantages and can be used for therapeutic and skin protection purposes. The adsorption and release of melatonin in the montmorillonite clay was investigated experimentally and theoretically. The drug-clay interaction products were prepared and characterized, showing a modified and improved diffusion and release of melatonin. The crystal structure and spectroscopic properties of melatonin and melatonin-water-mineral materials were studied by molecular modeling, finding that the adsorption of this drug is energetically favourable, and the results were consistent with the experimental data. Ab initio molecular dynamics simulations with the metadynamics methodology showed the release of melatonin from the confined interlayer nanospace of montmorillonite to the liquid bulk water with a 20 kcal/mol free energy barrier.

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.

Doxorubicin, a member of the anthracycline family, is a common anticancer agent often used as a first line treatment for the wide spectrum of cancers. Doxorubicin-based chemotherapy, although effective, is associated with serious side effects, such as irreversible cardiotoxicity or nephrotoxicity. Those often life-threatening adverse risks, responsible for the elongation of the patients' recuperation period and increasing medical expenses, have prompted the need for creating novel and safer drug delivery systems. Among many proposed concepts, polymeric nanocarriers are shown to be a promising approach, allowing for controlled and selective drug delivery simultaneously enhancing its activity towards cancerous cells and reducing toxic effects on healthy tissues. This article is a chronological examination of the history of the work progress on polymeric nanostructures, designed as efficient doxorubicin nanocarriers, with the emphasis on the main achievements of 2010-2020. Numerous publications have been reviewed to provide an essential summation of the nanopolymer types and their essential properties, mechanisms towards efficient drug delivery, as well as active targeting stimuli-responsive strategies that are currently utilized in the doxorubicin transportation field.

Polyhydroxyalkanoate (PHA) co-polymers show relatively higher in vivo degradation rate compared to other PHAs thus they received a great deal of attention for a wide range of medical applications. Nanoparticles (NPs) loaded with poorly water soluble anticancer drug docetaxel (DCX) were produced using poly 3-hydroxybutyrate-co-4-hydroxybutyrate, P(3HB-co-4HB), co-polymers biosynthesised from Cupriavidus sp. USMAA1020 isolated from Malaysian environment. Three co-polymers with different molar proportions of 4-hydroxybutirate (4HB) were used: 16% (PHB16), 30% (PHB30) and 70% (PHB70) 4HB-containing P(3HB-co-4HB). Blank and DCX loaded nanoparticles were then characterized for their size and size distribution, surface charge, encapsulation efficiency and drug release. Pre-formulation studies showed that an optimised formulation could be achieved through the emulsification/solvent evaporation method using PHB70 with the addition of 1.0% PVA, as stabilizer and 0.03% VitE-TPGS, as surfactant. DCX-loaded PHB70 nanoparticles (DCX-PHB70) gave the desired particle size distribution in term of average particles sizes around 150 nm and narrow particle size distribution (PDI below 0.100). The encapsulation efficiencies result showed that at 30% w/w drug-to-polymer ratio: DCX- PHB16 NPs were able to encapsulate up to 42% of DCX; DCX-PHB30 NPs encapsulated up to 46% of DCX and DCX-PHB70 NPs encapsulated up to 50% of DCX within the nanoparticles system. Approximately 60% of DCX was released from the DCX-PHB70 NPs within 7 days for 5%, 10% and 20% of drug to polymer ratio while for the 30% and 40% drug to polymer ratios, an almost complete drug release (98%) after 7 days of incubation was observed.

One-dimensional nanostructures such as silver nanowires (AgNWs) have attracted considerable attention owing to their outstanding electrical, thermal and antimicrobial properties; however, their application in the prevention of infections linked to bone tissue regeneration interventions has not yet been explored. Here we report on the development of an innovative scaffold prepared from chitosan, composite hydroxyapatite and AgNWs (CS-HACS-AgNWs) having both bioactive and antibacterial properties. In vitro results highlighted the antibacterial potential of AgNWs against both gram-positive and gram-negative bacteria. The CS-HACS-AgNWs composite scaffold demonstrated suitable Ca/P deposition, improved gel strength, reduced gelation time, and sustained Ag+ release within therapeutic concentrations. Antibacterial studies showed that the composite formulation was capable of inhibiting bacterial growth in suspension and of completely preventing biofilm formation on the scaffold in the presence of resistant strains. The hydrogels were also shown to be biocompatible, allowing cell proliferation. In summary, the developed CS-HACS-AgNWs composite hydrogels demonstrated significant potential as a scaffold material to be employed in bone regenerative medicine, as it presents enhanced mechanical strength combined with the ability to allow calcium salts deposition, while efficiently decreasing the risk of infections. The results presented justify further investigations into potential clinical applications of these materials.

