Breast cancer develops upon sequential acquisition of driver mutations in mammary epithelial cells; however how these mutations collaborate to transform normal cells remains unclear in most cases. We aimed to reconstitute this process in a particular case. To this end, we combined the activated form of the PI 3-kinase harboring the H1047R mutation with the inactivation of the histone lysine methyl-transferase KMT2D in the non-tumorigenic human mammary epithelial cell line MCF10A. We found that PI 3-kinase activation promoted cell cycle progression, especially when growth signals were limiting, as well as cell migration, both in a collective monolayer and as single cells. Furthermore, we showed that KMT2D inactivation had relatively little influence on these processes, except for single cell migration that KMT2D inactivation promoted in synergy with PI 3-kinase activation. Combination of these two genetic alterations induced expression of the ARPC5L gene that encodes a subunit of the Arp2/3 complex. ARPC5L depletion fully abolished the enhanced migration persistence exhibited by double-mutant cells. Our reconstitution approach in MCF10A has thus revealed both the cell function, single cell migration, and the underlying Arp2/3-dependent mechanism, which are synergistically regulated when KMT2D inactivation is combined with the activation of the PI 3-kinase.

IntroductionGlycogen synthase kinase 3 (GSK-3) has been associated with a lot of diseases, such as Alzheimer’s Disease and diabetes. Its role in depression is connected to stress and neuroinflammation. Lithium is an essential inhibitor of GSK-3. Some studies have suggested that the use of this psychiatric medication may lower suicide rates. Here, we outline the current understanding and discoveries regarding the link between GSK-3 and suicide. MethodWe used the PRISMA statement and defined the PECOS strategy, such as Population (P) = individuals; exposure (E) = GSK-3 alteration function; comparison (C) = without GSK-3 alteration function; outcome (O) = suicide; and study design(S) = all kinds of studies with an association between GSK-3 and suicide.ResultsTwelve studies were included in this review. GSK-3 appears to be related to suicidal behavior by activating inflammatory pathways, activating genes, altering neurotransmission, and increasing impulsivity. Clinical studies do not present robust results that allow defining an epidemiological profile of greater risk for suicidal behavior in association with changes in the functioning of GSK-3.ConclusionThe interference of GSK-3 functioning in suicidal behavior seems inevitable, with solid evidence from laboratory animal studies. However, there is a need for further clinical studies on this crucial topic to answer better some questions about the association between GSK-3 and suicide.

The polyomaviruses are small, non-enveloped DNA tumor viruses that cause serious disease in immunosuppressed people, including progressive multifocal leukoencephalopathy (PML) in patients infected with JC polyomavirus, but the molecular events mediating polyomavirus entry are poorly understood. Through genetic knockdown approaches, we identified phosphoinositide 3’ kinase γ (PI3Kγ) and its regulatory subunit PIK3R5 as cellular proteins that facilitate infection of human SVG-A glial cells by JCPyV, but not by adenovirus, an unrelated small, non-enveloped DNA tumor virus. PI3Kα appears less important for polyomavirus infection than PI3Kγ. CRISPR/Cas9-mediated knockout of PIK3R5 or PI3Kγ inhibited infection by authentic JCPyV and by JC pseudovirus. PI3Kγ knockout also inhibited infection by BK and Merkel Cell pseudoviruses, other pathogenic human polyomaviruses, and SV40, an important model polyomavirus. Reintroduction of the wild-type PI3Kγ gene into the PI3Kγ knock-out SVG-A cells rescued the JCPyV infection defect. Disruption of the PI3Kγ pathway did not block binding of JCPyV to cells or virus internalization, implying that PI3Kγ facilitates some intracellular step(s) of infection. These results imply that agents that inhibit PI3Kγ signaling may have a role in managing polyomavirus infections.

Over the past 10 years, developments in precision oncology have led to a rise in the demand for predictive tools that assist the screening and stratification of patients for treatment. The possibility digitizing tissue slide images has led to the creation of artificial intelligence (AI) and machine learning algorithms in digital pathology, which could ultimately improve patient care. In this context, we assessed a variety of AI-based computational models for digital pathology. In this review, we described the latest AI applications in oncology, current challenges and future prospects.

Mechanical ventilation (MV), used in patients with acute lung injury (ALI), induces diaphragmatic myofiber atrophy and contractile inactivity, termed ventilator-induced diaphragm dysfunction. Phosphoinositide 3-kinase- (PI3K-) is crucial in modulating fibrogenesis during the reparative phase of ALI; however, the mechanisms regulating the interactions among MV, myofiber fibrosis, and PI3K- remain unclear. We hypothesized MV with or without bleomycin treatment would increase diaphragm muscle fibrosis through the PI3K- pathway. Five days after receiving a single bolus of 0.075 units bleomycin intratracheally, C57BL/6 mice were exposed to 6 or 10 mL/kg MV for 8 h after receiving 5 mg/kg of AS605240 intraperitoneally. In wild-type mice, bleomycin exposure followed by MV 10 mL/kg prompted significant increases in disruptions of diaphragmatic myofibrillar organization, transforming growth factor-1, oxidative loads, Masson’s trichrome staining, extracellular collagen levels, positive staining of -smooth muscle actin, PI3K- expression, and myonuclear apoptosis (P < 0.05). Decreased diaphragm contractility and peroxisome proliferator activated receptor- coactivator-1 levels were also observed (P < 0.05). MV-augmented bleomycin-induced diaphragm fibrosis and myonuclear apoptosis were attenuated in PI3K-γ-deficient mice and through AS605240-induced inhibition of PI3K- activity (P < 0.05). MV-augmented diaphragm fibrosis after bleomycin-induced ALI is partially mediated through PI3K-γ. Therapy targeting PI3K-γ may ameliorate MV-associated diaphragm fibrosis.

Through the half-unit circle area computation using the integration of the corresponding curve power series representation, we deduce a slow converging positive infinite series to $\pi$. However, by studying the remainder of that series we establish sufficiently close inequalities with equivalent lower and upper bound terms allowing us to estimate, more precisely, how the series approaches $\pi$. We use the obtained inequalities to compute up to four-digit denominator, what are in this sense, the best rational numbers that can replace $\pi$. It turns out that the well-known convergents of the continued fraction of $\pi$, $22/7$ and $355/113$ called, respectively, Yuel\"{u} and Mil\"{u} in China are the only ones found. Thus we apply a similar process to find rational estimations to $\pi+e$ where $e$ is taken as the power series of the exponential function evaluated at $1$. For rational numbers with denominators less than $2000$, the convergent $920/157$ of the continued fraction of $\pi+e$ turns out to be the only rational number of this type.

This study analyzed the risk of falls in the elderly and the safety of the environment in a teaching hospital in Brazil. The Morse Falls Scale was used to stratify the risk of falls in 45 hospitalized elderly individuals, and a checklist was used to analyze the hospital environment. The analysis was based on the chi-square test and multiple regression. The moderate risk of falls was predominant (51.1%). The variable age group (p-value = 0.024) showed statistical evidence of association with the risk of falls. However, the multiple regression analysis showed no difference between the age groups and the risk situation for falls. The hospital wards showed an adequate arrangement of furniture, but some aspects had inadequacies, such as objects in the corridors, non-functional bells in some beds, and inadequacy of the toilet bowls in terms of the recommended height, the absence of non-slip flooring and the support bar in some bathrooms. In conclusion, the moderate risk of falls among the elderly and the adequacy of the hospital environment to technical standards were evident, with the exception of failures in the emergency communication system and sanitary installation.

Visceral leishmaniasis (VL) results from infection by the protozoa Leishmania infantum and L. donovani. HIV-coinfected patients may have a relapsing course of VL, even after secondary prophylaxis with amphotericin B. This study investigated whether host factors would explain the relapses. First, susceptibility to amphotericin B of L. infantum isolates was evaluated in vitro. Then, clinical data and the lipid profile of patients with relapsing and non-relapsing VL were assessed. Susceptibility to amphotericin B was similar between the isolates. CD4+ lymphocytes were reduced in both patients in the first episode and with relapsing VL. Still, the strongest blood cell associated with relapses was low total lymphocyte counts. Total plasma cholesterol, high-density lipoprotein, low-density lipoprotein, and, uniquely, triglycerides of the six individuals in the first episode and 23 with relapsing VL were lower in relapsing patients than those in the first episode. Deceased patients had extremely low, low-density lipoprotein. After CD4+ decrease, lymphocyte CD8+ reduction seem to be the final stage of the immunological failure. The lower lipid concentrations appear to be secondary to the depletion of fat stores by inflammation-induced cachexia provoked by the co-occurrence of both diseases, which can finally lead to death.

In this work, we study the dynamical behaviors of the electromagnetic fields and material responses in the hyperbolic metamaterial consisting of periodically arranged metallic and dielectric layers. The thickness of each unit cell is assumed to be much smaller than the wavelength of the electromagnetic waves, so the effective medium concept can be applied. When electromagnetic (EM) fields are present, the responses of the medium in the directions parallel to and perpendicular to the layers are like that of Drude and Lorentz media, respectively. We derive the energy density of the EM fields and the power loss in the effective medium based on Poynting theorem and the dynamical equations of the polarization field. We also show that the Lagrangian density of the system can be constructed. The Euler-Lagrangian equations yield the correct dynamical equations of the electromagnetic fields and the polarization field in the medium. The canonical momentum conjugates to every dynamical field can be derived from the Lagrangian density via differentiation or variation with respect to that field. We apply Legendre transformation to this system, and find that the resultant Hamitonian density is identical to the energy density, up to an irrelevant divergence term.

Embryo stage of oxidation of an epi Ge(001)-2×1 by atomic oxygen and molecular O₂ is studied via synchrotron radiation photoemission. The topmost surface buckled with the up- and down-dimer atoms and the first subsurface layer behave distinctly from the bulk by exhibiting surface core-level shifts in the Ge 3d core-level spectrum. The O₂ molecules become dissociated upon reaching the epi Ge(001)-2×1 surface. One of the O atom removes off the up-dimer atom, and the other bonds with the underneath Ge atom in the subsurface layer. Atomic oxygen adsorbed on the epi Ge(001)-2×1 preferentially in between the up-dimer atoms and the underneath subsurface atoms without affecting the down-dimer atoms. The electronic environment of the O-affiliated Ge up-dimer atoms becomes similar to that of the down-dimer atoms. Both exhibit an enrichment in charge, where the subsurface of the Ge layer is maintained in a charge-deficient state. The dipole moment originally generated in the buckled reconstruction no longer exists, thereby resulting in a decrease in the ionization potential. The down-dimer Ge atoms and the back-bonded subsurface atoms remain inert to atomic O and molecular O₂, a possible cause of low reliability in Ge-related metal-oxide-semiconductor (MOS) devices.

Cholangiocellular carcinoma (CCA) is the second most common primary liver cancer, with increasing incidence worldwide and inadequate therapeutic options. Intra- and extrahepatic bile ducts have distinctly different embryonic origins and developmental behavior, and accordingly intra- and extrahepatic CCAs (ICC vs. ECC) are molecularly different. A promising strategy in oncotherapy is targeted therapy, targeting proteins that regulate cell survival and proliferation; such as the MAPK/ERK and PI3K/AKT/mTOR signaling pathways. Inhibitors of these pathways have been tested previously in CCA cell lines. However, these cell lines could not be clearly assigned to ICC or ECC, and results indicated apoptosis induction by targeted therapeutics. We tested targeted therapeutics (selumetinib, MK2206) in three defined ICC cell lines (HuH28, RBE, SSP25). We observed cooperative effects of dual inhibition of the two pathways, in accordance with inhibition of phospho-AKT and phospho-ERK1/2 expression. Proliferation was blocked more effectively with dual inhibition than with each single inhibition, but cell numbers did not drop below baseline. Accordingly, we observed G1-phase arrest, but not apoptosis (cleaved caspase-3, AIFM1 regulation, subG1-phase) or necroptosis (phospho-MLKL). We conclude that dual inhibition of MAPK/ERK and PI3K/AKT/mTOR pathways is highly effective to block proliferation of ICC cell lines, but therapy must certainly be supplemented with standard therapies.

This paper introduces a rigorous and comprehensive approach for the assessment of marine shafting systems through the utilization of an advanced Pi-Theorem based scaling methodology. Integrating journal bearing similarity assessment and shaft-line scaling methodology with advanced dimensional analysis, the study aims to provide a methodology foundation for systematic replication and analysis of marine shafting systems through scaled models. The proposed scaling methodology ensures geometric and mechanical similarity in terms of shaft-line deflection, considering key scaling parameters such as shaft length, diameter, weight, loads, rotational speed, material properties, bearing locations, and offsets. The advanced dimensional analysis computes specific non-dimensional ratios to guarantee a close resemblance between a real-size system and a scaled lab model, enabling meaningful experimentation. The methodology is analytically derived and validated with numerical simulations for a case study, conducting comparative analysis, evaluating discrepancies, and utilizing the integrated framework for experimentation.

This research aims to apply Artificial Intelligence (AI) methods, specifically Artificial Immune Systems (AIS), to design an optimal control strategy for a multivariable control plant. Two specific industrial control approaches are investigated: I-PD (Integral-Proportional Derivative) and PI-D (Proportional-Integral Derivative) control. The motivation for using these variations of PID controllers is that they are functionally implemented in modern industrial controllers, where they provide precise process control. The research results in a novel solution to the control synthesis problem for the industrial system. In particular, the research deals with the synthesis of I-P control for a two-loop system in the technological process of a distillation column. This synthesis is carried out using the AIS algorithm, which is the first application of this technique in this specific context. Methodological approaches are proposed to improve the performance of industrial multivariable control systems by effectively using optimization algorithms and establishing modified quality criteria. The numerical performance index ISE justifies the effectiveness of the AIS-based controllers in comparison with conventional PID controllers (ISE₁ = 1.865, ISE₂ = 1.56). The problem of synthesis of the multi-input multi-output (MIMO) control system is solved, considering the interconnections due to the decoupling procedure.

