Inflammation is considered an important target for stroke therapy because it induces secondary brain damage after the initial ischemic insult. Peripheral monocytes migrate to the brain parenchyma after a central insult. They then differentiate to macrophages in a positive feedback fashion contributing to damage instead of ischemic resolution and inflammation control. A cyclic diterpenoid, (1S,2E,4R,6R,7E,11E)-cembra-2,7,11-triene-4,6-diol (4R), decreases neurodegeneration after ischemia with central anti-inflammatory activity. This study aims to determine whether the central anti-inflammatory effect of 4R is effective against peripheral inflammation triggered by brain ischemia. To investigate the anti-inflammatory effect of 4R, we treated macrophages with lipopolysaccharide (LPS) as an inflammatory model, followed by treatment with 4R. Microarray transcriptome analysis of over 30,000 genes identified the differential expression of 393 genes. Genes related to inflammation, cell adhesion, and transcription were validated with qPCR, and reduced expression was determined. Quantification of NF-kB phosphorylation served as a marker for the modulation of inflammation through gene transcription. Our results show that 4R was associated with a reduction in NFKB1 and ITGB5 gene expression, increased phosphorylation of NF-kB, and a decrease in macrophage adhesion in a blood-brain barrier model. These results indicate that 4R can partially modulate the peripheral immune response, making 4R a potential drug against post-ischemic inflammation.

Nowadays, the imidazolium-based ionic liquids containing acetate counter-ions are attracting much attention as both highly selective absorbents of the acidic gases and CO₂ carriers in the supported ionic liquid membranes. In this regard, the investigation of the gas transport properties of such membranes may be appropriate for better understanding of various factors affecting the separation performance and the selection of the optimal operating conditions. In this work, we have tested CH₄, CO₂ and H₂S permeability across the SILM impregnated by 1-butyl-3-methylimidazolium acetate (bmim[ace]) with the following determination of the ideal selectivity in order to compare the facilitated transport membrane performance with the SILM that dissolves acidic gases physically, namely, containing 1-butyl-3-methylimidazolium tetrafluoroborate (bmim[BF₄]). Both SILMs have showed modest individual gases permeability and ideal selectivity of CO₂/CH₄ and H₂S/CH₄ separation that achieves values up to 15 and 32, respectively. The effect of the feed gas mixture composition on the permeability of acidic gases and permeselectivity of the gas pair was investigated. It turned out that the permeation behavior for the bmim[ace]-based SILM toward the binary CO₂/CH₄, H₂S/CH₄ and ternary CO₂/H₂S/CH₄ mixtures was featured with high acidic gases selectivity due to the relatively low methane penetration through the liquid phase saturated by acidic gases.

Lignin has interesting functionalities to be exploited in adhesives for medicine, foods and textiles. Nanoparticles (NPs) <100 nm coated with poly(L-lysine), PL and poly(L-glutamic acid) PGA were prepared from the laccase treated lignin to coat nanocellulose fibrils (CNF) with heat. NPs ca. 300 nm were prepared, β-casein coated and cross-linked with transglutaminase (Tgase) to agglutinate chamois specimens. Size exclusion chromatography (SEC) and Fourier-transform infrared (FTIR) spectroscopy were used to characterize polymerized lignin, zetapotential and dynamic light scattering (DLS) to ensure coating of colloidal lignin particles (CLPs). Protein adsorption on lignin was studied by quartz crystal microbalance (QCM). Atomic force microscopy (AFM) was exploited to examine interactions between different polymers and to image NPs with transmission electron microscopy (TEM). Tensile testing showed, when using CLPs for the adhesion, the stress improved ca. 10 and strain ca. 6 times compared to polymeric lignin. For the β-casein NPs the values were 20 and 8, respectively, and for the β-casein coated CLPs between these two cases. When NPs were dispersed in adhesive formulation, the Young's moduli confirmed significant improvement in the elasticity of the joints over the adhesive alone. Exploitation lignin in nanoparticulate morphology is a potential method to prepare bionanomaterials for advanced applications.

According to Indonesia’s result of Basic Health Research of 2013, prevalence of acute respiratory infection in 2007 and 2013 were not different (25.5% and 25.0%, respectively). Identifying the cause of acute pharyngitis is a key point in determining the optimal treatment. The main purpose is to evaluate the rational use of drugs and its irrational impact as well as the correlation of the drug use with the incidence and prevalence of acute pharyngitis. This study was a descriptive and observational study, carried out retrospectively and concurrently at two community health centers located in Bandung and Cimahi, Indonesia. There were 80.01% over prescription of antibiotics, with a total of 8.98% is non-treatment option, and 62.43% irrational used of corticosteroids. The incidence and prevalence of acute pharyngitis at one health center in Bandung were 2.45% and 2.31%, respectively, with irrationality rate of 83.82%. Those recorded at one health center in Cimahi were 2.11% of incidence and 2.00% of prevalence with irrational rate of 91.29%. It can be concluded that there were still irrational use of medicines in the treatment of acute pharyngitis in community health center. The higher incidence and prevalence might indicate the declining health services quality.

Some evidence supports the influence of the implant macro-design and primary stability. Additionally, tactile perception can be used to assess implant stability when placing the implant. This research aimed to quantify the primary and secondary stability of three implant systems with two different macro geometries (cylindrical and conical) determined through the insertion torque and the implant stability quotient (ISQ) at the moment of implant placement as a function of implant-related factors (length, width, dental arch, and implant location in the arch), intraoperative factors (bone density determined subjectively by the clinician's tactile perception), and patient-related factors (age, gender and bone density determined objectively in the cone beam computed tomography (CBCT). Methods: 102 implants of three implant systems with two different macro geometries (conical and cylindrical) were placed in 53 patients. The insertion torque, the ISQ at the implant placement (ISQ0), and bone quality according to the clinician's tactile sensation were recorded on the day of the surgery. After a three-month healing period, the ISQ was re-evaluated (ISQ3). Results: Cylindrical implants exhibited significantly higher insertion torque and ISQ at the moment of the surgery and after three months than conical implants. Cylindrical implants also showed significantly lower indices of tactile evaluation of bone quality during the implant placement surgery. However, no differences were demonstrated in the bone density measured objectively in the CBCT. (4) Conclusions: The cylindrical implants achieved the highest values for primary stability (Ncm and ISQ) and secondary stability (ISQ after three months). Insertion torque was the variable that most influenced ISQ on the day of the surgery. Implant location (incisors-canines, bicuspids-molars) and the implant macro geometry were the variables that most influenced the secondary stability (ISQ at three months).

Electrospun ultrathin fibers based on binary compositions of polylactide (PLA) and poly(ε-caprolactone) (PCL) with different ratios of polymer components from 0/100 to 100/0 wt. % were studied. Using a combination of thermal (DSC) and relaxation (EPR) measurements, the effect of biopolymers content on the characteristics of the crystal structure of PLA and PCL and the diffusive rotational mobility of the stable TEMPO radical in the amorphous regions of PLA/PCL compositions was shown. It was revealed that after PLA and PCL blending, significant changes in the degree of crystallinity of PLA, PCL segmental mobility, sorption capacity of the radical as well as activation energy of rotational diffusion in the amorphous regions of PLA/PCL composition are observed. The characteristic region of biopolymers’ composition from 50/50 to 30/70 % PLA/PCL blends ratio was found, where the inversion transition of PLA from dispersive medium to dispersive phase where an inversion transition is assumed when the continuous medium of the PLA transforms into a discrete phase. The performed studies made it possible for the first time to carry out a comprehensive analysis of the effect of the system component ratio on the structural and dynamic characteristics of the PLA/PCL film material at the molecular level.

The vomeronasal system serves as a pivotal element in mammalian sensory biology, allowing the perception of chemical signals essential for social communication via the activation of two main receptor families, V1R and V2R. The expression of V1Rs and V2Rs is linked with that of the G-protein alpha-subunits, Gαi2 and Gαo, respectively. The exploration of the evolutionary pathways of V1Rs and V2Rs across all mammalian species remains a main challenge, juxtaposing available genomic data against emerging immunohistochemical evidence. However, recent investigations, in contrast to what is predicted by the currently annotated genomic sequences, have revealed the expression of Gαo in the vomeronasal neuroepithelium of wild canids, including wolves and foxes. In the present study, the employment of a specific antibody raised against the mouse V2R2, member of the C-family of vomeronasal receptors, V2Rs, has confirmed the expression of this receptor in the fox and wolf, but it has revealed the lack of expression in the dog. This may reflect the impact of domestication on the regression of the VNS in this species, in contrast to their wild counterparts, and underscores the effects of artificial selection on sensory functions. Thus, these findings suggest a more refined chemical detection capability in wild species.

A variational analysis of dispersion medium (electrolytes and surfactants) was carried out for the best nucleotide interactions with the presence of nanoparticles and the ability to formation of homogeneous coatings upon drying / lyophilization. Using UV-spectroscopy and transmission electron microscopy, the processes of immobilization of nucleotides on the surface of nanoparti-cles of the composition ZrO2-3mol% Y2O3 (YSZ) in the presence of various dispersing agents were investigated. Promising dispersing agents were established, the optimal composition of suspen-sions based on DNA nucleotides and YSZ nanoparticles, which is potentially suitable for adaptive technologies of bionanoelectronics, was selected. The aim of the work is to obtain and study functional media for molecular electronics based on heterojunctions biological molecule – wide-gap dielectric.

A variational analysis of dispersion medium (electrolytes and surfactants) was carried out for the best nucleotide interactions with the presence of nanoparticles and the ability to formation of homogeneous coatings upon drying / lyophilization. Using UV-spectroscopy and transmission electron microscopy, the processes of immobilization of nucleotides on the surface of nanoparti-cles of the composition ZrO2-3mol% Y2O3 (YSZ) in the presence of various dispersing agents were investigated. Promising dispersing agents were established, the optimal composition of suspen-sions based on DNA nucleotides and YSZ nanoparticles, which is potentially suitable for adaptive technologies of bionanoelectronics, was selected. The aim of the work is to obtain and study functional media for molecular electronics based on heterojunctions biological molecule – wide-gap dielectric.

The açaí (Euterpe oleracea Mart.) is a native fruit of the Amazon that is well-known due to its commercial value. Its production chain is centered in the state of Pará, largely supplied by extractivism. The processing of açaí fruits in nature generates huge amount of solid waste, which can pose serious risks to the environment if not used and managed properly. Due to a small number of systhematic studies on the effect of chemical activation by pyrolysis of açaí seeds and fibers, and with the aim of providing a basis for future applications of the waste generated by processing of açaí fruits, the present work proposes a study of the pyrolysis of açaí seeds and fibers and the physicochemical and compositional characterization of the aqueous phase products. In this way, açaí seeds were collected from a local artisan processing facility in the city of Belém, PA. The seeds were dried at 105°C until constant weight, and subsequently, the fibers were separated from the seeds in a rotating drum. The seeds and fibers were impregnated with NaOH solutions at 0.5M, 1.0M, and 2.0M, and then pyrolyzed at a laboratory scale at 450 °C and 1 atm. The liquid products from pyrolysis were characterized through acidity index analysis, Fourier-transform infrared spectroscopy, and gas chromatography. The increase in the concentration of the impregnating agent resulted in an increase in bio-oil yield from both the seeds and fibers, rising from 3.3% (raw seeds) to 6.6% (seeds impregnated with 2M NaOH) and from 1.2% (raw fibers) to 3.7% (fibers impregnated with 2M NaOH). The yield in the aqueous phase after biomass pyrolysis showed an inverse behavior to the bio-oil yield, decreasing from 33.7% (raw fibers) to 21.2% (fibers impregnated with 2M NaOH) and from 41% (raw seeds) to 37.5% (seeds impregnated with 2.0M NaOH). High acidity levels were found in the aqueous phase samples and bio-oils derived from the seeds and fibers, which decreased as the concentration of the impregnating agent increased. The increase in the concentration of the impregnating agent (NaOH) influenced the chemical composition of the obtained liquid products, leading to a decrease in oxygenated compounds and an increase in nitrogenous compounds in both experimental matrices, which was also evidenced by the reduction in acidity.

3D cell cultures have improved the evaluation of drugs for cancer therapy, due to their high similarity to solid tumors. In melanoma, autophagy appears to show a dual role depending on the progression of the disease. p62 protein has been proposed for the evaluation of autophagic flux since its expression is an indicator of the state of autophagy. Pentoxifylline (PTX) and Norcantharidin (NCTD) are drugs that have been shown to have anticancer effects in various types of cancer. In this work, B16F1 mouse melanoma cell line was used, from which two-dimensional (2D) monolayer cultures and three-dimensional (3D) organoids were carried out using the hanging drop technique. The expression of p62 was determined by western blot and immunofluorescences. Our results indicate that pentoxifylline reduces p62 expression in both types of culture. While Norcantharidin increases its expression in 3D cultures at 24 h. Therefore, these drugs could have a potential therapeutic use for the regulation of autophagy in melanoma, depending on the state of evolution of the disease.

The objective of this work was to investigate the deacidification of bio-oils (BOs) from triglyceride-based biomass through the application of liquid-liquid extraction (LLE) in a simple stage, using methanol and water as a binary solvent and feed/solvent ratio of 1/1. For this, the effects of process parameters such as the water content present in the solvent, the content of carboxylic acids present in the bio-oil, and the extraction temperature on the deacidification process through the efficiency and distribution coefficient were evaluated, as well as the effects of such parameters on the quality of deacidified bio-oils through physical-chemical analyzes and GC-MS analysis. The results show that such process parameters significantly affect the quality of deacidified bio-oils. The ideal condition to have the highest acid removal, i.e., the highest deacidification efficiency (72.65%), is the one in which the deacidification process is performed with aqueous methanol (5% water) at 35 °C and for BOs that have a total acid number (TAN) equal to 24.38 mg KOH/g. Therefore, the process of deacidification by LLE using aqueous methanol is a promising alternative for removing carboxylic acids and other oxygenated compounds, contributing significantly to the upgrading or improving biofuels produced by catalytic thermal cracking.

Efficient beam steerable high-gain antennas enable high-speed data rates over long-distance networks, including wireless backhaul, satellite communications (SATCOM), and SATCOM On-the-Move. These characteristics are essential for advancing contemporary wireless communication networks, particularly within 5G and beyond. Various beam-steering solutions have been proposed in the literature, with passive beam-steering mechanisms employing planar metasurfaces emerging as cost-effective, power-efficient, and compact options. These attributes make them well-suited for use in confined spaces, large-scale production and widespread distribution to meet the demands of the mass market. Utilizing a dual-band antenna terminal setup is often advantageous for full duplex communication in wireless systems. Therefore, this article presents a comprehensive review of the dual-band beam steering techniques for enabling full-duplex communication in modern wireless systems, highlighting their design methodologies, scanning mechanisms, physical characteristics, and constraints. Despite the advantages of planar metasurface-based beam steering solutions, literature on dual-band beam steering antennas supporting full duplex communication is limited. This review article identifies research gaps and outlines future directions for developing economically feasible passive dual-band beam-steering solutions for mass deployment.