We simulate elementary calcium release events (sparks) in a single calcium release unit in ventricular myocyte. Previously developed and tested electron-conformational model of the stochastic dynamics of RyR-channels is integrated to the calcium dynamics model in the cardiac cell. This approach allows to observe RyRs opening/closing in details on the macromolecular level during the calcium dynamics course. We simulate calcium diffusion in the dyadic space and “domino-like” RyR’s activation during the so-called “calcium induced-calcium release process”. Ca²⁺ sparks initiation, spread and termination are investigated in the computer experiments. Sparks’ initiation and termination rate dependence on the Ca²⁺ diffusion velocity is observed. We show that sarcoplasmic reticulum lumen local depletion and RyR’s stochastic attrition could be the reasons of Ca²⁺ spark termination.

The present study illustrates a brain-computer interface designed and developed to be wearable, portable, and user-friendly. Eight dry electroencephalographic sensors were adopted to acquire the brain activity associated with motor imagery. Multimodal feedback in extended reality was exploited to improve the detection of neurological phenomena. Twenty-seven healthy subjects used the proposed system in five sessions to investigate the effects of feedback on motor imagery. The sample was divided into two equal-sized groups: the "neurofeedback" group, which performed motor imagery while receiving feedback, and the "control" group, which performed motor imagery with no feedback. Several questionnaires were administrated to participants aiming to investigate the usability of the proposed system and individual’s ability to imagine movements. The highest mean classification accuracy across subjects of control group was about 62 % with 3 % associated type A uncertainty, and 69 % with 3 % uncertainty for neurofeedback group. Moreover, in some cases the results were significantly higher for the neurofeedback group. The perceived usability by all participants was high. Overall, the study highlights the advantages and the pitfalls of using a wearable brain-computer interface with dry sensors. Notably, the results and the perceived usability pave the way for the employment of the proposed system in tele-rehabilitation.

Thermodynamics and phase transitions of magnetic Anti-de Sitter black holes are studied. We consider an extended phase space thermodynamics with the cosmological constant being a thermodynamic pressure and the black hole mass is treated as a chemical enthalpy. The extended phase space thermodynamics of black holes mimics the behavior of the Van der Walls liquid. Quantities conjugated to the coupling of nonlinear electrodynamics (NED) and a magnetic charge are obtained. Thermodynamic critical points of phase transitions are investigated. It is demonstrated that the first law of black hole thermodynamics and the generalized Smarr relation take place. The Joule--Thomson adiabatic expansion of NED-AdS black holes is studied. The dependence of inversion temperature on pressure and the minimum of inversion temperature are found.

In this paper we address one of the most important topics in the field of Social Networks Analysis: the community detection problem with additional information. That additional information is modeled by a fuzzy measure that represents the possibility of polarization. Particularly, we are interested in dealing with the problem of taking into account the Polarization of nodes in the community detection problem. Adding this type of information to the community detection problem makes it more realistic, as a community is more probably to be defined if the corresponding elements are willing to maintain a peaceful dialogue. The polarization capacity is modeled by a fuzzy measure based on the JDJpol measure of polarization related to two poles. We also present an efficient algorithm for finding groups whose elements are no polarized. Hereafter, we work in a real case. It is a network obtained from Twitter, concerning the political position against the Spanish government taken by several influential users. We analyze how the partitions obtained change when some additional information related to how polarized that society is, is added to the problem.

Groundwater is a vital resource for human welfare. However, due to various factors, groundwater pollution is one of the main environmental concerns facing. Yet, it is challenging to simulate groundwater quality dynamics due to the insufficient representation of nutrient percolation processes in the soil and Water Assessment Tool model. The objectives of this study were extending the SWAT module to predict groundwater quality. The results proved a linear relationship between observed and calculated groundwater quality considering No3 and TDS with R2, NSE and PBIAS values in the satisfied ranges, albeit underestimation and overestimation were observed due to limited data availability. These results highlight that nitrate and TDS concentrations and variability in groundwater may used as a tool in surface water quality that have to be assumed for designing adaptive management scenarios. Hence, extended SWAT model could be a powerful tool for future regional to global scale modelling of nutrient loads supporting effective surface and groundwater management.