A novel flexible humidity sensor, incorporating gold nanoparticles (Au NPs) and a trifunctional organosilica compound, has been developed through the integration of sol-gel processing, free radical polymerization, and self-assembly techniques. The trifunctional organosilica was initially synthesized by modifying (3-mercaptopropyl)trimethoxysilane (thiol-MPTMS) with 3-(trimethoxysilyl)propyl methacrylate (vinyl-TMSPMA). Subsequently, a hydrophilic polyelectrolyte, [3(methacryloylamino)propyl]trimethyl ammonium chloride (MAPTAC), was grafted onto the MPTMS-TMSPMA gel. The Au NPs were assembled onto the thiol groups present in the MPTMS-TMSPMA-MAPTAC gel network. The compositional and microstructural properties of the Au NPs/MPTMS-TMSPMA-MAPTAC composite film were investigated utilizing Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The presence of thiol groups and mesoporous silica skeletons ensured the stability of the humidity-sensing film on the substrate under highly humid conditions, while the hydrophilic groups functioned as humidity-sensitive sites. This innovative humidity sensor demonstrated high sensitivity, acceptable linearity, minimal hysteresis, and rapid response time across a broad range of working humidity levels. Based on the complex impedance spectra analysis, hydronium ions (H₃O⁺) were determined to govern the conductance process of the flexible humidity sensor.

Background: Older adults with bipolar disorder (OABD) are individuals aged 50 years and older with bipolar disorder (BD). People with BD may have fewer coping strategies or resilience. A long course of the disease, such as in OABD, could impact the development of resilience strategies, but this remains under-researched in OABD. Therefore, this study aims to assess resilience levels within the OABD and explore associated factors, hypothesizing that resilience could improve psychosocial functioning, wellbeing and quality of life of OABD patients. Methods: This study sampled 33 OABD patients from the OABD cohort at the Bipolar and Depressive Disorders Unit of Hospital Clinic of Barcelona. This was an observational, descriptive and cross-sectional study. Demographic and clinical variables as well as psychosocial functioning, resilience and cognitive reserve were analyzed. Resilience was measured using the CD-RISC-10. Non-parametric tests were used for statistical analysis. Results: The average CD-RISC-10 score was 25.67 points (SD 7.87). Resilience negatively correlated with the total number of episodes (p = 0.034), depressive episodes (p = 0.001), and the FAST (p < 0.001). Participants with normal resilience had a lower FAST (p = 0.046), a higher CRASH (p = 0.026), and more EOBD (p = 0.037) compared to those with low resilience. Conclusions: OABD individuals may exhibit lower resilience levels which correlate with more psychiatric episodes, particularly the number of depressions and worse psychosocial functioning and cognitive reserve. Better understanding and characterization of resilience could aid in early identification of patients requiring additional support to foster resilience and enhance OABD management.

Meta-heuristic algorithms are methods that try to solve problems by imitating events and systems existing in nature. It can be very difficult to solve nonlinear problems with the help of known classical algorithms. In this study, a new meta-heuristic method, the Pi algorithm, is proposed. Pi is a special number that is not periodic and contains many different number combinations in its digits calculated so far. The most important part of meta-heuristic methods is the equations and parameters used to ensure the diversity of the created population. In this study, a specific Pi coefficient for each attribute was calculated with the help of the Monte-Carlo method. These coefficients were used in the Pi algorithm in other parts of the study. In the application for data clustering, experiments were made on 5 different data sets. The best accuracy rate of 95.5% was achieved. In this respect, it has been seen that the Pi algorithm works successfully as a meta-heuristic method. It can be studied on a population-based data clustering, classification, prediction, etc. It can be easily applied in all areas.

Buckypaper (BP), a flexible and porous material, exhibits photovoltaic properties when exposed to light. In this study, we have employed Radio Frequency (RF) Sputtering of Zinc Oxide (ZnO) followed by rapid thermal annealing to enhance the photovoltaic response of BP. We investigated the impact of various sputtering parameters, such as the gas flow ratio of argon to oxygen and deposition time, on the morphology, composition, resistivity, and photovoltaic characteristics of ZnO-modified BP. Additionally, the photovoltaic performance of the samples under different illumination modes and wavelengths was compared. It was found that optimal sputtering conditions—argon to oxygen flow ratio of 1:2, deposition time of 20 minutes, and power of 100 watts—resulted in a ZnO film thickness of approximately 45 nanometers. After annealing at 400°C for 10 minutes, the ZnO-modified BP demonstrated a significant increase in photocurrent and photovoltage, along with a reduction in resistivity, compared to unmodified BP. Moreover, under gradient illumination, the ZnO-modified BP exhibited a photovoltage enhancement of 14.70 times and a photocurrent increase of 13.86 times, compared to uniform illumination. Under blue light, it showed a higher photovoltaic response than under other colors. The enhancement in photovoltaic response is attributed to the formation of a Schottky junction between ZnO and BP, an increased carrier concentration gradient, and an expanded light absorption spectrum. Our results validate that ZnO sputtering followed by annealing is an effective method for modifying BP for photovoltaic applications such as solar cells and photodetectors.

In this paper, an adaptive proportional and integral (PI) controller for speed control of electric drives is developed. The adaptive PI controller is designed based on model reference adaptive identification and the Lyapunov function so that the system stability can be proved. To identify the inertia, the viscous friction torque coefficient, and the load torque simultaneously and smoothly, sinusoidal speed reference is usually employed. A modified motion equation considering the low-pass filter for feedback speed and the Coulomb friction torque is introduced and the relationship between the identified parameters and their actual values are clarified. A high-precision digital simulation model is built based on MATLAB/Simulink. The effectiveness of the proposed method is verified by simulations under various conditions.

Enclosed public spaces are the hotspots for airborne disease transmission. To measure and maintain indoor air quality in terms of airborne transmission, an open source, low cost and distributed array of Particulate Matter Sensors has been developed and named as Dynamic Aerosol Transport for Indoor Ventilation or DATIV system. This system can use multiple Particulate Matter Sensors (PMS) simultaneously and can be remotely controlled using a Raspberry Pie based operating system. The data acquisition system can be easily operated using the GUI within any common browser installed on a remote device such as a PC or Smartphone with corresponding IP address. The software architecture and validation measurements are presented together with possible future developments.

Various dietary supplements have been shown to extend the life span of Drosophila melanogaster, including several that promote autophagy, such as rapamycin and spermidine. The goal of the study presented here was to test numerous additional potential anti-aging supplements, primarily inhibitors of the target of rapamycin (TOR) and/or phosphatidylinositol 3-kinase (PI3K). Using a single, comparatively long-lived y w test strain, screening was performed in male flies supplemented either throughout adulthood or in a few cases beginning in middle or late adult life, with concentrations spanning 4-6 orders of magnitude in most cases. Supplementation with PP242 and deferiprone, an iron chelator, beginning in late adult life had no positive effect on life span. Lifelong supplementation with Ku-0063794, LY294002, PX-866-17OH, Torin2 and WYE-28 had no effect at any dose. Rapamycin, spermidine and wortmannin all had significant life-shortening effects at the highest doses tested. AZD8055, PI-103 hydrochloride and WYE-132 yielded slight beneficial effects at 1-2 doses, but only 100 nM AZD8055 was confirmed to have a minor (1.3%) effect in a replicate experiment, which was encompassed by other control groups within the same study. These compounds had no effect on fly fecundity (egg-laying) or fertility (development of progeny to adulthood), but equivalent doses of rapamycin abolished fertility. The solvent DMSO had no significant effect on life span at the concentrations used to solubilize most compounds in the fly medium, but it drastically curtailed both survival and fertility at higher concentrations. 2-hydroxypropyl-β-cyclodextrin also failed to extend the life span when provided throughout adulthood or beginning in mid-adult life. Collectively, the results suggest that inhibition of the TOR/PI3K pathway and autophagy through dietary intervention is not a straightforward anti-aging strategy in Drosophila, and that further extension of life is difficult in comparatively long-lived flies.

Reactions of quinones with compounds containing an amino group can produce a wide variety of addition or substitution products that depend on reactivity of both quinone and amino derivative. 6,7-Dichloropyrido[1,2-a]benzimidazole-8,9-diones undergo selective nucleophilic substitution reaction with different benzohydrazides and α-hydroxy-p-quinone imine derivatives stabilized by strong intramolecular hydrogen bond were isolated. Synthesized compounds represent a combination of several structural motifs: benzimidazole core fused with α-hydroxy-p-quinone imine which contains a benzamido fragment. The protonation/deprotonation processes were investigated in a solution using UV-Vis spectroscopy and 1H NMR titration experiment. X-ray crystallography analysis revealed a set of weak non-covalent interactions such as intra- and intermolecular hydrogen bonds and π-π stacking. Additionally, the redox behavior of 6,7-dichloropyrido[1,2-a]benzimidazole-8,9-dione and its p-imino derivative was investigated in acidic and neutral environment using cyclic voltammetry measurements. Cathode material based on 6,7-dichloropyrido[1,2-a]benzimidazole-8,9-dione could act as potential effective active electrode in aqueous electrolyte batteries, however further optimization is required.

Silicon (Si) is the major material of semiconductor element. For semiconductor element producing, Si need to refined into high-purity silicon crystals, which has the approximate characteristics of intrinsic semiconductor, then doping 13th group or 15th group trace element. Producing the high-purity silicon crystals with well-lattice structure need a lot of energy and highly cost. Besides, the high-purity silicon is very hard and fragile which limits the scope of application. For this reason, this study added low-grade non-complete lattice silicon in the elastic polymer, and then doped with high concentrations of fine carbon powder. This material can be conductive by physisorption;therefore, it can be used to making semiconductors. Using this material to produce electronic components can significantly reduce the cost of purification and crystallization, saving energy at the same time. Moreover, because this elastic polymer materials containing silicon, which has soft, warm, and durable physical properties. With those properties, the design of the device could be more flex, full scalability and close to the skin.

The purpose of this paper is to describe a feature selection algorithm and its application to enhance the accuracy of the reconstruction of phylogenetic trees by improving the efficiency of tree construction. Applying machine learning models for Arabic and Aramaic scripts such as Deep Neural Networks (DNN), Support Vector Machines (SVM) and Random Forests (RF) each model was used to compare the phylogenies. The methodology was utilized with a dataset containing Arabic and Aramaic scripts, demonstrating its relevance in a range of phylogenetic analyses. Results emphasize the essential role of feature selection by DNNs is outperforming other models in terms of Area Under the Curve (AUC) and Equal Error Rate (EER) across various datasets and fold sizes. Additionally, SVM and RF models show important understandings, advantages and limits of each approach within the context of phylogenetic analysis. This method not only simplifies the tree structures but also enhances their Consistency Index. Therefore offering a robust framework for evolutionary studies. The findings highlight the applications of machine learning in phylogenetics suggesting a path toward accurate and efficient evolutionary analyses and adding a deeper understanding of evolutionary relationships.

Aural rehabilitation with hearing aids can decrease the attentional requirements of cognitive resources by amplifying the deteriorated-frequency sound in hearing loss patients and improve the auditory discrimination ability like speech-in-noise perception. As aural rehabilitation with an intelligible-hearing sound also can be hopeful, the aim of this study was to evaluate the effectiveness of the aural rehabilitation with intelligible-hearing sound for hearing loss patients. Adult native Japanese speakers (17 males and 23 females, 68.43±9.23 years) showed over 30 dB at 125, 250, 500, 1000, 2000, 3000, 4000, 8000, 10000, and 12000Hz on any side, were recruited and underwent Mini-Mental State Examination Japanese. we conducted self-evaluation questionnaire for hearing problems of voice, gap detection test, fast speech test, and speech-in-noise test, pure tone audiogram, speech perception test using Japanese 67-S, cortical auditory evoked fields, and magnetic mismatch negativity before and after the non-intelligible-hearing (N=20) and intelligible-hearing (N=20) sound therapy with listening to music for one hour a day for 35 days. Better hearing ear was defined using a four-frequency pure-tone average at the thresholds of 500, 1000, 2000 and 4000 Hz. After the sound therapy, speech-in-noise test with signal to noise ratio +10 in better hearing ear showed significant improvement (p&lt;0.05), and N1m-P2m amplitudes showed the significant increase in Lt superior temporal gyrus at the stimulus from better hearing ear (p&lt;0.05). The significant enhancement of the magnetic mismatch negativity amplitude at Lt superior temporal gyrus was exhibited after the sound therapy (p&lt;0.01). Intelligible-hearing sound therapy can improve the ability of speech-in-noise perception in better hearing ear and the enhancement of central cortex response, which reflect the ability of working memory, was proved by cortical auditory evoked fields and magnetic mismatch negativity. Intelligible-hearing sound therapy can be a valuable aural rehabilitation method for sensory neural hearing loss as same as hearing aids.

ZrO2-YO1.5-TaO2.5(ZYTO) composite ceramic is considered to be the candidate of next generation of thermal barrier coatings as its excellent thermal stability and low thermal conductivity in high temperature, however, the mechanical properties and fracture tougheness of ZYTO system may be the shortcomings compared with the 8YSZ. In this study, ZYTO composite ceramics were successfully prepared by chemical coprecipitation reaction, the microsture of resulting composites were studied as a function of doping of M-YTaO4. Mechanical properties, including the density, porosity, hardness and Young's modulus, are determinate; the toughening mechanism were verified by the crack growth behavior of Vickers indentation test Results suggested that M-YTaO4 refines the fluorite phase grain and strengthens the grain interface in the composite ceramic. The thermal mismatch between the second phase and matrix produces residual stress in the bulk and affects the crack propagation behavior. With the increase of M-YTaO4 doping, the grain coarsening and ferroelastic domains are observed in the experiments. The ferroelastic domains with orthogonal polarization directions near crack tip evidences the ferroelastic toughening mechanism. The competition among these crack behaviors, such as cracks deflection, bridging and bifurcation, dominates the actual fracture toughness of the composite. The best toughening formula is determinate in the two-phase region and the highest fracture toughness is about to 3.1MPa·m1/2. Above all, mechanical properties of ZYTO composite ceramics look potential for thermal barrier coatings materials.

