Histone deacetylase 9 (HDAC9) is known to be upregulated in various cancers. Cancer-associated antigens (CAGEs) are cancer/testis antigens that play an important role in anti-cancer drug resistance. This study aimed to investigate the relationship between CAGEs and HDAC9 in relation to anti-cancer drug resistance. AGS^R cells with an anti-cancer drug-resistant phenotype showed higher levels of CAGEs and HDAC9 than normal AGS cells. CAGEs regulated the expression of HDAC9 in AGS and AGS^R cells. CAGEs directly regulated the expression of HDAC9. Rapamycin, an inducer of autophagy, increased HDAC9 expression in AGS, whereas chloroquine decreased HDAC9 expression in AGS^R cells. The downregulation of HDAC9 decreased the autophagic flux, invasion, migration, and tumor spheroid formation potential in AGS^R cells. The TargetScan analysis predicted that miR-512 was a negative regulator of HDAC9. An miR-512 mimic decreased expression levels of CAGEs and HDAC9. The miR-512 mimic also decreased the autophagic flux, invasion, migration, and tumor spheroid forming potential of AGS^R cells. The culture medium of AGS^R increased the expression of HDAC9 and autophagic flux in AGS. A human recombinant CAGE protein increased HDAC9 expression in AGS cells. AGS^R cells displayed higher tumorigenic potential than AGS cells. Altogether, our results show that CAGE–HDAC9–miR-512 can regulate anti-cancer drug resistance, cellular proliferation, and autophagic flux. Our results can contribute to the understanding of the molecular roles of HDAC9 in anti-cancer drug resistance. Full article

The purpose of this study is to discuss epidemic communication for drones to share information in flight and to develop a wireless system for implementation. Various theoretical studies have been conducted on epidemic communication, but their applications are not clear, so a system that assumes practical use is developed. As the main evaluation items, we analyzed the effect of communication interference between drones on the amount of data transmission, and furthermore, proposed an optimal transmission method depending on the flight speed. In these analysis results, we designed functions to be implemented in drones, developed wireless devices, and confirmed their operation through demonstration tests using actual drones. Based on the results of this research, we succeeded in identifying issues to be addressed in order to implement the system on drones and in developing an epidemic communication system based on the results of demonstration experiments, thereby contributing to the realization of inter-drone communication in the future. Full article

A major source in the research on Baltic cultural history (Latvia, Estonia), including studies dedicated to the clothing of local inhabitants, are the drawings and descriptions of Johann Christoph Brotze (1742–1823), which date back to the turn of the 18th and 19th centuries. They contain references to dyes and dyeing methods used by local peasants. The information recorded by J. C. Brotze, although fragmentary, is valuable because researchers lack documentary sources about the dyeing methods used in the 18th century in the territory of present-day Latvia. Additional research yields more extensive information about the contents of the descriptions. The current article will describe the experimental method that enabled the establishment of the specific dyeing technique, which, using Bixa orellana L., was employed to obtain the particular orange color referred to in the descriptions. Full article

The use of existing natural gas pipelines for the transport of hydrogen/natural gas mixtures can achieve large-scale, long-distance and low-cost hydrogen transportation. A jet fire induced by the leakage of high-pressure pure hydrogen and hydrogen-blended natural gas pipelines may pose a severe threat to life and property. Based on the Abel–Nobel equation of state and a notional nozzle model, an equivalent pipe leakage model is established to simulate high-pressure pipeline gas leakage jet fire accidents. Large-scale high-pressure hydrogen and natural gas/hydrogen mixture jet fires are simulated, showing the jet impingement process and obtaining an accurate and effective simulation framework. This framework is validated by comparing the simulated and experimental measured results of flame height, flame appearance and thermal radiation. Several combustion models are compared, and the simulated data show that the non-premixed chemical equilibrium combustion model is superior to other combustion models. The influence of the pipe pressure and the hydrogen blending ratio on the consequences of natural gas/hydrogen mixture pipeline leakage jet fire accidents is explored. It is found that when the hydrogen blending ratio is lower than 22%, the increase in the hydrogen blending ratio has little effect on the decrease in the thermal radiation hazard distance. Full article