In the present work, the charged dark matters of B1, B2 and B3 bastons are explained as the right-handed partners of the left-handed neutrinos. The new Higgs mechanism of SU(2)_DM×SU(2)_Weak×SU(2)_Strong including electromagnetic and gravitational forces is applied. And the rest masses of the elementary particles depend on their charge configurations. The left-handed neutrinos have only the lepton charges (LC) and the right-handed dark matters have only the electric charges (EC). This explains the fact that the rest masses of the left-handed neutrinos are so small, and the rest masses of the right-handed dark matters are relatively very large. The proposed rest mass (26.12 eV/c²) of the B1 dark matter is indirectly confirmed from the supernova 1987A data. The missing neutrinos are newly explained by using the dark matters and lepton charge force. The neutrino excess anomaly of the MinibooNE data is explained by the B1 dark matter scattering within the Cherenkov detectors. The quark mixing and neutrino mixing are not required in the present model. It is shown that our matter universe and its partner antimatter universe can be created from the big bang in the point of view of time -, charge -, space -, and quantum state – symmetric universe evolution.

The main objective of this present paper is to establish the extension of an extended fractional derivative operator by using an extended beta function recently defined by Parmar et al. by considering the Bessel functions in its kernel. Also, we give some results related to the newly defined fractional operator such as Mellin transform and relations to extended hypergeometric and Appell's function via generating functions.

This study investigated the prevalence of embryonic and connective tissue elements in the filum terminale (FT) of patients with tethered cord syndrome (TCS), examining both typical and pathological histology. FT specimens from 288 patients who underwent spinal cord detethering from 2013-2021 were analyzed. Histopathological examination involved routine hematoxylin and eosin staining and specific immunohistochemistry when needed. Patient details were extracted from electronic medical records. The study found that 97.6% of FT specimens had peripheral nerves, and 70.8% had regular ependymal cell linings. Other findings included ependymal cysts and canals, ganglion cells, neuropil, and prominent vascular features. Notably, 41% showed fatty infiltration, and 7.6% had dystrophic calcification. Inflammatory infiltrates, an underreported finding, were observed in 3.8% of the specimens. The research highlights peripheral nerves and ganglion cells as natural components of the FT, with ependymal cell overgrowth and other tissues potentially linked to TCS. Enlarged vessels may suggest venous congestion due to altered FT mechanics. The presence of lymphocytic infiltrations and calcifications provides new insights into structural changes and mechanical stress in the FT, contributing to our understanding of TCS pathology.

Mesoporous silica nanoparticles (MSNs) can be used as carrier materials for the controlled release of pesticides while reducing their negative environmental impact. In this study, we screened an active ingredient, p-cymene (PC), with an excellent inhibitory effect on rice bacterial blight. Subsequently, the PC was successfully loaded onto MSNs via physisorption(PC@MSNs). PC@MSNs, characterized by a regular spherical shape, smooth surface, and an MSN average size of 262.9 nm, achieved an 8.6 % drug loading capacity. The release kinetics of the PC from the PC@MSNs demonstrated a sustained release (288 h) pattern influenced by drug diffusion. The efficacy of the PC@MSNs against Xanthomonas oryzae pv. Oryzae paralleled those of PC. Acute toxicity assays re-vealed that the PC@MSNs were less toxic to aquatic life (LC50=257.867 mg/L) and that the formu-lation showed no adverse effects on rice seedling growth. In summary, these results suggest that PC@MSNs can broaden PC's application scope in managing rice diseases.

Transdermal drug delivery systems have become an intriguing research topic in healthcare technology and one of the most frequently developed pharmaceutical products in the global market. In recent years, researchers and pharmaceutical companies have made significant progress in developing new solutions in the field. This study sheds light on current trends, collaboration patterns, research hotspots, and emerging frontiers of transdermal drug delivery. Herein, a bib-liometric and patent analysis of data recovered from Scopus and The Lens databases, respectively, is reported over the last 20 years. From 2000 to 2022, the annual global publications increased from 131 in 2000 to 659 in 2022. Researchers in the United States, China, and India produced the highest number of publications. Likewise, most patent applications have been filed in the USA, China, and Europe. The recovered patents are 7,275, grouped into 2,997 patent families, of which 314 were granted. This study could support the work of decision-makers, scientific managers, or scientists to create new business opportunities or save money, time, and intellectual capital, thus, defining when a research or technology project should be a priority or not.