Pore structure characterization and fractal analysis have great significance for understanding and evaluating tight limestone reservoirs. In this work, the pore structure of tight limestone is characterized combined with low-temperature nitrogen adsorption (LTNA) and low-field nuclear magnetic resonance (NMR), and the fractal dimension of tight limestone pore structure is discussed based on LTNA and NMR data. The results indicate that the pores of tight limestone have H3 and H4 types, the pore size distribution (PSD) of H3 type is a wave distribution ranging from 2 to 10 nm, and the PSD of H4 type is a unimodal distribution ranging from 2 to 10 nm. The transverse relaxation time (T2) spectrum of tight limestone shows single peak (DF), double peak (SF) and three peak (TF), and the T2 spectrums for micropores, mesopores and macropores range from 0.1 to 10 ms, from 10 to 100 ms, and greater than 100 ms, respectively. The LTNA fractal dimension of tight limestone (DL) ranges between 2.4446 and 2.7688, with an average of 2.5729, and the NMR fractal dimensions of micropores (DNMR1), mesopores (DNMR2) and macropores (DNMR3) are distributed between 0.3744 to 1.1293, 2.4263 to 2.9395 and 2.6582 to 2.9989, respectively. Moreover, there is no correlation between fractal dimension and permeability and porosity, a negative correlation between DL and average pore radius, a positive correlation between DL and specific surface area, and a positive correlation between DNMR2 and DNMR3 and micropore content, while DNMR2 and DNMR3 are negatively correlated with the content of mesopores and macropores.

A Cu₂ZnSnS₄ (CZTS) film with a thickness of approximately 1.5 μm was fabricated on a Mo-coated glass substrate by annealing a CZTS precursor fabricated from nanoparticle ink. The chemical states of the elements in the CZTS thin film in the depth direction were studied to identify the presence of secondary phases, which are detrimental to the performance of solar cells containing CZTS. X-ray diffraction was unable to detect any secondary phases in CZTS because of their small relative amount. Instead, X-ray photoelectron spectroscopy (XPS), which is highly sensitive to chemical state, was conducted at different depths in the CZTS film to further check the presence of secondary phases. XPS analysis revealed peaks shift consistent with the presence of secondary phases. For the CZTS film annealed in a S atmosphere at 575 °C for 3 h, the film surface consisted of a secondary-phase layer composed of CuS, ZnS, and SnSx (x=1 or 2) originating from the decomposition of CZTS. At depths below 80 nm, the film was pure CZTS. Formation of MoS2 at the CZTS–Mo interface was confirmed by XPS analysis of Mo and S.

A Q-switched Nd:YAG laser was focused on Pb-Ti alloy samples in several Laser Induced Breakdown experiments in order to measure the Stark parameters of several spectral lines (58) of single ionized Titanium including the 3504.89 Å, and the 3510.83 Ålines (where we aported new experimental and theoretical values).Diagnostics of the laser induced plasmas (electron density and electron temperature) was performed using Balmer’s H alpha line (6562.7 Å).Temperatures were obtained by the Boltzmann Plot technique with spectral lines of Pb I (after correction for its evident self-absorption).Subsequently, calculations by the Griem approach of the Stark broadening parameters for several spectral lines were performed using the Gaunt factors proposed by Van Regemorter and those proposed by Douglas H. Sampson. In the latter cases the values obtained were very close to the experimental values. It allows us to assume that the calculations made for the spectral lines of Ti II, without experimental information, are more accurate using the Gaunt factors proposed by Sampson.

This paper aims to present a smart high speed battery charger, powered by a photovoltaic module array, for a LiFePO4 battery as a solar energy storage device. With a battery charging strategy, the presented battery charger involves a Buck converter as the core equipped with a simple maximum power point (MPP) tracker. Considering complexity reduction and easy hardware implementation, a constant voltage MPP tracking approach is adopted such that the maximum amount of output power can be delivered to the load in response to an arbitrary change in the solar radiation. A smart two-stage charging strategy, with a constant current mode followed by a constant voltage mode, is employed in such a way that the battery charge process can be accelerated largely, while the damage caused by overcharging can be prevented. In the end, the performance of this proposal is validated experimentally.

Algal-bacterial granular sludge, a new biological technology, has been widely recognized due to its highly effective pollutant treatment and energy efficiency. This study investigated the effects of environmental concentrations of Cr(VI) (0.5-2.5 mg/L) on the performance of algal-bacterial gran-ular sludge and self-defensive responses after 90 days of cultivation. The results showed that Cr(VI) affected chemical oxygen demand (COD), ammonia-N and phosphate removal with different trends being apparent. A linear decline in COD removal was observed, whereas an initial de-creasing and then increasing ammonia-N and phosphate removal took place. Algal-bacterial granular sludge effectively removed Cr(VI) from wastewater through biological adsorption and reduction, showing the potential to treat Cr(VI)-contaminated wastewater. Cr(VI) affected the community abundance of the algal-bacterial granular sludge, in which Chlorophyceae and cya-nobacteria were vulnerable under Cr(VI)-induced stress. To reduce the toxicity of Cr(VI), over-produced EPS-PN and antioxidant enzymes (MDA, SOD and CAT) acted as self-defensive responses to resist oxidative damage. This study showed that algal-bacterial granular sludge can remove 00.5 mg/L of Cr(VI) without performance loss. It is hoped that this study can provide useful information for improved engineering feasibility of algal-bacterial granular sludge.

This study addresses the urgent need for sustainable protein sources in aquaculture due to the depletion of marine resources and rising costs. Animal protein sources, particularly poultry by-product meal (PBM) and insect exuviae meal, are investigated as viable alternatives to fishmeal (FM). Research confirms the successful replacement of FM with a combination of PBM and insect exuviae meal (up to 50%) in the diet of European seabass without compromising growth, feed conversion, gut health and liver fat content. In particular, growth performance was robust with both PBM formulations, with the 25% PBM diet showing better results. Histological examinations showed good gut and liver health, contradicting the concerns of previous studies. The study emphasizes the importance of holistic analyzes that go beyond growth parameters and include histomorphological investigations. The results show that PBM in combination with insect/exuviae meal is well tolerated by seabass, which is consistent with literature reports of mitigating negative effects on gut health. A detailed analysis of the microbiota revealed a decrease in the Firmicutes/Proteobacteria ratio due to an increase in potentially pathogenic bacteria. However, the formulation containing insect exuviae partially counteracted this effect by preserving the beneficial Lactobacillus and promoting the synthesis of short-chain fatty acids (SCFA), particularly butyrate. Chitin-rich components from insect exuviae were associated with improved gut health, which was supported by increased production of SCFA, which are known for their anti-inflammatory properties. The study concludes that a combination of PBM and insect/exuviae meal can replace up to 50% of FM in the diet of seabass, supporting sustainable aquaculture practices. Despite some changes in the microbiota, the negative effects are mitigated by the addition of insect exuviae, highlighting their potential as a prebiotic to increase fish productivity and contribute to a circular economy in aquaculture.

More than 700 thousand human deaths from mosquito bites are observed annually in the world. It is more than 2 times the number of annual murders in the world. In this regard, the invention of new more effective methods of protection against mosquitoes is necessary. In this article for the first time, comprehensive studies of mosquito neutralization using machine vision and a 1 W power laser are considered. Developed laser installation with Raspberry Pi that changing the direction of the laser with a galvanometer. We developed a program for mosquito tracking in real. The possibility of using deep neural networks, Haar cascades, machine learning for mosquito recognition was considered. We considered in detail the classification problems of mosquitoes in images. A recommendation is given for the implementation of this device based on a microcontroller for subsequent use as part of an unmanned aerial vehicle. Any harmful insects in the fields can be used as objects for control.

This manuscript presented an autonomous home farm for predicting metrological characteristics that can not only automate the process of growing crops but also, due to a neural network, significantly increase the productivity of the farm. The developed farm monitors and manages the following indicators: illumination, soil PH, air temperature, earth temperature, air humidity, CO2 concentration, and soil moisture. The presented farm can also be considered as a device for testing various weather conditions to determine the optimal temperature characteristics for different crops. This farm as a result is completely autonomous grows tomatoes at home.

The treatment of the bulky Rind-based dibromosilanes, (Rind)2SiBr2 (2) [Rind = 1,1,7,7-tetra-R1-3,3,5,5-tetra-R2-s-hydrindacen-4-yl: EMind (a: R1 = Et, R2 = Me) and Eind (b: R1 = R2 = Et)], with two equivalents of tBuLi in Et2O at low temperatures resulted in the formation of blue solutions derived from the diarylsilylenes, (Rind)2Si: (3). Upon warming the solutions above −20 °C, the blue color gradually faded, accompanying the decomposition of 3 and yielding the cyclic hydrosilanes (4) via intramolecular C−H bond insertion at the Si(II) center. The molecular structures of the bulky Eind-based 3b and 4b were confirmed by X-ray crystallography. Thus, at −20 °C, blue crystals were formed (Crystal-A), which were identified as mixed crystals of 3b and 4b. Additionally, colorless crystals of 4b as a singular component were isolated (Crystal-B), whose structure was also determined by an X-ray diffraction analysis. Although the isolation of 3 was difficult due to their thermally-labile nature, their structural characteristics and electronic properties were discussed based on the experimental findings complemented by computational results. We also examined the hydrolysis of 3b to afford the silanol, (Eind)2SiH(OH) (5b).

Our recent analysis of empirical limit order flow data in financial markets reveals a power-law distribution in limit order cancellation times. These times are modeled using a discrete probability mass function derived from the Tsallis q-exponential distribution, closely aligned with the second form of the Pareto distribution. We elucidate this distinctive power-law statistical property through the lens of agent heterogeneity in trading activity and asset possession. Our study introduces a novel modeling approach that combines fractional Lévy stable motion for limit order inflow with this power-law distribution for cancellation times, significantly enhancing the prediction of order imbalances. This model not only addresses gaps in current financial market modeling but also extends to broader contexts such as opinion dynamics in social systems, capturing the finite lifespan of opinions. Characterized by stationary increments and a departure from self-similarity, our model provides a unique framework for exploring long-range dependencies in time series. This work paves the way for more precise financial market analyses and offers new insights into the dynamic nature of opinion formation in social systems.

The comprehensive analysis of cross-country skiing races is a pivotal step in establishing effective training objectives and tactical strategies. This study aimed to establish a method for the classifi-cation of sub-techniques and analyzing skiing characteristics during cross-country skiing skating style timed races on snow using high-precision kinematic GNSS devices. The study involved at-taching GNSS devices to the heads of two athletes during skating style timed races on cross-country ski courses. These devices provided precise positional data and recorded vertical and hor-izontal head movements and ground over velocity (VOG). Sub-techniques were classified by de-fining waveform patterns for G2, G3, G4, and G6 based on these data. The validity of classifica-tion was verified by comparing GNSS data with video analysis, a process that yielded classifica-tion accuracies ranging from 94.0% to 99.3% for G2, G3, G4, and G6. Notably, G4 emerged as the fastest technique, with sub-technique selection varying among skiers and being influenced by skiing velocity and course inclination. The study's findings have practical implications for ath-letes and coaches, as they demonstrate that high-precision kinematic GNSS devices can accurate-ly classify sub-techniques and detect skiing characteristics during skate-style cross-country skiing races, thereby providing valuable insights for training and strategy development.

To stabilize the Earth’s climate a large-scale transition is needed to non-carbon emitting renewable energy technologies like wind and solar energy. Although these renewable energy sources are now lower-cost than fossil fuels, their inherent intermittency make them unable to supply a constant load without storage. To address these challenges rechargeable electric batteries are currently the most promising option; however, their high capital costs limit current deployment velocities. To both reduce the cost as well as improve performance 3D printing technology has emerged as a promising solution. This literature review provides the state-of-the-art enhancements of battery properties with 3D printing including efficiency, mechanical stability, energy and power density, customizability and sizing, production process efficiency, material conservation and environmental sustainability as well as the progress in solid-state batteries. The principles, advantages, limitations, and recent advancements associated with the most common types of 3D printing are reviewed focusing on their contributions to the battery field. 3D printing batteries offer design flexibility, material flexibility, reduces pack weight, minimizes material waste, increases the range of applications and has the potential to reduce costs. As 3D printing technologies become more accessible, the prospect of cost-effective production for customized batteries is extremely promising.

Aquifer Thermal Energy Storage (ATES) systems are garnering attention as high-efficiency air conditioning technologies that contribute to the realization of a carbon-neutral society. This study focuses on an ATES system constructed in Japan, characterized by its complex geological conditions and thin aquifer layers. Through performance analysis using four years of operational data, we achieved a Coefficient of Performance (COP) of 5 on the building load side. This paper confirms the equivalence of the dimensionless production temperature and heat recovery rate, observing nearly identical changes in the dimensionless production temperature over four cycles (eight seasons). Furthermore, we propose an operational method for the following fiscal year that maintains the balance between accumulated storage quantity and pumping volume, based on predictions from this plant's operational pattern.