In this paper, we investigate a class of multi-term implicit fractional differential equation with boundary conditions. The application of the Schauder fixed point theorem and the Banach fixed point theorem allows us to establish the criterion for a solution that exists for the given equation, and the solution is unique. Afterwards, we give the criteria of Ulam–Hyers stability and Ulam–Hyers–Rassias stability. Additionally, we present an example to illustrate the practical application and effectiveness of the results. Full article

The recent rise in the applications of advanced technologies in the sustainable design and construction of transportation infrastructure demands an appropriate medium for their integration and utilization. The relatively new concept of Civil Integrated Management (CIM) is such a medium; it enhances the development of digital twins for infrastructure and also embodies various practices and tools, including the collection, organization, and data-management techniques of digital data for transportation infrastructure projects. This paper presents a comprehensive analysis of advanced CIM tools and technologies and categorizes its findings into the following research topics: application of advanced surveying methods (Advanced Surveying); geospatial analysis tools for project planning (Geospatial Analysis); multidimensional virtual design models (nD Modeling); Integrated Geospatial and Building Information Modeling (GeoBIM); and transportation infrastructure maintenance and rehabilitation planning (Asset Management). Despite challenges such as modeling complexity, technology investment, and data security, the integration of GIS, BIM, and artificial intelligence within asset-management systems hold the potential to improve infrastructure’s structural integrity and long-term performance through automated monitoring, analysis, and predictive maintenance during its lifetime. Full article

In this paper, I examine Johannes de Silentio’s presentation of the faith of Abraham, deriving therefrom a new way of conceiving his notion of faith as a paradoxical co-inhabiting of both the aesthetic and the ethical stages, rather than as a rejection, synthesis, or overcoming of them. Relying largely upon Silentio’s account of Abraham’s faith as anxious but not doubting, I argue that the interpretations of Fear and Trembling by Alastair Hannay and Mark C. Taylor fail to account for some essential aspects of Silentio’s depiction. I conclude that faith, as it is described in Fear and Trembling, cannot be philosophically understood as it is not an object for thought but an existential perspective one lives. Full article

The concept of pseudocapacitance is explored as a rapid and universal method for the state of health (SOH) determination of batteries and supercapacitors. In contrast to this, the state of the art considers the degradation of a series of full charge/discharge cycles. Lithium-ion batteries, sodium-ion batteries and supercapacitors of different cell chemistries are studied by impedance spectroscopy during lifetime testing. Faradaic and capacitive charge storage are distinguished by the relationship between the stored electric charge and capacitance. Batteries with a flat voltage–charge curve are best suited for impedance spectroscopy. There is a slight loss in the linear correlation between the pseudocapacitance and Ah capacity in regions of overcharge and deep discharge. The correct calculation of quantities related to complex impedance and differential capacitance is outlined, which may also be useful as an introductory text and tutorial for newcomers to the field. Novel diagram types are proposed for the purpose of the instant performance and failure diagnosis of batteries and supercapacitors. Full article

This study investigates the impact of melatonin (MT) treatment at varying concentrations (0, 25, 50, 75, 100 µmol L⁻¹) on the post-harvest quality and shelf life of long green pepper fruits stored under low temperature for 28 days. Every 4 days, pepper fruits were examined for the chilling injury (CI) index, weight loss (WL), respiration rates, firmness, electrolyte leakage (EL), reactive oxygen species (ROS), malondialdehyde (MDA) levels, non-enzymatic antioxidant (NEA) content, antioxidant (AO) enzyme activity (superoxide dismutase (SOD), catalase (CAT), and peroxidases (PODs)), and cellular degrading enzymes (polygalacturonase (PG), pectin methylesterase (PME), phospholipase D (PLD), and lipoxygenase (LOX)). MT-treated samples exhibited delayed and reduced CI stress compared to controls, with higher exogenous MT concentrations (>50 µmol L⁻¹) offering significant (p < 0.05) CI reductions. During storage, WL was notably mitigated by MT treatment in the tested samples compared to control samples. This study also demonstrated that MT-treated pepper fruits effectively decelerated respiration rates and consequently preserved pepper firmness. A higher concentration of MT-treated pepper fruits demonstrated a significantly (p < 0.05) lowered level of ROS and MDA while maintaining membrane stability, as evidenced by reduced EL. MT treatment with increasing concentration increased the levels of glutathione (GSH), glutathione disulfide (GSSG), ascorbic acid (AsA), dehydroascorbate (DHA), and total phenolic content (TPC) in the pepper fruits compared to control and thus significantly (p < 0.05) suppressed the ROS production (superoxide anion (O₂^•−) and hydrogen peroxide (H₂O₂) radicals) in the pepper fruits. Furthermore, AO enzymes such as SOD, CAT, and POD were also high in the pepper fruits that were treated with higher concentrations of MT (>50 µmol L⁻¹). Additionally, the activities of cellular degrading enzymes (PG, PME, PLD, and LOX), which are linked to senescence and stress-induced physiological disorders, were also effectively regulated by MT-treated (>75 µmol L⁻¹) pepper fruits. Overall, the application of MT at higher concentrations (>75 µmol L⁻¹) demonstrated substantial benefits in preserving the quality and extending the shelf life of pepper fruits during cold storage. Full article