Lipofibromatous hamartoma, first reported in 1953, is a rare, slowly-progressive soft tissue tumor, characteristics of which include enlargement of the affected nerve by epineurial and perineurial proliferation of adipose and fibrous tissues. Out of previously reported 200 cases of lipofibromatous hamartoma of the median nerve, there have been approximately 40 pediatric cases under the age of 18. Herein, we report a case of lipofibromatous hamatoma of the median nerve in a 3-year-old female patient, who was surgically decompressed by carpal tunnel release only and histologically confirmed. The patient was followed-up on outpatient clinic basis annually along with ultrasonography, and the postoperative 10th year follow-up did not show recurrence or any deficits in motor and sensory functions

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

The pond slider (Trachemys scripta) was designated as an invasive alien species in South Korea in 2001. Although the prevention and control of invasive species have received considerable atten-tion worldwide, studies on the current status and effective management of T. scripta in South Korea are lacking. This study aimed to elucidate the status of domestic reuse of T. scripta and provide effective management suggestions. Analysis of the National Institute of Ecology's “Na-tionwide Survey of Non-native Species in Korea” conducted from 2015 to 2022 confirmed the habitats of 1,440 T. scripta individuals at 295 sites. T. scripta is the most frequently observed among invasive turtles identified in the Korean Peninsula. To determine the reuse of T. scripta, 13 tradi-tional markets were surveyed; five markets were confirmed to have T. scripta. Although the exact distribution route is unknown, individuals living or abandoned in the region might be resold in the market. T. scripta is mostly sold for ritual purposes. Moreover, T. scripta accounted for 31% of freshwater turtles abandoned between 2019 and 2022. Their continuous reuse has been confirmed 22 years after their designation as an invasive alien species. Therefore, effective and fundamental management measures for T. scripta are required.

Low-temperature accumulation is one of the essential stages in the growth process of woody ornamental plants. In this study, two different low-temperature treatments, 6℃ and 10℃, were used to analyze the effects of different low-temperature treatments on dormancy release and flowering of the 'Gulihong' plant using artificial low temperatures. Based on the experimental results, four typical early-blooming Prunus mume cultivars widely planted in Yangling area of Henan Province, China, including 'Zaoyudie', 'Zaohualve', 'Nanjing gongfen', and 'Gulihong', were selected as the experimental materials. The effects of low-temperature accumulation on the flowering characteristics of different cultivars were analyzed using a 6℃ artificial low-temperature treatment. The suitable cultivation temperature for early-blooming P. mume cultivars was screened to provide a theoretical basis for further exploration of P. mume bonsai cultivation techniques. The results showed that the flowering rate, flower diameter, flowering quantity, flowering uniformity, and bud development in the 6℃ treatment were significantly better than those in the 10℃ treatment. The flowering rate and quality of different cultivars gradually increased with the accumulation of low-temperature. Therefore, chill accumulation plays a significant role in promoting flowering quality.

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.

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

The 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.

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

In the autonomous navigation of mobile robots, precise positioning is crucial. In forest environments with weak satellite signals or in sites disturbed by complex environments, satellite positioning accuracy has difficulty in meeting the requirements of autonomous navigation positioning accuracy for robots. This article proposes a binocular vision SLAM/UWB tightly coupled localization method. The core of this algorithm is based on an Extended Kalman Filter (EKF), which utilizes the displacement increment output by binocular vision ORB-SLAM and the positioning coordinates calculated via UWB positioning as measurement information to achieve data fusion. The research utilized the constructed experimental platform to collect images and UWB ranging data in outdoor environments and experimentally validated the combined positioning method. The experimental results show that this algorithm outperforms the use of the individual UWB or visual SLAM localization methods in terms of positioning accuracy. Compared with traditional single positioning algorithms, this algorithm exhibits better practicality and stability, and can effectively suppress the impact of UWB non line of sight errors. The average error under normal line of sight conditions is 0.058 m, the root mean square error (RMSE) is 0.080, and the average error under non-line-of-sight conditions is 0.081 m, with an RMSE of 0.084. There is no significant jump or drift. Through the tightly coupled processing of binocular vision SLAM and UWB positioning, more reliable and accurate mobile robot positioning can be achieved, providing a useful reference for the autonomous navigation of mobile robots in complex environments.