In recent years there has been an increasing interest in developing novel materials based on natural biopolymers as a renewable alternative of petroleum-based plastics. The availability of proteins derived from agricultural by-products, along with their favourable properties, has fostered a renewed interest in protein-based materials, promoting research in innovative technologies. In this study we propose the use of rapeseed protein-rich meal as main ingredient for the preparation of novel sustainable materials combining excellent environmental properties such as biodegradability and renewable origin. Application as sustainable products in the present high-tech society needs modification of basic native properties of these natural compounds. The original route proposed in this paper consists in the preparation via compression moulding of flexible biomaterials stabilized by crosslinkers/chain extenders. Investigation of the effects of different denaturing and disulfide bond reducing agents, crosslinkers, and preparation conditions on the material mechanical behaviour demonstrated that the novel materials have appreciable strength and stiffness. The results show the potential of utilizing full meal from vegetable by-products to prepare protein-based materials with granted ecofriendly characteristics and mechanical properties adequate to specific structural applications.

The present study was performed to examine that transforming growth factor beta (TGF-β) in root-surrounding tissues on deciduous teeth during the physiological root resorption regulates the differentiation induction into odontoclast. We prepared root-surrounding tissues with (R) or without (N) physiological root resorption scraped off at three regions (R1-R3 or N1-N3) from the cervical area to the apical area of the tooth and measured both TGF-β and the tartrate-resistant acid phosphatase (TRAP) activities. The TGF-β activity level was increased in N1-N3, whereas the TRAP activity was increased in R2 and R3. In vitro experiments for RANKL-mediated osteoclast differentiation revealed that TGF-β in N1-N3 and R1-R3 enhanced the TRAP activity in RAW264 cells. A genetic study indicated that the mRNA level of TGF-β1 in N1 and N2 was significantly increased, and corresponded with that of osteoprotegerin (OPG). In contrast, the expression level of receptor activator of NF-κB ligand (RANKL) was increased in R2 and R3. Our findings suggest that TGF-β is closely related to the regulation of OPG induction and RANKL-mediated odontoclast differentiation depending on the timing of RANKL and OPG mRNA expression in the root-surrounding tissues of deciduous teeth during physiological root resorption.

Testicular cancer accounts for approximately 1% of adult cancers and 5% of all urologic cancers. The most common histopathological diagnosis of testicular neoplastic lesions are germ cell tumors (90-95% of cases), among which the majority of cases are seminomas, the most common malignant tumors among men aged 15-44. For better clinical diagnosis and treatment, it is important to understand the molecular mechanisms of tumor formation. In this study, the expression of the CacyBP/SIP protein and ERK1/2 and p38 kinases was analyzed for the first time in seminomas and normal testicular tissues. The research was carried out using archival tissue material from 30 patients undergoing surgery due to testicular seminoma, whereas the comparative material consisted of the adjacent normal tissues. Immunohistochemistry and qRT-PCR were used to identify the expression of CacyBP/SIP, ERK1/2, and p38. A very clear weakening of both immunoreactivity and gene expression of all tested parameters was demonstrated in seminomas compared to healthy tissues. Our findings suggest the involvement of the CacyBP/SIP protein in the ERK1/2 and p38 signalling pathways, which may be involved in the processes of testicular seminoma carcinogenesis. The results of our research provide the basis for further research in this area.

Healthcare professionals constantly face situations that reflect ecosystems’ degradation. These can negatively affect their mental health. Research suggests that hope and resilience can play an important role in this scenario, since they are related to/predict mental health in highly heterogeneous samples (considering geography, age, profession, health, etc.). In this context, the aims of the present study are: to characterize and explore the relationship between hope, resilient coping and mental health of Portuguese healthcare professionals. Using Google Forms, 276 healthcare professionals answered to the GHQ-28, the (adult) Trait Hope Scale, and the Brief Resilient Coping Scale (cross-sectional study). The minimum and maximum possible scores were reached, with the exception of the maximum score of GHQ-28-Total. Regarding Hope, 19.6% scored below the midpoint (M=43.46, SD=11.97); 29.3% revealed low resilience (M=14.93, SD=4.05); and the average of 4 of the 5 Mental Health scores (exception: Severe Depression) indicates the probability of a psychiatric case. Hope correlated with Social Dysfunction and GHQ-28-Total; resilient coping proved to be a (weak) predictor of 4 of the 5 GHQ-28 indicators (exception: Severe depression). The results support the need to promote the sample's mental health, hope and resilient coping. They also suggest that stimulating resilient coping may contribute to improving healthcare professionals’ mental health.

The signaling complex around voltage-gated sodium (Nav) channels includes accessory proteins and kinases crucial for regulating neuronal firing. Previous studies showed that one such kinase, WEE1—critical to the cell cycle—selectively modulates Nav1.2 channel activity through the accessory protein fibroblast growth factor 14 (FGF14). Here, we tested whether WEE1 exhibits crosstalk with the AKT/GSK3 pathway for coordinated regulation of FGF14/Nav1.2 channel complex assembly and function. Using the in-cell split luciferase complementation assay (LCA), we found that the WEE1 inhibitor II and GSK3 inhibitor XIII reduce FGF14/Nav1.2 complex formation, while the AKT inhibitor triciribine increases it. However, combining WEE1 inhibitor II with either one of the other two inhibitors abolished its effect on FGF14/Nav1.2 complex formation. Whole-cell voltage-clamp recordings of sodium currents (INa) in HEK293 cells co-expressing Nav1.2 channels and FGF14-GFP showed that WEE1 inhibitor II significantly suppresses peak INa density, both alone and in the presence of triciribine or GSK3 inhibitor XIII, despite the latter inhibitors’ opposite effects on INa. Additionally, WEE1 inhibitor II slowed the tau of fast inactivation, and caused depolarizing shifts in the voltage dependence of activation and inactivation. These phenotypes either prevailed or were additive when combined with triciribine but were outcompeted when both WEE1 inhibitor II and GSK3 inhibitor XIII were present. Concerted regulation by WEE1 inhibitor II, triciribine and GSK3 inhibitor XIII were also observed on long-term inactivation and use-dependence of Nav1.2 currents. Overall, these findings suggest a complex role for WEE1 kinase—in concert with the AKT/GSK3 pathway—in regulating the Nav1.2 channelosome.

Advanced glycation end-products (AGEs) form through non-enzymatic glycation of various proteins. Optic nerve degeneration is a frequent complication of diabetes, and retinal AGEs accumulation is strongly linked to diabetic retinopathy development. Type 2 diabetes mellitus (T2DM) is a major risk factor for Alzheimer's disease (AD), with patients often exhibiting optic axon degeneration in the nerve fiber layer. Notably, a gap exists in our understanding of how AGEs contribute to neuronal degeneration in the optic nerve within the context of both diabetes and AD. Our previous work demonstrated that glyceraldehyde (GA)-derived toxic advanced glycation end-products (TAGE) disrupt neurite outgrowth through TAGE-β-tubulin aggregation and tau phosphorylation in neural cultures. In this study, we further illustrated GA-induced suppression of optic nerve axonal elongation via abnormal β-tubulin aggregation in mouse retinas. Elucidating this optic nerve degeneration mechanism holds promise for bridging the knowledge gap regarding vision loss associated with DM and AD.

We construct a repeated quantum game with public goods by the quantum entanglement and strong reciprocity. By using the paradigm of quantum game analysis, we obtain that both the quantum entanglement and strong reciprocity are helpful to intensify cooperation and achieving Pareto optimality. In addition, under an example which is greenhouse green viable planting industry, we verify that the quantum entanglement and strong reciprocity have a positive role in cooperation.

Objectives: This study investigated the efficacy and safety of performing phacoemulsification using the eight-chop technique with iris hooks in patients with small pupils. Methods: The iris hooks and control groups each included 65 eyes. Cataract surgeries were performed using the eight-chop technique. The operative time, phaco time, aspiration time, cumulative dissipated energy, and volume of fluid used were measured. Best-corrected visual acuity, corneal endothelial cell density (CECD), and intraocular pressure (IOP) were measured preoperatively and postoperatively. Results: In total, 130 eyes of 107 patients (mean age, 75.9 ± 7.1 years; 58 men, 72 women) with cataracts were evaluated. The mean operative time, phaco time, aspiration time, cumulative dissipated energy, and volume of fluid used were 10.6 min, 20.7 s, 101.1 s, 7.8, and 38.0 mL, respectively, in the iris hooks group and 4.6 min, 16.2 s, 72.1 s, 7.0, and 28.9 mL, respectively, in the control group. The decrease in CECD at 19 weeks postoperatively was 2.1% and 1.2% for the iris hooks and control groups, respectively. In both groups, IOP decreased significantly (all p &lt; .01) at 7 and 19 weeks postoperatively. No intraoperative complications were observed in either group. Conclusions: The eight-chop technique using iris hooks resulted in a small postoperative reduction in CECD and excellent values for intraoperative outcome measures. In addition, those cataract surgeries were very short, efficient, and safe, without complications. The eight-chop technique using iris hooks could provide an ideal solution for patients with small pupils.

Coronavirus disease 2019 (COVID-19) has affected medical practice. More than 7,000,000 patients died worldwide after being infected with COVID-19; however, no specific laboratory markers have yet been established to predict death related to this disease. In contrast, electrocardiographic changes owing to COVID-19 include QT prolongation and ST-T changes; however, there have been no studies on ambulatory electrocardiographic markers of COVID-19. We encountered three patients diagnosed as having COVID-19 who did not have a prior history of significant structural heart diseases. All had abnormalities in ambulatory echocardiogram parameters detected by high-resolution 24-h electrocardiogram monitoring: positive late potentials (LPs) and T-wave alternans (TWA), abnormal heart rate variability (HRV), and heart rate turbulence (HRT). Case 1 involved a 78-year-old woman with a history of chronic kidney disease, Case 2 a 76-year-old man with hypertension and diabetes, and Case 3 a 67-year-old man with renal cancer, lung cancer, and diabetes. None of them had a prior history of significant structural heart disease. Although no significant consistent increases in clinical markers were observed, all three patients died, mainly because of respiratory failure with mild heart failure. LP, TWA, HRV, and HRT were all positive in three cases with no significant structural cardiac disease at the initial phase of admission. There is a possibility that LP, TWA, HRV, and HRT have the potential to be risk stratifiers of COVID-19 pneumonia in the early phase of admission. Further accumulation of data regarding ambulatory electrocardiographic markers in patients with COVID-19 is needed.

The involvement of the angiotensin II type 1 receptor in the Frank-Starling Law of the Heart, where the various activations are very limited, allows simple analysis of the kinase systems involved and thence extrapolation of the mechanism to that of angiotensin control of activation of cardiac and skeletal muscle contraction. The involvement of phosphorylation of the myosin light chain in the control of contraction is accepted but not fully understood. The involvement of troponin-I phosphorylation is also indicated but of unknown mechanism. There is no known signal for activation of myosin light chain kinase or Protein Kinase C-βII other than Ca²⁺/calmodulin but the former is constitutively active and thus has to be under control of a regulated inhibitor, the latter kinase may also be the same. Ca²⁺/calmodulin is not activated in Frank-Starling, i.e. there are no diastolic or systolic [Ca²⁺] changes. I suggest here that that the regulated inhibition is by myosin light chain phosphatase and/or β-arrestin. Angiotensin activation is by translocation of the β-arrestin from the sarcoplasm to the PM thus reducing its kinase inhibition action in the sarcoplasm, this reduced inhibition has been wrongly attributed to a mythical downstream agonist property of β-arrestin.

Yaba monkey tumor virus (YMTV) and Tanapox virus (TPV) are members of the Yatapoxvirus genus and can infect humans and other primates. Despite the threat posed by yatapoxviruses, the factors determining their host range are poorly understood. In this study, we analyzed the ability of YMTV and TPV orthologs of vaccinia virus K3 (called 012 in YMTV and TPV), which share 75% amino acid identity with one another, to inhibit PKR from 15 different primate species. We first used a luciferase-based reporter, and found that YMTV and TPV K3 orthologs inhibited PKR in a species-specific manner and showed distinct PKR inhibition profiles. TPV 012 inhibited PKR from 11 primates, including human, substantially better than YMTV 012. In contrast, both K3 orthologs inhibited the other four primate PKRs comparably well. Using YMTV 012 and TPV 012 hybrids, we mapped the region responsible for the differential PKR inhibition to the C- terminus of the K3 orthologs. Next, we generated chimeric vaccinia virus strains to investigate whether TPV K3 and YMTV K3 orthologs could rescue replication of a vaccinia virus strain that lacks PKR inhibitors K3L and E3L. Virus replication in primate-derived cells generally correlated with the patterns observed in the luciferase-based assay. Together, these observations demonstrate that yatapoxvirus K3 orthologs have distinct PKR inhibition profiles and inhibit PKR in a species-specific manner, which may contribute to the differential susceptibility of primate species to yatapoxvirus infections.

The ubiquitous presence of microplastics (MPs) in the environment poses a threat to ecosystems and increases concerns about their exposure to the human body. However, despite being consumed for health improvement, limited research has been conducted on MPs in functional foods. This study aimed to investigate the occurrence of MPs and the relation of the source of raw material or the manufacture in various omega-3 oil in the Korean market. MPs in omega-3 capsule and raw oil, sourced from both plant-based (PB) and animal-based (AB) sources, were investigated. We developed the method by direct filtration with acetone washing and analyzed MPs greater than 5 μm using microscope-Raman spectroscopy. The average number of MPs was found to be 1.2 ± 1.7 MPs/g for PB raw oil, 2.2 ± 1.7 MPs/g for AB raw oil, 3.5 ± 3.9 MPs/g for PB capsule oil, and 10.6 ± 8.9 MPs/g for AB capsule oil. Polypropylene and polyethylene terephthalate were major specious (83-95 %) found in omega-3 oil. The ratio of size range remained consistent across all groups, with a trend of higher detection rates as the size diminished. The results reveal that the main reason of MPs contamination is not the source of raw material but the manufacturing and packaging process for omega-3 oil.