Nanocomposite gels consist of nanoparticles dispersed in a gel matrix. The main aim of this work was to develop nanocomposite gels for topical delivery of Flurbiprofen (FB) for humans and farm animals. Nanocomposite gels were prepared stemming from nanoparticles (NPs) freeze-dried with two different cryoprotectants, D-(+)-trehalose (NPs-TRE) and polyethylene glycol 3350 (NPs-PEG), sterilized by gamma (γ) irradiation, and gelled with Sepigel^® 305. Nanocomposite gels with FB-NPs-TRE and FB-NPs-PEG were physiochemically characterized in terms of appearance, pH, morphological studies, porosity, swelling, degradation, extensibility, and rheological behavior. The drug release profile and kinetics were assessed, as well as, the ex vivo permeation of FB was assessed in human, porcine and bovine skin. In vivo studies in healthy human volunteers were tested without FB to assess the tolerance of the gels with nanoparticles. Physicochemical studies demonstrated the suitability of the gel formulations. The ex vivo skin permeation capacity of FB-NPs nanocomposite gels with different cryoprotectants allowed us to conclude that these formulations are suitable topical delivery systems for human and veterinary medicine. However, there were statistically significant differences in the permeation of each formulation depending on the skin. Results suggested that FB-NPs-PEG nanocomposite gel was most suitable for human and porcine skin, and the FB-NPs-TRE nanocomposite gel was most suitable for bovine skin. Full article

The aim of this study is to delve into the intricate the mechanism through which alterations in currency exchange rates give rise to shifts in inflation rates, while taking into careful consideration the country’s economic cycle. In order to accomplish this objective, we used a dataset that spanned from 1 January 1999 to 1 July 2023, focusing our analytical lens on three specific geographic areas, namely the Eurozone, the United Kingdom, and Canada. In our pursuit of understanding this complex relationship, we employed the Markov Switching Vector Autoregressive model. Our research outcomes can be succinctly encapsulated as follows: in the initial stages, particularly during phases characterized by robust economic growth, the transmission of exchange rate effects onto inflation levels appeared to exhibit a partial impact across all geographic areas under examination. However, during periods marked by economic downturns, both the United Kingdom and Canada displayed a distinctly more comprehensive transmission of these effects. Moreover, the prevailing projections for the forthcoming time horizon, across all the countries encompassed by our study, strongly indicate the onset of an expansionary phase that is projected to extend over a span of 25 months. Lastly, concerning the implications of unexpected disturbances or shocks, it is noteworthy that the response of exchange rates to inflation induced shocks was neither immediate nor as pronounced as the corresponding reaction of inflation to sudden shifts in exchange rates. Full article

In recent years, there has been a notable increase in the clinical adoption of instrumental upper limb kinematic assessment. This trend aligns with the rising prevalence of cerebrovascular impairments, one of the most prevalent neurological disorders. Indeed, there is a growing need for more objective outcomes to facilitate tailored rehabilitation interventions following stroke. Emerging technologies, like head-mounted virtual reality (HMD-VR) platforms, have responded to this demand by integrating diverse tracking methodologies. Specifically, HMD-VR technology enables the comprehensive tracking of body posture, encompassing hand position and gesture, facilitated either through specific tracker placements or via integrated cameras coupled with sophisticated computer graphics algorithms embedded within the helmet. This review aims to present the state-of-the-art applications of HMD-VR platforms for kinematic analysis of the upper limb in post-stroke patients, comparing them with conventional tracking systems. Additionally, we address the potential benefits and challenges associated with these platforms. These systems might represent a promising avenue for safe, cost-effective, and portable objective motor assessment within the field of neurorehabilitation, although other systems, including robots, should be taken into consideration. Full article