This study examined the relationships between attitude, subjective norms, perceived behavioral control, and behavioral intention through the perceived value of Pilates participants. The participants of this study were 301 Pilates students using Pilates studios located in Busan, Ulsan, and Gyeongbuk Province. The participants were selected by convenient sampling, a non-probability sampling method. The collected data were analyzed using descriptive analysis, reliability analysis, correlation analysis, confirmatory factor analysis, and structural equation modeling analysis using SPSS 22.0 and AMOS 24.0. The results can be summarized as follows. First, among the three subfactors of perceived value, functional and social values had a positive effect on attitude. Second, attitude, subjective norms, and perceived behavioral control, which are three main components of the Theory of Planned Behavior, had a positive effect on the behavioral intention for Pilates. These results suggest that Pilates instructors require meticulous planning and efforts to develop an environment for promoting spontaneous interest and participation to attract students and engage their attention and interest in the field.

The combination of wet-lab experimental data on multi-site combinatorial mutations and machine learning is an innovative method in protein engineering. In this study, we present an improved innovative sequence–activity relationship (innov'SAR) methodology based on novel descriptors and digital signal processing (DSP) to construct a predictive model. In this improved approach, 21 experimental (R)-selective amine transaminases from Aspergillus terreus (AT-ATA) were used as an input to predict higher thermostability than that predicted using the existing data. We successfully improved the determination coefficient (R2) of the model from 0.66 to 0.92. In addition, root mean square deviation (RMSD) and root mean square fluctuation (RMSF) were estimated and conformation analysis based on molecular dynamics simulations was performed to verify the enhanced thermal stability of the screened mutants. The improved innov'SAR algorithm enhanced the predictive accuracy, suggesting a method for modifying the stability of AT-ATA, which may help in directed evolutionary screening and open up new avenues for protein engineering.

Matrix-variate Gaussian type or Wishart type distributions in the real domain are widely used in the literature. When the exponential trace has an arbitrary power and when a factor involving a determinant enters into the model or a matrix-variate gamma type or Wishart type model with exponential trace having an arbitrary power, is extremely difficult to handle. Evaluation of the normalizing constant in such a model is the most important part because when studying the properties of such a model, the method used in the evaluation of the normalizing constant will be the relevant steps in all the computations involved. One such model with a factor involving a trace and the exponential trace having an arbitrary power, in the real domain, is known in the literature as Kotz' model. No explicit evaluation of the normalizing constant in the model involving trace with an exponent and determinant with an exponent entering into the model and at the same time the exponential trace having an arbitrary exponent seems to be available in the literature. The normalizing constant widely used in the literature and interpreted as the normalizing constant in the general model and refers to as a Kotz' model does not seem to be correct. Corresponding model in the complex domain, with the correct normalizing constant, does not seem to be available in the literature. One of the main contributions in this paper is the matrix-variate distributions in the complex domain belonging to Gaussian type, gamma type, type-1 and type-2 beta type when the exponential trace has an arbitrary power. All these models are believed to be new. A second main contribution is the explicit evaluation of the the normalizing constants, in the real and complex domains especially in the complex domain, in a matrix-variate model involving a determinant and a trace as multiplicative factors and at the same time the exponential trace having an arbitrary power. Another main contribution is the introduction of matrix-variate models with exponential trace having an arbitrary exponent, in the categories of type-1 beta, type-2 beta and gamma distributions or in the family of Mathai's pathway models [1], both in the real and complex domains. Another new contribution is the logistic-based extensions of models in the real and complex domains with exponential trace having an arbitrary exponent and connecting to extended zeta functions introduced by this author recently. Some properties of such models are indicated but not derived in detail in order to limit the size of the paper. The techniques and steps used at various stages in this paper will be highly useful for people working in multivariate statistical analysis as well as people applying such models in engineering problems, communication theory, quantum physics and related areas, apart from statistical applications.