The primary purpose of this article is to study the asymptotic and numerical estimates in detail for higher degree polynomials in $\pi(x)$ having a general expression of the form, \begin{align*} P(\pi(x)) - \frac{e x}{\log x} Q(\pi(x/e)) + R(x) \end{align*} $P$, $Q$ and $R$ are arbitrarily chosen polynomials and $\pi(x)$ denotes the \textit{Prime Counting Function}. The proofs require specific order estimates involving $\pi(x)$ and the \textit{Second Chebyshev Function} $\psi(x)$, as well as the famous \textit{Prime Number Theorem} in addition to certain meromorphic properties of the \textit{Riemann Zeta Function} $\zeta(s)$ and results regarding its non-trivial zeros. A few generalizations of these concepts have also been discussed in detail towards the later stages of the paper, along with citing some important applications.

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

Dust storms play a crucial role in the climate system and the space environment of Mars and have a great impact on human’s Mars exploration activities. The Martian dust storms exhibit significant regional, seasonal and interannual variations due to various controlling factors such as the large-scale atmospheric circulation, varying solar radiation forcing, and Martial orbital and rotational motions and their coupling to the atmospheric dynamics. This paper focuses on the review of cur-rent understandings on Martian dust storms. This paper begins by elucidating the basic properties of dust storms, and their driving mechanisms and impacts on atmospheric dynamics, atmospheric electric property, space environment, topography, and Mars explorations. Then it introduces the observation methods on different platforms including orbiters and landers/rovers, and the da-tasets constructed based on these historical observations for Martian dust storms. Finally, we pro-posed the dust storm monitoring and forecasting for the upcoming Chinese Tianwen-3 Mars sam-pling returning mission. It concludes by depicting the future research topics to systematically un-derstand the Martian dust storms.

It is an utmost importance to characterize drug candidates as early in the development pipeline as possible. Appropriate application of the emerging high throughput analytical techniques unlocks the opportunities to obtain experimental data for in vitro absorption, distribution, metabolism and elimination (ADME) profiling of large compound libraries which is crucial for selection of lead compounds. In an usual scenario, only one drug candidate will be selected from thousands of early compounds based on several stability and screening results. A high to medium throughput screening approaches could significantly accelerates the subsequent research and production phases. Traditionally, the analysis of metabolic stability assays heavily relies on high throughput LC-MS/MS techniques to meet with the lead profiling demands. In this study presented an innovative experimental approach that can offer a refreshing alternative. Laser Assisted Rapid Evaporative Ionization Mass Spectrometry (LA-REIMS) is a quick and efficient method for characterizing complex biological samples without laborious sample preparation and chemical separation. Therefore, using an automated LA-REIMS well plate reader as fast as 8 seconds per sample, we assessed the oxidative metabolic stability of active agents using biomimetic metalloporphyrin-based oxidative model reactions at various pH for commercially available drug substances and compared stability measurements with traditional HPLC-DAD-MS results.

The 5-hydroxymethylfurfural (HMF) is a six-carbon heterocyclic organic compound with two substituents an aldehyde group and an alcohol group. It is formed from saccharides as a result of two reactions: the Maillard reaction and the caramelization of saccharides. It has both a negative and a positive effect on the human body, which makes it, even more, an attractive research object. The objective of the study was to determine HMF content in honey samples available on the Polish market using three varied methods and compare the results obtained. The methodology used included: two spectrophotometric methods (by White and Winkler) and the HMF determination method based on the LC-MS/MS technique developed uniquely for this study. The determined HMF content in all tested honey samples did not exceed the applicable standard. All results are within the scope of the European Council Directive 2001/110/EC of 20 December 2001, i.e. they do not exceed HMF content in honey, which is 40 mg/kg.

Non-coding RNAs have been described as crucial regulators of gene expression and guards for cellular homeostasis. Some recent papers are focused on vault RNAs, one of the classes of non-coding RNA, and their role in cell proliferation, tumorigenesis, apoptosis, cancer response to therapy, and autophagy, which made them potential therapy targets in oncology. In the human genome, four vault RNA paralogues can be distinguished. They are associated with vault complexes, considered the largest ribonucleoprotein complex. The protein part of these complexes consists of a major vault protein (MVP) and two minor vault proteins (vPARP and TEP1). The name of the complex, as well as vault RNA, comes from the hollow barrel-shaped structure that reminds a vault. Their sequence and structure are highly evolutionary conserved and show many similarities in comparison with different species, but vault RNAs show various roles. Vaults were discovered in 1986, and their functions remained unclear for many years. Although not much is known about their contribution to cell metabolism, it has become clear that vault RNAs are involved in various processes and pathways associated with cancer progression and modulating cell functioning in normal and pathological stages. In this review, we discuss known functions of the human vault RNAs in the context of cellular metabolism, emphasizing processes related to cancer and cancer therapy efficacy.

Background and Objectives: The deltopectoral (DP) flap represents a reconstructive option for head and neck. It is a fasciocutaneous flap raised from the anterior chest wall below the clavicle. Its role partially declined with the arise of free flaps. However, it still remains a valid option in patients that could not undergo a reconstruction with free flaps. The aim of this retrospective study was to evaluate the role of the DP flap in head and neck reconstruction, with a focus on surgical outcomes and complications. Materials and Methods: Thirty-one patients who underwent head and neck reconstruction with DP flap were included in the study. The delayed technique was not used in any procedure to harvest the flap beyond the deltopectoral groove. The patients’ characteristics, the recipient site, the closure of the donor site and the flap-related complications were recorded. Results: The median time to autonomization of DP flap was 23 days. Post-operative complications were observed in 10 subjects (32.3%). A partial necrosis was seen in 5 patients (16.1%), while a complete necrosis developed only in one case (3.2%). The diabetes mellitus was the only parameter associated to post-operative complications. In particular, the percentage of necrosis in subjects with or without diabetes was 66.7% and 8.0%, respectively. Conclusions: The DP has a wide range of applications in head and neck reconstruction and a low complication rate can be observed. The delayed technique does not necessarily need to be applied, and the flap can be extended beyond the deltopectoral groove when necessary. However, patients with diabetes mellitus have a higher risk of postoperative necrosis of the distal portion of the flap.

Anti-interferon (IFN)-γ autoantibodies are linked to varicella-zoster virus (VZV) infection. Given the elevated risks of herpes zoster (HZ) in rheumatoid arthritis (RA) patients treated with Janus kinase inhibitors (JAKi), we aimed to examine the relationship between anti-IFN-γ autoantibodies with HZ development in JAKi-treated patients. In twenty-four RA patients with new-onset HZ and forty-two without HZ, serum titers of anti-IFN-γ autoantibodies, plasma levels of IFN-γ, monocyte chemoattractant protein-1 (MCP-1), and IFN-γ inducible protein-10 (IP-10) were measured by ELISA. Significantly lower MCP-1 levels were observed in patients with HZ compared to those without (median, 98.21pg/ml, interquartile range (IQR) 77.63-150.30pg/ml versus 142.3pg/ml, IQR 106.7-175.6pg/ml, p&lt;0.05). There was no significant difference in anti-IFN-γ titers, IFN-γ levels, or IP-10 levels between patients with and without HZ. Three of 24 patients with HZ had severe HZ with multi-dermatomal involvement. Anti-IFN-γ titers were significantly higher in patients with severe HZ than in those with non-severe HZ (median 24.8ng/ml, IQR 21.0-38.2ng/ml versus 10.5ng/ml, IQR 9.9-15.0ng/ml, p&lt;0.005). In conclusion, patients with HZ had significantly lower MCP-1 levels than those without HZ, and patients with severe HZ had significantly higher titers of anti-IFN-γ than those with non-severe HZ. Given small sample size, our results need further validation in future studies.

Introduction Atherosclerotic disease is a major contributor to heart failure, stroke, and myocardial infarction, significantly lowering the quality of life and life expectancy, with a significant burden on healthcare. Not all lesions deemed non-significant are benign, and conversely, not all significant lesions are causative of ischemia. Fractional flow reserve (FFR) provides a functional assessment of coronary lesions, while optical coherence tomography (OCT) offers detailed imaging of plaque morphology, aiding in therapeutic decision-making. The objective of this study was to evaluate the utility of OCT and FFR as adjunctive tools in the catheterization laboratory for guiding therapeutic decisions in patients with multivessel disease for non-culprit vessels. Specifically, we aimed to assess how OCT and FFR influence therapeutic decision-making in patients with multi-vessel coronary artery disease. Methods 36 patients with acute coronary syndrome (ACS) and multivessel disease were randomized 1:1 into two groups: one guided by FFR alone, and the other by a combination of FFR and OCT. For the FFR group, revascularization decisions for non culprit lesions were based solely on FFR measurements. If the FFR was >0.8, the procedure concluded, and the patient received maximal medical treatment. If the FFR was ≤0.8, a stent was placed. For the FFR + OCT group, if the FFR was >0.8, the revascularization decision was based on OCT findings. If there were no vulnerable plaques (VP), the procedure concluded, and the patient received maximal medical treatment. If OCT imaging indicated VP, then the patient underwent revascularization. If the FFR was ≤0.8, the patient underwent revascularization regardless of OCT findings. Results OCT imaging altered the therapeutic decision in 11 cases where FFR measurements were above 0.8, but the lesions were characterized as VP. Analyzing the total change in the decision to stent, 4 cases in the FFR group and 15 cases in the FFR and OCT group (4 based on FFR and 11 on OCT) revealed a statistically significant difference (p = 0.0006; Relative Risk = 0.2556; 95% CI: 0.1013 to 0.5603). When analyzing the change in the total decision both to stent and not to stent, we observed a statistically significant difference, with Group 1 having 7 cases and Group 2 having 15 cases (p = 0.0153; Relative Risk = 0.4050; 95% CI: 0.2004 to 0.7698) Conclusion Based on the findings of this study, OCT significantly increases the percentage of stenting procedures by identifying vulnerable lesions. The use of intracoronary imaging facilitates the timely identification and treatment of these vulnerable lesions. This underscores the crucial role of OCT in enhancing the precision of coronary interventions by ensuring timely intervention for vulnerable lesions, thereby potentially improving patient outcomes Acknowledgment funding „This work was supported by the University of Medicine, Pharmacy, Science and Technology ,, George Emil Palade’’ of Targu Mures Research Grant number 510/14/17.01.2022”

This study employed High-Performance Liquid Chromatography coupled with Diode Array De-tector and Mass Spectrometry (HPLC-DAD-MS) to characterize bioactive compounds in olive leaf extracts. The analysis revealed a diverse metabolic profile, predominantly composed of tyrosol, flavonoids, and hydroxycinnamic acid. The antioxidant activity of the extracts demonstrated their efficacy, with variations observed between neutral and acidic pH conditions. Encapsulation was explored as a preservation method, successfully maintaining the integrity of phenolic compounds in both liquid and powdered forms. All four extracts have an undeniable antimicrobial effect. Moreover, the antibacterial activity tested on E. coli ATCC 25922 and S. aureus ATCC 25923 strains significantly improved post-encapsulation, particularly for the acidic pH extract. The findings suggest that encapsulation can potentially conserve and/or enhance the antimicrobial activity of olive leaf extract, paving the way for developing functional products with improved shelf life and nutritional properties. Further investigations are recommended to elucidate underlying mecha-nisms and optimize encapsulation processes to maximize the benefits of olive leaf extract in di-verse applications.

A simple protocol for preparation of O-acylated enol form - (R/S)-ethyl-2-acetoxy-4-phenyl-4H-chromene-3-carboxylate 5 was presented. The compound was characterized by 1H-, 13C-and DEPT135 NMR spectra, including {1H,1H} COSY, {1H,13C} HSQC, {1H,13C} HMBC and 2D-NOESY spectra. The preferred regioselectivity for O-acylation of 3,4-dihydrocoumarin 5 in the presence of substituent in 4-th position in the chroman ring and accounting the steric hindrance of the ester group in 3-th place was confirmed.

The presence of antibiotic residues in honey has recently become a growing public health concern due to the overuse of these products in beekeeping and their transfer to the food industry. The aim of this study was to develop and validate a simple, selective and sensitive method for the simultaneous identification and quantification of residues of twenty-two sulfonamides, trimethoprim and dapsone in honey using a rapid and reliable liquid chromatography–tandem mass spectrometry (LC–MS/MS) method. The developed method showed good linearity, specificity, precision (repeatability and intra-laboratory reproducibility) and recovery. The decision limit (CCalpha) ranged between 2.16-22.12 µg/kg for CCα, while the detection capability (CCbeta) was between 2.16- 2.67-27.36 µg/kg. The method proved to be rapid, reliable and effective for the determination of sulfonamides, trimethoprim and dapsone from honey samples. The average recoveries were estimated to be between 70 and 106%. The relative standard deviations (RSDs) were between 6-18%. In practice, the method is essential to check the honey sold on the market and ensure its safety before it reaches the consumer.

Outbreaks of the crown-of-thorns seastar (CoTS) represent a major cause of coral loss on the Great Barrier Reef. Outbreaks might be explained by enhanced larval survival supported by higher phytoplankton availability after flood events, yet little is known about CoTS larvae feeding behaviour, in particular their potential for selective feeding. Here, single- and mixed-species feeding experiments were conducted on CoTS bipinnaria larvae using five algae (Phaeodactylum tricornutum, Pavlova lutheri, Tisochrysis lutea , Dunaliella sp. and Chaetoceros sp.) and two algal concentrations (1000 and 2500 algae mL^-1). Cell counts using flow-cytometry at the beginning and end of each incubation experiment allowed us to calculate the filtration and ingestion rates of each species by CoTS larvae. In line with previous studies, CoTS larvae ingested more algae when initial algal concentration was higher. We found evidence for the selective ingestion of some species (Chaetoceros sp., Dunaliella sp.) over others (P. lutheri, P. tricornutum). The preferred algal species had the highest energy content, suggesting that CoTS selectively ingested the most energetic algae. Ultimately, combining these results with spatio-temporal patterns in phytoplankton communities will help elucidate the role of larval feeding behaviour in determining the frequency and magnitude of CoTS outbreaks.