Biska, a traditional Istrian herbal spirit, is produced by macerating mistletoe leaves and twigs in a water–ethanol base, usually grape marc spirit. The aim of this study was to determine the optimal mistletoe maceration parameters (ethanol content, concentration of plant material, and duration) for the production of biska, which have not yet been the subject of scientific research. The prepared mistletoe macerates and the collected biska samples were subjected to phenolic compound characterization, including total phenolic content (TPC), total flavonoid content (TFC), and polyphenolic profile, by ultra-high-performance liquid chromatography coupled with mass spectrometry (UPLC-ESI-MS²). In addition, the macerates and the biska samples were analyzed for their biological properties: antioxidant and antiproliferative activity. The results showed that both the macerates and the biska samples contain phenolic compounds of mistletoe such as phenolic acids, flavonoids, and coumarins, which contribute to the observed biological activities—significant antioxidant activity and antiproliferative effect. By applying the maceration parameters, which yielded the highest content of phenolic compounds as well as volatile aromatic compounds (40–80 g/L of mistletoe, 40–55% v/v ethanol, and 21 days’ maceration time), the production process can be improved to produce biska with better aromatic and biological properties. Full article

The residue from roselle beverage production is rich in polyphenols and dietary fiber. We investigated its potential as a preventive and therapeutic agent for type 2 diabetes mellitus (T2DM). Male Wistar rats were fed a high-fat high-fructose diet (HFFD) for 17 weeks, reaching insulin resistance by week 9, and induced to T2DM with streptozotocin (STZ) at week 13. Roselle beverage residue (RBR) was administered ad libitum mixed at 6% with the HFFD. Rats received HFFD+RBR as a preventive strategy starting at week 1 (healthy) and week 9 (insulin resistant), whereas the treatment strategy in T2DM rats started at week 14 alone or in combination with metformin (200 mg/kg/day), with a control metformin-treated group. All RBR-supplemented groups showed reduced serum glucose levels (1.4-fold to 1.8-fold) compared with the HFFD+STZ control group. Preventive RBR administration enhanced pancreatic function, leading to improved insulin sensitivity (6.5-fold to 7.9-fold). Gene expression analysis identified slight alterations in hepatic and skeletal muscle glucose metabolism. Additionally, RBR supplementation demonstrated a preventive role in mitigating hyperuricemia (2.1-fold to 2.2-fold), with no effect on glomerular hyperfiltration. While the exact mechanisms underlying RBR effects remain to be fully elucidated, our findings highlight its promising potential as a dietary supplement for preventing and treating T2DM. Full article

Drug-induced liver injury (DILI) poses a significant challenge for the pharmaceutical industry and regulatory bodies. Despite extensive toxicological research aimed at mitigating DILI risk, the effectiveness of these techniques in predicting DILI in humans remains limited. Consequently, researchers have explored novel approaches and procedures to enhance the accuracy of DILI risk prediction for drug candidates under development. In this study, we leveraged a large human dataset to develop machine learning models for assessing DILI risk. The performance of these prediction models was rigorously evaluated using a 10-fold cross-validation approach and an external test set. Notably, the random forest (RF) and multilayer perceptron (MLP) models emerged as the most effective in predicting DILI. During cross-validation, RF achieved an average prediction accuracy of 0.631, while MLP achieved the highest Matthews Correlation Coefficient (MCC) of 0.245. To validate the models externally, we applied them to a set of drug candidates that had failed in clinical development due to hepatotoxicity. Both RF and MLP accurately predicted the toxic drug candidates in this external validation. Our findings suggest that in silico machine learning approaches hold promise for identifying DILI liabilities associated with drug candidates during development. Full article