The main problem in pursuing multiple extended targets tracking is distinguishing the origins of the measurements. The association of measurements to the possible origins within the target’s extent is difficult, especially for the occlusions or the detection blind zone which cause the intermittent measurements. To solve the problem, a hierarchical network-based tracklets data association algorithm is proposed. At the low level, the min cost network flow model is used to extract possible tracklets from the divided measurement set. At the high-level, the trajectories are estimated from the tracks produced by the previous low level network. The experimental results show that the hierarchical network-based tracklets data association algorithm outperforms the JPDA and RFS-based method when the measurement is intermittently unavailable.

In the last years, interactive exhibitions based on digital technologies are becoming widely common, thanks to their flexibility and effectiveness in engaging visitors and creating memorable experiences. One of the topics in which digital technologies can be particularly effective is the communication of abstract concepts that are difficult for the human mind to imagine. An emblematic example is the astronomy discipline, which requires us to imagine and understand phenomena far away from our everyday life. In this paper, the authors present a research project, MARSS, in which digital technologies are used effectively to enhance the Users’ Experience of the Museo Astronomico di Brera located in Milan. Specifically, the MARSS project aims at designing and developing a new digital journey inside the museum to allow different categories of visitors to enjoy the exhibition in an engaging and interactive way. The paper presents the design and development phases of the experience and its evaluation with users. The results of the evaluation indicate that the digital interactive experience has been appreciated by users and is successful in translating the content of high scientific value into more engaging and easily understandable elements.

Linear elastic fracture modeling coupled with empirical material tension data result in good quantitative agreement with experimental measurements of fracture failure for both brittle and tough epoxy nanocomposites. The nanocomposites comprise diglycidyl ethers of bisphenol A cured with O,O’ bis (2-aminopropylpropylene glycol) (Jeffamine D230) and doped with rubber nanoparticles of varying concentrations. Toughness, critical load, and critical displacement in quasi-static single edge-notched three-point bending are predicted accurately using both surface-based cohesive zone (CZS) and extended finite element (XFEM) methods implemented in Abaqus software. Fracture initiation within a crack is taken at the yield stress from uniaxial tension data. Prediction of fracture processes using a generalized truncated linear traction-separation law was significantly improved by considering the case of a linear softening function. There are no adjustable parameters in the XFEM model. The CZS model requires only optimization of the element displacement at fracture parameter. Thus, these continuum methods describe these materials in mode I fracture with a minimum number of independent parameters.

This paper proposes the use of non-uniform extended surfaces installed externally to the tubes of the radiation section of fired heaters, in order to obtain a better heat flux distribution to the coils. To this end, the heat transfer mechanisms present in such equipment were studied through computational fluid dynamics (CFD), using simplified geometries that represent typical sizes of fired heaters. Also, a simplified model for the combustion was considered. Although this model oversimplifies the physics of the problem, it was able to give satisfactory results for the parameters being optimized, considering the main objective of this paper, that is to minimize the non-uniformity of heat flux in the tubes of the radiant section of fired heaters. It was possible to obtain optimized geometric parameters for different types of extended surfaces evaluated, coupling the results of these models with the Particle Swarm optimization method through the use of a response surface technique,. The results indicate a significant improvement in the uniformity of the heat flux distribution to the tubes through the use of the proposed extended surfaces. Thus, this solution reveals to be an interesting alternative to reduce the risks of fluid degradation and coking formation. Future studies must investigate the non-uniformity of the heat flux due to the presence of the flame and consider the interaction between the reactive flow and the participating medium. Nevertheless, this paper presents some results that justify the optimization of such extended surfaces taking into consideration thermal radiation.

This study was to designed to develop sorafenib-loaded polymeric nanoparticles, surface-modified with pluronic F-127 for the effective treatment of hepatocellular (HCC) and renal cell carcinomas (RCC). Poly lactic coglycolic acid (PLGA) was used to encapsulate different concentrations of sorafenib by a simple modified solvent evaporation method applying pluronic F-127 as a surfactant and coating agent. The preformulation and characterization studies were conducted to evaluate the incompatibilities among sorafenib, PLGA and pluronic F-127, and physicochemical properties of the formulations, respectively. The sizes of the coated and plain PLGA nanoparticles were ~140 ± 14.7 nm and ~ 120 ± 10.1 nm, respectively. It has been confirmed from the in vitro release studies that PLGA sustained the release of sorafenib, avoiding the initial burst release, while the in vivo studies demonstared that surface-modified nanoparticles have greater affinity in the target aorgans than plain PLGA nanoparticles and free drug keeping the dose constant (20 mg/kg body weight). The delivery of sorafenib-loaded polymeric PLGA nanoparticles into the target tissues and their pharmacokinetic parameters have been improved significantly compared to the reported formulations.