Transportation plays an important role in urban development. Population growth and environmental burden have turned the efforts of cities globally towards smarter and greener mobility. Cooperative and Connected Automated Mobility (CCAM) serves as a concept with the power and potential to help achieve these goals building upon technological fields like Internet of Things, computer vision and distributed computing. However, its implementation is hindered by various challenges covering technical parameters such as performance and reliability in tandem with other issues, such as safety, accountability and trust. To overcome these issues, new distributed and decentralized approaches like blockchain and smart contracts are needed. This paper aims at identifying a comprehensive inventory of CCAM challenges and use it as a framework to describe methodologies using blockchain and smart contracts to address them. It provides a comparative analysis of the findings to draw useful conclusions and discuss future directions in CCAM and relevant blockchain applications. The paper contributes to intelligent transportation systems’ research by offering an integrated view of the difficulties in substantiating CCAM and providing insights on the most prominent blockchain and smart contract technologies that tackle them.

The work presents the results of studying dilute aqueous solutions of commercial Ln(NO3)3 · xH2O salts with Ln=Ce-Lu using X-ray diffraction (XRD), IR spectroscopy, X-ray absorption spectroscopy (XAS: EXAFS/XANES) and pH measurements. As a reference point, XRD and XAS measurements for characterized Ln(NO3)3 · xH2O microcrystalline powder samples were performed. The local structure of Ln-nitrate complexes in 20 mM Ln(NO3)3 · xH2O aqueous solution was studied under total external reflection conditions and EXAFS geometry was applied to obtain high-quality EXAFS data for solutions with low concentrations of Ln3+ ions. Results obtained by EXAFS spectroscopy showed significant contraction of the first coordination sphere during the dissolution process for metal ions located in the middle of the lanthanide series. It was established that in Ln(NO3)3 · xH2O solutions with Ln=Ce, Sm, Gd, Yb (c=134, 100, 50 and 20 mM) there are coordinated and, to a greater extent, non-coordinated nitrate groups with bidentate and predominantly monodentate bonds with Ln ions, the number of which increases upon transition from cerium to ytterbium. Cross-relationships between the concentration of solutions, pH value and antimicrobial activity with the type of Ln = Ce, Sm, Gd, Yb were established, as well as the absence of biocidal properties of solutions with a concentration of 20 mM, except for Ln = Yb. The important role of experimental conditions in obtaining and interpreting the results was noted.

Preterm birth accounts for about 10% of births worldwide. Studying risk factors for perinatal brain damage is essential, as findings suggest that almost 20% of disabilities are linked to risks in the early stages of development. This research aimed to study longitudinal changes in intelligence from 6 to 8 years of age in a sample of 39 preterm children with a history of risk of brain damage and a control group of 35 children born at term. The Wechsler Intelligence Scale (WISC-IV) was used for cognitive measurement. The results showed that the preterm group obtained significantly lower scores than the control group. The working memory indicator significantly affected the interaction between age and prematurity. We consider that it is crucial to expand the knowledge we have about the neurocognitive development of premature infants both in specific cognitive domains and in age ranges so that the information obtained helps to predict the probability of presenting cognitive alterations from early stages and, therefore, to implement intervention strategies and programs based on scientific evidence and complemented in their design by clinical experience, empirical and theoretical knowledge of the different professionals involved in infant cognitive intervention.

Stroke is the number one cause of morbidity in the United States and number two cause of death worldwide. There is a critical unmet medical need for more effective treatments of ischemic stroke, and this need is increasing with the shift in demographics to an older population. Recently, several studies have reported the therapeutic potential of stem cell derived exosomes as new candidates for cell-free treatment in stoke. This review focuses on the use of stem cell-derived exosomes as a potential treatment tool for stroke patients. Therapy using exosomes can have a clear clinical advantage over stem cell transplantation in terms of safety, cost, and convenience, as well as reducing bench-to-bed latency due to fewer regulatory milestones. In this review article, we focus on 1) the therapeutic potential of exosomes in stroke treatment, 2) the optimization process of upstream and downstream production, and 3) preclinical application in stroke animal model. Finally, we discuss the limitations and challenges faced by exosome therapy in future clinical applications.

Ionizing radiation-induced damage in cancer and normal cells leads to apoptosis and cell death, through the intracellular oxidative stress, DNA damage and disorders of their metabolism. Irradiation doses that do not lead to the death of tumor cells can result in the emergence of radioresistant clones of these cells, due to the rearrangement of metabolism and the emergence of new mutations, including those in the genes responsible for DNA repair. The search for the substances capable of modulating the functioning of the tumor cell repair system is an urgent task. Here we analyzed the effect of cerium(III) fluoride nanoparticles (CeF3 NPs) on normal (human mesenchymal stem cells – hMSCs) and cancer (MCF-7 line) human cells after X-ray radiation. CeF3 NPs effectively prevent the formation of hydrogen peroxide and hydroxyl radicals in an irradiated aqueous solution, showing pronounced antioxidant properties. CeF3 NPs are able to protect hMSCs from radiation-induced proliferation arrest, increasing their viability and mitochondrial membrane potential, and, conversely, inducing the cell death of MCF-7 cancer cells, causing radiation-induced mitochondrial hyperpolarization. CeF3 NPs provided a significant decrease in the number of double-strand breaks (DSBs) in normal cells, while in MCF-7 cells the number of γ-H2AX foci dramatically increased in the presence of CeF3 4 hours after irradiation. In the presence of CeF3 NPs, there was a tendency to modulate the expression of most analyzed genes associated with the development of intracellular oxidative stress, cell redox status and the DNA repair system after X ray irradiation. Cerium-containing nanoparticles are capable of providing selective protection of normal cells from radiation-induced injuries and are considered as a platform for the development of promising clinical radioprotectors.

Abattoir workers are liable to zoonotic infections from animals and animal products, pri-marily to diseases with asymptomatic and chronic clinical manifestations in animals such as brucellosis. No published reports exist on the seroprevalence of brucellosis in abattoir workers in South Africa. Therefore, this cross-sectional study was conducted to estimate the occurrence and risk factors for Brucella exposure in abattoir workers in Gauteng Province. A total of 103 abattoir workers and managers from six abattoirs, where brucellosis-positive slaughtered cattle and sheep were previously detected, were interviewed, and tested with serological assays using the Rose Bengal test (RBT), BrucellaCapt, and IgG-ELISA. A pre-tested questionnaire was administered to consenting respondents to obtain infor-mation on risk factors for brucellosis. Of the 103 respondents tested, the distribution of fe-male and male workers was 16 (15.5%) and 87 (84.5%), respectively. The seroprevalence for exposure to brucellosis was 21/103 (20.4%, 95%CI: 13.1-29.5) using a combination of RBT, BrucellaCapt, or IgG-ELISA. For test-specific results, seroprevalences by RBT, BrucellaCapt, and IgG-ELISA were 13/103 (12.6%, 95%CI: 6.9-20.6), 9/103 (8.74%, 95%CI: 4.1-15.9) and 18/103 (17.5%, 95%CI: 10.7-26.2), respectively. Low-throughput abattoirs were identified as associated risk as 29.3% of workers were seropositive compared to 12.7% of workers in high-throughput abattoirs, which highlights that direct contact at abattoirs poses higher risk to workers than indirect and direct contact outside abattoirs. This study confirmed the occurrence of Brucella spp. antibodies among abattoir workers in South Africa, possibly due to occupational exposure to Brucella spp. and highlight the occupational hazard to workers. Furthermore, findings underscore that abattoir facilities can serve as points for active and passive surveillance for indicators of diseases of public health importance. We recommend periodic implementation of brucellosis testing of abattoir workers country-wide to establish baseline data for informing appropriate preventive practices and reduce the potential burden of infection rate among these high-risk workers.

The natural flavonoid epigallocatechin gallate (EGCG) has a wide range of biological activities including binding to nucleic acids; however, mechanisms of interaction of EGCG with DNA organized in chromatin have not been systematically studied. In this work, interaction of EGCG with chromatin in cells, and with nucleosomes and chromatosomes in vitro was studied using fluorescent microscopy and single particle Förster resonance energy transfer approaches, respectively. EGCG effectively penetrates into the nuclei of living cells and binds to DNA there. Interaction of EGCG with nucleosomes in vitro induces large-scale, reversible uncoiling of nucleosomal DNA that occurs without dissociation of DNA or core histones at sub- and low-micromolar concentrations of EGCG. EGCG does not reduce the catalytic activity of poly(ADP-ribose) polymerase 1 (PARP1), but causes modulation of the structure of the PARP1-nucleosome complex. EGCG significantly changes the structure of chromatosomes, but does not cause dissociation of the linker histone. Reorganization of nucleosomes and chromatosomes by EGCG might facilitate access of protein factors involved in DNA repair, replication and transcription to DNA and thus might contribute to the modulation of gene expression by EGCG that was reported earlier.

The research results conducted on binderless tungsten carbide (WC) ceramics obtained by Spark Plasma Sintering (SPS) of WC powders with different average particle sizes (0.095, 0.8, 3 μm) are presented. Nonuniform distribution of crystalline phases and microstructure of the WC ceramics was studied using layer-by-layer XRD analysis and SEM. Surface layers of the WC-based ceramics are characterized by nonuniform distribution of W2C crystalline phase and grain sizes, including the appearance of abnormally large grains. Thickness of the nonuniform layer was at least 50 μm. The effect under study is associated with an intense carbon diffusion from graphite foil. On the one hand, this contributed to a decrease in the intensity of W2C phase particle formation, which is transformed into α-WC phase due to the carbon. On the other hand, it caused abnormal grain growth in the layer where the carbon diffused. The obtained value of the carbon diffusion depth exceeds the values known from the literature (up to 1 μm in the case of volume diffusion even at temperature of 2370℃ and exposure time of ~ 60 h). The use of boron nitride (BN) as a protective coating on graphite mold parts did not prevent the formation of nonuniform layer on the ceramic surface.

: Given that cancer is a disease that is rampant in the world and especially in Africa where the population has enormous difficulty in treating it, plants are a safer and less expensive alterna-tive. Cassava is one of the plant species valued in Benin because of its numerous medicinal and nutritional virtues. This study evaluated the biological activities of amygdalin from the organs of three cassava varieties most produced in Benin (BEN, RB, and MJ). HPLC analysis was used to quantify amygdalin in cassava organs and derivatives. Phytochemical screening was performed to determine secondary metabolite groups. DPPH and FRAP methods were used to assess anti-oxidant activity. Cytotoxicity of the extracts was tested on Artemia salina larvae. The an-ti-inflammatory activity was evaluated in vivo on albino mouse paw edema model induced by 5% formalin. The anticancer activity was evaluated in vivo on Wistar rats rendered cancerous by 1,2-dimethylhydrazine (DMH) using 5-fluorouracil as reference molecule. The results showed that the organs of all three-cassava varieties contained glycosides, flavonoids, saponosides, ster-oids, tannins, coumarins, and cyanogenic derivatives. Young stems and fresh leaves of cassava had the highest amygdalin concentration with 11142.99 µg 10 g-1 and 9251.14 µg 10 g-1 respec-tively. The Agbeli derivative was more concentrated in amygdalin with a content of 401.56 µg 10 g-1 than the others derivatives. The antioxidant activity results showed that the amygdalin ex-tracts were found to be DPPH radical scavengers with IC50 values ranging from 0.18 mg mL-1 to 2.35 mg mL-1. The cytotoxicity test showed no toxicity of the extracts toward shrimp larvae. Ad-ministration of amygdalin extracts from the leaves of BEN and MJ varieties prevents inflamma-tory edema. The percentages of edema inhibition varied between 21.77% and 27.89%. These val-ues are similar (p> 0.05) to that of acetylsalicylic acid (25.20%). Amygdalin extract of BEN variety significantly (p<0.0001) reduces edema. Cancer induction with DMH was inhibited by both BEN extract. In both preventive and curative treatments, rats fed with amygdalin extracts showed low anti-cancer activity under the effect of DMH and the significant difference in biochemical results. Thus, the organs of all three cassava varieties studied have secondary metabolites and good an-tioxydant activity. The leaves contain high levels of amygdalin and can be used as an-ti-inflammatory and anticancer agents.

The cost to train a basic qualified U.S. Navy fighter aircraft pilot is nearly $10M. The training includes primary, intermediate, and advanced stages, with the advanced stage involving extensive flight training and being very expensive as a result. Despite the screening tests in place and early-stage attrition taking place, 4.5% of aviators undergo attrition in this most expensive stage. Key reasons for aviator attrition include poor flight scores, voluntary withdrawals, and medical causes. Reduction in late-stage attrition offers several financial and operational benefits to the U.S. Navy. To that end, this research leverages feature extraction and machine-learning techniques on the very sparse flight test grades of student aviators to identify those with a high risk of attrition early in training. Using about 10 years of historical U.S. Navy pilot training data, trained models accurately predicted 50% of attrition with a 4% false positive rate. Such models could help the U.S. Navy save nearly $20M a year in attrition costs. In addition, machine-learning models were trained that can recommend a suitable training aircraft type for each student aviator. These capabilities could help better answer the need for pilots and reduce the time and cost to train them.

Abstract: Background: Non-invasive acquistion of beat-to-beat pulse transit time (PTT) via piezoelectric/piezocapacitive sensors (PES/PCS) may expand perioperative hemodynamic monitoring. This study evaluated the ability for PTT via PES/PCS to correlate with systolic, diastolic, and mean invasive blood pressure (SBPIBP, DBPIBP, and MAPIBP) and to detect SBPIBP fluctuations. Methods: PES/PCS and IBP measurements were performed in 20 patients undergoing abdominal, urological, and cardiac surgery. A Pearson’s correlation analysis (r) between 1/PTT and IBP was performed. The predictive ability of 1/PTT with changes in SBPIBP was determined by area under the curve (reported as AUC, sensitivity, specificity). Results: Significant correlations between 1/PTT and SBPIBP were found for PES (r=0.64) and PCS (r=0.55) (p<0.01), as well as MAPIBP/DBPIBP for PES (r=0.6/0.55) and PCS (r=0.5/0.45) (p<0.05). A 7% decrease in 1/PTTPES predicted a 30% SBPIBP decrease(0.82, 0.76, 0.76), while a 5.6% increase predicted a 30% SBPIBP increase (0.75, 0.7, 0.68). A 6.6% decrease in 1/PTTPCS detected a 30% SBPIBP decrease (0.81, 0.72, 0.8), while a 4.8% 1/PTTPCS increase detected a 30% SBPIBP increase (0.73, 0.64, 0.68). Conclusions: Non-invasive beat-to-beat PTT via PES/PCS demonstrated significant correlations with IBP and detected significant changes in SBPIBP. Thus PES/PCS as a novel sensor technology may augment intraoperative hemodynamic monitoring during major surgery.