Cordyceps sinensis is a rare and endangered medicinal herb in China and a typical medicinal and food plant. Most of the research related to Cordyceps sinensis focuses on its pharmacological effects, artificial cultivation and clinical applications. However, there are few comprehensive evaluations on the quality of Cordyceps sinensis under different drying methods. In this study, the effects of vacuum freeze-drying (DG), oven-drying (HG) and air-drying (YG) on the morphological characteristics, microstructure, antioxidant activity and metabolites of Cordyceps sinensis were investigated using wild Cordyceps sinensis as the research object. The results showed that in their appearance and morphology, the YG- and HG-method Cordyceps sinensis samples were darker in color and wilted, while the DG- method Cordyceps sinensis samples were golden yellow in color and had better fullness. In terms of microstructure, the stomata of the YG and HG method Cordyceps sinensis samples were relatively small and irregularly shaped, whereas those of the DG method Cordyceps sinensis samples were larger and neat. In terms of antioxidant capacity, the HG-method samples were the lowest, followed by the YG group, and the DG group had the highest total antioxidant capacity. A correlation analysis revealed a significant relationship between antioxidant capacity and lipids, lipid molecules, nucleosides, nucleotides, and analogs. A metabolomics analysis identified 1937 metabolites from 18 superclasses, with lipids, lipid-like molecules, organic acids and derivatives, organoheterocyclic compounds, and organic oxygen compounds being the predominant metabolites in Cordyceps sinensis. Differentially accumulated metabolites (DAMs) in DG samples showed higher levels of lipids and lipid molecules, organic oxygen compounds, organic acids and derivatives, and organoheterocyclic compounds compared to the other drying methods, suggesting DG as the optimal preservation method for Cordyceps sinensis. These findings offer insights for selecting appropriate drying methods and maintaining the post-drying quality of Cordyceps sinensis. Full article

In this study, a traveling wave Mach-Zehnder intensity modulator (TW-MZM) was designed and optimized for six different electro-optical (EO) crystals: lithium niobate (LNB), potassium niobate (KNB), lithium titanate (LTO), beta barium borate (BBO), cadmium telluride (CdTe), and indium phosphide (InP). The performance of each EO crystal, including optical and radio frequency (RF) loss, applied voltage, and modulation bandwidth, was estimated and compared. The results suggest that, in theory, KNB, LTO, BBO, and CdTe have the potential to outperform LNB. However, it should be noted that the loss associated with KNB and LTO is comparable to that of LNB. The findings demonstrated that BBO and CdTe exhibit a modulation bandwidth exceeding 100 GHz and demonstrate the lowest loss among the considered crystals based on the assumed geometry. Full article

The spray characteristics of liquid ammonia under various ambient pressures and temperatures were analyzed in a constant volume chamber to cover a wide range of superheat degrees. The injection pressure was set as 70 and 80 MPa with ambient pressure ranging from 0.2 to 4 MPa. The ambient temperature was 500 K. The results showed that the higher the injection pressure, the greater the kinetic energy obtained. The droplet fragmentation was enhanced, and the phenomenon of gradual separation of the gas–liquid region occurred with increasing injection pressure. Under flash boiling spray conditions, the spray developed faster than non-flash boiling and transition flash boiling spray under the same injection pressure. In addition, the flash boiling spray tip penetration of the gas and liquid increased more than that of cold spray, and the fluctuation of the late stage of the injection was relatively large. Therefore, the injection pressure has a greater effect on the spray tip penetration of flash boiling spray. Moreover, ambient pressure greatly influences the flare flash boiling spray. The spray resistance phenomenon was found during the spray development in the flare flash boiling condition. With the increase in ambient pressure, the spray tip penetration of flash boiling spray decreases due to the reduction in the pressure difference inside and outside the spray hole and the restriction of ambient gas. Meanwhile, owing to the low ambient pressure and ambient density, the liquid penetration in the initial phase of the flare flash boiling spray will be abnormally shorter than that of the non-flash boiling spray. Full article

The Sharpe ratio is a widely used tool for assessing investment strategy performance. An essential part of investing involves creating an appropriate portfolio by determining the optimal weights for desired assets. Before constructing a portfolio, selecting a set of investment opportunities is crucial. In the absence of a risk-free asset, investment opportunities can be identified based on the Sharpe ratios of risky assets and their correlation. The maximum squared Sharpe ratio serves as a useful metric that summarizes the performance of an investment opportunity in a single value, considering the Sharpe ratios of assets and their correlation coefficients. However, the assumption of a normal distribution in asset returns, as implied by the Sharpe ratio and related metrics, may not always hold in practice. Non-normal returns with a non-linear dependence structure can result in an overestimation or underestimation of these metrics. Copula functions are commonly utilized to address non-normal dependence structures. This study examines the impact of asset dependence on the squared maximum Sharpe ratio using copulas and proposes a copula-based approach to tackle the estimation issue. The performance of the proposed estimator is illustrated through simulation and real-data analysis. Full article