Grape pomace is a byproduct of wineries and sustainable source of bioactive phenolic compounds. Encapsulation of phenolics with a well-chosen coating may be a promising means of delivering them to the intestine, where they can then be absorbed and exert their health-promoting properties. Ionic gelation of grape pomace extract with natural coatings (sodium alginate and its combination with maltodextrins, gelatin, chitosan, tragacanth gum, and gum arabic) was performed, and the resulting hydrogel microbeads were then air-, vacuum-, or freeze-dried to prevent their spoilage. The physicochemical characterization (size, shape, texture, and morphology) of the microbeads and the in vitro release of phenols from microbeads were studied and a good relationship between them was established. Freeze-dried microbeads showed the highest cumulative release of phenols as in the intestinal phase (23.31 – 43.27 mgGAE/gMB), followed by vacuum-dried (23.31 - 35.41 mgGAE/gMB) and air-dried (22.74 – 31.38 mgGAE/gMB), while the most suitable release dynamics in the intestinal phase were observed for alginate-based microbeads combined with gelatin (58.4 %), gum arabic (34 %) and 1.5 % w/v chitosan (15.3 %). The results highlight the importance of developing encapsulated formulations containing a natural source of bioactive compounds that can be used in various functional foods and pharmaceutical products.

Transdermal drug delivery (TDD) is one of the key approaches for treating diseases, avoiding first-pass effects, reducing systemic adverse drug reactions and improving patient compliance. Microneedling, iontophoresis, electroporation, laser ablation and ultrasound facilitation are often used to improve the efficiency of TDD. Among them, microneedling is a relatively simple and efficient means of drug delivery. Microneedles usually consist of micron-sized needles (50-900 μm in length) in arrays that can successfully penetrate the stratum corneum and deliver drugs in a minimally invasive manner below the stratum corneum without touching the blood vessels and nerves in the dermis, improving patient compliance. Hydrogel-forming microneedles (HFMNs) are safe, non-toxic, no residual matrix material, high drug loading capacity, controlled drug release and are suitable for long-term, multiple drug delivery. This work reviewed the characteristics of skin structure and transdermal drug delivery; introduced TDD strategies based on hydrogel microneedles; summarised the characteristics of HFMNs TDD systems and the evaluation methods of HFMNs; and the application of HFMNs drug delivery systems in disease treatment. The HFMNs drug delivery system has a wide scope for development, but the translation to clinical application still has more challenges.

Antibody-Drug Conjugates (ADCs) are a powerful therapeutic modality for cancer treatment. ADCs are multi-functional biologics in which a disease-targeting antibody is conjugated to an effector payload molecule through a linker. The success of currently used ADCs has been largely attributed to the development of linker systems which allow targeted release of cytocidal payload drugs inside cancer cells. Many lysosomal proteases are over-expressed in human cancers. They can effectively cleave a variety of peptide sequences, which can be exploited in the design of ADC linker systems. As a well-established linker, valine-citrulline-p-aminobenzyl carbamate (ValCitPABC) is used in many ADCs that are already approved or under preclinical and clinical development. Although ValCitPABC and related linkers are readily cleaved by cathepsins in the lysosome while remaining reasonably stable in human plasma, many studies have shown that they are susceptible to carboxylesterase 1C (Ces1C) in mouse and rat plasma, which hinders preclinical evaluation of the ADCs. Furthermore, neutropenia and thrombocytopenia, two of the most commonly observed dose-limiting adverse effects of ADCs, are believed to result from the premature hydrolysis of ValCitPABC by human neutrophil elastase. In addition to cathepsin-cleavable linkers, there is also growing interest in legumain-sensitive linkers for ADC development. Increasing plasma stability while maintaining lysosomal cleavability of ADC linkers is an objective of intensive current research. This review reports recent advances in the design and structure-activity relationship studies of various peptide/peptidomimetic linkers in this field.

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.