Background: Combinatorial therapy- “nano antibiotics” is an emerging field in nanoscience. In this present investigation, we attempted to combine the green synthesized noble metal nanoparticle and the antibiotic Streptomycin to form bio-conjugated nanoparticles. The newly synthesized Nano antibiotics acted as the antibiotic carrier, functioned as cargo, and delivered the antibiotic. Methods: Comparative studies between the noble metal nanoparticles were attempted for the first time on the grounds of their antibacterial activity. The antibacterial activity of the three noble metal nanoparticles was assessed against Streptomycin-resistant Bacillus sp.; the results obtained proved that silver nanoparticles were a potent antibacterial agent. Still, no antibacterial activity was exerted by gold, and platinum nanoparticles were for the Streptomycin-resistant strain Bacillus sp. To our surprise, the gold and platinum fabricated/bio-conjugated nanoparticle with the antibiotic showed 100% antibacterial activity, whose antibacterial activity was zero when functioning as a nanoparticle alone. Results: The combinatorial therapy of two different clauses of drugs majorly increased antibacterial activity. It enhanced the antibiotic to overcome the resistance exhibited by the bacterial pathogen, and the possible mechanism is elucidated in the present study. Also, an attempt has been made to assess the nanotoxicity of the nano-bioconjugates on RBC and compare their hemocompatibility. The results obtained in the current investigation demonstrate the enhanced antibacterial activity of the green synthesized nanoparticles conjugated with the streptomycin; their efficacy for combinational therapy against resistance in pathogenic organisms highlights the novelty of the work and the comparative study of three different noble metals nanoparticles (Ag, Au, Pt) from single agro-waste for the first time.

Background: Strongyloidiasis, a neglected disease caused by intestinal nematodes of the genus Strongyloides, is endemic to tropical and subtropical areas such as Vietnam. The morphological diagnosis of larvae by Hara Mori culture technique and microscopicare are considered the standard diagnostic procedures in the endemic areas of Strongyloides spp. However, they could only identify the genus, not the species of Strongyloides. DNA-molecular techniques which are highly sensitive and more cost-effective have been increasingly utilized in detection of Strongyloides species. This study aims to determine prevalence and the species of Strongyloides among resident population in Duc Hoa district, Long An province, Southern Vietnam. Methods: A cross-sectional study was conducted using 1,190 stool samples collected in Duc Hoa district, Long An province, Vietnam, from July, 2017 to November 2018. The stool specimens were transported to the Laboratory of Medical Parasitology, Pham Ngoc Thach University of Medicine within two hours of collection at an appropriate temperature of 25 oC. All samples were stored at 2 - 8°C and processed within 48 hours for microscopic examination. Molecular detection was carried out at Laboratory of Molecular Biology, Pham Ngoc Thach University of Medicine, Hochiminh city, VietNam. Results: Of the 1,190 samples tested, Strongyloides spp. larvae were detected in 79 specimens (6.6%) by two classical parasitological methods, namely direct microscopy and the modified Harada-Mori filter paper culture. DNA was extracted from 70 of the 79 samples of Strongyloides spp. larvae, which was subsequently characterized by real-time PCR amplification of the 18S and 28S regions of the rDNA gene. The results showed that 97.1% of the DNA samples were S. stercoralis, 2.9% were co-infections with S. ratti and S. stercoralis, and 2.9% belonged to S. ratti. For all 14 isolates, nucleotide sequencing was compared with other human pathogenic species of Strongyloides whose sequences are available in GenBank. The identity of 12/14 sequences were confirmed as S. stercoralis with a high level of similarity (91.3% - 100%) and over 98% for S. ratti. Between the two co-infection samples, the higher similarity belonged to S. stercoralis. Conclusion: A molecular amplification of small subunit ribosome RNA followed by sequence analysis has been proved to be a suitable method for discrimination of Strongyloides spp. retrieved from stool samples.

Emerging infectious disease threats require rapid response tools to inform diagnostics, treatment, and outbreak control. RNA-based metagenomics offers this; however, most approaches are time-consuming and laborious. Here, we present a simple and fast protocol – the RAPIDprep assay – with the aim to provide cause agnostic laboratory diagnosis of infection within 24 hours of sample collection by sequencing ribosomal RNA-depleted total RNA. The method is based on the synthesis and amplification of double-stranded cDNA followed by short-read sequencing with minimal handling and clean-up steps to improve processing time. The approach was optimized and applied to a range of clinical respiratory samples to demonstrate diagnostic and quantitative performance. Our results showed robust depletion of both human and microbial rRNA, and library amplification across different sample types, qualities and extraction kits using a single protocol without input nucleic acid quantification or quality assessment. Furthermore, we demonstrate the genomic yield of both known and undiagnosed pathogens with complete genomes recovered in most cases to inform molecular epidemiological investigations and vaccine design. The RAPIDprep assay is a simple and effective tool, and representative of an important shift towards integration of modern genomic techniques to infectious disease investigations.

Secretory leucoprotease inhibitor (SLPI) has multifaceted functions, including inhibition of protease activity, antimicrobial functions, and anti-inflammatory properties. In this study, we show that SLPI plays a role in controlling pulmonary P. aeruginosa infection. Mice lacking SLPI were highly susceptible to P. aeruginosa infection, however had no difference in bacterial burden. Utilising a model of P. aeruginosa LPS-induced lung inflammation, human recombinant SLPI (hrSLPI) administered intraperitoneally suppressed the recruitment of inflammatory cells in the bronchoalveolar lavage fluid (BALF) and resulted in reduced BALF and serum levels of inflammatory cytokines and chemokines. This anti-inflammatory effect of hrSLPI was similarly demonstrated in a systemic inflammation model induced by intraperitoneal injection of LPS from various bacteria or lipoteichoic acid, highlighting the broad anti-inflammatory properties of hrSLPI. Moreover, in bone-marrow-derived macrophages, hrSLPI reduced LPS-induced phosphorylation of p-IkB-α, p-IKK-α/β, p-P38, demonstrating that the anti-inflammatory effect of hrSLPI was due to the inhibition of the NFB and MAPK pathways. In conclusion, administration of hrSLPI attenuates excessive inflammatory responses and is therefore, a promising strategy to target inflammatory diseases such as acute respiratory distress syndrome or sepsis and could potentially be used to augment antibiotic treatment.

We present a simple strategy to generate a family of carbon dot/iron oxide nanoparticles (C/Fe-NPs) that relies on the thermal decomposition of iron (III) acetylacetonate in the presence of a highly fluorescent carbon-rich precursor, while polyethylene glycol serves as the passivation agent. By varying the molar ratio of the reactants, a series of C/Fe-NPs have been synthesized with tuneable elemental composition in terms of C, H, O, N, Fe. The quantum yield is enhanced from 6% to 9% as the carbon content increases from 27% to 36%, while the room temperature saturation magnetization is improved from 4.1 emu/g to 17.7 emu/g as the iron content is enriched from 17 to 31%. In addition, the C/Fe-NPs show excellent antimicrobial properties, minimal cytotoxicity and demonstrate promising bioimaging capabilities, thus showing great potential for the development of advanced diagnostic tools.

Current interventions are not effectives in preventing sepsis-induced acute kidney injury and its long-term outcomes or even after second renal insult. Therapeutic strategies using lipid mediators, as aspirin-triggered resolvin D1 (ATRvD1), can contribute for resolution of acute and chronic inflammation. In this study, we examined the potential effect of ATRvD1 on long-term kidney dysfunction after severe sepsis. Fifteen days after cecal ligation and puncture (CLP), sepsis-surviving BALB/c mice were subjected to a tubulointerstitial injury through intraperitoneal injections of bovine serum albumin (BSA) for 7 days, called subclinical acute kidney injury (subAKI) animal model. ATRvD1 treatment was performed right before BSA injections. On day 22 after CLP, urinary protein/creatinine ratio (UPC), histologic parameters, fibrosis, cellular infiltration, apoptosis, inflammatory markers levels, and mRNA expression were determined. ATRvD1 treatment mitigated tubulointerstitial injury by reducing the proteinuria excretion, UPC ratio, glomerular cell number and extracellular matrix deposition. Pro-fibrotic markers, as transforming growth factor β (TGFb), type 3 collagen and metalloproteinase (MMP)-3 and -9 were reduced after ATRvD1 administration. Post-septic mice treated with ATRvD1 were protected from renal apoptosis and recruitment of F4/80+ cells. Interleukin-1b (IL-1b) levels were increased in subAKI animal model, being attenuated by ATRvD1. Tumor necrosis factor-a (TNF-a), IL-10 and IL-4 mRNA expression was increased in the kidney of BSA-challenged post-septic mice and it was also reduced after ATRvD1. These results suggest that ATRvD1 protects the kidney against a second insult as BSA-induced tubulointerstitial injury and fibrosis by suppressing inflammatory and pro-fibrotic mediators in renal dysfunction after sepsis.

A new approach to fabricate TiNi surfaces combining the advantages of both monolithic and porous materials for implants is used in this work. New materials were obtained by depositing a porous TiNi powder onto monolithic TiNi plates followed by sintering at 1200°C. Then, further modification of the material surface with a high-current-pulsed electron beam (HCPEB) was carried out. Three materials obtained (one after sintering and two after subsequent beam treatment by 20 and 30 pulses, respectively) were studied by XRD, SEM, EDX, EIS methods, profilometry and OCP measurements. Structural and compositional changes caused by HCPEB treatment were investigated. Surface properties of the samples during their storage in saline for 10 days were studied and a model experiment with cell growth (MCF-7) was carried out for the sample unmodified with electron beam to detect cell appearance on different surface locations.

Empirical evidence is lacking on the nexus between coffee commodity output, climate change and commodity price volatility of Africa’s most populous country, Nigeria and other developing countries. To fill this gap, this study analyzed the reaction of coffee output to climate change and commodity price volatility. We used secondary data from 1961 to 2015 from reliable sources for Nigeria. The study adopted GARCH, ARCH and FMOLS in analysis of coffee output reaction to climate change and commodity price volatility. The findings show that coffee output in Nigeria is influenced by climate change and the international commodity price of coffee. The study demonstrates the potential benefits of improving coffee output and export through climate mitigation and adaptation measures and revival of Agricultural Commodity Marketing in Nigeria and other developing countries.

Açaí, a fruit from the Amazon, is valuable both economically and nutritionally. Its seeds, often discarded, can be transformed into bio-oil through pyrolysis (a thermochemical degradation process of residual biomass), providing a sustainable alternative to fossil fuels. This study investigates how temperature and molarity influence the antimicrobial, antioxidant, and cytotoxic activities of the produced bio-oil. Tests were conducted using Gas Chromatography-Mass Spectrometry (GC-MS) and assays to evaluate antimicrobial, antioxidant, and cytotoxic activities at different temperatures (350, 400, and 450 °C) and molarities (0.5 M, 1.0 M, and 2.0 M). Phenolic compounds were the most abundant in the bio-oil (55.70%), followed by cyclic and aromatic hydrocarbons (11.89%) and linear hydrocarbons (9.64%). Despite a reduction in oxygenated compounds, the bio-oil maintained bacteriostatic activity against Escherichia coli and Staphylococcus aureus across various temperature ranges, particularly at 350 °C. Antioxidant activity was highest at 350 °C and at lower molarities. Additionally, lower concentrations of acid impregnation exhibited cytotoxic effects at higher temperatures. Thus, bio-oil from açaí seeds produced via pyrolysis demonstrates potential for antioxidant and antimicrobial activities, suggesting viability for further testing at dilutions with lower cytotoxicity.

The layered oxyselenide BiCuSeO has garnered significant interest because of its ability to exhibit low thermal conductivity and a high Seebeck coefficient. This study involved the preparation of Bi1−xNaxCuSeO1−xFx(x=0, 0.05, 0.10, 0.15, and 0.20) ceramics through the processes of high energy ball milling and cold isostatic pressing. A systematic study was conducted to investigate the impact of co−doping Na/F on the thermoelectric performance of BiCuSeO ceramics. Replacing Bi3+ with Na+ results in the introduction of a considerable amount of holes, leading to a notable enhancement in the electrical conductivity and power factor. The conductivity was significantly increased from 9.10 S cm−1 in the pure BiCuSeO to 94.5 S cm−1 in Bi0.85Na0.15CuSeO0.85F0.15 at 323 K. At 823 K, the power factor of the Bi0.85Na0.15CuSeO0.85F0.15 sample achieved 44.8×10−5 W/ m K2. Moreover, the Bi1−xNaxCuSeO1−xFx ceramics exhibit a minimum thermal conductivity of 0.43 W m−1 K−1. As a result, the Bi0.85Na0.15CuSeO0.85F0.15 sample achieves a maximum ZT value of 0.78, which is 7.09 times greater than that of the pure BiCuSeO sample (0.11) .

Mitochondrial DNA copy number (mtDNAcn) is associated with mitochondrial function contributing various diseases. Understanding of the association between mtDNAcn and infant neurodevelopment, as well as the role of racial disparities, remains unknown. A cohort study was conducted with 55 preterm infants and a single blood sample was collected from each infant during their NICU stay to measure mtDNAcn. NICU Network Neurobehavioral Scale (NNNS) and Bayley Scale of Infant Developmental testing Edition III was assessed during NICU until 2 years of corrected age (CA). Linear regression models were performed to investigate the relationship between the clinical characteristics, neurobehavioral outcomes and mtDNAcn. Majority of our subjects were male, White, non-Hispanic, had C-section, and without preterm premature rupture of membrane (PPROM). Increased mtDNAcn was found associated with younger birth gestational age (GA), nonoptimal neurodevelopment. However, the opposite associations between mtDNAcn and neurodevelopmental outcomes were observed between Black and White infants up to 1 year of CA. Adverse early life experience, together with increased mtDNAcn in White infants, and decreased mtDNAcn in Black infants may be considered as significant positive predictors of poor early life neurodevelopmental outcomes in infants.

CD44 regulates cell adhesion, proliferation, survival, and stemness and has been considered a tumor therapy target. CD44 possesses the shortest CD44 standard (CD44s) and a variety of CD44 variant (CD44v) isoforms. Since the expression of CD44v is restricted in epithelial cells and carcinomas compared to CD44s, CD44v has been considered a promising target for monoclonal antibody (mAb) therapy. We previously developed an anti‐CD44v10 mAb, C44Mab-18 (IgM, kappa) to recognize the variant exon 10-encoded region. In the present study, a mouse IgG2a version of C44Mab-18 (C44Mab-18-mG2a) was generated to evaluate the antitumor activities against CD44-positive cells compared with previously established anti-pan CD44 mAb, C44Mab-46-mG2a. C44Mab-18-mG2a exhibited higher reactivity compared with C44Mab-46-mG2a to CD44v3–10-overexpressed CHO-K1 (CHO/CD44v3–10) and oral squamous cell carcinoma cell lines (HSC-2 and SAS) in flow cytometry. C44Mab-18-mG2a exerted a superior antibody‐dependent cellular cytotoxicity (ADCC) against CD44v3–10. In contrast, C44Mab-46-mG2a showed a superior complement‐dependent cytotoxicity (CDC) against CD44v3–10. A similar tendency was observed in ADCC and CDC against HSC-2 and SAS. Furthermore, administering C44Mab-18-mG2a or C44Mab-46-mG2a significantly suppressed CD44v3–10, HSC-2, and SAS xenograft tumor growth compared with the control mouse IgG2a. These results indicate that C44Mab-18-mG2a could be a promising therapeutic regimen for CD44v10-positive tumors.