Following the detection of highly pathogenic avian influenza (HPAI) virus in countries bordering Kenya to the west, we conducted surveillance among domestic and wild birds along the shores of Lake Victoria. In addition, between 2018 and 2020, we conducted surveillance among poultry and poultry workers in live bird markets and among wild migratory birds in various lakes that are resting sites during migration to assess introduction and circulation of avian influenza viruses in these populations. We tested 7,464 specimens (oropharyngeal and cloacal swabs) from poultry and 6,531 fresh fecal specimens from wild birds for influenza A viruses by real-time RT-PCR. Influenza was detected in 3.9% (n=292) of specimens collected from poultry and 0.2% (n=10) of fecal specimens from wild birds. On hemagglutinin subtyping, most of the influenza A positives from poultry (274/292, 93.8%) were H9. Of 34 H9 specimens randomly selected for further subtyping, all were H9N2. On phylogenetic analysis, these viruses were genetically similar to other H9 viruses detected in East Africa. Only two of the ten influenza A positive specimens from the wild bird fecal specimens were successfully subtyped; sequencing analysis of one specimen collected in 2018 was identified as low pathogenicity avian influenza H5N2 virus of the Eurasian lineage and the second specimen, collected in 2020, was subtyped as H11. A total of 18 OP/NS swabs from poultry workers with ARI (12%) were collected; none were positive for influenza A virus. We observed significant circulation of H9N2 influenza viruses in poultry in live bird markets in Kenya. During the same period, low pathogenic H5N2 virus was detected in a fecal specimen collected in a site hosting a variety of migratory and resident birds. Although HPAI H5N8 was not detected in this survey, these results highlight the potential for introduction and establishment of highly pathogenic avian influenza viruses in poultry populations and the associated risk of spillover to human populations.

The recent increase in global consumption of rice has led to increased demand for sustainable water management in paddy cultivation. In this study, we propose an enhanced paddy simulation module to be introduced to Soil and Water Assessment Tool (SWAT) to evaluate the sustainability of paddy cultivation. The enhancements added to SWAT include: (1) modification of water balance calculation for impounded fields, (2) addition of an irrigation management option for paddy fields that are characterized by flood irrigation with target water depth, and (3) addition of a puddling operation that influences the water quality and infiltration rate of the top soil layer. In a case study, the enhanced model, entitled SWAT-Paddy, was applied to an agricultural watershed in Japan. The results showed that the SWAT-Paddy successfully represented paddy cultivation, water management, and discharge processes. Simulated daily discharge rates with SWAT-Paddy (R² = 0.8) were superior to the SWAT result (R² = 0.002). SWAT-Paddy allows the simulation of paddy management processes realistically, and thus can enhance model accuracy in paddy-dominant agricultural watersheds.

The reaction of 2-((diphenylmethylene)amino)acetonitrile with (E)-1-phenyl-3-(thiophen-2-yl)prop-2-en-1-one was performed by using 33% NaOH in CH3CN for 30 min at 0°C. The main product - rel-(2R,3S)-2-((diphenylmethylene)amino)-5-oxo-5-phenyl-3-(thiophen-2-yl)pentanenitrile was isolated and characterized by IR, 1H NMR, 13C NMR and high-resolution mass spectrometry (HRMS).

(1) Background: Previous systematic review suggested a beneficial effect of progressive muscle relaxation (PMR) for cancer patients receiving chemotherapy. However, poor quality of eligible studies impaired the reliability and validity of findings. Moreover, additional potential studies with good quality published in Chinese language have been published recently. The aim of the present systematic review was to investigate the value of PMR training in preventing and alleviating nausea and vomiting caused by chemotherapy among cancer patients. (2) Methods: We assigned two independent investigators to search all potential studies in PubMed, Cochrane Controlled Register of Trial (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), China Biomedical Literature database (CBM), China National Knowledge Infrastructure (CNKI), and Wanfang data. We used data extraction sheet extracted all essential information, and used the Cochrane risk of bias assessment tool to appraise the quality of eligible studies. Finally, we qualitatively summarized the results of all included studies. (3) Results: Six studies enrolling 288 patients were considered to meet our selection criteria finally. Of these 6 studies, three were labeled as moderate quality, and the remaining studies were low quality. All included studies consistently suggested that PMR has a positive impact on nausea and vomiting caused by chemotherapy among cancer patients especially alleviating the incidence, frequency and degree of delayed nausea and vomiting. (4) Conclusions: Independent studies indicated that PMR was a beneficial approach to prevent and alleviate nausea and vomiting caused by chemotherapy among cancer patients. However, further studies considering other types of primary tumors should be designed in order to increase the generality of PMR because studies included in the present systematic review mainly enrolled lung cancer and breast cancer.

Galectin-3 (Gal-3) is a lectin associated with fibrosis and inflammation, and increased circulating concentrations are considered a risk factor for atrial fibrillation (AF) in humans. This retrospective study aimed to evaluate the serum concentration of Gal-3 in dogs with cardiac disease, both with and without AF. Dogs with AF associated with congenital and acquired heart diseases were selected, while clinically healthy dogs and dogs with heart diseases but without AF served as controls. We statistically compared the serum concentration of Gal-3, assessed using a commercial canine-specific ELISA kit, among healthy dogs and dogs with heart disease with and without AF. Additionally, associations between Gal-3 and clinical and echocardiographic variables were evaluated. A total of 80 dogs were included, of which 17/80 (21.2%) were clinically healthy and 63/80 (78.8%) had heart disease, with 30/63 (47.6%) having AF. No significant difference in Gal-3 concentration was found between healthy dogs (3.90 ± 0.38 ng/mL) and dogs with heart disease, either with or without AF (3.45 ± 0.28 ng/mL, P=0.226 and 4.46 ± 0.27 ng/mL, P=0.286, respectively). Gal-3 showed a significant positive correlation with age (r=0.46, P &lt; 0.001). The results of this study suggest that Gal-3 does not have predictive value for the development of AF in dogs, but it is associated with advanced age.

Cannabidiol (CBD), a non-psychotropic main component of the Cannabis plant, is approved as a drug in the European Union (EU) under the name “Epidyolex”. However, the approval process as a food ingredient under the Novel Food Regulation was paused by the European Food Safety Authority (EFSA) due to a lack of safety data. Nevertheless, there is a growing, unregulated market in which CBD is advertised with various health claims and different dosage instructions. Of particular concern is its toxic effect on the liver and possible reproductive toxicity in humans. Studies suitable for calculating a benchmark dose were identified from the available data. Animal studies yielded a Benchmark Dose Lower Confidence Limit (BMDL) of 43 mg/kg bw/day, which translates into a safe human dose of approximately 15 mg/day. Only a Lowest Observed Adverse Effect Level (LOAEL) of 4.3 mg/kg bw/day could be identified from the human data. This updated risk assessment confirmed the Health-based Guidance Value (HBGV) of 10 mg/day based on human LOAEL. Despite existing data gaps, preliminary regulation appears advisable as the current form of the gray CBD market is unacceptable from the standpoint of consumer safety and protection.

Theoretical studies on the generation of nondiffracting and nondispersive light pulses and their experimental implementation are one of the renowned problems within electromagnetics. Current technologies enable creation of short-duration pulses of a few cycles with high power and fluency. An application of these techniques to the field of nondiffracting and nondispersive pulses requires a proper mathematical description of highly focused vector pulses. In this work, we study vector optical bullets in a dielectric medium with different polarization structures: linear, azimuthal, and radial. We report the differences caused by the vector model compared to the scalar model. We analyze effects caused by superluminal, subluminal, or even negative group velocity on properties of vector optical bullets inside a dielectric material.

Puccinia graminis f. sp. tritici (Pgt), the causal agent of wheat stem rust, poses a significant threat to global wheat production. Genetic resistance offers a cost-effective and sustainable solution. The durum wheat landrace PI 94701 was previously hypothesized to carry two stem rust resistance (Sr) genes, but their chromosomal locations were unknown. In this study, we mapped and characterized an all-stage Sr gene in PI 94701, temporarily designated as SrPI94701. In seedling tests, SrPI94701 was effective against all six Pgt races tested. Using a large segregating population (2,302 gametes), we mapped SrPI94701 within a 0.17-cM region flanked by markers pku69124 and pku69228, corresponding to 1.04- and 2.15-Mb genomic regions in the Svevo and Chinese Spring reference genomes. Within the candidate region, eight genes exhibited differential expression between the Pgt-inoculated resistant and susceptible plants. Among them, two NLR genes, TraesCS5B03G1334700 and TraesCS5B03G1335100, showed high polymorphism between parental lines, with upregulation observed in the resistant F4 line compared to its susceptible sister line. However, the flanking and completely linked markers developed in this study could not accurately predict the presence of SrPI94701 in uncharacterized wheat genotypes. SrPI94701 holds promise as a valuable component in breeding programs aimed at enhancing resistance against Pgt.

This study investigates the impact of plasma gradient modification and gradient illumination on the optoelectronic properties of buckypaper (BP), a flexible and large-scale material composed of multi-walled carbon nanotubes (MWCNTs). The BP samples were subjected to argon ion plasma treatment at varying power levels and durations, thereby creating different carrier concentration gradients on the surface. The photovoltage and photocurrent responses of the samples were then measured under uniform full illumination and gradient illumination conditions. The findings revealed that both plasma gradient modification and gradient illumination significantly enhanced the optoelectronic performance of BP. Notably, the combined application of these two methods yielded superior results compared to the application of either method alone. Specifically, the optimal plasma power for improving BP was found to be 20W. Under conditions of plasma gradient modification and gradient illumination, a photovoltage of 267.76 μV was generated, which represents a 21.44 times increase, and a photocurrent of 15.69 μA, reflecting a 32.69 times enhancement. The mechanism underlying this optoelectronic effect can be attributed to the presence of π-bonds in the carbon atoms. These π-bonds are excited by photons, resulting in the generation of small voltages and currents. This study underscores the potential of BP as an optoelectronic material and introduces a novel approach to enhance its optoelectronic properties through plasma gradient modification and gradient illumination.

In previous papers we have derived equations of motion with radiation terms and proved the existence-uniqueness of periodic solution of the 3-body problem of classical electrodynamics. The number of equations of motion – 12 is more than the number of unknown functions – 9. It turns out that 9 equations are independent and the rest 3 ones are consequences of them. These three equations have a solution and they give the expressions for the energy of the moving particles. The main goal of the present paper is to estimate the energy of rounding about the nuclei particles and compare it with the values given by quantum mechanics.

Omega-3 polyunsaturated fatty acids (ɷ-3 PUFAs) offer diverse health benefits, such as supporting cardiovascular health, improving cognitive function, promoting joint and musculoskeletal health, and contributing to healthy aging. Despite their advantages, challenges like oxidation susceptibility, low bioavailability, and potential adverse effects at high doses persist. Nanoparticle encapsulation emerges as a promising avenue to address these limitations while preserving stability, enhanced bioavailability, and controlled release. This comprehensive review explores the therapeutic roles of omega-3 fatty acids, critically appraising their shortcomings and delving into modern encapsulation strategies. Furthermore, it explores the potential advantages of Metal-organic framework nanoparticles (MOF NPs) compared to other commonly utilized nanoparticles in improving the therapeutic effectiveness of omega-3 fatty acids within drug delivery systems (DDS). Additionally, it outlines future research directions to fully exploit the therapeutic benefits of these encapsulated omega-3 formulations for cardiovascular disease treatment.

The buildup dynamics of diode-pumped passively mode-locked solid-state laser is thoroughly explored by the real-time measurement with temporal sampling rate up to 40 GHz. A concise cavity is developed to ensure the transient dynamics purely arising from the gain medium and saturable absorber. Experimental results reveal that the laser output in the buildup process exhibits numerous passively Q-switched pulses followed with a damped relaxation oscillation prior to the stable mode locking. Furthermore, it is confirmed that the laser output has already displayed single clean mode-locked pulses inside the first several Q-switched envelopes before stepping into the stage of relaxation oscillation. The present real-time exploration is expected to provide important information for practical applications with temporal modulation of the pump intensity.

The cell case temperature versus time profiles of a multistage fast charging technique (4C-1C-CV)/fast discharge (4C) in a 2.3 Ah cylindrical lithium-ion cell are analyzed using a 1D thermal model. Heat generation is dominated by the irreversible component associated to cell overpotential, although evidences of the reversible component are also observed, associated to the heat related to entropy from the electrode reactions. The final charging stages (i.e., 1C-CV) significantly reduce heat generation and cell temperature during charge, resulting in a thermally safe charging protocol. Cell heat capacity was determined from cell specific heats and cell materials thickness. The 1D model adjustment of the experimental data during the 2 min. resting period between discharge and charge allowed us to calculate both the time constant of the relaxation process and the cell thermal resistance. The obtained values of these thermal parameters used in the proposed model are almost equal to those found in the literature for the same cell model, which suggests that the proposed model is suitable for its implementation in thermal management systems.