Diabetes exposure during pregnancy affects health outcomes in offspring; however, little is known about in utero exposure to preexisting parental youth-onset type 2 diabetes. Offspring born to participants during the Treatment Options for Type 2 Diabetes in Adolescent and Youth (TODAY) study were administered a questionnaire at the end of the study. Of 457 participants, 37% of women and 18% of men reported 228 offspring, 80% from female participants. TODAY mothers had lower household income (<$25,000) compared to TODAY fathers (69.4% vs. 37.9%, p = 0.0002). At 4.5 years of age (range 0–18 years), 16.7% of offspring were overweight according to the parental report of their primary care provider, with no sex difference. Offspring of TODAY mothers reported more daily medication use compared to TODAY fathers (50/183, 27.7% vs. 6/46, 12.2%, [p = 0.04]), a marker of overall health. TODAY mothers also reported higher rates of recidivism (13/94) than TODAY fathers (0/23). An Individualized Education Plan was reported in 20/94 (21.3%) offspring of TODAY mothers compared to 2/23 (8.7%) of TODAY fathers. This descriptive study, limited by parental self-reports, indicated offspring of participants in TODAY experience significant socioeconomic disadvantages, which, when combined with in utero diabetes exposure, may increase their risk of health and educational disparities. Full article

This work investigated the impact and piercing load resistance (energy absorption capabilities) of 3D-printed composites plates manufactured by means of the Fused-Filament-Fabrication (FFF) technique. Two sets of reinforced composite plates were produced. The first set of plates was printed with short-carbon-fiber-reinforced polyamide-12, while the second set was reinforced with continuous fibers. The plates were tested with quasi-static indentation tests at various Span-to-Punch ratios and with three different indenter nose shapes (blunt, hemispherical, and conical). The quasi-static measurements were subsequently elaborated to estimate the energy absorption capability of the plates during a ballistic impact. The addition of continuous fibers increased the quasi-static energy absorption capability by 20–185% with respect to the short-fiber-reinforced plates. The quasi-static results showed that by including the continuous reinforcement in the plates, the normalized energy absorbed increased by an order of magnitude. Finally, a comparison with data from the literature concerning continuous-reinforced composite plates manufactured by means of traditional techniques was carried out. The comparison revealed that FFF-printed composite plates can compete with traditional composite ones in terms of both ballistic and quasi-static penetrating load conditions, even if limited by the lower fiber volume fraction. Thus, these findings confirm that this novel Additive Manufacturing technique is promising and worth investigating further. Full article

The urokinase-type plasminogen activator receptor (uPAR) is a unique protease binding receptor, now recognized as a key regulator of inflammation. Initially, uPA/uPAR was considered thrombolytic (clot-dissolving); however, recent studies have demonstrated its predominant immunomodulatory functions in inflammation and cancer. The uPA/uPAR complex has a multifaceted central role in both normal physiological and also pathological responses. uPAR is expressed as a glycophosphatidylinositol (GPI)-linked receptor interacting with vitronectin, integrins, G protein-coupled receptors, and growth factor receptors within a large lipid raft. Through protein-to-protein interactions, cell surface uPAR modulates intracellular signaling, altering cellular adhesion and migration. The uPA/uPAR also modifies extracellular activity, activating plasminogen to form plasmin, which breaks down fibrin, dissolving clots and activating matrix metalloproteinases that lyse connective tissue, allowing immune and cancer cell invasion and releasing growth factors. uPAR is now recognized as a biomarker for inflammatory diseases and cancer; uPAR and soluble uPAR fragments (suPAR) are increased in viral sepsis (COVID-19), inflammatory bowel disease, and metastasis. Here, we provide a comprehensive overview of the structure, function, and current studies examining uPAR and suPAR as diagnostic markers and therapeutic targets. Understanding uPAR is central to developing diagnostic markers and the ongoing development of antibody, small-molecule, nanogel, and virus-derived immune-modulating treatments that target uPAR. Full article