Synaptopodin 2-like protein (SYNPO2L) is localized in the sarcomere of cardiomyocytes and is involved in heart morphogenesis. However, the molecular function of SYNPO2L in the heart is not fully understood. We investigated the interaction of SYNPO2L with sarcomeric alpha-actinin and actin filaments in cultured mouse cardiomyocytes. Immunofluorescence studies showed that SYNPO2L colocalized with alpha-actinin and actin filaments at the Z-discs of the sarcomere. Recombinant SYNPO2La or SYNPO2Lb caused bundling of actin filaments in the absence of alpha-actinin and enhanced alpha-actinin-dependent formation of actin bundles. In addition, high-speed atomic force microscopy revealed that SYNPO2La directly bound to alpha-actinin via its globular ends. The interaction between alpha-actinin and SYNPO2La stabilized the two proteins on actin filaments. These results strongly suggest that SYNPO2L cooperates with alpha-actinin during actin bundle formation to facilitate sarcomere formation and maintenance.

A number of studies suggested that influenza vaccination can provide protection against COVID-19 but the underlying mechanisms that could explain this association is still unclear. In this study, the effect of the 2021/2022 seasonal influenza vaccination on the immune response to the booster dose of anti-SARS-CoV-2 vaccination was evaluated in a cohort of healthy individuals. One hundred and thirteen participants were enrolled, and 74 of them with no prior COVID-19 diagnosis or significant co-morbidities were considered for the analysis. Participants received the anti-influenza tetravalent vaccine and the booster dose of the anti-SARS-CoV-2 vaccine or the anti-SARS-CoV-2 vaccine alone. Blood was collected before and 4 weeks after each vaccination and 12 weeks after SARSCoV2 vaccination and analyzed for anti-flu and anti-spike-specific antibody titers and for in vitro influenza and SARS-CoV-2 neutralization capacity. Results indicated an increased reactivity in subjects who received both influenza and SARSCoV2 vaccinations, as compared to those who received only the SARS-CoV-2 vaccine, with sustained anti-spike antibody titers up to 12 weeks post-vaccination. Immune response to influenza vaccine was evaluated and individuals were stratified as high or low responders. High responders showed increased antibody titers against SARSCoV2 vaccine both after 4- and 12-weeks post-vaccination. On the contrary, the individuals classified as low responders were less responsive to the SARS-CoV-2 vaccine. These data indicate that both external stimuli, such as influenza vaccination, and the host's intrinsic ability to respond to stimuli play a role in the response to vaccine.

(1) Background Diabetic Retinopathy (DR) is the primary cause of poor vision in young adults. Screening for DR is important but many patients do not attend; (2) Methods: We validated an algorithm for predicting DR and its progression by conducting a retrospective study of 11 children in a population of 120,389 T2DM (3) Results: By applying the algorithm to the population showed an AUC of 0.93 (95% CI, 0.92–0.94) for any-DR and 0.90 (95% CI, 0.89–0.91) for referable-DR(4) Conclusions: The algorithm is useful for predicting patients who could develop referable forms of DR and also for any-DR. This would allow a personalized screening plan to be drawn up for each patient.

In the pursuit of functional foods that promote health, nanoliposomal carriers have been used to enhance the stability and functionality of dairy products such as yogurt, promising therapeutic benefits. This study aimed to evaluate the impact of fucoxanthin-loaded nanoliposomes in yogurt on its antioxidant, physico-chemical, and rheological properties under cold storage (21 days). Fucoxanthin-loaded nanoliposomes were prepared using the ultrasonic film dispersion technique and added at concentrations of 0%, 5% and 10% at the yogurt (Y-C, Y-FXN-5, Y-FXN-10). Homogeneous and uniform nanoliposomes (98.28 nm) were ob-tained, preserving their integrity and functionality, and ensuring prolonged release and bioavailability of fucoxanthin. Y-FXN-10 maintained the highest antioxidant activity according to the DPPH (52.96%), ABTS (97.97%), and FRAP (3.16 mmol ET/g) methods. This formulation exhibited enhanced erythroprotective potential, inhibiting hemolysis, photohemolysis, and heat-induced hemolysis, thereby preventing lipid pe-roxidation. However, viscosity and firmness decreased, affecting the texture and appearance. Sensory properties such as color, flavor, aftertaste, texture, and overall acceptance improved with the 10% fuco-xanthin-enriched yogurt formulation. These results suggest that nanoliposomal are suitable for carries fuco-xanthin, their incorporation into food matrices is key to developing functional foods. Regulatory approvals and consumer perceptions regarding nanotechnology-based products must be addressed, emphasizing their safety and health benefits.

This study explores the transformative potential of integrating Building Information Modeling (BIM) and Generative Design methodologies in heritage conservation and building management. By utilizing BIM, detailed architectural, structural, and MEP models were created, facilitating precise design and effective stakeholder collaboration. Generative Design enabled the exploration of multiple design solutions, optimizing spatial layouts and structural integrity. The project also integrated automated management systems and IoT sensors to enhance real-time monitoring, energy efficiency, and user comfort through the development of a digital twin. Despite encountering challenges such as technical complexities and budget constraints, the project successfully preserved the cinema's historical essence while incorporating modern functionalities. The findings highlight the contributions of BIM and Generative Design to the AEC industry, emphasizing their role in improving design accuracy, operational efficiency, and sustainability. This research provides valuable insights for future projects in heritage conservation, offering a blueprint for balancing historical preservation with contemporary needs. The revitalization of the "Ex Cinema Santa Barbara" in Paternò exemplifies these advancements, demonstrating how these technologies can restore and modernize culturally significant historical buildings effectively.

The prevalence of autism has been increasing at an alarming rate. Even accounting for the expansion of autism spectrum disorder diagnostic (ASD) criteria throughout the 1990’s, there has been an over 300% increase in ASD prevalence since the year 2000. The often debilitating personal, familial, and societal sequelae of autism are generally believed to be lifelong. However, there have been several encouraging case reports demonstrating reversal of autism diagnoses with a therapeutic focus on addressing the environmental and modifiable lifestyle factors believed to be largely underlying the condition. This case report describes the reversal of autism among dizygotic, female twin toddlers and provides a review of related literature describing associations between modifiable lifestyle factors, environmental exposures, and various clinical approaches to treating autism. The twins were diagnosed with Level 3 severity ASD “requiring very substantial support” at approximately 20 months of age following concerns of limited verbal and non-verbal communication, repetitive behaviors, rigidity around transitions, and extensive gastrointestinal symptoms, among other common symptoms. A parent-driven, multidisciplinary, therapeutic intervention involving a variety of licensed clinicians focusing primarily on addressing environmental and modifiable lifestyle factors was personalized to each of the twin’s symptoms, labs, and other outcome measures. Dramatic improvements were noted within several months in most domains of the twins’ symptoms, which was manifested in reductions of Autism Treatment Evaluation Checklist (ATEC) scores from 76 to 32 in one of the twins and from 43 to 4 in the other twin. The improvement in symptoms and ATEC scores has remained relatively stable for six months at last assessment. While prospective studies are required, this case offers further encouraging evidence of ASD reversal through a personalized, multidisciplinary approach focusing predominantly on addressing environmental and lifestyle risk factors.

Analyses of the three predominant types of sedimentation – clastic, carbonate and black shale – revealed their discontinuity/continuity in different facies environments of the Middle and Late Devonian of the central part of the Volga-Urals petroleum province, namely (1) in depressions, both condensed and non-condensed, (2) on the slopes of depressions and (3) in shallow water environments represented by tectonic arches or localised biohermal uplifts. The regional zonation of conodonts, correlated with the global chronostratigraphic scheme, substantiates the stratigraphic completeness of the general Devonian sequence in this area. In particular, the sedimentation of organic-rich black shales, traditionally considered as source rocks, lasted more than 29 million years, starting from the Late Eifel and ending at the Devonian-Carboniferous boundary. There was only one hiatus in the deposition of both black shales and carbonate sediments, lasting about 2.5 million years at the end of the Frasnian. That interval is dominated by clastic sediments, which are considered to be the most productive reservoirs of the Volga-Ural province. In the time interval from the beginning of the Eifel to the end of the Frasnian (about 17 Ma), (a) clastic sediments show the highest accumulation rates; (b) the most complete sequences occur in depressions; and (c) arches and uplifts show the most significant gaps in the geological record. During Famennian, (a) clastic sedimentation has completely ceased; (b) differences between the slopes of troughs and shallow-water environments have diminished, resulting in stable accumulation of carbonate sediments in both settings; (c) the decrease in sequence thickness (up to 50 m) in depressions suggests reduced accumulation rates of deep-water organic-rich black shales. The results help to understand the complex spatial relationship between different coexisting sedimentation types and focus attention to the incompleteness of the geological record in different environments.

(1) Background: Most patients with atrial fibrillation, on warfarin therapy, are at higher risk of morbidity and mortality. However, data targeting patients with atrial fibrillation, who take warfarin therapy, are limited in Jordan. This study aimed to provide in-depth analysis of a cohort of patients with atrial fibrillation on warfarin regarding patients’ characteristics, atrial fibrillation related symptoms, interventions, comorbidities, and 12-months outcomes. (2) Methods: The study enrolled 645 patients with atrial fibrillation, on warfarin, from 28 health settings across Jordan. Standardized clinical data form was utilized to collect data upon enrollment, at one, six, and 12 months post initial assessment. Descriptive statistics were used for the description of variables. (3) Results: The most commonly reported symptoms were palpitation (41.4%) shortness of breath (39.1%) and fatigue (26.2%). The prevalent comorbidities associated with atrial fibrillation were congestive heart failure (22.5%), valvular heart diseases (16.6%), and cerebral vascular accident (16.3%). The embolic (32.4%) and thrombotic cerebral vascular accident (16.2%) were the most common type. Major bleeding associated with hospitalization was the most frequent type of bleeding (10 out of 24). (4) Conclusions: Jordanians, using anticoagulation, need to be constantly monitored in terms of their characteristics, symptoms, and any potential complications, to ensure its optimal therapeutic dose and prevent any potential health complications.

Base excision repair (BER) is the predominant pathway to remove most forms of hydrolytic, oxidative and alkylative DNA damage. The precise functioning of BER is achieving by the regulation of each step by regulatory/accessory proteins, with the most important of which being poly(ADP-ribose) polymerase 1 (PARP1). The PARP1 regulatory functions extend to many cellular processes including regulation of mRNA stability and decay. PARP1 can therefore affect BER both at the level of the BER proteins and at the level of their mRNAs. Systematic data on how the PARP1 content affects the activities of key BER proteins and the levels of their mRNAs in human cells are extremely limited. In this study the CRISPR/Cas9 based technique has been used to knocked out the PARP1 gene in the human HEK 293FT line. The obtained cell clones with putative PARP1 deletion were characterized by several approaches including: PCR analysis of deletions in genomic DNA, Sanger sequencing of genomic DNA, qPCR analysis of PARP1 mRNA, western-blot analysis of whole-cell-extract proteins with anti-PARP1 antibodies, and the PAR synthesis in the whole-cell-extracts. qPCR analysis of mRNAs coding the BER related proteins: PARP2, uracil DNA glycosylase 2, AP endonuclease 1, DNA polymerase β, DNA ligase III and XRCC1 did not reveal crucial influence of PARP1 knockout. The corresponding catalytic activities in the whole-cell extracts (WCEs) evaluated in parallel did not differ significantly between mutant and parental cell lines. No considerable influence of poly(ADP-ribose) synthesis on the activity of the above WCE enzymes was revealed.

At the molecular level, aging is often accompanied by dysfunction of stress-induced membrane-less organelles (MLOs) and changes in their material state. In this work, we analyzed the proteins included in the proteome of stress granules (SGs) and P-bodies for their tendency to transform the material state of these MLOs. Particular attention was paid to proteins whose gene expression changes during replicative aging. It was shown that the proteome of the studied MLOs practically does not differ in the analyzed characteristics and consists of completely or partially intrinsically disordered proteins, 30 - 40% of which are potentially capable of liquid-liquid phase separation (LLPS). At the same time, the proportion of proteins capable of spontaneous LLPS is relatively small, which indicates the leading role of nucleic acids in the biogenesis of these membrane-less organelles. Proteins whose gene expression changes during the transition of human cells to a senescent state make up about 20% of the studied proteomes. There is a statistically significant increase in the number of positively charged proteins in both datasets studied compared to the complete proteomes of these organelles. An increase in the relative content of DNA-, but not RNA-binding proteins, was also found in the stress-granules dataset with senescence-related processes. Among SG proteins potentially involved in senescent processes, there is an increase in the abundance of potentially amyloidogenic proteins compared to the whole proteome. The hnRPDL protein has the highest degree of disorder and highest propensity for LLPS among such proteins, which allows us to consider it as “potentially dangerous.” Proteins common to SGs and P bodies, potentially involved in processes associated with senescence, form clusters of interacting proteins. The largest cluster is represented by RNA-binding proteins involved in RNA processing and translation regulation. These data indicate that SG proteins, but not proteins of P-bodies, are more likely to transform the material state of MLOs. Furthermore, these MLOs can participate in processes associated with aging in a coordinated manner.

The genus Colias Fabricius, 1807 includes numerous taxa and forms with uncertain status and taxonomic position. Among such taxa are Colias mongola Alphéraky, 1897 and Colias tamerlana Staudinger, 1897, interpreted in the literature either as conspecific forms, as subspecies of different but morphologically somewhat similar Colias species, or as distinct species-level taxa. Based on mitochondrial and nuclear DNA markers, we reconstruct a phylogeographic pattern of the taxa in question. We recover and include in our analysis DNA barcodes of the century-old type specimens, the lectotype of C. tamerlana deposited in the Natural History Museum (Museum für Naturkunde), Berlin, Germany (ZMHU), the paralectotype of C. tamerlana and the lectoptype of C. mongola deposited in the Zoological Institute, Russian Academy of Sciences, Saint-Petersburg, Russia (ZISP). Our analysis grouped all specimens within four (HP_I-HP-IV) deeply divergent but geographically poorly structured clades which did not support nonconspecifity of C. mongola–C. tamerlana. We also show that all studied females of the widely distributed haplogroup HP_II were infected with a single Wolbachia strain belonging to the supergroup B, while the males of this haplogroup, as well as all other investigated specimens, were not infected. Our data underline the relevance of large-scale sampling dataset analysis and the need of testing for Wolbachia infection to avoid erroneous phylogenetic reconstructions and species misidentification.

Pregnant women are especially vulnerable to respiratory diseases. We aimed to study seroconversion rate during pregnancy in a cohort of consecutive pregnancies tested in the first and third trimesters and to compare maternal and obstetric complications between women who seroconverted in the first versus the third trimester. This is an observational, cohort study carried out at Hospital Universitario de Torrejón, in Madrid, Spain, during the first peak of the COVID-19 pandemic. All consecutive singleton pregnancies with a viable fetus attending their 11-13 weeks scan between January 1st and May 15th, 2020, were included and monthly follow up until delivery. Antibodies against SARS-CoV-2 (IgA and IgG) were analyzed on stored serum samples obtained from the first and third trimester routine antenatal bloods in 470 pregnant women. Antibodies against SARS-CoV-2 were detected in 31 (6.6%) women in the first trimester and in 66 (14.0%) in the third trimester, including 48 (10.2%) that were negative in the first trimester (seroconversion during pregnancy). Although the rate of infection was significantly higher in the third versus the first trimester (p = 0.003), no significant differences in maternal or obstetric complications were observed in women testing positive in the first versus the third trimester.