The use of omega-3 fatty acids (omega-3 FA) in the treatment of atopic dermatitis (AD) is an area of ongoing research. Some studies suggest that dietary supplementation with omega-3 FA can help manage symptoms of AD by reducing lesion severity, skin inflammation, dryness and itching, while other show no significant beneficial effect. The aim of this study was to evaluate the effect of omega-3 FA form fish oil in combination with GLA form blackcurrant seed oil in children with AD. This is a longitudinal, prospective, randomized, triple blind, placebo-controlled parallel clinical trial. The study was conducted during the 2-year period from autumn, winter, and spring avoiding the summer when AD usually improves. Children were randomized to receive the active study product (Mega Kid®) containing specific blend of omega-3 and omega-6 fatty acids or placebo. Primary outcomes were change in severity of AD measured using SCORing Atopic Dermatitis (SCORAD) patient oriented SCORAD (PO-SCORAD) and the difference in TCS use. Secondary outcomes were change in itch intensity, sleep quality and Family Dermatology Life Quality Index (FDLQI). Data were analyzed for 52 children (26 in the intervention group and 26 in the placebo group). In children receiving active product intention-to-treat analysis showed that after 4 months of treatment, there was a significant decrease in the SCORAD index (from median 42 to 25, p < 0.001) and use of topical corticosteroids (from median 30 to 10 mg/day, p < 0.001) but also significant improvement in itch, sleep quality and overall quality of life. Omega-3 fatty acids in combination with GLA and vitamin D has a great beneficial effect in treatment of atopic dermatitis in children. Therefore, we can conclude that supplementation with this specific combination could be considered a safe and effective intervention that can significantly reduce the severity of AD in pediatric patients.

There is a need for cost-effective and non-invasive methods of monitoring feeding behavior in livestock operations, considering the significant impact of feed costs on economic efficiency and assisting in detecting health issues of group-fed animals. This paper proposes using deep learning-based computer vision techniques to detect pen-fed beef cattle feeding behavior using Mask Region-based Convolutional Neural Network (RCNN). A deep learning model was pre-trained on the Common Objects in Context (COCO) dataset to generate cattle instance segmentation. Manually defined feed bunk polygons are compared with these segmentation masks to derive feeding time for each bunk. A full day’s worth of video data and the corresponding physical sensor data are collected for the experiment. By benchmarking the computer vision detected data with physical ground truth over random time segments from morning to evening (thus various lighting conditions), the optimal thresholds for Mask RCNN are determined to be 0.7 for bounding boxes and 0.1 for masks. Using these parameters. The reports suggest that the computer vision system achieved a precision of 87.2% and a recall of 89.1%, signifying precise detection of feeding events. Our study, to the best of our knowledge, was one of the first investigations of instance segmentation on feeding time sense, which combines deep learning methods with traditional computer vision logistics, reporting on feeding time data collection and processing, camera testing and adjustment, and performance evaluation. Future research directions include computer vision applied in feed grading and animal re-identification for individual production analysis.

In order to sustain the marine environment relationship between the environmental factors and marine biota must be investigated. This study aims to study such a correlation in the adjacent waters of Nan Wan Bay, Kenting, Taiwan, and to explore the covariance of environmental factors on marine life (whether they enhance or diminish it). To achieve these objectives, factor analysis was used to identify potential latent variables that could affect the water quality of the adjacent waters, including phytoplankton (quantity), zooplankton (quantity), and fish (quantity and species). These potential variables were named based on the results of past studies and related literature. Finally, a structural equation model (SEM) was constructed to establish a marine ecological model among the potential variables. The factor analysis results revealed that nutrients, upwelling, and primary productivity are the primary factors affecting the environmental changes in the adjacent waters of Nan Wan Bay. The comprehensive SEM showed that nutrients and primary productivity significantly impact plankton. Path analysis indicated that primary productivity has the highest direct effect on the phytoplankton cluster. However, the upwelling has a low significance in its effect on phytoplankton, zooplankton, and fish clusters. Compared to the results of past related studies, the SEM proposed in this study can reflect a considerable degree of change in the waters.

White oak mortality is a significant concern in forest ecosystems due to its impact on biodiversity and ecosystem functions. Understanding the factors influencing white oak mortality is crucial for effective forest management and conservation efforts. In this study, we aimed to investigate the spatial pattern of white oak mortality rates at different locations of the eastern US and explore the underlying processes involved with the spatial distribution patterns. Multicycle Forest Inventory and Analysis data were compiled to capture white oak plots across the eastern US. White oak mortality data were collected across plot systems that utilized Diameter at Breast Height between two periods. Ripley’s K function was used to study the spatial pattern of white oak mortality rate. Results found clustered patterns at both local and broad scales and random patterns at broad scales only across the southern and northern regions. However, the central region indicated both clustered and random patterns at local scale only. We found uniform patterns at a broad scale across all regions. Our findings demonstrated the importance of the spatial pattern of the white oak mortality rate and the underlying factors associated with it. This research can inform forest management practices for the conservation of white oak populations at varying scales. Future research is needed for a comprehensive assessment of biotic and abiotic factors for forest management strategies at various spatial scales aimed at mitigating white oak mortality.

It is vital to analyze ship collision risk for preventing collisions and improving safety at sea. This paper takes Ningbo-Zhoushan Port, a typical complex navigable water, as the research object, propose a probabilistic conflict detection method to estimate the potential collision risk by using a dynamic domain model driven by AIS data. Combined with the algorithm of fast modularity optimization and spectral clustering, a ship group extraction method from the perspective of water navigation management was proposed. Aiming at ship traffic characteristics in complex navigable waters, conduct dynamic calculation of ship collision risk from individual, regional and local multi-scale perspectives. The results show that the proposed method can detect the collision risk in a timely, reliable and effective manner under complex dynamic conditions. As such, they provide valuable insights for ship collision risk prediction and the development of risk mitigation measures.

A mathematical procedure enabling the transformation of an arbitrary tessellation of a surface into a bi-colored complete graph is introduced. Polygons constituting the tessellation are represented by vertices of the graphs. Vertices of the graphs are connected by two kinds of links/edges, namely, by a green link, when polygons have the same number of sides, and by a red link, when the polygons have a different number of sides. This procedure gives rise to a semi-transitive, complete, bi-colored Ramsey graph. The Ramsey number was established as R_trans (3,3)=5. Shannon entropies of the tessellation and graphs are introduced. Ramsey graphs emerging from random Voronoi and Poisson Line tessellations were investigated. The limits ζ=lim┬(N→∞)⁡〖N_g/N_r 〗, where N is the total number of green and red seeds, N_g and N_r, were found ζ=0.272±0.001 (Voronoi) and ζ= 0.47±0.02 (Poisson Line). The Shannon Entropy for the random Voronoi tessellation was calculated as S= 1.690±0.001 and for the Poisson line tessellation as S =1.265±0.015.

To elucidate mesenchymal stromal cells (MSC)-tumor intricate and ambiguous interactions, the reliable cell labeling and tracking techniques are imperative. Traditional methods of cell labelling have limitations mostly relevant to need for genetic modification what demands the exploration for alternative strategies. Here, we propose using fluorescent photoconvertible microcapsules containing Rhodamine B (RhB) to study mMSC migration in brain tumors. These 3 μm sized microcapsules are readily internalised by cells and undergo photoconversion under 561 nm laser exposure with fluorescence blue shift on demand. Optimal photoconversion was achieved with a laser irradiation duration of 0.4 ms, which provide a maximal brightness of photoconverted label without an excessive laser exposure on cells. Capsules modified with polyallylamine hydrochloride demonstrated the best potential for intracellular uptake without significantly affecting cell viability, motility, or proliferation. The optimal ratio of 20 capsules per mMSC was determined for labeling. Moreover, migration of individual mMSCs within 2D and 3D glioblastoma cell (EPNT-5) colonies over 2 days and in vivo tumor settings over 7 days was tracked. Our study unveils a robust platform for investigating MSC-tumor dynamics, offering insights into therapeutic strategies. Photoconvertible microcapsules could also become an indispensable tool for studying complex fundamental processes of cell-cell interactions for a wide range of problems in biology and medicine.

Childhood obesity has become a global epidemic, with significant increases in prevalence over recent decades. While excessive calorie consumption and physical inactivity are known factors, emerging research highlights the role of Endocrine-Disrupting Chemicals (EDCs), particularly obesogens, in obesity's pathogenesis. This review explores the historical context of the environmental obesogens hypothesis, their sources, mechanism of action, impact on prenatal and postnatal development and epigenetics. Additionally, it discusses the long-term consequences of childhood obesity and proposes prevention strategies that will mitigate the negative health effects. Obesogens were found to disrupt hormonal balance and metabolic processes through various mechanisms such as altering gene expression, hormonal interference, and inflammation. Especially significant, was exposure during critical windows of development which correlates with increased risk of obesity in childhood or adolescence. Long-term effects of childhood obesity include chronic health conditions and psychosocial issues. A comprehensive approach is necessary to address childhood obesity, encompassing genetic, environmental, and lifestyle factors. Prevention strategies should focus on reducing obesogens exposure, promoting healthy lifestyles, and implementing regulatory policies. Future research should investigate obesogens-diet interactions, microbiome impacts, and combined obesogens effects. Long-term human studies are also crucial for validating findings from animal models and allow for inform decision-making to combat the obesity pandemic.

Terrestrial orchid tubers are an important source of food in some parts of Africa and are traditionally included in the diets of most rural communities in Malawi. However, there is limited information on the nutritional and phytochemical content of the Malawian orchids to substantiate their traditional use. The present study evaluates the nutritional and phytochemical variation of four orchid species: Disa zombica, Satyrium buchananii, Satyrium carsonii, and Satyrium trinerve, collected from the same ecological zone of Malawi. The proximate content, minerals, phytochemicals, and functional properties were analysed using official procedures. Protein ranged from 2.19% to 4.65%, whereas carbohydrate ranged from 65.24% to 80.22%, with S. carsonii and S. trinerve registering the highest protein and carbohydrate contents, respectively. Iron and potassium were highest in D. zombica, while sodium and calcium were highest in S. buchananii. The total phenolics ranged from 228.56 to 500.00 mg GAE/100 g, with D. zombica registering the highest. The water absorption capacity ranged from 4.10 to 10.88 g/g. Albeit variable levels, the study provides evidence that orchid species contain essential nutrients and phytochemicals important for human nutrition and health. Furthermore, the functional properties can be utilised in the development of food products, such as baked products.

Autoimmune disorders and some types of blood cancer originate when B lymphocytes malfunction. In particular, when B cells produce antibodies recognizing the body’s proteins, it leads to various autoimmune disorders. And when B cells of various developmental stages transform into cancer cells, it results in blood cancers, including multiple myeloma, lymphoma, and leukemia. Thus, new methods of targeting B cells are required for various patient groups. Here, we used protein kinase inhibitors alectinib, brigatinib, ceritinib, crizotinib, entrectinib, and lorlatinib previously approved as drugs treating anaplastic lymphoma kinase (ALK)-positive lung cancer cells. We hypothesized that the same inhibitors will efficiently target leukocyte tyrosine kinase (LTK)-positive, actively protein-secreting mature B lymphocytes, including plasma cells. We isolated CD19-positive human B cells from the blood of healthy donors and used two alternative methods to stimulate cell maturation toward plasma cells. Using cell proliferation and flow cytometry assays, we found that ceritinib and entrectinib eliminate plasma cells from B cell populations. Alectinib, brigatinib, and crizotinib also inhibited B cell proliferation, while lorlatinib had no or limited effect on B cells. More generally, we concluded that several drugs previously developed to treat ALK-positive malignant cells can be also used to treat LTK-positive B cells.

Endolysin of bacteriophage T5 (EndoT5) is a Zn2+-dependent and Ca2+-activated L-alanyl-D-glutamate peptidase that hydrolyses peptidoglycans during the destruction of the cell wall of the phage host bacterium Escherichia coli. To elucidate the mechanism of calcium activation, the spatial solution structure of EndoT5 in a complex with two ions - catalytic Zn2+ and regulatory Ca2+ (EndoT5-Zn2+Ca2+, PDB ID: 8P3A) was determined by high-resolution NMR and deposited in the Protein Data Bank. We show that coordination of the Ca2+ ion fix the spatial position of polar amino acid residues D113, N115 and S117. As a result, the intramolecular mobility of extended protein loops (residues 40-70 and 111-132) is significantly reduced compared to the mobility of these loops in the structure of an enzyme containing only a catalytic a Zn2+ ion (EndoT5-Zn2+, PDB ID: 2MXZ). In the stabilized EF-like calcium-binding loop (residues 111-132), the number of van der Waals interactions with amino acid residues of the globular core of the protein increases. The binding of the Ca2+ ion is accompanied by the selection of the functional states of both extended loops of the enzyme (residues 40-70 and 111-132), because of which EndoT5-Zn2+Ca2+ acquires the structural integrity necessary for catalysis. Therefore, the mechanism of activation of L-alanyl-D-glutamate peptidase of bacteriophage T5 by Ca2+ ions involves stabilization of the enzyme molecule in a catalytically active “open” conformation. This work sheds light on the structural grounds of the ion-dependent functional proteoforms of this interesting protein.

This paper presents the work done to transition the lab scale synthesis (1 g) to a large scale (400 g) synthesis of the 3-5-diamino-1H-Pyrazole Disperazol; a new pharmaceutical for treatment of antibiotic resistant Pseudomonas aeruginosa biofilm infections. The potentially hazardous diazotisation step in the lab scale synthesis was transformed to a safe and easy to handle flow chemistry step. Additionally, the paper presents an OSHA recommended safety assessment of the active compound E, performed by Fauske and Associates, LLC.