Listerias of the phylogenetic lineage II (PLII) are common in the European environment, and are hypovirulent. Despite this, they caused more than a third of sporadic cases of listeriosis, and multi-country foodborne outbreaks. L. monocytogenes ST37 is one of them. During the COVID-19 pandemic ST37 appeared in the clinical cases and ranked second in occurrence among food isolates in the Moscow region. The aim of this study was to describe the genomic features of ST37 isolates from different sources. All clinical cases of ST37 were in the cohort of male patients (age, 48-81 years) with meningitis-septicemia manifestation, and COVID-19 or Influenza in the anamnesis. The core genomes of the fish isolates were closely related. The clinical and meat isolates revealed a large diversity. Prophages (2-4/genome) were the source of the unique genes. Two clinical isolates displayed the pseudolysogeny, and excided prophages were A006-like. Absence of the plasmids, the assortment of virulence factors and resistance determinants in chromosome corresponded to the hypovirulent characteristics. However, all clinical isolates caused severe disease with deaths in four cases. Thus, these studies allow us to speculate that a previous viral infection increases a human susceptibility to listeriosis.

Progesterone receptor (PGR) expression level determines biological characteristics of the serous ovarian carcinoma, and low PGR expression appears to be associated with chemoresistance and worse outcome. In this study, we aimed to find relationships between tumor progesterone receptor level and RNA-profile (miRNAs, piwiRNAs, and mRNAs), determining its biological characteristics and behavior. For this purpose, we applied next generation sequencing of small noncoding RNAs, quantitative RT-PCR, and immunohistochemistry to analyze FFPE and frozen tumor samples as well as blood plasma from patients with benign cystadenoma (BSC), serous borderline tumour (SBT), low-grade and high-grade serous ovarian carcinoma (LGSOC and HGSOC, respectively). We found significant upregulation of MMP7 and MUC16 and downregulation of PGR in LGSOC and HGSOC in comparison with BSC. The tissue content of miR-199a-5p, miR-214-3p, miR-424-3p, miR-424-5p, miR-125b-5p significantly inversely correlated with the expression level of MUC16 and blood serum CA125 concentration, and significantly directly correlated with the PGR expression level in tumor tissue. On the contrary, the tissue content of miR-16-5p, miR-17-5p, miR-20a-5p, miR-93-5p, responsible for epithelial-mesenchymal transition (EMT) of the cell, significantly directly correlated with the blood serum CA125 concentration and significantly inversely correlated with the PGR expression level in the tumor tissue. Levels of the EMT-associated miRNAs significantly directly correlated with the content of hsa_piR_022437, hsa_piR_009295, hsa_piR_020813, hsa_piR_004307, hsa_piR_019914 in tumor tissues. Among them, expression level of hsa_piR_004307 significantly inversly correlated with the PGR expression level in the tumor. Two optimal logistic regression models were developed based on the quantitation of hsa_piR_020813, miR-16-5p, hsa_piR_022437 or hsa_piR_004307, hsa_piR_019914, miR-93-5p in the tumor tissue, both of which significantly diagnose PGR-negative tumor phenotype with 93% sensitivity. According to FunRich3.1.3 functional enrichment analysis tool, 72 gene-targets of miRNA and piRNA identified here as markers of PGR-negative ovarian tumor phenotype were proven to be mutated in different cancers such as ovarian, breast, colorectal, liver, stomach, lung, endometrial, thyroid cancer. Among them, the blood plasma levels of miR-16-5p and hsa_piR_022437 can be used to diagnose PGR-negative tumor phenotype with 86% sensitivity before surgery and chemotherapy to choose the treatment strategy for this most aggressive type of ovarian cancer (for instance, neoadjuvant chemotherapy followed by cytoreduction in combination with hyperthermic intraperitoneal chemotherapy) to increase the effectiveness of treatment and longevity of the patient.

The study of phytotherapy in dentistry is relevant due to the low occurrence of research in the treatment of oral pathologies, such as caries and periodontal disease. Thus, the aim of this research was to characterize the chemical composition of extracts from the leaves of Couroupita guianensis Aubl, including toxicological evaluation and the antioxidant and antimicrobial potential against Staphylococcus aureus, Streptococcus mutans and Candida albicans. Three extracts were prepared using assisted ultrasound, originating the Crude Ultrasound Extract (CUE) and Soxhlet apparatus, originating the Crude Soxhlet Extract (CSE) and the Ethanol Soxhlet Extract (ESE). In the analysis of the chemical composition, the presence of flavonoids, tannins and saponins were detected. LC-DAD analysis revealed the presence of caffeic acid, sinapic acid, rutin, quercetin, luteolin, kaempferol and apigenin in all extracts. In the GC-MS analysis, stigmasterol and β-sitosterol were identified in CUE and CSE. The antioxidant potentials, determined by the DPPH• and ABTS•+ methods, the ESE showed higher antioxidant activity (2.98 ± 0.96 and 4.93 ± 0.90, respectively). In the evaluation of toxicity, the CUE 50µg/mL and the ESE 50 µg/mL presented growth stimulation of Allium cepa roots. At a concentration of 750µg/mL, all extracts inhibited root growth. None of the extracts showed toxicity against Artemia salina. Antibacterial action was detected in all extracts, mainly against the microorganisms S. aureus and S. mutans; however, the antifungal action against C. albicans was not detected. From the results, the extracts of C. guianensis have therapeutic potential for use in the control of microorganisms in the oral microbiota.

Al-6%Mg-Sc-Zr alloys with the total ratio of Sc + Zr = 0.32 wt.% make up the target of this research. The content of scandium and zirconium varied with an increment of 0.02%. The alloys were produced by induction casting. Their ultrafine-grained (UFG) microstructure was formed with Equal Channel Angular Pressing (ECAP). Such cast alloys have a homogeneous macrostructure formed by small equiaxed grains in the central part of the ingot and columnar crystals along the edges of the cross section. After ECAP, the average grain size in the alloy specimens is 0.5–1 µm. The average grain size does not depend on the ratio of Sc and Zr in these alloys. Superplasticity tests were performed at temperatures ranging from 300 to 500 °C and at a strain rate varying between 3.3·10-3 and 3.3·10-1 s-1. UFG Al-6%Mg-0.20%Sc-0.12%Zr and Al-6%Mg-0.18%Sc-0.14%Zr alloys exhibit the highest superplasticity. It was suggested that changes in Sc:Zr ratio affect spatial distribution and composition of the following precipitating particles: Al3Sc, Al3Zr, Al3(ScxZr1-x). An increase in Zr concentration is shown to reduce the susceptibility of UFG alloys to cavitation fracture.

This work presents the first evidence that dissolved globular proteins change the arrangement of hydrogen bonds in water, with different proteins showing quantitatively different effects. Using ATR-FTIR (Attenuated Total Reflection – Fourier Transform Infrared) spectroscopic analysis of OH-stretch bands, we obtain quantitative estimates of the relative amounts of the previously reported four subpopulations of water structures coexisting in a variety of aqueous solutions. Where solvatochromic dyes can measure the properties of solutions of non-ionic polymers, the results correlate well with ATR-FTIR measurements. In protein solutions to which solvatochromic dye probes cannot be applied, NMR (Nuclear Magnetic Resonance) spectroscopy was used for the first time to estimate the hydrogen bond donor acidity of water. We found strong correlations between the solvent acidity and arrangement of hydrogen bonds in aqueous solutions for several globular proteins. Even quite similar proteins are found to change water properties in dramatically different ways.

The report introduces hybrid polyelectrolyte-stabilized colloids combining blue and green emitting building blocks, that are citrate carbon dots (CDs) and [TbL]+ chelate complexes with 1,3-diketonate derivatives of calix[4]arene. The joint incorporation of green and blue emitting blocks into the polysodium polystyrenesulfonate (PSS) aggregates is carried out through the solvent-exchange synthetic technique. The coordinative binding between Tb3+ centers and CD surface groups in initial DMF solutions both facilitates joint incorporation of [TbL]+ complexes and the CDs into the PSS-based nanobeads and affects fluorescence properties of [TbL]+ complexes and CDs, as well as their ability to temperature sensing. The variation of the synthetic conditions is represented herein as a tool for tuning the fluorescent response of the blue and green emitting blocks upon heating and cooling. The revealed regularities enable developing either dual band luminescent colloids for monitoring temperature changes within 25-50 C through double color emission, or to transform the colloids into ratiometric temperature sensors via simple concentration variation of [TbL]+ and CDs in initial DMF solution. Novel hybrid carbon dots-terbium chelate PSS-based nanoplatform opens an avenue for new generation of sensitive and customizable single excited dual band nanothermometers.

The human adenovirus phylogenetic tree is split across seven species (A-G). Species D adenoviruses offer potential advantages for gene therapy applications, with low rates of preexisting immunity detected across screened populations. However, many aspects of the basic virology of species D, such as their cellular tropism, receptor usage and in vivo biodistribution profile, remain unknown. Here, we have characterized human adenovirus type 49 (HAdV-D49), a relatively understudied species D member. We report that HAdV-D49 does not appear to use a single pathway to gain cell entry but appears able to interact with various surface molecules for entry. As such, HAdV-D49 can transduce a broad range of cell types in vitro, with variable engagement of blood coagulation FX. Interestingly, when comparing in vivo biodistribution to adenovirus type 5, HAdV-D49 vectors show reduced liver targeting whilst maintaining transduction of lung and spleen. Overall, this presents HAdV-D49 as a robust viral vector platform for ex vivo manipulation of human cells and for in vivo applications where the therapeutic goal is to target the lung or gain access to immune cells in the spleen whilst avoiding liver interactions, such as intravascular vaccine applications.

Background: The abrupt implementation of COVID-19 lockdown had impacted the management of diabetes mellitus. Limited access to health facilities and alterations in daily lifestyle put metabolic control among patients at risk. Thus, we observed the differences in metabolic control parameters in diabetic patients before and during the lockdown. Methods: We performed searches from five databases. Meta-analyses were done using random or fixed-effect approaches with glycemic control parameters (HbA1c, RBG, FBG, TIR, TAR, TBR) as primary outcomes. Mean difference (MD), Confidence Interval (CI), and p-value were calculated. Lipid profile presented as secondary outcome. Results: 21 studies with 3992 diabetic patients were included in the study. Meta-analysis presented an increase on HbA1c of T1D and T2D patients [MD=+0.06% (95%CI -0.10–0.23), I²=77%, p=0.45], TBR of T1D patients [MD=-0.05% (95%CI -0.38–0.28), I²=0%, p=0.77], FBG of T2D patients [MD=+3,47 mg/dL (95%CI 1.22–5.73), I²=0%, p=0.002], and lipid profile on qualitative analysis. However, TIR, TAR, and RBG of T1D patients were improved [MD=+3.52% (95%CI 0.29–6.74), I²=76%, p=0.03; MD=-3.36% (95%CI -6.48–-0.25), I²=75%, p=0.03; MD=-0.91 mg/dL (95%CI -4.52–6.34), I²=88%, p=0.74]. Conclusion: Lockdown enforcement did not worsen the glycemic control parameter in diabetic patients. Particular parameters inclined to improve during the lockdown.

Small RNAs are essential for the coordination of many cellular processes, including the regulation of gene expression patterns, the prevention of genomic instability, and the suppression of mutagenic transposon activity. These processes determine aging, longevity, and sensitivity of cells and an organism to stress factors (particularly, ionizing radiation). The biogenesis and activity of small RNAs are provided by proteins of the Argonaute family. These proteins participate in the processing of small RNA precursors and the formation of an RNA-induced silencing complex. However, the role of Argonaute proteins in the regulation of lifespan and radioresistance remains poorly explored. We studied the effect of knockdown of Argonaute genes (AGO1, AGO2, AGO3, piwi) in various tissues on the Drosophila melanogaster lifespan and survival after the γ-irradiation at a dose of 700 Gy. In most cases, these parameters were reduced or did not change significantly in flies with tissue-specific RNA interference. Surprisingly, piwi knockdown in both the fat body and the nervous system caused a lifespan increase. But changes in radioresistance depended on the tissue in which the gene was knocked out. In addition, analysis of changes in retrotransposon levels and expression of stress response genes allowed us to determine associated molecular mechanisms.

Globally, rotavirus group A (RVA) remains a major cause of severe childhood diarrhea, despite the use of vaccines in &gt; 100 countries. RVA sequencing for local outbreaks facilitates investigation into strain composition, origins, spread, and vaccine failure. In 2018, we collected 248 stool samples from children aged &lt;13 years admitted with diarrheal illness to Kilifi County Hospital, coastal Kenya. Antigen screening detected RVA in 55 samples (22.2%). Of these, VP7 (G) and VP4 (P) segments were successfully sequenced in 48 (87.3%) and phylogenetic analysis based on the VP7 sequences identified seven genetic clusters with six different GP combinations; G3P[8], G1P[8], G2P[4], G2P[8], G9P[8] and G12P[8]. The G3P[8] strains predominated the season (n=37, 67.2%) and comprised three G3 genetic clusters that fell within Lineage I and IX (the latter also known as equine-like G3 lineage). Both two G3 lineages have been recently detected in several countries. Our study is the first to document African children infection with G3 lineage IX. These data highlight the global nature of RVA transmission and the importance of increasing global rotavirus vaccine coverage.

Background Increasingly, healthcare organizations are using technology for the efficient management of data. The aim of this study was to compare the data quality of digital records with the quality of the corresponding paper-based records by using data quality assessment framework. Methodology We conducted a desk review of paper-based and digital records over the study duration from April 2016 to July 2016 at six enrolled TB clinics. We input all data fields of the patient treatment (TB01) card into a spreadsheet-based template to undertake a field-to-field comparison of the shared fields between TB01 and digital data. Findings A total of 117 TB01 cards were prepared at six enrolled sites, whereas just 50% of the records (n=59; 59 out of 117 TB01 cards) were digitized. There were 1,239 comparable data fields, out of which 65% (n=803) were correctly matched between paper based and digital records. However, 35% of the data fields (n=436) had anomalies, either in paper-based records or in digital records. 1.9 data quality issues were calculated per digital patient record, whereas it was 2.1 issues per record for paper-based record. Based on the analysis of valid data quality issues, it was found that there were more data quality issues in paper-based records (n=123) than in digital records (n=110). Conclusion There were fewer data quality issues in digital records as compared to the corresponding paper-based records. Greater use of mobile data capture and continued use of the data quality assessment framework can deliver more meaningful information for decision making.

The recognition of a place as a World Heritage Site (WHS) by UNESCO is fundamental to preserve its historical and artistic inheritance and, at the same time, to encourage visits to that area. The purpose of this article is to contribute to the study of the relationship between WHS and cultural tourism, with a marked sustainable character, through the presentation of the results of research conducted in the city of Cordoba (Spain) and which analyses the sociodemographic profile of the tourists, the variables that influence their level of satisfaction and of their loyalty and the classification of the travelers through different variables. The principal results of the research show the significant educational level of the surveyed tourists, as well as the high level of satisfaction with the visit, the high number of countries of origin and the outstanding motivation for knowing the city’s heritage roots.

Chagas disease (CD) is a neglected tropical parasitic disease caused by the protozoan Trypanosoma cruzi. Unfortunately, the current etiological treatment for CD is unsatisfactory, due to the high toxicity and low cure efficacy of compounds, mainly during the chronic phase of this disease. Thus, the discovery of new drugs for the treatment of CD is urgent. In the present study, we report the synthesis of a series of guanidines and its evaluation in in vitro assays to determine the trypanocidal effects on the Tulahuen T. cruzi strain, transfected with a β-galactosidase reporter gene, in comparison to the cytotoxic effects on vertebrate cells. The most potent and selective compounds LQOF-G1 and LQOF-G29 were considered good drug prototypes and candidates for in vivo tests using mice. Both compounds possess an electron withdrawing group on the aniline moiety, namely a NO2 and Br group, respectively, which effectively decrease the electron density. LQOF-G29 stands out among the investigated compounds due to the replacement of the benzyl group by methyladamantane.

In this study the impact of climate change on drought conditions in Serbia is investigated trough the multifractal analysis of standardized precipitation evapotranspiration index (SPEI). The SPEI time series for accumulation time scale of 1, 3, 6 and 12 months were calculated using the high resolution meteorological gridded dataset E-OBS with a resolution of 0.10 in regular latitude/longitude coordinates and time span from 1961 to 2020. The multifractal analysis was performed for two standard climatic periods (1961−1990 and 1991−2020) using multifractal detrended fluctuation analysis method (MFDFA) which is suitable for nonstationary temporal series. In each of 1278 grid cells that cover Serbian territory we analyzed 4 SPEI time series for two 30 years periods (which totals 10224 MFDFA runs) and calculated multifractal spectrum parameters that describe persistence, degree of multifractality and the influence of small/large fluctuations. We found that all the analyzed SPEI series show multifractal properties with the dominance of small fluctuations. The short and medium drought conditions described by SPEI-1, SPEI-3 and SPEI-6 are persistent (the position of maximum of multifractal spectrum is in the range 0.5&lt;α0&lt;1), stronger persistence is found at higher accumulation time scales, while SPEI-12 time series are antipersistent (0&lt;α0-1&lt;0.5). The degree of multifractality (width of multifractal spectrum W) increases from SPEI-1 to SPEI-6 and decreases for SPEI-12. For all series multifractal spectrum is right skewed (skew parameter r&gt;0) indicating that small SPEI temporal fluctuations contribute more to multifractality than large fluctuations. In the second period SPEI-1 SPEI-3 and SPEI-6 series become more persistent with weaker multifractality, indicating that short and medium drought conditions (which are related to soil moisture and crop stress) become easier to predict, while SPEI-12 changed toward random regime and stronger multifractality in eastern and central part of country, indicating that long term drought conditions (related to streamflow, reservoir levels, and groundwater levels) become more difficult for modeling and prediction.

In this work, we introduce the first pipeline that combines a refraction-aware Structure-from-Motion (SfM) method with a deep learning model specifically designed for airborne bathymetry. We accurately estimate the 3D positions of the submerged points by integrating refraction geometry within the SfM optimization problem. This way, no refraction correction as post-processing is required. Experiments with simulated data that approach the real-world capturing conditions demonstrate that SfM with refraction correction is extremely accurate, with submillimeter errors. We integrate our refraction-aware SfM within a deep learning framework that also takes into account radiometrical information, developing a combined spectral and geometry-based approach, with further improvements on accuracy and robustness to different seafloor types, both textured and textureless. We conducted experiments with real-world data at 2 locations in the southern Mediterranean Sea, with varying seafloor types which demonstrate the benefits of refraction correction for the deep learning framework. We open-source our refraction-aware SfM, providing researchers in airborne bathymetry with a practical tool to apply SfM in shallow water areas.

In recent years, using pre-sprouted seedlings for sugarcane establishment has been developed in Brazil. Despite yielding promising results, the optimal irrigation management for this method during the Brazilian winter planting season has yet to be determined. Additionally, information regarding water demand and seedling behavior when subjected to different irrigation levels remains unclear. This study aimed to assess the response of pre-sprouted sugarcane seedlings to different irrigation levels during the winter in southeastern Brazil. Pre-sprouted sugarcane seedlings were subjected to different irrigation levels during the winter season in the region of Piracicaba, using a sprinkler irrigation system. Periodic evaluations were conducted, such as seedlings mortality rate, root size, root dry mass, number of sugarcane tillers sprouted per meter, total number of tillers, plant height, leaf area index, shoot dry mass, and total leaf chlorophyll index. The findings of this investigation indicate that a 10 mm irrigation level facilitated optimal fixation depth and achieved a 97.8% survival rate. Moreover, a correlation between seedling mortality rate and irrigation management was observed, emphasizing the critical role of irrigation in establishing and developing seedlings. Based on these findings, a 10 mm irrigation may represent the optimal irrigation strategy for pre-sprouted sugarcane seedlings in this scenario.

Strain L. fermentum U-21 secretes chaperones into the medium and it is considered as the candidate for the development of drugs, so-called disaggregases, for Parkinson’s disease therapy. This study is devoted to characterization of secreted protein encoded by C0965_000195 locus. Analysis of sequence and predicted structure of the protein encoded by C0965_000195 allows us to attribute it to the ClpL, homologs of which are known to be chaperones. The chaperone activity of ClpL L. fermentum U-21 was evaluated in vivo by refolding of differing in thermostability luciferases from Aliivibrio fischeri and Photorhabdus luminescens in Escherichia coli cells. It was observed that clpL from L. fermentum U-21 can compensate for the deficiency in the clpB gene and enhance the ability to refold thermodenatured proteins in clpB- cells. In vitro experiments have demonstrated the ability of a spent culture medium containing proteins secreted by L. fermentum U-21 cells, including ClpL, to prevent thermodenaturation of luciferases partially.We suggest that the ClpL protein from L. fermentum U-21 strain, which exhibits disaggregase properties against aggregating proteins, may be one of the clue components that play a role in the pharmabiotic properties of this strain.

Present research focus on the effect of different processing routes on physical and mechanical properties of nano Ti(CN) based cermet’s with metallic binders. Tungsten carbide (WC) is added as secondary carbide and Ni-Co are added as metallic binders in nano Ti(CN) based cermet processed via Conventional and Spark Plasma Sintering (SPS). Systematic comparison of composition and sintering conditions for different cermet’s’ systems is done to design the novel composition and sintering conditions. Nano TiCN powder was prepared by 30hr of ball milling. Highest density of >98.5% percent was achieved for SPS processed cermet’s sintered at 1200°C and 1250°C for 3 min. at 60 MPa pressure in comparison to conventionally sintered cermet’s at 1400°C for 1hr with two stage compaction process, uniaxially at 150 MPa and isostatically at 300 MPa pressure respectively. Comparison of XRD analysis of milled powders of different time intervals was done to understand the characteristics of the as received and milled powders. Peak broadening was observed after 5 hr. of ball milling, and it increased till 30hr. Also, peak broadening and refined carbide size was observed in XRD and SEM micrograph of SPS processed cermet. TEM analysis of milled powder showed internal structure having regular periodic arrangement of planes. SEM (BSE) images of all cermets primarily showed three major microstructural phases of core-rim-binder with black, grey and white contrast respectively. In the present sintering conditions high hardness of ~16 GPa and fracture toughness of ~9 MPa m1/2 was obtained for SPS processed cermets sintered at higher temperature.

The dimensional effect of the accumulation of an electric charge with a density of up to 270 μF/g by the system of compacted zirconium dioxide nanoparticles during exposure in an electric field (5000 V/m) under normal physical conditions is determined. Based on a qualitative complex analysis of the forms of appearance of the effect, it is shown that the place of localization of different charge carriers is the surface of nanoparticles. The supposed mechanism of this effect is considered using the theory of dispersed systems, the band theory, and the theory of contact phenomena in semiconductors. It was concluded that this mechanism is due to the phenomenon of localization of electron-type charge nanoparticles in the near-surface zone of the material in contact with the adsorption ion atmosphere. This effect is relevant for modern nanoelectronics, microsystem technology, and printed electronics.

Background: Historically, a large gender-related disparity in vascular access (AV) has been demonstrated, with a lower prevalence of women with arteriovenous fistula (AVF) compared to men and worse maturity rates. The cause of this difference is not entirely clear, although several reasons that could contribute to it have been hypothesized. The emergence of new percutaneous FAV (pFAV) systems could be an alternative for reducing these differences. Objective: The study aims to determine if there is a gender difference in the creation of AVFs using the new percutaneous systems. Material and Methods: A systematic review of the literature was conducted by searching PubMed and Google Scholar using the following terms: "percutaneous arteriovenous fistula", "endovascular arteriovenous fistula", and "hemodialysis". All clinical trials, comparative studies, and descriptive studies involving patients who underwent a pAVF were included. Results: Finally, the review includes 19 studies, comprising 14 retrospective and 5 prospective studies. Of these, 6 studies are comparative, 5 of which compare pAVF with surgically created AVFs (sAVF), and 1 comparing pAVFs performed using different systems with each other. A total of 1,269 patients were included in the review. Of the total number of patients, only 414 were women, representing 32.62%. Conclusion: The number of women included in the various studies analyzing pAVF remains very low, representing less than one-third of all patients. Although the causes of this difference are not entirely clear, several reasons have been hypothesized such as socio-economic factors, anatomical factors, or even patients' preferences. Given these results, further studies are needed to try to clarify the reasons for this gender disparity and to establish different strategies to mitigate the barriers faced by women in accessing the creation of an AVF.

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

Climate change has altered the frequency and severity of extreme weather, which can affect vegetation condition and habitat quality for wildlife. Declines in vegetation productivity during droughts and heatwaves can negatively impact animals that depend on vegetation for water and nutrition. The ability to detect such effects on habitat suitability can reveal refugia, which can be prioritised for protection to improve threatened species conservation. We used the normalised difference vegetation index (NDVI) to look at relationships between vegetation productivity and the presence of koalas (Phascolarctos cinereus) in potential habitat throughout much of their range. Using a large, long-term koala presence dataset, we tested the hypothesis that locations where koalas had been observed would exhibit higher NDVI values than a random, representative sample from the same vegetation group (i.e. woodlands, open forests or tall open forests). We also identified the minimum NDVI threshold at which koalas occurred across time for each vegetation group and compared these to the minimum NDVI values observed across potential koala habitat before and during the millennium drought; one of the worst recorded in Australia. Additionally, we investigated whether vegetation above the minimum NDVI thresholds was significantly closer to perennial water than unsuitable vegetation. We found that koalas tend to occur at locations exhibiting higher NDVI than average for all vegetation groups. We also found that 49% of all vegetation groups maintained a minimum NDVI above the koalas’ NDVI threshold before drought, equating to 190,227 km2, which declined to 166,746 km2 during drought (a 12% reduction). We also found that unsuitable vegetation tended to occur farther from perennial water than suitable vegetation for some vegetation groups. Areas that remained above the NDVI thresholds during the drought should be considered potential refugia for populations during an event of similar magnitude and could indicate future core habitat extent.

The Congo River Basin is the second-largest watershed globally, flowing through nine countries before reaching the Atlantic Ocean. The Kasai River Basin (KARB), containing about one-fourth of Congo’s freshwater resources, plays a strategic role in sustaining navigation, food production, and hydroelectricity generation in Central Africa. A multi-model framework suited for data scarce regions is applied for climate change impacts on water availability in the KARB to propose effective development plans in the future. This includes consideration of two conceptual hydrological models calibrated using four reanalysis datasets and fed with bias-corrected outputs of 19 climate models under two future Representative Climate Pathways (RCPs). Changes in mean annual discharge in the KARB from -18% to +3% are projected depending on the considered modeling configuration. This shows the sensitivity of impact assessment to the choice of models as well as input data. Moreover, about 9%, 18%, and 13% decline in streamflow signatures (Q10, Q50 and Q90) are projected based on the ensemble of models under RCP 8.5. A decrease of 14% and 5% in annual hydropower potential of the mainstream is estimated under RCPs 4.5 and 8.5, respectively. These changes in flows conditions should be considered in decision-making around constructing reservoirs and hydroelectricity generation.

Our study utilized density functional theory (DFT) to explore a 2D MoP2 surface for hydrogen storage. Optimization determined a gravimetric capacity for pristine MoP2 of 5.72%, with an adsorption energy of ‒ 0.13 eV/molecule. For this surface with 12.5% Mo vacancies, we achieved 6.02% and ‒ 0.14 eV/molecule. We then introduced a novel criterion to test the attraction forces in hydrogen storage at a given temperature. This involved a first-principles molecular dynamics approach at various temperatures. To determine the number of molecules adsorbed on the surface at temperature T1, we conducted an FPMD calculation at T1, using the optimization as the initial system configuration. Subsequently, we performed a second FPMD calculation at a temperature T2 (with T2 ‹‹ T1), using the stable configuration of the first FPMD calculation as the initial configuration. If there were attraction forces on the molecules, they would move towards the surface. We identified as adsorbed molecules at temperature T1, only those that moved back toward the surface at temperature T2. The defective surface gave the best gravimetric capacity, ranging from 5.27% at 300 K to 6.02% at 77 K. The latter met the requirement from the US-DOE, indicating the potential practical application of our research in hydrogen storage.

Papain-like protease PLpro, a domain within a large polyfunctional protein nsp3, plays key roles in the life cycle of SARS-CoV-2, being responsible for the first events of cleavage of a polyprotein into individual proteins (nsp1-4) as well as for the suppression of cellular immunity. Here, we developed a new genetically encoded fluorescent sensor, named PLpro-ERNuc, for detection of PLpro activity in living cells using translocation-based readout. The sensor was designed as follows. A fragment of nsp3 protein was used to direct the sensor on the cytoplasmic surface of endoplasmic reticulum (ER) membrane, thus closely mimicking the natural target of PLpro. The fluorescent part included two bright fluorescent proteins - red mScarlet I and green mNeonGreen, separated by a linker with the PLpro cleavage site. Nuclear localization signal (NLS) was attached to ensure accumulation of mNeonGreen into the nucleus upon cleavage. We tested PLpro-ERNuc in the model of recombinant PLpro expressed in HeLa cells. The sensor demonstrated expected cytoplasmic reticular network in the red and green channels in the absence of protease, and efficient translocation of the green signal into nuclei in the PLpro-expressing cells (14-fold increase of the nucleus/cytoplasm ratio). Then, we used PLpro-ERNuc in the model of Huh7.5 cells infected with SARS-CoV-2 virus, where it showed robust ER-to-nucleus translocation of the green signal in the infected cells 24 h post infection. We believe that PLpro-ERNuc represents a useful tool for screening PLpro inhibitors as well as for monitoring virus spread in a culture.