Liver X receptors (LXR) are deemed as potential drug targets for atherosclerosis, whereas a role in adipose tissue expansion and its relation to insulin sensitivity remains unclear. To assess the metabolic effects of LXR activation, C57BL/6 mice on a high-fat diet (HFD) were treated with the dual LXRα/β agonist T0901317 (30 mg/kg per day) for 3 weeks. Differentiated 3T3-L1 was used for analysing the effect of T0901317 on glucose uptake.T0901317 reduced fat mass, accompanied by a massive fatty liver and lower adipokine levels in circulation of HFD mice. Increased adipocyte apoptosis and macrophage infiltration were found in epididymal fat of T0901317-treated HFD mice. In addition, T0901317 treatment promoted basal lipolysis, but blunted the anti-lipolytic action of insulin. Furthermore, LXR activation antagonized PPARγ target genes in epididymal fat and PPARγ-PPRE binding activity in 3T3-L1 adipocytes. Although the glucose tolerance was comparable to that in vehicle-treated HFD mice, the insulin tolerance was significantly decreased in T0901317-treated HFD mice, indicating decreased insulin sensitivity by T0901317 administration, and which was further supported by impaired insulin signalling found in epididymal fat and decreased insulin-induced glucose uptake in 3T3-L1 by T0901317administration. These findings reveal that LXR activation impairs adipose expansion which contributes to decreased insulin sensitivity.

Drainage systems are usually dimensioned for design storms based on intensity-duration-frequency (IDF) curves of extreme precipitation. For each location, different IDF curves are established based on local hydrological conditions. Recent research shows that these curves also vary with time, and should be updated with recent data. The purpose of this study is to evaluate IDF curves obtained from precipitation simulations from the Eta RCM, comparing them with IDF curves obtained from data of a rainfall station. Climate models can be a useful tool for assessing the impacts of climate changes on drainage systems, referring precipitation forecasts. In this study, the Eta RCM was forced by two global climate models: HadGEM2-ES and MIROC5. The bias of the precipitation data, generated by RCM models, was corrected using a Gamma distribution. The Juqueriquerê River Basin, in the cities of Caraguatatuba and São Sebastião, São Paulo State, Brazil, was chosen as a case study. The results show a good correlation between the IDF curves of simulated and observed rainfall for the control period (1960-2005), indicating the strong possibility of using the Eta RCM precipitation forecasts for 2007 - 2099 to establish future IDFs thereby, taking into account climate changes in urban drainage design.

The DNA Damage Response (DDR) network and the mitogen-activated protein kinase (MAPK) signaling pathway are crucial mechanisms for the survival of all living beings. An accumulating body of evidence suggests that there is a crosstalk between these two systems, thus favoring the appropriate functioning of multi-cellular organisms. On the other hand, aberrations within these mechanisms are thought to play a vital role in the onset and progression of several diseases, including cancer, as well as in the emergence of drug resistance. Here, we provide an overview of the current knowledge regarding alterations in the DDR machinery and the MAPK signaling pathway, as well as abnormalities in the DDR-MAPK functional crosstalk in multiple myeloma, the second most common hematologic malignancy. We also present the latest advances in the development of anti-myeloma drugs targeting crucial DDR- and MAPK-associated molecular components. These data could potentially be exploited to discover new therapeutic targets and effective biomarkers, as well as for the design of novel clinical trials. Interestingly, they might provide a new approach to increase the efficacy of anti-myeloma therapy by combining drugs targeting the DDR network and the MAPK signaling pathway.

Spinocerebellar ataxia type 3 is a neurodegenerative disease caused by an abnormal expansion of CAG repeats in the disease gene ATXN3, leading to prolonged polyglutamine (polyQ) tracts in the respective protein ataxin-3. The polyQ-expanded protein forms polyQ-containing aggregates in several brain regions which leads to neuronal cell loss. Autophagy is thought to play a significant role in clearing these polyQ-containing protein aggregates. Therefore, the autophagy mechanism was investigated in SCA3 with focus on the autophagic protein p62/sequestosome-1. Human and mouse RNA sequencing data were analyzed to determine RNA expression level of autophagic genes. Additionally, autophagy was studied in the SCA3 304Q knock-in mouse model and through several cell culture experiments using HEK-293T cells transfected with ATXN3 of differ-ent polyQ lengths. For cell culture experiments, autophagy was induced with rapamycin treat-ment, proteasomal degradation was blocked with MG132 and degradation of autophagic pro-teins was investigated using cycloheximide treatment. Here, we report an increased autophagy impairment with SCA3 disease progression seen in HEK-293T cells transfected with ATXN3 plasmid with expanded polyQ tracts, higher aged 304Q-knock-in mice, or human post-mortem brain material. Furthermore, co-localized aggregation of the autophagic protein p62 and the dis-ease protein ATXN3 was observed in the course of SCA3 disease. Therefore, we suggest a signifi-cant role for p62 in aggregate formation seen in the neurodegenerative disease SCA3.

The collection of photo shoots during the systematic monitoring activities is useful to witness the ecological role of marine phanerogams as hosts for a rich variety of organisms in coastal and transitional waters. Cymodocea nodosa is present in the Taranto seas. In the Mar Piccolo, it reached high covers in short times, up to 100%, due to the bettering of the environmental conditions. The most recent observations showed that it offers welcoming towards several vertebrates and invertebrates, native and non-indigenous, as well as to micro and macroalgae. The NPPR funded activities will make these observations more robust and structural.

Diastolic dysfunction, a prevalent condition characterized by impaired relaxation and filling of the left ventricle, significantly contributes to heart failure with preserved ejection fraction (HFpEF). Galectin-3, a β-galactoside-binding lectin, has garnered attention as a potential biomarker and mediator of fibrosis and inflammation in cardiovascular diseases. This comprehensive review investigates the impact of galectin-3 on diastolic dysfunction. We explore its molecular mechanisms, including its involvement in cellular signaling pathways and interaction with components of the extracellular matrix. Evidence from both animal models and clinical studies elucidates galectin-3's role in cardiac remodeling, inflammation, and fibrosis, shedding light on the underlying pathophysiology of diastolic dysfunction. Additionally, we examine the diagnostic and therapeutic implications of galectin-3 in diastolic dysfunction, emphasizing its potential as both a biomarker and a therapeutic target. This review underscores the significance of comprehending galectin-3's role in diastolic dysfunction and its promise in enhancing diagnosis and treatment approaches for HFpEF patients.

As a precious natural resource, forests are being destroyed. In previous studies, there is a lack of interactive assessment of its distribution that comprehensively considers multiple external disturbances. This paper takes the Barcelona Metropolitan Region as an example. Based on remote sensing, it analyzes the development process of the forest from 2006 to 2018 through multiple landscape indicators, and OLS models were established to analyze variables that have direct and indirect effects on forest distribution. In addition, the ecological structure of the forest was analyzed based on NDVI. It was found that the forest area is the largest but has been decreasing, becoming more complex in distribution structure. Much of the forest was converted to agricultural land and grassland. The green quality of forests was increasing, and the broad-leaved forest, the second largest area, contributes the most. NDVI is the most important positively correlated variable, and daytime surface temperature is an important inverse factor related to NDVI. In addition, NDBI is also a negative condition that inhibits forest development. In conclusion: The BMR forest area is decreasing and becoming more fragmented. NDVI and daytime LST are the two most significant factors. Climate warming may lead to worse forest development.

In the Vietnamese Mekong delta, soil quality and crop yield are steadily declining under rice monocultures with three crops per year. The objective of this study was to evaluate the medium-term effects of rotating rice with upland crops and adding organic amendments on rice yield and relate it to soil quality. A field trial with split-plot design including two factors and three replicates was carried out from 2017 to 2020, over the course of nine consecutive cropping seasons. Crop rotations and organic amendments were applied as main-plot and subplot factors, respectively. The rotations were: 1) rice–rice–rice (R–R–R), 2) soybean–rice–rice (So–R–R), and 3) sesame–rice–rice (Se–R–R), while organic amendment treatments included: i) no amendment (NO-AM); ii) compost of rice straw and cow manure (RS+CM), and iii) sugarcane compost (SGC); the composts were applied at a rate of 2.0 t ha-1. The rotation cycle started with the so-called spring–summer (SS), followed by summer–autumn (SA) and ended with the winter–spring (WS) season. Rice yield significantly (P &lt; 0.05) increased by organic amendments after nine growing seasons (2019–2020 WS), with an increment of 5.1% for RS+CM (7.07 ton/ha) and 6.1% for SGC (7.14 ton/ha). Contrary to our expectation, rotations with upland crops did not significantly increase rice yield. Rice yield significantly and positively correlated with an integrated soil quality index SQI (r = 0.86) for the topsoil (0–15 cm), but not for the subsoil (15–30 cm). The increased availability of soil nutrients (Si and marginally also P) and improved soil physical properties probably induced by organic amendments, along with other soil properties under study, cumulatively attributed to enhanced rice yield. Use of a SQI involving several soil quality indicators enables to overall quantify the importance of soil fertility for rice yield versus other factors and it provides an effective means of quantifying the integrated effect of improved management. Moreover, integrating a wide range of soil quality indicators in a SQI ensures its applicability across diverse settings, including different crop rotations and various soil types.

The rationalization of single molecule magnets’ (SMMs) magnetic properties by quantum mechanical approaches represents a major task in the field of the Molecular Magnetism. The fundamental interpretative key of molecular magnetism is the phenomenological Spin Hamiltonian and the understanding of the role of its different terms by electronic structure calculations is expected to steer the rational design of new and more performing SMMs. This paper deals with the ab initio calculation of isotropic and anisotropic exchange contributions in the Fe(III) dimer [Fe₂(OCH₃)₂(dbm)₄]. This system represents the building block of one of the most studied Single Molecule Magnets ([Fe₄RC(CH₂O)₃)₂(dpm)₆] where R can be an aliphatic chain or a phenyl group just to name the most common functionalization groups) and its relatively reduced size allows the use of a high computational level of theory. Calculations were performed using CASSCF and NEVPT2 approaches on the X-ray geometry as assessment of the computational protocol, which has then be used to evinced the importance of the outer coordination shell nature through organic ligand modelization. Magneto-structural correlations as function of internal degrees of freedom for isotropic and anisotropic exchange contributions are also presented, outlining for the first time the extremely rapidly changing nature of the anisotropic exchange coupling.

Powders with phase composition including syngenite K2Ca(SO4)2·H2O and/or calcium sulfate di-hydrate (gypsum) CaSO4·2H2O were synthesized from powder of calcium carbonate CaCO3 and water solutions of potassium hydrosulfate KHSO4 of various (0.5M, 1M and 2M) concentrations. Molar ratio of starting salt KHSO4/CaCO3=2 were used to provide formation of syngenite K2Ca(SO4)2·H2O. But when using 0.5M water solution of potassium hydrosulfate KHSO4 the phase composition of synthesized powder was presented by calcium sulfate dihydrate (gypsum) CaSO4·2H2O. When using 1M and 2M water solution of potassium hydrosulfate KHSO4 the syn-genite K2Ca(SO4)2·H2O was found as predominant phase in synthesized powders. According es-timations made from thermal analysis data when 1.0M and 2.0M water solutions of potassium hydrosulfate KHSO4 were used the content of calcium sulfate dihydrate (gypsum) CaSO4·2H2O in these powders were not higher then as 7.9 and 1.9 % respectively. Phase composition of products isolated from mother liquors via water evaporation consisted of syngenite K2Ca(SO4)2·H2O and potassium sulfate (arcanite) K2SO4. Synthesized powders can be used in preparation of biocom-patible bioresorbable materials with phase composition in the K2O‑CaO‑SO3‑H2O system; as matrix of thermo- or photo-luminescent materials; as components reducing the setting time and increasing strength of sulfate cements; in the fertilizing industry and also as a components of Martian regolith simulant.

Dysregulation of the Cyclin-dependent kinase 8 (CDK8) activity has been associated to many diseases including the colorectal and breast cancer. As usual in the CDK family, the activity of CDK8 is controlled by a regulatory protein called cyclin C (CycC). But while human CDK family members are generally activated in two steps that is, the binding of the cyclin to CDK and the phosphorylation of a residue in the CDK activation loop, CDK8 does not require the phosphorylation step to be active. Another peculiarity of CDK8 is its ability to be associated to CycC while adopted an inactive form. These specificities raise the question of the role of CycC in the complex CDK8-CycC, which appears to be more complex than for the other members of CDK family. Through MD simulations and binding free energy calculations, we investigated the effect of CycC on the structure and dynamics of CDK8 on the one hand, and the structural molecular basis of the protein-protein interaction between the two partners on the other hand. We found that CycC has a stabilizing effect on CDK8 and identified specific interaction hotspots within its interaction surface compared to other human CDK/Cyc pairs. Targeting these specific interaction hotspots could be a promising approach in terms of specificity, to effectively disrupt the interaction between CDK8. The simulation of the conformational transition from the inactive to the active form of CDK8 suggests that the residue Glu99 of the CycC may assume the role of the missing phosphorylation step in the activation mechanism of CDK8. In a more general view, these results point the importance of keeping the CycC in computational studies when studying the human CDK8 protein in both the active and the inactive form.

The inclusion of various chemical substances in personal care products (PCPs) and cosmetic formulations can be associated with disruption and damage to the nervous system. Microplastics, benzophenones, parabens, phthalates and metals are among the most common chemical substances found in cosmetics that have been shown to induce neurotoxic mechanisms. Although cosmetic neurotoxin exposure is believed to be minimal, different exposure scenarios of cosmetics suggest that these neurotoxins remain a threat. Special attention should be paid to early exposure in the first gestation weeks, when critical processes, like the migration and proliferation of the neural crest derived cells start to form the ENS. Importantly, cosmetic’s neurotoxins can cross the placenta barrier and so affect the future embryo, but are also secreted in the breast milk, so that babies remain exposed for longer periods, even after birth. In this review we explore how neurotoxins contained in cosmetic and PCPs may have a role in the pathogenesis of various neurodevelopment disorders and neurodegenerative diseases, and therefore also in congenital enteric aganglionosis as well as in postnatal motility disorders. Understanding the mechanisms of these chemicals used in cosmetic formulations and their role in neurotoxicity is crucial to determining the safety of use for cosmetic products during pregnancy.