The aim of our study was a comprehensive comparative assessment of the effect of consumption of 1 and 2% cholesterol as part of a standard diet with and without regular moderate physical activity on the main biomarkers of lipid and cholesterol metabolism, as well as the intestinal microbiota of male Wistar rats. The animals were randomly divided into 5 groups according to body weight and Open Field test results: Control (n=10), 1% Chol (n=10), 2% Chol (n=10), 1% Chol + RUN (n=10) and 2% Chol + RUN. The cholesterol was additionally added in the amount of 1g or 2g/100g, respectively, to the diet of animals. The rats of experimental groups 1% Chol + RUN and 2% Chol + RUN were subjected to regular (2 days a week) physical activity on a Treadmill. In rats of four experimental groups, when compared to the Control, a response of 39 indicators was revealed. The largest number of changes in biomarkers - 29 (statistically significant, p

The application potential of cellulosic materials in natural composites and other fields needs to be explored to develop innovative, sustainable, lightweight, functional biomass materials that are also environmentally friendly. This study investigated Typha augostifolia (Typha sp.) as a potential new raw material for extracting cellulose nanocrystals (CNCs) for application in wastewater treatment composites. Alkaline treatments and bleaching were used to remove cellulose from the stem fibers. The CNCs were then isolated from the recovered cellulose using acid hydrolysis. The study showed a few distinct functional groups (O-H, -C-H, =C-H and C-O, and C-O-C) in the Fourier Transform Infrared (FTIR) spectra. Scanning electron microscope (SEM) revealed the smooth surface of CPC and CNCs that resulted from removing lignin and hemicellulose from powdered Typha augostifolia. Based on the crystalline index, the powdered Typha augostifolia, CPC, and CNCs were 42.86%, 66.94% and 77.41%. The loss of the amorphous section of the Typha sp. fiber resulted in a decrease in particle size. It may be inferred from the features of a Typha sp. CNC that CNCs may be employed as reinforcement in composites for wastewater treatment.

Abstract: Placenta accreta spectrum (PAS) is a severe complication of pregnancy associated with excessive invasion of cytotrophoblast cells at the sites of the endometrial-myometrial interface and the myometrium itself in cases of adherent (creta) and invasive (increta and percreta) forms, respectively. Despite advancements in ultrasound protocols and found associations of alpha-fetoprotein, PAPP-A, hCG, PLGF, sFlt-1, IL-8, and IL-33 peripheral blood levels with PAS, the condition remains undiagnosed before delivery because of the lacking clear evaluation criteria for each of the three grades of PAS. This leads to a high risk of massive blood loss, maternal hysterectomy, and preterm birth. While using deep sequencing, miRNA signatures of placental tissue, myometrium, and blood plasma from women with PAS in the third trimester of pregnancy, as well as miRNA profile in exosomes from the blood serum of women in the first trimester with physiologically progressing pregnancy, complicated by PAS or preeclampsia, were obtained. Two logistic regression models were constructed, both featuring statistically significant parameters related to the levels of miR-26a-5p, miR-17-5p, and miR-101-3p quantified by real-time PCR in native blood serum. These models demonstrated 100% sensitivity in detecting PAS during the first pregnancy screening. These miRNAs were identified as specific markers for PAS, showing significant differences in their blood serum levels during the first trimester in the PAS group compared to those in physiological pregnancies, early- or late-onset preeclampsia groups. Furthermore, these miRNAs exhibited differential expression in the PAS placenta and/or myometrium in the third trimester and, according to literature data, control angiogenesis. Significant correlations were found between extracellular hsa-miR-101-3p and nuchal translucency thickness, hsa-miR-17-5p and uterine artery pulsatility index, and hsa-miR-26a-5p and hsa-miR-17-5p with PLGF. The developed test system for early non-invasive PAS diagnosis based on the blood serum level of extracellular miR-26a-5p, miR-17-5p, and miR-101-3p can serve as an auxiliary method for 1st trimester screening pregnant women, subject to validation on independent test samples.

Climate change mainly affects production and consumption systems, such as: food, livelihoods, production (e.g., reduced milk production), water, and land use. The role of local knowledge has been recognized as important for decision-making under changing circumstances. This study was conducted in the northern part of the Ecuadorian Andes using a sample of 170 dairy-cattle-producing households. The objectives were: i) to characterize the rural livelihoods of dairy cattle farmers, ii) to evaluate access to climate information and perceptions of climate change, and iii) to determine the relationship between livelihoods and perceptions of climate change. Significant differences were identified between the groups evaluated in relation to the dairy farmers’ livelihoods. In addition, 85.29% of the respondents mentioned that climate information is important, but 67.83% do not trust the sources of information. It was found that there is a significant relationship between the level of education and age with the variables of climate change perceptions. This combined knowledge allows people to promote agri-environmental and educational policies to achieve climate literacy at a rural level.

The cortical motor system can be reorganized following a stroke, with an increasing recruitment of the contralesional hemisphere. However, it is unknown whether a similar hemispheric shift occurs in the somatosensory system to adapt to this motor change, and whether this is related to movement impairments.  This proof-of-concept study assessed somatosensory evoked potentials (SEPs), P50 and N100, in hemiparetic stroke participants and age-matched controls using high-density electroencephalograph (EEG) recordings during tactile finger stimulation. The laterality index was calculated to determine hemispheric dominance of the SEP and re-confirmed with source localization.  The study found that latencies of P50 and N100 were significantly delayed in stroke brains when stimulating the paretic hand. The amplitude of P50 was negatively correlated with Fügl-Meyer Upper Extremity Motor Score in stroke. Bilateral cortical responses were detected in stroke, while only contralateral cortical responses were shown in controls, resulting in a significant difference in the laterality index.  These results suggested that somatosensory reorganization after stroke involves increased recruitment of ipsilateral cortical regions. This reorganization delays the latency of somatosensory processing after a stroke.  This research provided new insights related to the somatosensory reorganization after stroke, which could enrich future hypothesis-driven therapeutic rehabilitation strategies from a sensory or sensory-motor perspective.

Delayed cancer detection is one of the common causes of poor prognosis in case of many cancers including the cancers of the oral cavity. Despite improvement and development of new and efficient gene therapy treatments, very little has been done to algorithmically assess the impedance of these carcinomas. In this work, we attempt to annotate viable attributes in oral cancer gene datasets for identification of gingivobuccal cancer (GBC). We further apply supervised and unsupervised machine learning methods to the gene datasets revealing key candidate attributes for GBC prognosis. Our work highlights the importance of automated identification of key genes responsible for GBC that could perhaps be easily replicated to other forms of oral cancer detection.

Mutations within the hepatitis B virus (HBV) genome have been associated with rapid progres-sion to hepatocellular carcinoma (HCC); however, there is limited information regarding the prevalence and impact of these mutations in most of sub-Saharan Africa, including Botswana. We aimed to determine the prevalence of HBV mutations known to be associated with progression to HCC using a retrospective, cross-sectional analysis of 48 previously generated HBV sequences from adults with concomitant HBV/HIV initiating HIV antiretroviral therapy in Botswana. The sequences were aligned with reference sequences, and HCC-associated mutations were manually identified using BioEdit. Sixteen (33.3 %) of 48 participant samples had 20 HCC-associated mu-tations. Seven HCC mutations were present in the core region, 4 in the preCore region, 7 in the X region, and one mutation in the surface region, as well as deletions within the preSurface 1 region. Seven of the 16 participants (43.8%) had multiple HCC-associated mutations. There were also previously uncharacterized mutations at positions with known HCC-associated mutations. HCC-associated mutations were common in this cohort; hence, some participants may require close clinical monitoring as they might be more prone to rapid disease progression. Other functionally uncharacterized polymorphisms were also detected and require characterization in future studies.

Human Perrault syndrome (PRLTS) is defined by autosomal recessive inheritance with primary ovarian insufficiency and early hearing loss. Most PRLTS disease proteins modulate mitochondrial transcription or translation. Among the genetic causes are ClpP mutations, which trigger also complete azoospermia, whose cellular and molecular underpinnings are unknown. Here, the ClpP-null mouse model was studied by global transcriptomics, proteomics, RT-qPCR, immunoblots, tissue fractionation, testis histology, and was crossed with STING/IFNAR mutants. Spermatogenesis showed accumulated early spermatocytes, versus deficits of desynapsis and kinetochore factors; excess Dazl/Stra8 and acetylSMC3, versus deficient SHCBP1L, were molecular correlates. Spermiogenesis showed few round spermatids, tsHMG/TFAM in elongated spermatids was absent; transcripts for tail/acrosome factors were downregulated from start. Nuclear anomalies included a failed Rec8 induction, early BRDT deficiency, histone H3 cleavage, and cGAMP increase, among antiviral responses typical of ClpP-mutants. However, deletion of downstream innate immune signals STING/IFNAR failed to reestablish fertility. As mitochondrial triggers, we observed accumulation of ClpX, with PTCD1, POLDIP2, GRSF1, ALKBH7, DNAJA3, AURKAIP1, VWA8, and Perrault proteins ERAL1, PEO1, HARS2, partially showing nuclear redistribution. ClpP-depletion is known to cause extra-mitochondrial release of mispacked mtDNA/mtRNA/protein complexes. Now we define nuclear inflammatory responses and meiotic arrest as consequences, similar to observations in mito-mice and mutator-mice.

Human Perrault syndrome (PRLTS) is defined by autosomal recessive inheritance with primary ovarian insufficiency and early hearing loss. Most PRLTS disease proteins modulate mitochondrial transcription or translation. Among the genetic causes are ClpP mutations, which trigger also complete azoospermia, whose cellular and molecular underpinnings are unknown. Here, the ClpP-null mouse model was studied by global transcriptomics, proteomics, RT-qPCR, immunoblots, tissue fractionation, testis histology, and was crossed with STING/IFNAR mutants. Spermatogenesis showed accumulated early spermatocytes, versus deficits of desynapsis and kinetochore factors; excess Dazl/Stra8 and acetylSMC3, versus deficient SHCBP1L, were molecular correlates. Spermiogenesis showed few round spermatids, tsHMG/TFAM in elongated spermatids was absent; transcripts for tail/acrosome factors were downregulated from start. Nuclear anomalies included a failed Rec8 induction, early BRDT deficiency, histone H3 cleavage, and cGAMP increase, among antiviral responses typical of ClpP-mutants. However, deletion of downstream innate immune signals STING/IFNAR failed to reestablish fertility. As mitochondrial triggers, we observed accumulation of ClpX, with PTCD1, POLDIP2, GRSF1, ALKBH7, DNAJA3, AURKAIP1, VWA8, and Perrault proteins ERAL1, PEO1, HARS2, partially showing nuclear redistribution. ClpP-depletion is known to cause extra-mitochondrial release of mispacked mtDNA/mtRNA/protein complexes. Now we define nuclear inflammatory responses and meiotic arrest as consequences, similar to observations in mito-mice and mutator-mice.

Background: Fullerenes and metallofullerenes can be considered promising nanopharmaceuticals themselves and as a basis for chemical modification. As reactive oxygen species homeostasis plays a vital role in cells, the study of their effect on genes involved in oxidative stress and anti-inflammatory response is of particular importance. Methods: Human fetal lung fibroblasts were incubated with aqueous dispersions of C60, C70, and Gd@C82 in concentrations of 5 nM and 1.5 µM for 1, 3, 24, and 72 hours. Cell viability, intracellular ROS, NOX4, NFκB, PRAR-γ, NRF2, heme oxygenase 1, and NAD(P)H quinone dehydrogenase 1 expression have been studied. Results &amp; conclusion: The aqueous dispersions of C60, C70, and Gd@C82 fullerenes are active participants in ROS homeostasis. Low and high concentrations of AFDs have similar effects. C70 was the most inert substance, C60 was the most active substance. All AFDs have both a “prooxidant” and “antioxidant” effect, but with a different balance. Gd@C82 was a substance with more pronounced antioxidant and anti-inflammatory properties, while C70 had more pronounced “prooxidant” properties.

Ecology is working to face its colonial roots and institutional inequities. As we build more diverse, equitable, and inclusive (DEI) institutions we must work to support new ecologists by empowering them with the knowledge and tools to succeed. Undergraduate research experiences (UREs) are critical for a student’s professional and interpersonal skill development and key for recruiting more diverse groups of students to ecology. Here, we highlight DEI dimensions of a URE in ecology, acknowledge safety considerations for field ecology, including harassment and assault, and provide tools to support the URE. This is written primarily for all URE students and secondarily for their advisors. We welcome students from underrepresented groups and encourage allyship from students from non-underrepresented groups. After reading this paper, we hope that all students feel more confident and excited about their URE and that advisors see how to improve DEI in their lab.

Although researchers have investigated widely the impact of IOD phases on human lives, only a few have examined such impacts on fisheries. In this study, we analyzed the influence of negative (positive) of IOD on a chlorophyll a (Chl-a) concentration as an indicator of phytoplankton biomass and small pelagic fish production in the eastern Indian Ocean (EIO) off Java. We also conducted field surveys in the EIO off Palabuhanratu Bay at the peak (October) and the end (December) of the 2019 positive IOD phase. Our findings show that the Chl-a concentration had a strong and robust association with the 2016 (2019) negative (positive) IOD phases. The negative (positive) anomalous Chl-a concentration in the EIO off Java associated with the negative (positive) IOD phase induced strong downwelling (upwelling), leading to the preponderant decrease (increasing) of small pelagic fish production in the EIO off Java.

IoT system becomes hot topic nowadays for smart home, IoT helps devices to communicate together without human intervention inside home, so it is offering many challenges. A new smart home IoT platform powered using electromagnetic energy harvesting is proposed in this paper. It contains a high gain transmitted antenna array and efficient circular polarized array rectenna system to harvest enough power from any direction to increase life time of the batteries used in IoT system. Optimized energy consumption, the software with adopting the Zigbee protocol of the sensor node and low power microcontroller are used to operate in lower power modes. The proposed system has an 84.6 days lifetime which is approximately 10 times the lifetime for similar system. On the other hand, the proposed power management circuit operated at 0.3 V DC to boost the voltage to ~3.7V from radio frequency energy harvesting and manage battery level to increase the batteries lifetime. A predictive indoor environment monitoring system is designed based on a novel hybrid system to provide a non-static plan, approve energy consumption and avoiding failure of sensor nodes in smart home.

In this paper we describe a nonparametric maximum likelihood (NPML) method for estimating multivariate mixing distributions. Given $N$ independent observations, convexity theory shows that the NPML estimator is discrete with at most $N$ support points. The original infinite NPML problem then becomes the finite dimensional problem of finding the location and probability of the support points. The probability of the support points is found by a Primal-Dual Interior-Point method; the location of the support points is found by an Adaptive Grid method. Our method is able to handle high-dimensional and complex multivariate mixture models.An important application is discussed for the problem of population pharmacokinetics and a non-trivial example is treated.Our algorithm has been successfully applied in hundreds of published pharmacometric studies. In addition to population pharmacokinetics, this research also applies to empirical Bayes estimation and many other areas of applied mathematics.

Background: Glioblastoma remains a challenging brain tumor to treat due to its infiltrative nature. Accurately identifying tumor boundaries during surgery is crucial for successful tumor resection. This study introduces an innovative intraoperative visualization method utilizing a surgical fluorescence microscope to precisely locate tumor cells. The focus of the study is on IR-Glint, a novel preparation comprising Cy7.5-labeled aptamers Gli-233nt and Gli-55_3L specific to human glioblastoma. Methods: The aptamers were modified using molecular modeling and quantum chemical techniques. The effectiveness of the preparation was assessed using flow cytometry and microscopy on primary cultures of human glioblastoma. In vivo studies were conducted on mouse and rabbit models, employing orthotopic xenotransplantation of human brain glioblastoma with various imaging techniques, including PET/CT, in vivo fluorescence visualization, confocal laser scanning, and surgical microscopy. Results: The experiments validated the potential of IR-Glint for intraoperative visualization of glioblastoma using infrared imaging. Surface application of the aptamer-based formulation on the brain allowed clear visualization of the tumor, aiding surgeons in tumor resection. This approach also reduces the dosage required and mitigates potential toxic effects on the patient. Conclusions: This study demonstrates the promising potential of using in-frared dye-labeled aptamers for intraoperative visualization of glioblastoma. By improving surgical treatment outcomes in neurosurgery, this novel approach may pave the way for future advancements in the field.

The photophysical properties of Cu(II) complexes with 5,10,15,20-meso-tetrakis(phenyl)porphyrin and 5,10,15,20-meso-tetrakis(N-methylpyridium-4-yl)porphyrin were examined by luminescence and femtosecond time-resolved absorbance methods respectively. These studies were supported by DFT and TD-DFT calculations which highlight the important role played by a ligand-to-metal charge-transfer states in directing the system towards either intersystem crossing to the triplet hypersurface or coordinative expansion to a five-coordinate quasi-stable intermediate. The latter processes occurs when the porphyrin is photolyzed in the presence of suitably located Lewis bases. Femtosecond time resolved absorbance measurements on Cu(II)-5,10,15,20-meso-tetrakis(N-methylpyridium-4-yl)porphyrin confirm that the coordinative expansion in water occurs in approximately 700 fs while crossing to the triplet hypersurface takes approximately 140 fs in the same solvent. These processes are mutually exclusive, but both can occur simultaneously depending on the environment of the porphyrin. The ratio of the two processes depends on the relative orientation of the Lewis base with respect to the copper atom at the time of excitation. As a consequence, copper porphyrins such as these, are excellent probes to the environment of the porphyrin, and can be used to identify the location of the porphyrin when interacting with DNA fragments.

Background: Dietary quality and the consumption of antioxidant-rich foods has been shown to protect against memory decline. Therefore, this double-blind, randomized, placebo-controlled study aimed to investigate the effects of a nutritional supplement on changes in cognitive performance. Methods: In adults aged 40 to 70 years with subjective memory complaints, participants were randomly allocated to take a supplement containing vitamin E, astaxanthin, and grape juice extract daily for 12 weeks or a matching placebo. The primary outcomes comprised changes in cognitive tasks assessing episodic memory, working memory, and verbal memory. Secondary and exploratory measures included changes in the speed of information processing, attention, and self-report measures of memory, stress, and eye and skin health. Moreover, changes in plasma concentrations of brain-derived neurotrophic factor, malondialdehyde, tumor-necrosis factor-α, and interleukin-6 were measured, along with changes in skin carotenoid concentrations. Results: compared to the placebo, nutritional supplementation was associated with larger improvements in episodic memory, a self-report measure of everyday memory, increased plasma brain-derived neurotrophic factor, decreased plasma malondialdehyde, and increased skin carotenoid concentrations. However, there were no group differences in changes in the remaining outcome measures. Conclusions: Twelve weeks of supplementation with a nutritional supplement was associated with improvements in episodic memory and several biological markers associated with cognitive health. Future research will be essential to extend and validate the current findings.

Gene regulation is vital for cellular function and homeostasis, involving diverse mechanisms controlling specific gene products and contributing to tissue-specific gene expression. Dysregulation leads to diseases, emphasizing the need for understanding these mechanisms. Non-coding regions, notably enhancers and super-enhancers (SEs), act as crucial gene regulators, orchestrating transcriptional activity via transcription factors (TFs). SEs, with high activity, are pivotal in cell identity and disease progression. Current computational approaches focus on individual regulators like TFs and miRNAs, neglecting SE interactions. We emphasize incorporating SEs into models to enhance understanding. Experimental studies have recently linked miRNAs and TFs to SEs. Chromatin immunoprecipitation followed by sequencing (ChIP-Seq) provides valuable SE information. In this review, we categorize computational methods leveraging TF and miRNA data into three areas and explore challenges integrating enhancers/SEs. These include unraveling indirect regulatory networks, identifying network motifs, and enriching pathway identification by dissecting gene regulators, including SEs. We hypothesize that addressing these challenges will enhance our understanding of gene regulation, aiding in identifying therapeutic targets and disease biomarkers. We believe that understanding the role of ChIP-Seq data in predicting the effect of miRNA on gene regulation is crucial to construct statistical/computational model that would tackle these challenges.

Vision impairment may delay responses to hazards when driving. In a proof-of-concept driving simulator study, we evaluated a hazard warning device designed for vision impaired drivers. Three groups participated: 11 persons with central vision loss (CVL; median age 60 years), 12 with homonymous field loss (HFL; 52 years) and 11 with normal vision (NV; 60 years). CVL is characterised by impaired visual acuity and contrast sensitivity while HFL is a loss of vision in the same half of the visual field (blind side) in both eyes. Participants completed drives with and without the device which gave a directional vibro-tactile warning for an approaching pedestrian hazard when collision risk exceeded a pre-defined threshold. Warnings significantly (p< 0.001) reduced brake response times for CVL (∆= 0.54s) and HFL (∆= 0.30s), but not NV participants. For HFL participants, the reduction was greater (p = 0.02) for hazards on the blind (∆= 0.57s) than seeing side (∆= 0.10s). The warnings significantly reduced collision rates for CVL participants from 11 to 0% (all hazards) and for HFL participants from 30 to 1.7% (blind side hazards). Thus, hazard warnings may be beneficial in improving safety of vision impaired drivers; further research is warranted.

Button batteries pose a significant threat to young children and are found in many household items and children’s toys. Along with product manufacturers and retailers, parents and caregivers have a role in button battery ingestion prevention through vigilance regarding items containing button batteries in the home, and knowledge of button battery ingestion symptoms. There is limited information available about parent and caregiver perspectives towards button battery safety. Identifying the areas where increased education is required is important for informing safety campaigns and delivering targeted education. This study aimed to examine parent and caregiver elemental perspectives on button battery safety. One hundred and seventy-four parents and caregivers of children aged 0 to 5 completed a cross-sectional online survey. Distribution occurred via social media. The survey contained multiple-choice questions pertaining to button battery perspectives, and one open-ended question. Respondents recognized the dangers of button battery ingestion, yet only 37% reported being familiar with button battery ingestion symptoms. While 68% knew of household items containing button batteries, only 21% were aware of product recall information sources. Approximately 64% understood immediate post-ingestion steps and 17% found current safety labels unsatisfactory. In an open-ended question, parents and caregivers provided comments about button battery safety that revealed five broad themes; supervision and education; safe storage of button batteries in the home; ensuring children cannot access button batteries; disposing of button batteries safely; and avoiding purchasing items containing button batteries. This study provides a foundation for ongoing investigation of parent and caregiver perspectives on button battery home safety.

Introduction: The predictive value of the risk stratification scales in elderly patients with IPAH might differ from that in younger. It is unknown whether young and older IPAH patients have the same survival dependence on PAH-specific therapy numbers. The aim of the study was to evaluate the prognostic relevance of risk stratification scales and PAH medication numbers in elderly in comparison with young IPAH patients. Material and methods: 119 patients from a prospective single-center PAH registry were divided on to group I <60 years old (n=89) and group II ≥60 years old (n=30). ESC/ERS, REVEAL, and REVEAL 2.0 risk stratification scores were assessed at baseline, as well as H2FpEF- score and survival at follow-up. Results: During a mean follow-up period of 2.9 years (1.63; 6.0) 42 (35.3%) patients died; at 1, 2, 3, 5, 7, and 10 years survival was 95%, 88.6%, 78.5%, 61.7%, 48.5% and 33.7%, respectively. No survival difference was observed between the two groups despite the use of monotherapy in elderly patients. The best predictive value exhibited the REVEAL in group II (IPAH patients ≥60 years) - AUC 0.73 (0.56-0.91), p = 0.03; and in patients with LHD comorbidities in the entire cohort - AUC 0.73 (0.59-0.87), p<0.009. Factors independently associated with death in the entire cohort were CKD (p=0.01, HR 0.2), the right-to-left ventricle dimension ratio (p=0.0047, HR 5.97), and NT-proBNP >1400 pg/ml (p=0.008, HR 3.18). Conclusion: Risk stratification in elderly IPAH patients requires a fundamentally different approach than that of younger patients, taking into account the initial limitations in physical performance and comorbidities that interfere with current assessment scores. The REVEAL score reliably stratifies patients at any age and LHD comorbidities. The initial monotherapy seems to be reasonable in patients over 60 years. Selection tools for initial combination PAH therapy in older IPAH patients with comorbidities need to be validated in prospective observational studies.

The functionalization of copolyfluorenes containing dicyanophenanthrene units by closo-decaborate anion is described. Target copolyfluorenes were analyzed using UV-vis, luminescence, NMR and Fourier-transform infrared (FTIR) spectroscopy. The effect of complexation with the closo-decaborate anion on the photophysical properties was studied both experimentally and theoretically. The PL data indicate an efficient charge transfer from fluorene to the dicyanophenanthrene units coordinated to closo-decaborate. The coordination of closo-decaborate clusters to the nitrile groups of copolyfluorenes provides an important route to new materials for sensors and light-emitting devices while at the same time serving as a platform for further study of the nature of boron clusters.

The microbiome, once considered peripheral, is emerging as a relevant player in the intricate web of factors contributing to cancer development and progression. These often overlooked microorganisms, in the context of urological malignancies, have been investigated primarily focusing on the gut microbiome, while exploration of urogenital microorganisms remains limited. In light of this, our systematic review delves into the complex role of these understudied actors in various neoplastic conditions, including prostate, bladder, kidney, penile, and testicular cancers. Our analysis found a total of 37 studies, with prostate cancer-12, bladder cancer-20, kidney cancer-4, penile/testicular cancer-1, which reveals distinct associations specific to each condition, hinting at potential therapeutic avenues and future biomarker discoveries. It becomes evident that further research is imperative to unravel the complexities of this domain and provide a more comprehensive understanding.

Metagenomic analysis of mosquitoes allows the genetic characterization of mosquito-associated viruses in different regions of the world. This study applied the metagenomic approach to search for novel viral sequences in seven species of mosquitoes collected from the Novosibirsk region of Western Siberia. Using NGS sequencing, we identified 15 coding-complete viral polyproteins (genomes) and 15 viral-like partial sequences in mosquitoes. The complete sequences for novel viruses or partial sequences of capsid proteins, hypothetical viral proteins, and RdRp were used to identify their taxonomy. The novel viral sequences were classified within the orders Tymovirales and Picornavirales, the families Partitiviridae, Totiviridae, Tombusviridae, Iflaviridae, Nodaviridae, Permutotetraviridae, Solemoviridae, with several attributed to four unclassified RNA-viruses. The main part of the novel putative viruses and viral sequences was associated with Coquillettidia richardii mosquito. This study is intended to increase our understanding of viral diversity in mosquitoes found in the natural habitats of Siberia, characterized by very long, snowy, and cold winters.

Background: Early rehabilitation is an important strategy for the treatment of severe diseases. The study aimed to assess the efficacy of early rehabilitation of patients with mild-to-moderate COVID-19. Methods: The retrospective single-center study with propensity score matching. Results: 180 patients (54 (44 - 62.3) yo) divided into three equal groups: 1 - physical exercises; 2 - physical exercises and chest massage in an electrostatic field; 3 - no rehabilitation. The length of stay (LOS) in the hospital in group 1 was 14 (11-15) days, group 2 - 13 (11-15) days, group 3 - 15 (13-18) days, p=0.0026. Physical exercises for patients with CT-1 improved the quality of life, assessed by the EQ-5D questionnaire, by reducing the level of anxiety and depression. The Hazard Ratio (HR) for desaturation (<93%) was 2.34 (95% Confidence Interval (CI) 1.18-4.63) for group 2, p=0.001. The HR for C-reactive protein level above 50 mg/l in patients with CT-2 was 2.33 (95% CI 1.56-3.47), p=0.0001. Conclusions: Rehabilitation programs are safe for СOVID-19-patients; reduce hospital LOS; improve the quality of life. Continuous monitoring of a patient's condition during rehabilitation is essential. ClinicalTrials.gov ID: NCT0580836

Abstract: The study aimed to investigate the antitumor efficacy of anti-LMP1 antibodies in EBV-positive nasopharyngeal and stomach cell lines and xenograft models. The study also exam-ined the NF-κB expression and cell cycle activation of NPC serum exosome-associated LMP1. An-ti-LMP1 antibody treatment before or during cell implantation prevented tumor growth in nude mice. A small dose of antibodies resulted in complete tumor regression for at least three months af-ter the tumors had grown in size. The consumption of antigen-antibody complexes by tumor cells limited tumor growth. In vitro experiments showed that anti-LMP1 antibodies killed EBV-positive NPC- or GC-derived epithelial cell lines and EBV-positive human B cell lines but not EBV-negative cell lines. Treatment with anti-LMP1 reduced NF-κB expression in cells. The animal model experi-ments showed anti-LMP1 inhibited and prevented NPC- or GC-derived tumor growth. The results suggest that LMP1 antibody immunotherapy could cure nasopharyngeal cancer, EBV-positive gastric carcinoma, and EBV-associated lymphomas. However, further validation of these findings is required through human clinical trials.

This paper investigates the density, phase composition, microstructure and mechanical properties (microhardness, fracture toughness) of binderless WC + SiC ceramics obtained by conventional pressureless sintering (CPS) and Spark Plasma Sintering (SPS). α-WC nanopowders obtained by DC arc plasma chemical synthesis and β-SiC powders have been used as raw materials. The content of SiC particles was 1, 3, 5% wt. Excess graphite (0.3, 0.5% wt.) was added to α-WC nanopowders to decrease the volume fraction of W2C particles that negatively affect the mechanical properties of ceramics. WC + 1% wt. SiC + 0.3% wt. C ceramics are shown to have a homogeneous fine-grained microstructure, high relative density, increased microhardness and Palmquist fracture toughness. The CPS and SPS activation energies of WC + SiC nanopowders at an intensive shrinkage stage are determined using the Young-Cutler model. The effect of carbon and SiC particles on the CPS and SPS activation energies of tungsten carbide nanopowders has been analyzed. The CPS activation energies of WC, WC + C and WC + SiC + C nanopowders are shown to be closer to the carbon diffusion activation energy along α-WC grain boundaries. The SPS activation energies of WC and WC + SiC nanopowders turn out to be lower than the carbon grain boundary diffusion activation energy of α-WC.